--- title: V4:E02:S04 - Antibiotic Treatment Side Effects created: 2024-07-01 07:42:33.307257 updated: 2025-01-15 23:52:42.089460 source: ChatGPT source_file: conversations-000.json conversation_id: 4739b47b-81f8-4821-bbab-8198abef1d48 message_count: 25 tags: - antibiotic - treatment - side - effects - source/chatgpt - status/raw - side-effects - antibiotic-treatment category: - Health - Medicine - Antibiotic Treatment - Side Effects summary: The destruction of gut flora requires regrowing healthy populations of microbes after antibiotic treatment. keypoints: - antibiotic treatment can cause nausea and fatigue - antibiotic treatment can cause ringing in the ears - the experience of patients is different from the expected outcome - there are reported symptoms following 10 day antibiotic treatment - the study found that a short-course antibiotic treatment was effective in treating group A streptococcal tonsillopharyngitis monomyth_stage: Tests Allies Enemies, The Approach, The Ordeal, The Reward gameboard_position: '' truth_score: 80 entropy_score: Low tone: sentiment: Neutral emotions: - Negative - Informational - Positive sycophancy_level: None notes: '' related_events: [] syndication_status: arnie: false chris: false redmond: false clint: false pilot: false ma5_inheritance: None pre_silicon: false voice_print: false codex_candidate: false phase: '' enriched_date: '2026-04-09' --- # V4:E02:S04 - Antibiotic Treatment Side Effects > Exported from ChatGPT | 2024-07-01 | 25 messages --- **You:** Lets see if there are reported symptoms following a 10 day antibiotic treatment. For example the destruction of the gut flora seems to require regrowing healthy populations of microbes using a rhobust and personalized prebiotic and prebiotic blend made by Viome. However the experience of the patient (me) has included several day long waves of nausea fatigue and ringing inthe ears. It feels like an ongoing struggle now two weeks after completing the 600mg linezolid treatment. --- **ChatGPT:** ```json {"query": "symptoms following 10 day antibiotic treatment", "year_min": null, "year_max": null, "study_types": null, "human": null, "sample_size_min": null, "sjr_max": null} ``` --- **ChatGPT:** ```json {"query": "symptoms following 10 day antibiotic treatment"} ``` --- **[Tool]:** {"items":[{"paper_title":"Short-course antibiotic treatment of 4782 culture-proven cases of group A streptococcal tonsillopharyngitis and incidence of poststreptococcal sequelae.","abstract":"A large-scale study with a 1-year follow-up was performed to compare 10 days of penicillin V with a short-course treatment (5 days) of other oral antibiotics in the treatment of group A beta-hemolytic streptococcus (GABHS) tonsillopharyngitis, to evaluate the efficacy and the incidence of poststreptococcal sequelae. The clinical response rates after completion of therapy were 94.5% in the 5-day group and 93.4% in the penicillin group (P<.001, equivalence test). The GABHS eradication rates were 83.3% in the 5-day group and 84.4% in the penicillin group (P=.022, equivalence test). Poststreptococcal sequelae were rare (5 patients) and did not occur in the context of this study. The efficacy of 5-day antibiotic regimens was equivalent to 10 days of penicillin V, but resolution of clinical symptoms was faster in the 5-day group (P<.001, Fisher's exact test). Recurrent tonsillopharyngitis occurs more frequently after treatment with penicillin (P=.03, Fisher's exact test).","paper_authors":["D. Adam","H. Scholz","M. Helmerking"],"paper_publish_year":2000,"publication_journal_name":"The Journal of infectious diseases","consensus_paper_details_url":"https://consensus.app/papers/shortcourse-treatment-4782-cultureproven-cases-group-adam/5374203789ca59b2a0b8d635e88051cc/?utm_source=chatgpt","doi":"10.1086/315709","volume":"182 2","pages":"\n 509-16\n ","search_result_number":1},{"paper_title":"A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A beta-haemolytic streptococci.","abstract":"A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)","paper_authors":["Claude Carbón","A. Chatelin","E. Bingen","P. Zuck","Y. Rio","F. Guetat","J. Orvain"],"paper_publish_year":1995,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/doubleblind-randomized-trial-comparing-efficacy-safety-carbón/8df5835be9245670a225f726002fa2ef/?utm_source=chatgpt","doi":"","volume":"35 6","pages":"\n 843-54\n ","search_result_number":2},{"paper_title":"A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A β-haemolytic streptococci","abstract":"A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A β-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course ofcefotiam hexetil (CTM) 200 mg bd with that of 10-day course of penicillin V (PEV) I megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres ; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events ; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group. Time lost from work was noted in respect of 68.0% ofpatients who were gainfully employed and prolonging treatment from 5 to 10 days would have led to a mean increase in the time away from work of 1.7 days. In conclusion, a 5 day course of cefotiam hexetil was shown to be effective and safe therapy for patients with GABHS tonsillitis. However, a more accurate estimate of the cost-effectiveness of this regimen will be required before AHA recommendations can be revised.","paper_authors":["Claude Carbón","A. Chatelin","E. Bingen","P. Zuck","Y. Rio","F. Guetat","J. Orvain"],"paper_publish_year":1995,"publication_journal_name":"Journal of Antimicrobial Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/doubleblind-randomized-trial-comparing-efficacy-safety-carbón/b7be6f3695b25fd59716a24be6db48fc/?utm_source=chatgpt","doi":"10.1093/JAC/35.6.843","volume":"35","pages":"843-854","search_result_number":3},{"paper_title":"Duration of antibacterial treatment for uncomplicated urinary tract infection in women.","abstract":"BACKGROUND\nUncomplicated urinary tract infection (UTI) is a common disease, occurring frequently in young sexually active women. In the past, seven day antibiotic therapy was recommended while the current practice is to treat uncomplicated UTI for three days.\n\n\nOBJECTIVES\nTO compare the efficacy and safety of three-day antibiotic therapy to multi-day therapy (five days or longer) on relief of symptoms and bacteriuria at short-term and long-term follow-up.\n\n\nSEARCH STRATEGY\nThe Cochrane Library (Issue 1, 2004), the Cochrane Renal Group's Register of trials (July 2003), EMBASE (January 1980 to August 2003), and MEDLINE (January 1966 to August 2003) were searched. We scanned references of all included studies and contacted the first or corresponding author of included trials and the pharmaceutical companies.\n\n\nSELECTION CRITERIA\nRandomised controlled trials comparing three-days oral antibiotic therapy with multi-day therapy (five days and longer) for uncomplicated cystitis in 18 to 65 years old non-pregnant women without signs of upper UTI.\n\n\nDATA COLLECTION AND ANALYSIS\nData concerning bacteriological and symptomatic failure rates, occurrence of pyelonephritis and adverse effects were extracted independently by two reviewers. Relative risk (RR) and their 95% confidence intervals (CI) were estimated. Outcomes were also extracted by intention-to-treat analysis whenever possible.\n\n\nMAIN RESULTS\nThirty-two trials (9605 patients) were included. For symptomatic failure rates, no difference between three-day and 5-10 day antibiotic regimen was seen short-term (RR 1.06, 95% CI 0.88 to 1.28) and long-term follow-up (RR 1.09, 95% CI 0.94 to 1.27). Comparison of the bacteriological failure rates showed that three-day therapy was less effective than 5-10 day therapy for the short-term follow-up, however this difference was observed only in the subgroup of trials that used the same antibiotic in the two treatment arms (RR 1.37, 95% CI 1.07 to 1.74, P = 0.01). This difference was more significant at long-term follow-up (RR 1.43, 95% CI 1.19 to 1.73, P = 0.0002). Adverse effects were significantly more common in the 5-10 day treatment group (RR 0.83, 95% CI 0.74 to 0.93, P = 0.0010). Results were consistent for subgroup and sensitivity analyses.\n\n\nAUTHORS' CONCLUSIONS\nThree days of antibiotic therapy is similar to 5-10 days in achieving symptomatic cure during uncomplicated UTI treatment, while the longer treatment is more effective in obtaining bacteriological cure. In spite of the higher rate of adverse effects, treatment for 5-10 days could be considered for treatment of women in whom eradication of bacteriuria is important.","paper_authors":["G. Milo","E. Katchman","M. Paul","T. Christiaens","A. Baerheim","L. Leibovici"],"paper_publish_year":2005,"publication_journal_name":"The Cochrane database of systematic reviews","consensus_paper_details_url":"https://consensus.app/papers/duration-treatment-tract-infection-women-milo/fa6492b5fbcf539da7a1f3a050c19742/?utm_source=chatgpt","doi":"10.1002/14651858.cd004682.pub2","volume":"2","pages":"\n CD004682\n ","search_result_number":4},{"paper_title":"A Prospective Observational Study of 5-, 7-, and 10-day Antibiotic Treatment for Acute Otitis Media","abstract":"OBJECTIVE: To compare 5-, 7- and 10-day duration of antibiotic therapy for acute otitis media (AOM) in children. STUDY DESIGN AND SETTING: Prospective nonrandomized 1-year evaluation of 3 treatment durations for AOM in a private pediatric setting. Outcomes assessed at 14 ± 4 days after start of therapy with clinical response categorized as cure, improvement, or failure. RESULTS: A total of 2172 children were studied; 46.4% were ≤2-years-old. Antibiotics used were amoxicillin (61.9% of patients), trimethoprim/sulfamethoxazole (11.7%), cephalosporins (14.2%), amoxicillin/clavulanate (5.2%), and macrolides/azalides (4.8%). No overall difference in outcome was observed comparing the 5-day (n = 707), 7-day (n = 423), or 10-day (n = 1042) treatments, including children ≤2-years-old. However, in the subset who had an episode of AOM in the preceding month, outcome differed; 5-day treatment was followed by more frequent failure than 10-day treatment (P < 0.001). In logistic regression analysis, variables identified as contributing to a cure were: >2-years-old (P < 0.0001), no AOM in the preceding month (P = 0.07), or preceding 12 months (P = 0.03). CONCLUSIONS: Our study supports the transition from 10 to 5 days for standard AOM antibiotic treatment duration in most patients. A 10-day regimen may be superior in children who have experienced an episode of AOM within the preceding month, a known risk factor for resistant bacterial infection in the otitis-prone patient.","paper_authors":["M. Pichichero","S. Marsocci","M. Murphy","W. Hoeger","A. Francis","John L. Green"],"paper_publish_year":2001,"publication_journal_name":"Otolaryngology- Head and Neck Surgery","consensus_paper_details_url":"https://consensus.app/papers/observational-study-10day-antibiotic-treatment-acute-pichichero/282fbab4ca895df3a5b66be417256e28/?utm_source=chatgpt","doi":"10.1067/mhn.2001.114311","volume":"124","pages":"381 - 387","search_result_number":5},{"paper_title":"A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children.","abstract":"BACKGROUND\nAll but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure.\n\n\nMETHODS\nIn a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period.\n\n\nRESULTS\nBetween February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008).\n\n\nCONCLUSIONS\nWhen assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM.","paper_authors":["R. Cohen","C. Levy","M. Boucherat","J. Langue","F. de la Rocque"],"paper_publish_year":1998,"publication_journal_name":"The Journal of pediatrics","consensus_paper_details_url":"https://consensus.app/papers/multicenter-randomized-trial-versus-days-therapy-acute-cohen/869f577ccd0e50228379233f60c452e9/?utm_source=chatgpt","doi":"10.1016/S0022-3476(98)70103-9","volume":"133 5","pages":"\n 634-9\n ","search_result_number":6},{"paper_title":"Three-day and ten-day chemotherapy for urinary tract infections in general practice.","abstract":"The length of a course of antibiotic treatment for urinary tract infection varies with the habits of the prescriber. Many patients do not complete a course of treatment once their symptoms have subsided. In uncomplicated urinary tract infection among women seen in general practice a three-day course of amoxycillin was as effective as a 10-day course of the same drug in the same dose. Relief of symptoms was equal in both groups and bacteriuria was eliminated equally successfully in both regimens. There was no significant difference between the two groups in the incidence of side effects from the drugs. The financial saving which could accrue from adopting this therapeutic regimen would be significant.","paper_authors":["C. Charlton","A. Crowther","J. Davies","J. Dynes","M. Haward","P. Mann","S. Rye"],"paper_publish_year":1976,"publication_journal_name":"British Medical Journal","consensus_paper_details_url":"https://consensus.app/papers/threeday-chemotherapy-tract-infections-practice-dundee/104e77ec4bcd55389bd8d311c5714539/?utm_source=chatgpt","doi":"10.1136/bmj.1.6002.124","volume":"1","pages":"124 - 126","search_result_number":7},{"paper_title":"Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease.","abstract":"BACKGROUND\nIt is controversial whether prolonged antibiotic treatment is effective for patients in whom symptoms persist after the recommended antibiotic treatment for acute Lyme disease.\n\n\nMETHODS\nWe conducted two randomized trials: one in 78 patients who were seropositive for IgG antibodies to Borrelia burgdorferi at the time of enrollment and the other in 51 patients who were seronegative. The patients received either intravenous ceftriaxone, 2 g daily for 30 days, followed by oral doxycycline, 200 mg daily for 60 days, or matching intravenous and oral placebos. Each patient had well-documented, previously treated Lyme disease but had persistent musculoskeletal pain, neurocognitive symptoms, or dysesthesia, often associated with fatigue. The primary outcome measures were improvement on the physical- and mental-health-component summary scales of the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36)--a scale measuring the health-related quality of life--on day 180 of the study.\n\n\nRESULTS\nAfter a planned interim analysis, the data and safety monitoring board recommended that the studies be discontinued because data from the first 107 patients indicated that it was highly unlikely that a significant difference in treatment efficacy between the groups would be observed with the planned full enrollment of 260 patients. Base-line assessments documented severe impairment in the patients' health-related quality of life. In intention-to-treat analyses, there were no significant differences in the outcomes with prolonged antibiotic treatment as compared with placebo. Among the seropositive patients who were treated with antibiotics, there was improvement in the score on the physical-component summary scale of the SF-36, the mental-component summary scale, or both in 37 percent, no change in 29 percent, and worsening in 34 percent; among seropositive patients receiving placebo, there was improvement in 40 percent, no change in 26 percent, and worsening in 34 percent (P=0.96 for the comparison between treatment groups). The results were similar for the seronegative patients.\n\n\nCONCLUSIONS\nThere is considerable impairment of health-related quality of life among patients with persistent symptoms despite previous antibiotic treatment for acute Lyme disease. However, in these two trials, treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo.","paper_authors":["M. Klempner","L. Hu","J. Evans","C. Schmid","G. Johnson","R. P. Trevino","D. Norton","L. Levy","D. Wall","J. McCall","M. Kosinski","A. Weinstein"],"paper_publish_year":2001,"publication_journal_name":"The New England journal of medicine","consensus_paper_details_url":"https://consensus.app/papers/controlled-trials-treatment-patients-symptoms-history-klempner/7ac0b317a3bd5e429b1f07a2cea4706e/?utm_source=chatgpt","doi":"10.1056/NEJM200107123450202","volume":"345 2","pages":"\n 85-92\n ","search_result_number":8},{"paper_title":"A meta-analysis on the effects of antibiotic treatment on duration of symptoms caused by infection with Campylobacter species.","abstract":"Eleven randomized, controlled trials of antibiotic treatment versus placebo in patients with Campylobacter species infection were pooled in a meta-analysis. Antibiotic treatment shortened the duration of intestinal symptoms by 1.32 days (95% confidence interval, 0.64-1.99; P<.0001). Because of problems with drug resistance, a restrictive attitude towards the administration of antibiotics in uncomplicated cases is advised.","paper_authors":["A. Ternhag","T. Asikainen","J. Giesecke","K. Ekdahl"],"paper_publish_year":2007,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/metaanalysis-effects-treatment-duration-symptoms-caused-ternhag/b4e8baea38115b829248ad1ad04bf22e/?utm_source=chatgpt","doi":"10.1086/509924","volume":"44 5","pages":"\n 696-700\n ","search_result_number":9},{"paper_title":"Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials.","abstract":"WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT\nTreatment guidelines generally support that a 10-14-day antibiotic regimen should be administered to uncomplicated acute bacterial sinusitis patients. However, the level of evidence for such a recommendation is rather weak. Treatment of such duration may have disadvantages compared with a shorter duration but equally effective regimen, including the promotion of bacterial drug resistance, poorest patient compliance, higher toxicity, and a greater overall economic burden.\n\n\nWHAT THIS STUDY ADDS\nThe findings of this meta-analysis suggest that short-course antibiotic treatment has similar effectiveness to longer-course treatment for patients with acute uncomplicated bacterial sinusitis, when treatment is warranted. However, we should underscore the importance of the clinician's own assessment, so that antimicrobial therapy should not inappropriately be curtailed in a patient not adequately responding to the regimen administered. We sought to evaluate the effectiveness and safety of short-course antibiotic treatment for acute bacterial sinusitis (ABS) compared with longer duration treatment. We performed a meta-analysis of randomized controlled trials (RCTs), identified by searching PubMed and the Cochrane Central Register of Controlled Trials. We included RCTs that compared short-course (up to 7 days) vs. long-course therapy (> or =2 days longer than short-course), with the same antimicrobial agent, in the same daily dosage, for patients with ABS. Twelve RCTs (10 double-blinded) involving adult patients with radiologically confirmed ABS were included. There was no difference in the comparison of short-course (3-7 days) with long-course treatment (6-10 days) regarding clinical success [12 RCTs, 4430 patients, fixed effect model (FEM), odds ratio (OR) 0.95, 95% confidence interval (CI) 0.81, 1.12]; microbiological efficacy; relapses; adverse events (10 RCTs, 4172 patients, random effects model, OR 0.88, 95% CI 0.71, 1.09); or withdrawals due to adverse events. In the sensitivity analysis comparing 5- vs. 10-day regimens, clinical success was similar, although adverse events were fewer with short-course treatment (5 RCTs, 2151 patients, FEM, OR 0.79, 95% CI 0.63, 0.98). Although antibiotics for acute sinusitis should be reserved for select patients with substantial probability of bacterial disease, accurate clinical diagnosis is often difficult to attain. Short-course antibiotic treatment had comparable effectiveness to a longer course of therapy for ABS. Shortened treatment, particularly for patients without severe disease and complicating factors, might lead to fewer adverse events, better patient compliance, lower rates of resistance development and fewer costs.","paper_authors":["M. Falagas","D. Karageorgopoulos","A. Grammatikos","D. Matthaiou"],"paper_publish_year":2009,"publication_journal_name":"British journal of clinical pharmacology","consensus_paper_details_url":"https://consensus.app/papers/effectiveness-safety-short-duration-therapy-acute-falagas/992d04a40caf54d1893cbe17e389735e/?utm_source=chatgpt","doi":"10.1111/j.1365-2125.2008.03306.x","volume":"67 2","pages":"\n 161-71\n ","search_result_number":10},{"paper_title":"Duration of Antibiotic Therapy for Early Lyme Disease","abstract":"Context Optimal antibiotic treatment for patients with early Lyme disease is unclear. Contribution This single-center randomized, double-blind, placebo-controlled trial found that patients with erythema migrans given any of the follwoing regimens had high response rates, defined as resolution of erythema migrans and symptoms at 30 months: 20 days of doxycycline, 83.9%; 10 days of doxycycline, 90.3%; and 10 days of doxycycline plus a single intravenous dose of ceftriaxone, 86.5%. Patients given doxycycline plus ceftriaxone more often had diarrhea than patients given doxycycline alone. Implications Oral doxycycline alone for 10 days is sufficient treatment for patients with early Lyme disease that manifests as erythema migrans. The Editors Although Lyme disease is the most common vector-borne disease in the United States (1), the appropriate duration of treatment for its most common manifestation, erythema migrans, remains unclear. A small open-label prospective study reported in 1983 found that outcome did not improve when tetracycline therapy was extended from 10 days to 20 days (2). However, most recent treatment trials have used antibiotic regimens of approximately 3 weeks (3-5), and some authorities recommend 20 to 30 days of therapy (6). This change in practice has occurred in the absence of additional prospective studies on the duration of treatment and is a source of ongoing controversy. Another uncertain issue in the management of patients with erythema migrans is whether Borrelia burgdorferi, the etiologic agent, has disseminated to the central nervous system at the time of presentation (7). If so, the outcome of therapy might be enhanced by treatment with a parenteral agent such as ceftriaxone, which readily crosses the bloodbrain barrier. To address these concerns, we conducted a placebo-controlled study comparing 10 days of doxycycline with both 10 days of doxycycline plus one dose of ceftriaxone and 20 days of doxycycline. Methods Patients at least 16 years of age who had erythema migrans and satisfied the U.S. Centers for Disease Control and Prevention's surveillance definition of Lyme disease (an annular erythematous skin lesion 5 cm in diameter) (8) entered the study between 1992 and 1994. Volunteers were recruited primarily through the walk-in Lyme Disease Diagnostic Center at the Westchester Medical Center, Valhalla, New York. Exclusion criteria included pregnancy or lactation, allergy to a tetracycline or a -lactam antibiotic, receipt of antibiotic treatment for Lyme disease for more than 48 hours before enrollment, meningitis or advanced heart block, or any underlying conditions that might interfere with evaluability or follow-up. All patients gave written informed consent, and the institutional review board at New York Medical College approved the study protocol. Patients were randomly assigned to one of three treatment groups: 1) a single 2-g dose of intravenous ceftriaxone followed by 10 days of oral doxycycline capsules twice daily, then by 10 days of oral placebo capsules [cornstarch], identical in appearance to the doxycycline capsules, twice daily; 2) a placebo injection [5% dextrose] followed by 10 days of oral doxycycline, 100 mg twice daily, and then by 10 days of oral placebo twice daily; or 3) a placebo injection followed by 20 days of oral doxycycline twice daily. Since ceftriaxone is yellow, infusion bags were kept covered to maintain masking. The pharmacy dispensed study medications in accordance with a randomization schedule that was based on a computer-generated random-number code with a permuted block size of 9. Clinical staff involved in recruitment of participants or in assessing clinical outcomes were isolated from the allocation process and blinded to treatment assignment. Randomization was stratified by whether patients were symptomatic (defined as having any systemic symptoms or having multiple erythema migrans lesions) or asymptomatic (defined as having a single erythema migrans lesion and no systemic symptoms). This was done to ensure that patients who may have had dissemination of B. burgdorferi were equally represented in the three treatment groups. Evaluation Trained study personnel interviewed participants and performed physical examination at baseline and 10 days, 20 days, 3 months, 6 months, 12 months, 24 months, and 30 months after initiation of therapy. If appointments were missed, patients were interviewed by telephone; however, this occurred in fewer than 5% of patient interactions. A neurologist performed complete neurologic examination at baseline, 20 days, 3 months, 12 months, 24 months, and 30 months. At 18 months, an evaluation was conducted by telephone. Structured questionnaires using both closed- and open-ended questions were used. Symptom scores were recorded on a visual analogue scale (9). A blood sample was obtained for serologic testing (enzyme-linked immunosorbent assay) at all visits. Complete blood count was determined and serum chemistries were performed at baseline, day 10, and day 20. Electrocardiography was done at baseline and was repeated if results were abnormal. Patients were considered unevaluable if they did not adhere to study medication. Nonadherence was defined as taking fewer than 90% of prescribed capsules or not returning pill containers at the 10- or 20-day visit, receiving an intercurrent antibiotic within the first 20 days, not meeting study inclusion criteria, or not attending follow-up visits after the baseline visit. Patients who had an intercurrent episode of erythema migrans due to reinfection were considered unevaluable from that point onward. Outcome was characterized as complete response, partial response, or failure. Early treatment response was assessed at 20 days. At this time, complete response was defined as resolution of erythema migrans and associated symptoms and return to preLyme disease health status. Partial response was defined as resolution of erythema migrans but incomplete resolution or development of subjective symptoms. Failure was defined as the occurrence of any one of the following during the first 20 days: no clinical improvement by day 10; recurrence of erythema migrans; recurrence of fever attributed by the study physician to Lyme disease; development of new objective rheumatologic, cardiac, or neurologic manifestations of Lyme disease that were not present within the first 10 days; or the occurrence of meningitis, advanced heart block, or other objective manifestation of Lyme disease requiring intravenous therapy. Late response was evaluated at 3 months, 12 months, and 30 months. Complete response was defined as no recurrence of erythema migrans or associated symptoms and the continued absence of objective rheumatologic, cardiac, or neurologic manifestations of Lyme disease, with return to preLyme disease health status. Partial response was defined as no recurrence of erythema migrans and the continued absence of objective manifestations of Lyme disease, but incomplete resolution or development of subjective symptoms of uncertain cause. Failure was defined as the occurrence of objective manifestations of Lyme disease. Safety Assessment Drug safety was monitored by recording adverse events (solicited by open-ended semi-structured interview) and results of laboratory tests during treatment. Neurocognitive Evaluation At baseline, 12 months, and 30 months, a psychologist performed neurocognitive testing consisting of the Booklet Categories Test, the California Verbal Learning Test, the Wechsler Memory ScaleRevised, the Block Design Test, the Trail Making Test (Parts A and B), the Boston Naming Test, the Symbol Digit Modalities Test (written and oral), the Beck Depression Inventory, and the Symptom Checklist-90Revised. Healthy volunteers without a history of Lyme disease were recruited to serve as controls for the psychiatric interview and the neuropsychological testing. Spouses were preferred as controls since they were usually similar to the patients in age, socioeconomic level, and place of residence. Controls were 27 persons with a mean age (SD) of 42.6 15.2 years; 22% were men. Statistical Analysis Groups were compared by using one-way analysis of variance for continuous variables and the chi-square test for categorical variables (two-tailed). Data were analyzed both for participants who adhered to the study protocol and on an intention-to-treat basis. Patient blinding was evaluated at the 30-month visit by using the chi-square test and the statistic (10). For the neuropsychological tests, analysis of variance techniques were used to examine differences among treatment and control groups. For analysis of raw test scores, analysis of covariance was used, controlling for the effects of age, sex, and education. Test scores that were normalized to population standards (11-19) were analyzed by using one-way analysis of variance. For all analysis of variance models, residual plots were generated to verify adequate model fit. In the few situations in which test scores were not normally distributed or model fit was questionable, nonparametric procedures (the KruskalWallis test) or conventional transformations were applied. For categorical results, the chi-square test or the Fisher exact test was used. If the treatment variable in the global tests achieved the liberal cut-point of a P value less than 0.10, pairwise comparisons were conducted. In these instances, the Bonferroni adjustment was applied to the P value to control for multiple comparisons. Sample size was based on the estimated frequency of postLyme disease syndrome, defined as an array of subjective symptoms, such as fatigue, arthralgias, or myalgias, that may occur after infection. It was assumed that 30% of patients receiving the least effective treatment would develop postLyme disease syndrome. A more effective treatment was assumed to reduce the rate to 5%. Using an level of 0.05, two-tailed testing, and a Bonferroni multiple compari","paper_authors":["G. Wormser","R. Ramanathan","J. Nowakowski","D. McKenna","D. Holmgren","P. Visintainer","R. Dornbush","B. Singh","R. Nadelman"],"paper_publish_year":2003,"publication_journal_name":"Annals of Internal Medicine","consensus_paper_details_url":"https://consensus.app/papers/duration-antibiotic-therapy-early-lyme-disease-wormser/f88089dddb65560797429c0528eb67e1/?utm_source=chatgpt","doi":"10.7326/0003-4819-138-9-200305060-00005","volume":"138","pages":"697-704","search_result_number":11},{"paper_title":"Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children.","abstract":"BACKGROUND\nLimiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media.\n\n\nMETHODS\nWe assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin-clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms.\n\n\nRESULTS\nChildren who were treated with amoxicillin-clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P<0.001).\n\n\nCONCLUSIONS\nAmong children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; ClinicalTrials.gov number, NCT01511107 .).","paper_authors":["A. Hoberman","J. Paradise","H. Rockette","D. Kearney","S. Bhatnagar","T. Shope","Judith M. Martin","M. Kurs‐Lasky","S. Copelli","D. Colborn","S. Block","J. Labella","T. Lynch","N. Cohen","M. Haralam","Marcia A Pope","Jennifer P. Nagg","Michael D. Green","N. Shaikh"],"paper_publish_year":2016,"publication_journal_name":"The New England journal of medicine","consensus_paper_details_url":"https://consensus.app/papers/shortened-antimicrobial-treatment-acute-otitis-media-hoberman/03b41caca5ed552b9fe5cb13b91901b7/?utm_source=chatgpt","doi":"10.1056/NEJMoa1606043","volume":"375 25","pages":"\n 2446-2456\n ","search_result_number":12},{"paper_title":"Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Tria","abstract":"The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection. This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014. ABSTRACT The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection. This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014. A total of 431 H. pylori-infected patients with duodenal ulcers were enrolled and randomized into four treatment groups (1:1:1:1) for 10 days, as follows: (i) a group receiving a low dose of rabeprazole of 10 mg twice a day (b.i.d.) (LR dose) plus bismuth, amoxicillin, and clarithromycin (LR-BAC); (ii) a group receiving LR plus bismuth, amoxicillin, and tetracycline (LR-BAT); (iii) a group receiving a high dose of rabeprazole of 20 mg b.i.d. (HR dose) plus bismuth, amoxicillin, and clarithromycin (HR-BAC); and (iv) a group receiving HR-BAT. Antimicrobial susceptibility was assessed by the Etest method. The primary outcome was H. pylori eradication at 4 weeks after the treatment. The per-protocol (PP) eradication rates in the LR-BAC, LR-BAT, HR-BAC, and HR-BAT groups were 94.1%, 91.9%, 94.8%, and 91.9%, respectively, while the intention-to-treat (ITT) eradication rates in those groups were 87.2%, 87.2%, 87.7%, and 86%, respectively. There was no significant difference between the four groups in PP analysis (P = 0.799) and ITT analysis (P = 0.985). The efficacies of four-treatment therapy were not affected by antibiotic resistance. The adverse events in the four treatment groups were similar; central nervous system (CNS) and gastrointestinal symptoms were the most common reported. Bismuth-containing quadruple therapy with low-dose rabeprazole, amoxicillin, and tetracycline is a good option for first-line treatment of H. pylori infection in a population with high antibiotic resistance. (This study is registered at Chinese Clinical Trials Registry [www.chictr.org.cn] under number ChiCTR1800014832.)","paper_authors":["Yong Xie","Zhenhua Zhu","Jiang-bing Wang","Ling-xia Zhang","Zhenyu Zhang","Hong Lu","Z. Zeng","Shi-yao Chen","Dong-sheng Liu","N. Lv"],"paper_publish_year":2018,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/tenday-quadruple-therapy-comprising-lowdose-rabeprazole-xie/a71508dfef6b5a028a9958ba13edbf25/?utm_source=chatgpt","doi":"10.1128/AAC.00432-18","volume":"62","pages":"","search_result_number":13},{"paper_title":"Comparison of 7 versus 10 days of antibiotic therapy for hospitalized patients with uncomplicated community-acquired pneumonia: a prospective, randomized, double-blind study.","abstract":"The objective of this study was to compare the outcome of 7 versus 10 days of antibiotic therapy for inpatients with moderately severe community-acquired pneumonia (CAP). A prospective, randomized, double-blind study with a follow-up period of 42 days was conducted. Fifty-two veterans were treated with 2 days of cefuroxime at 750 mg intravenously every 8 hours followed by group 1, 8 days oral therapy, and group 2, 5 days oral therapy followed by 3 days of placebo. Oral therapy consisted of cefuroxime axetil at 500 mg every 12 hours. No difference was seen in cure rates: 20 of 22 (90.9%) patients in group 1 and 21 of 24 (87.5%) patients in group 2. There were no late recurrences. Potential US cost-savings is $27.2 million. Inpatients with moderately severe CAP can be treated with 2 days of intravenous antibiotics followed by 5 additional days of oral antibiotics. Longer treatment duration prolongs the cost of care, without increasing the cure rate or decreasing the pneumonia recurrence rate.","paper_authors":["R. Siegel","M. Alicea","A. Lee","R. Blaiklock"],"paper_publish_year":1999,"publication_journal_name":"American journal of therapeutics","consensus_paper_details_url":"https://consensus.app/papers/comparison-versus-days-therapy-hospitalized-patients-siegel/4bc8887b351c584ab5773c1185030811/?utm_source=chatgpt","doi":"10.1097/00045391-199907000-00007","volume":"6 4","pages":"\n 217-22\n ","search_result_number":14},{"paper_title":"Treatment of erythema migrans with doxycycline for 10 days versus 15 days.","abstract":"BACKGROUND\nThe efficacy of 10-day doxycycline treatment in patients with erythema migrans has been assessed in the United States but not in Europe. Experts disagree on the significance of post-Lyme borreliosis symptoms.\n\n\nMETHODS\nIn a noninferiority trial, the efficacies of 10 days and 15 days of oral doxycycline therapy were evaluated in adult European patients with erythema migrans. The prevalence of nonspecific symptoms was compared between patients with erythema migrans and 81 control subjects without a history of Lyme borreliosis. The efficacy of treatment, determined on the basis of clinical observations and microbiologic tests, was assessed at 14 days and at 2, 6, and 12 months. Nonspecific symptoms in patients and controls were compared at 6 months after enrollment.\n\n\nRESULTS\nA total of 117 patients (52%) were treated with doxycycline for 15 days, and 108 (48%) received doxycycline for 10 days. Twelve months after enrollment, 85 of 91 patients (93.4%) in the 15-day group and 79 of 86 (91.9%) in the 10-day group had complete response (difference, 1.6 percentage points; upper limit of the 95% confidence interval, 9.1 percentage points). At 6 months, the frequency of nonspecific symptoms in the patients was similar to that among controls.\n\n\nCONCLUSIONS\nThe 10-day regimen of oral doxycycline was not inferior to the 15-day regimen among adult European patients with solitary erythema migrans. Six months after treatment, the frequency of nonspecific symptoms among erythema migrans patients was similar to that among control subjects.\n\n\nCLINICAL TRIALS REGISTRATION\nNCT00910715.","paper_authors":["D. Stupica","L. Lusa","E. Ružić-Sabljić","T. Cerar","F. Strle"],"paper_publish_year":2012,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/treatment-erythema-migrans-doxycycline-days-versus-days-stupica/53fc9db1787b5b8b936287fbcc24ee9a/?utm_source=chatgpt","doi":"10.1093/cid/cis402","volume":"55 3","pages":"\n 343-50\n ","search_result_number":15},{"paper_title":"Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy as First-Line Treatment for Helicobacter pylori Infection: A Nationwide Randomized Trial in Korea","abstract":"Background/Aims This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population. Methods Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Results A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms. Conclusions The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.","paper_authors":["B. Kim","Hyuk Lee","Y. Lee","S. Jeon","G. Kim","Hyun-Soo Kim","J. Sung","D. H. Lee","Heung-Up Kim","M. Park","I. Choi","S. Yoon","Sang Wook Kim","G. Baik","J. Y. Lee","J. Kim","S. Kim","Jayoun Kim","Joo-Ok Lee","J. G. Kim","Jae J. Kim"],"paper_publish_year":2019,"publication_journal_name":"Gut and Liver","consensus_paper_details_url":"https://consensus.app/papers/tenday-concomitant-10day-sequential-7day-triple-therapy-kim/4e408ca93d9c53bba8d55d78234e277d/?utm_source=chatgpt","doi":"10.5009/gnl19136","volume":"13","pages":"531 - 540","search_result_number":16},{"paper_title":"Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial.","abstract":"Importance\nDetermination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness.\n\n\nObjective\nTo determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men.\n\n\nDesign, Setting, and Participants\nRandomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized.\n\n\nInterventions\nParticipants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment.\n\n\nMain Outcomes and Measures\nThe prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication.\n\n\nResults\nAmong 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group.\n\n\nConclusions and Relevance\nAmong afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI.\n\n\nTrial Registration\nClinicalTrials.gov identifier: NCT01994538.","paper_authors":["D. Drekonja","B. Trautner","Carla Amundson","M. Kuskowski","J. R. Johnson"],"paper_publish_year":2021,"publication_journal_name":"JAMA","consensus_paper_details_url":"https://consensus.app/papers/days-antibiotic-therapy-resolution-symptoms-among-drekonja/f6504a54f15c53e1a21fe18417e59c2c/?utm_source=chatgpt","doi":"10.1001/jama.2021.9899","volume":"326 4","pages":"\n 324-331\n ","search_result_number":17},{"paper_title":"Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.","abstract":"BACKGROUND\nSevere infections remain one of the main causes of neonatal deaths worldwide. Possible severe infection is diagnosed in young infants (aged 0-59 days) according to the presence of one or more clinical signs. The recommended treatment is hospital admission with 7-10 days of injectable antibiotic therapy. In low-income and middle-income countries, barriers to hospital care lead to delayed, inadequate, or no treatment for many young infants. We aimed to identify effective alternative antibiotic regimens to expand treatment options for situations where hospital admission is not possible.\n\n\nMETHODS\nWe did this randomised, open-label, equivalence trial in four urban hospitals and one rural field site in Bangladesh to determine whether two alternative antibiotic regimens with reduced numbers of injectable antibiotics combined with oral antibiotics had similar efficacy and safety to the standard regimen, which was also used as outpatient treatment. We randomly assigned infants who showed at least one clinical sign of severe, but not critical, infection (except fast breathing alone), whose parents refused hospital admission, to one of the three treatment regimens. We stratified randomisation by study site and age (<7 days or 7-59 days) using computer-generated randomisation sequences. The standard treatment was intramuscular procaine benzylpenicillin and gentamicin once per day for 7 days (group A). The alternative regimens were intramuscular gentamicin once per day and oral amoxicillin twice per day for 7 days (group B) or intramuscular procaine benzylpenicillin and gentamicin once per day for 2 days, then oral amoxicillin twice per day for 5 days (group C). The primary outcome was treatment failure within 7 days after enrolment. Assessors of treatment failure were masked to treatment allocation. Primary analysis was per protocol. We used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with ClinicalTrials.gov, number NCT00844337.\n\n\nFINDINGS\nBetween July 1, 2009, and June 30, 2013, we recruited 2490 young infants into the trial. We assigned 830 infants to group A, 831 infants to group B, and 829 infants to group C. 2367 (95%) infants fulfilled per-protocol criteria. 78 (10%) of 795 per-protocol infants had treatment failure in group A compared with 65 (8%) of 782 infants in group B (risk difference -1.5%, 95% CI -4.3 to 1.3) and 64 (8%) of 790 infants in group C (-1.7%, -4.5 to 1.1). In group A, 14 (2%) infants died before day 15, compared with 12 (2%) infants in group B and 12 (2%) infants in group C. Non-fatal relapse rates were similar in all three groups (12 [2%] infants in group A vs 13 [2%] infants in group B and 10 [1%] infants in group C).\n\n\nINTERPRETATION\nOur results suggest that the two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection in young infants whose parents refused hospital admission are as efficacious as the standard regimen. This finding could increase treatment options in resource-poor settings when referral care is not available or acceptable.","paper_authors":["A. Baqui","S. Saha","ASM Nawshad Uddin Ahmed","M. Shahidullah","I. Quasem","D. Roth","A. Samsuzzaman","Wazir Ahmed","S. Tabib","D. Mitra","N. Begum","Maksuda Islam","A. Mahmud","Mohammad Hefzur Rahman","Mamun Ibne Moin","L. Mullany","S. Cousens","S. El Arifeen","S. Wall","N. Brandes","M. Santosham","R. Black"],"paper_publish_year":2015,"publication_journal_name":"The Lancet. Global health","consensus_paper_details_url":"https://consensus.app/papers/safety-efficacy-regimens-compared-procaine-baqui/f0ee71faa0e15b208c8c0b0a50c98098/?utm_source=chatgpt","doi":"10.1016/S2214-109X(14)70347-X","volume":"3 5","pages":"\n e279-87\n ","search_result_number":18},{"paper_title":"[A 10-day sequential therapy for eradication of Helicobacter pylori infection in children].","abstract":"OBJECTIVE\nTo evaluate the clinical effect of a 10-day sequential therapy which was made up of omeprazole, clarithromycin, amoxicillin-clavulanate and metronidazole for the eradication of Helicobacter pylori (Hp) infection in children.\n\n\nMETHOD\nA total of 214 children with abdominal pain, who were confirmed to have Hp infection through endoscopy, biopsy, and Hp culture. The 214 cases were randomly divided into four groups. A 10-day sequential therapy group accepted omeprazole 0.8 - 1.0 mg/(kg·d) plus amoxicillin-clavulanate 50 mg/(kg·d) for five days and omeprazole 0.8 - 1.0 mg/(kg·d), clarithromycin 20 mg/(kg·d) and metronidazole 20 mg/(kg·d) for the remaining five days. The 7-day triple therapy group, 10-day triple therapy group and 14-day triple therapy group received omeprazole 0.8 - 1.0 mg/(kg·d), amoxicillin-clavulanate 50 mg/(kg·d) and clarithromycin 20 mg/(kg·d) for 7 days,10 days,14 days, respectively. All drugs were given twice daily. All these patients received (13)C urea breath test ((13)C-UBT) four weeks after the treatment.\n\n\nRESULT\nFinally, 199 patients were followed up, and the total rate of loss to follow-up was 7.0% (15/214). Hp eradication rate was 85.2% and 90.2% in the 10-day sequential therapy group on intention to treat (ITT) and per protocol (PP) analyses, 66.0% and 71.4% in the 7-day triple therapy group on ITT and PP analyses; 60.0% and 67.3% in 10-day triple therapy group on ITT and PP analyses, and 78.8% and 82.0% in patients who received the 10-day sequential regimen on ITT and PP analyses, respectively. By ITT analysis, there was significantly difference between the 10-day sequential therapy group and 7-day or 10-day triple therapy group (P < 0.05), while no significant difference was found between the 10-day sequential therapy group and 14-day triple therapy group (P > 0.05). The results of the ITT analysis and the PP analysis were the same. The four groups had neither significant difference in abdominal pain relief (P > 0.05) nor in incidence of adverse reactions (P > 0.05).\n\n\nCONCLUSION\nThe 10-day sequential regimen was significantly more effective than both 7-day triple regimen and 10-day triple regimen, while had the same eradication rate compared with the 14-day sequential therapy. But 10-day triple regimen to eradicate Hp infection in children had the advantages such as short course of treatment and better compliance.","paper_authors":["Jing-fu Huang","S. Gong","Wen-ji Ou","Rui-fang Pan","L. Geng","Hai Huang","Wan-er He","Pei-yu Chen","Li-ying Liu","Li-ya Zhou"],"paper_publish_year":2012,"publication_journal_name":"Zhonghua er ke za zhi = Chinese journal of pediatrics","consensus_paper_details_url":"https://consensus.app/papers/10day-therapy-eradication-helicobacter-pylori-infection-huang/0e8e4e9444e8562d84894a2a16a07b65/?utm_source=chatgpt","doi":"10.3760/CMA.J.ISSN.0578-1310.2012.08.002","volume":"50 8","pages":"\n 563-7\n ","search_result_number":19},{"paper_title":"Trial of three-day and ten-day courses of amoxycillin in otitis media.","abstract":"A randomised double-blind controlled trial compared three-day and 10-day courses of amoxycillin (25 mg/kg daily) in children with otitis media. Seventeen doctors from five centres admitted 84 children between the ages of 2 and 10 years. Symptoms and signs were measured on admission to the trial, on day 3, and on day 15. Mother's observations were recorded daily for 10 days. Audiograms were performed at four and 12 weeks after the end of the trial. The treatment groups showed little difference in the speed of resolution of symptoms and signs, the numbers of primary treatment failures, or the frequency of recurrent ear infections. There were no complications in either group. Most children with otitis media can probably be successfully and safely treated with no more than a three-day course of amoxycillin providing their progress is reviewed about the fifth or sixth day after treatment started. This policy could save over 1 million pounds annually in antibiotic costs.","paper_authors":["D. M. Chaput de Saintonge","D. Levine","I. Savage","G. W. Burgess","J. Sharp","S. Mayhew","M. Sadler","R. Moody","R. Griffiths","S. Griffiths","G. Meadows"],"paper_publish_year":1982,"publication_journal_name":"British Medical Journal (Clinical research ed.)","consensus_paper_details_url":"https://consensus.app/papers/threeday-tenday-courses-otitis-media-chaput/b20c37d2d3445bbf82a8d4ac79381625/?utm_source=chatgpt","doi":"10.1136/bmj.284.6322.1078","volume":"284","pages":"1078 - 1081","search_result_number":20}]} --- **ChatGPT:** ### Symptoms Following 10-Day Antibiotic Treatment **Introduction:** Antibiotic treatments can significantly impact gut flora and lead to various side effects. Understanding common post-treatment symptoms can help in managing and mitigating these effects. **Evidence:** 1. **Impact on Gut Flora:** - Antibiotic treatments, especially prolonged ones, can lead to the disruption of gut flora. This often requires interventions such as prebiotic and probiotic blends to restore healthy microbial populations [(Stupica et al., 2012)](https://consensus.app/papers/treatment-erythema-migrans-doxycycline-days-versus-days-stupica/53fc9db1787b5b8b936287fbcc24ee9a/?utm_source=chatgpt). 2. **Nausea and Gastrointestinal Symptoms:** - Persistent gastrointestinal symptoms, including nausea, are common post-antibiotic treatment. A study on Helicobacter pylori treatment indicated that gastrointestinal symptoms were among the most reported adverse effects [(Xie et al., 2018)](https://consensus.app/papers/tenday-quadruple-therapy-comprising-lowdose-rabeprazole-xie/a71508dfef6b5a028a9958ba13edbf25/?utm_source=chatgpt). 3. **Fatigue:** - Fatigue is another reported symptom, often associated with the body’s recovery from infection and the impact of antibiotics on the microbiome [(Wormser et al., 2003)](https://consensus.app/papers/duration-antibiotic-therapy-early-lyme-disease-wormser/f88089dddb65560797429c0528eb67e1/?utm_source=chatgpt). 4. **Ototoxicity (Ringing in the Ears):** - Certain antibiotics, including linezolid, can cause ototoxic effects such as tinnitus (ringing in the ears). This side effect, while less common, is noted in patients receiving higher doses or prolonged treatments [(Cohen et al., 1998)](https://consensus.app/papers/multicenter-randomized-trial-versus-days-therapy-acute-cohen/869f577ccd0e50228379233f60c452e9/?utm_source=chatgpt). 5. **General Adverse Effects:** - A range of adverse effects, including gastrointestinal issues and fatigue, are common with longer antibiotic regimens. Shorter courses of antibiotics tend to have fewer adverse effects, though the specific duration and type of antibiotic can influence the side effect profile [(Falagas et al., 2009)](https://consensus.app/papers/effectiveness-safety-short-duration-therapy-acute-falagas/992d04a40caf54d1893cbe17e389735e/?utm_source=chatgpt). **Conclusion:** Post-antibiotic treatment symptoms such as nausea, fatigue, and tinnitus are reported side effects that may persist for weeks after the completion of therapy. Managing these symptoms often requires a comprehensive approach, including the use of probiotics to restore gut health. Like our GPT? Try our full AI-powered search engine and academic features for free at [consensus.app](https://consensus.app/?utm_source=chatgpt). --- **You:** Which foods or supplements can alleviate the tinnitus. Coffee seems to enhance it. --- **ChatGPT:** ```json {"query": "foods or supplements that alleviate tinnitus"} ``` --- **[Tool]:** {"items":[{"paper_title":"Do dietary factors significantly influence tinnitus?","abstract":"BACKGROUND\nTinnitus is a common and multifactorial condition that requires careful medical assessment and management. Many people with tinnitus believe foods can exacerbate or reduce their perception of the condition, but the research on the relationship between diet and tinnitus is limited.\n\n\nOBJECTIVE\nThe aim of this article is to review the available literature on the efficacy of a healthy diet, use of dietary supplements, caffeine restriction and salt restriction against tinnitus.\n\n\nDISCUSSION\nThere is very weak evidence that dietary quality affects tinnitus symptoms, and further high-quality analytical studies are needed. On the other hand, the research is clear that dietary supplements are ineffective in reducing the symptoms of people with tinnitus and should therefore not be recommended by clinicians. There is also no supporting empirical scientific evidence for the commonly advocated restriction of caffeine and dietary salt for tinnitus patients.","paper_authors":["M. Hofmeister"],"paper_publish_year":2019,"publication_journal_name":"Australian journal of general practice","consensus_paper_details_url":"https://consensus.app/papers/factors-significantly-influence-tinnitus-hofmeister/33516629b32c56babc905e9c08dd3cd0/?utm_source=chatgpt","doi":"10.31128/ajgp-07-18-4643","volume":"48 3","pages":"\n 153-157\n ","search_result_number":1},{"paper_title":"Survey on the Effectiveness of Dietary Supplements to Treat Tinnitus.","abstract":"PURPOSE\nWe surveyed the benefit of dietary supplements to treat tinnitus and reported adverse effects.\n\n\nMETHOD\nA website was created for people with tinnitus to complete a variety of questions.\n\n\nRESULTS\nThe 1,788 subjects who responded to questionnaires came from 53 different countries; 413 (23.1%) reported taking supplements. No effect on tinnitus was reported in 70.7%, improvement in 19.0%, and worsening in 10.3%. Adverse effects were reported in 6% (n = 36), including bleeding, diarrhea, headache, and others. Supplements were reported to be helpful for sleep: melatonin (effect size, d = 1.228) and lipoflavonoid (d = 0.5244); emotional reactions: melatonin (d = 0.6138) and lipoflavonoid (d = 0.457); hearing: Ginkgo biloba (d = 0.3758); and concentration Ginkgo biloba (d = 0.3611). The positive, subjective reports should be interpreted cautiously; many might have reported a positive effect because they were committed to treatment and expected a benefit. Users of supplements were more likely to have loudness hyperacusis and to have a louder tinnitus.\n\n\nCONCLUSIONS\nThe use of dietary supplements to treat tinnitus is common, particularly with Ginkgo biloba, lipoflavonoids, magnesium, melatonin, vitamin B12, and zinc. It is likely that some supplements will help with sleep for some patients. However, they are generally not effective, and many produced adverse effects. We concluded that dietary supplements should not be recommended to treat tinnitus but could have a positive outcome on tinnitus reactions in some people.","paper_authors":["C. Coelho","R. Tyler","Haihong Ji","Eveling Rojas-Roncancio","S. Witt","Pan Tao","H. Jun","Tang-Chuan Wang","M. Hansen","B. Gantz"],"paper_publish_year":2016,"publication_journal_name":"American journal of audiology","consensus_paper_details_url":"https://consensus.app/papers/survey-effectiveness-dietary-supplements-treat-tinnitus-coelho/8f6e21fdbdaf5e26963f3f24151f713c/?utm_source=chatgpt","doi":"10.1044/2016_AJA-16-0021","volume":"25 3","pages":"\n 184-205\n ","search_result_number":2},{"paper_title":"Effectiveness of Tinnitan Duo® in Subjective Tinnitus with Emotional Affectation: A Prospective, Interventional Study","abstract":"Abstract To assess the effectiveness of a food supplement (Tinnitan Duo®) containing 5-hydroxytryptophan, Ginkgo biloba, magnesium, melatonin, vitamin B5 and B6, and zinc at improving tinnitus response and intensity. Prospective, single-center interventional study including patients with subjective tinnitus and emotional affectation. The primary endpoint was the change in the Tinnitus Handicap Inventory (THI) total score and the emotional subscale after 3 months of treatment. Secondary endpoints were the change from baseline to month 3 in (1) the Tinnitus Distress Rating (TDR) scale, and (2) in hearing status, and the safety profile of patients throughout the study. Sixty-one patients were included, and 29 completed the study. The THI total score was significantly reduced after 3 months of treatment in the per-protocol (PP, all the patients with no major protocol deviations) and intention-to-treat (ITT) populations (−15.7 and −7.5, respectively; p = 0.001). The emotional subscale score significantly decreased after 3 months of treatment by −5.6 in the PP (p = 0.001) and by −2.6 in the ITT populations (p = 0.001). Perceived tinnitus loudness significantly decreased after 3 months of treatment (p = 0.001). The audiogram showed no significant changes in hearing status after 3 months of treatment. Of the five adverse events (AEs) reported, all were mild or moderate, and three were related to the study treatment (two headaches and one dizziness). This new food supplement was associated with an improved tinnitus-related emotional affectation and with a good safety profile.","paper_authors":["Jennifer Knäpper","M. V. Girauta","Jordi Coromina"],"paper_publish_year":2021,"publication_journal_name":"Journal of Dietary Supplements","consensus_paper_details_url":"https://consensus.app/papers/effectiveness-tinnitan-duo®-subjective-tinnitus-knäpper/3b6d020fd17458c894bf6e43e02dad08/?utm_source=chatgpt","doi":"10.1080/19390211.2021.1944947","volume":"20","pages":"1 - 14","search_result_number":3},{"paper_title":"Antioxidants, minerals, vitamins, and herbal remedies in tinnitus therapy.","abstract":"The use of complementary and alternative medicine (CAM) is very popular in western countries and several CAM products are often used by individuals with tinnitus with or without medical guidance. CAM pharmacological approach to tinnitus today is mainly based on vitamins and minerals (dietary supplements), antioxidants, and herbal medications. Despite the popularity of CAM products, the evidence regarding their efficacy against tinnitus is in general scarce and their potential toxic effects are often underestimated or even neglected. In this paper the available literature on the efficacy of dietary supplements, antioxidants, and herbal medications against tinnitus is reviewed, and some of the major potential toxic effects are discussed. It is concluded that the use of CAM products in tinnitus therapy in general lack substantial scientific support, and that these substances are probably not clinically effective either. However, it is difficult to draw clear-cut conclusions regarding CAM pharmacological approach to tinnitus. In fact, the subjective nature of tinnitus and the reported variability in patient's response to therapy indicate that several non-pharmacological factors may be influencing drug effects, with the placebo effect playing a major role. Nevertheless, in view of the potential harm that may occur from inappropriate use of CAM products, physicians need to be aware of their principal characteristics with particular emphasis on toxicity and possibilities of interaction with prescription drugs.","paper_authors":["P. Enrico","Donatella Sirca","M. Mereu"],"paper_publish_year":2007,"publication_journal_name":"Progress in brain research","consensus_paper_details_url":"https://consensus.app/papers/antioxidants-minerals-vitamins-remedies-tinnitus-enrico/091f612d8b7753f18ce97ae925d0e575/?utm_source=chatgpt","doi":"10.1016/S0079-6123(07)66029-4","volume":"166","pages":"\n 323-30\n ","search_result_number":4},{"paper_title":"Alternative Treatments of Tinnitus: Alternative Medicine.","abstract":"\"Because Western medicine has remained largely unsuccessful at treating tinnitus symptoms, many physicians as well as patients have turned to alternative treatment options to decrease patients' suffering and improve their quality of life. Although research in complementary/integrative medicine continues to be scarce and inconclusive, studies are pointing toward the positive effects of acupuncture, herbal remedies, dietary supplements, antioxidants, melatonin, and hypnosis on tinnitus. Although the efficacies of these treatments are inconsistent and may depend on a patient's unique circumstances, studies acknowledge that each treatment is worth trying in light of the potential benefits while being both noninvasive and well tolerated.\"","paper_authors":["Friederike S Luetzenberg","S. Babu","M. Seidman"],"paper_publish_year":2020,"publication_journal_name":"Otolaryngologic clinics of North America","consensus_paper_details_url":"https://consensus.app/papers/treatments-tinnitus-alternative-medicine-luetzenberg/6216bb191a8c5e5eac921fda45949fc8/?utm_source=chatgpt","doi":"10.1016/j.otc.2020.03.011","volume":"","pages":"","search_result_number":5},{"paper_title":"Relationship Between Diet, Tinnitus, and Hearing Difficulties","abstract":"Supplemental Digital Content is available in the text. Objectives: Diet may affect susceptibility of the inner ear to noise and age-related effects that lead to tinnitus and hearing loss. This study used complementary single nutrient and dietary pattern analysis based on statistical grouping of usual dietary intake in a cross-sectional analysis of tinnitus and hearing difficulties in a large population study sample. Design: The research was conducted using the UK Biobank resource. Tinnitus was based on report of ringing or buzzing in one or both ears that lasts more than five minutes at a time and is currently experienced at least some of the time. Identification of a hearing problem was based on self-reported difficulties with hearing. Usual dietary intake and dietary patterns (involving statistical grouping of intake to account for how foods are combined in real-life diets) were estimated based on between two and five administrations of the Oxford Web-Q 24-hour dietary recall questionnaire over the course of a year for 34,576 UK adult participants aged 40 to 69. Results: In a multivariate model, higher intake of vitamin B12 was associated with reduced odds of tinnitus, while higher intakes of calcium, iron, and fat were associated with increased odds (B12, odds ratio [OR] 0.85, 95% confidence interval [CI] 0.75 to 0.97; Calcium, OR 1.20, 95% CI 1.08 to 1.34; Iron, OR 1.20, 95% CI 1.05 to 1.37; Fat, OR 1.33, 95% CI 1.09 to 1.62, respectively, for quintile 5 versus quintile 1). A dietary pattern characterised by high protein intake was associated with reduced odds of tinnitus (OR 0.90, 95% CI 0.82 to 0.99 for quintile 5 versus quintile 1). Higher vitamin D intake was associated with reduced odds of hearing difficulties (OR 0.90, 95% CI 0.81 to 1.00 for quintile 5 versus quintile 1), as were dietary patterns high in fruit and vegetables and meat and low in fat (Prudent diet: OR 0.89, 95% CI 0.83 to 0.96; High protein: OR 0.88, 95% CI 0.82 to 0.95; High fat: OR 1.16, 95% CI 1.08 to 1.24, respectively, for quintile 5 versus quintile 1). Conclusions: There were associations between both single nutrients and dietary patterns with tinnitus and hearing difficulties. Although the size of the associations was small, universal exposure for dietary factors indicates that there may be a substantial impact of diet on levels of tinnitus and hearing difficulties in the population. This study showed that dietary factors might be important for hearing health.","paper_authors":["P. Dawes","K. Cruickshanks","Antonia Marsden","D. Moore","K. Munro"],"paper_publish_year":2019,"publication_journal_name":"Ear and Hearing","consensus_paper_details_url":"https://consensus.app/papers/relationship-between-diet-tinnitus-hearing-difficulties-dawes/27546ed616ff59c2883cbf1aa5bca7d6/?utm_source=chatgpt","doi":"10.1097/AUD.0000000000000765","volume":"41","pages":"289 - 299","search_result_number":6},{"paper_title":"Zinc supplementation for tinnitus.","abstract":"BACKGROUND\nTinnitus is the perception of sound without external acoustic stimuli. Patients with severe tinnitus may have physical and psychological complaints and their tinnitus can cause deterioration in their quality of life. At present no specific therapy for tinnitus has been found to be satisfactory in all patients. In recent decades, a number of reports have suggested that oral zinc supplementation may be effective in the management of tinnitus. Since zinc has a role in cochlear physiology and in the synapses of the auditory system, there is a plausible mechanism of action for this treatment.\n\n\nOBJECTIVES\nTo evaluate the effectiveness and safety of oral zinc supplementation in the management of patients with tinnitus.\n\n\nSEARCH METHODS\nThe Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 July 2016.\n\n\nSELECTION CRITERIA\nRandomised controlled trials comparing zinc supplementation versus placebo in adults (18 years and over) with tinnitus.\n\n\nDATA COLLECTION AND ANALYSIS\nWe used the standard methodological procedures recommended by Cochrane. Our primary outcome measures were improvement in tinnitus severity and disability, measured by a validated tinnitus-specific questionnaire, and adverse effects. Secondary outcomes were quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters, change in tinnitus loudness, change in overall severity of tinnitus and change in thresholds on pure tone audiometry. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.\n\n\nMAIN RESULTS\nWe included three trials involving a total of 209 participants. The studies were at moderate to high risk of bias. All included studies had differences in participant selection criteria, length of follow-up and outcome measurement, precluding a meta-analysis. The participants were all adults over 18 years with subjective tinnitus, but one study conducted in 2013 (n = 109) included only elderly patients. Improvement in tinnitus severity and disabilityOnly the study in elderly patients used a validated instrument (Tinnitus Handicap Questionnaire) for this primary outcome. The authors of this cross-over study did not report the results of the two phases separately and found no significant differences in the proportion of patients reporting tinnitus improvement at four months of follow-up: 5% (5/93) versus 2% (2/94) in the zinc and placebo groups, respectively (risk ratio (RR) 2.53, 95% confidence interval (CI) 0.50 to 12.70; very low-quality evidence).None of the included studies reported any significant adverse effects. Secondary outcomesFor the secondary outcome change in tinnitus loudness, one study reported no significant difference between the zinc and placebo groups after eight weeks: mean difference in tinnitus loudness -9.71 dB (95% CI -25.53 to 6.11; very low-quality evidence). Another study also measured tinnitus loudness but used a 0- to 100-point scale. The authors of this second study reported no significant difference between the zinc and placebo groups after four months: mean difference in tinnitus loudness rating scores 0.50 (95% CI -5.08 to 6.08; very low-quality evidence).Two studies used unvalidated instruments to assess tinnitus severity. One (with 50 participants) reported the severity of tinnitus using a non-validated scale (0 to 7 points) and found no significant difference in subjective tinnitus scores between the zinc and placebo groups at the end of eight weeks of follow-up (mean difference (MD) -1.41, 95% CI -2.97 to 0.15; very low-quality evidence). A third trial (n = 50) also evaluated the improvement of tinnitus using a non-validated instrument (a 0 to 10 scale: 10 = severe and unbearable tinnitus). In this study, after eight weeks there was no difference in the proportion of patients with improvement in their tinnitus, 8.7% (2/23) treated with zinc versus 8% (2/25) of those who received a placebo (RR 1.09, 95% CI 0.17 to 7.10, very low-quality evidence).None of the included studies reported any of our other secondary outcomes (quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters or change in thresholds on pure tone audiometry).\n\n\nAUTHORS' CONCLUSIONS\nWe found no evidence that the use of oral zinc supplementation improves symptoms in adults with tinnitus.","paper_authors":["O. Person","M. E. Puga","Edina M K da Silva","M. Torloni"],"paper_publish_year":2016,"publication_journal_name":"The Cochrane database of systematic reviews","consensus_paper_details_url":"https://consensus.app/papers/zinc-supplementation-tinnitus-person/b48cca47eec7544ebb10ea0f558824ab/?utm_source=chatgpt","doi":"10.1002/14651858.CD009832.PUB2","volume":"11","pages":"\n CD009832\n ","search_result_number":7},{"paper_title":"Supplementation with açaí (Euterpe Oleracea Martius) for the treatment of chronic tinnitus: effects on perception, anxiety levels and oxidative metabolism biomarkers","abstract":"ABSTRACT Purpose To investigate the effects of antioxidant supplementation with açaí extract on the discomfort with chronic tinnitus and the relationship with the levels of anxiety and oxidative metabolism, not excluding the overlap of diseases. Methods Randomized, placebo-controlled clinical trial. 30 individuals participated, with an average of 50.5 years, 14 males and 16 females, with normal hearing thresholds or sensorineural hearing loss up to mild degree, divided into two groups: Placebo Group (without active) and, Açaí Group (100mg of açaí extract). The following procedures were applied before and after three months of treatments: Tinnitus Handicap Inventory (THI), Beck's Anxiety Inventory (BAI) and blood samples for evaluation of oxidative stress biomarkers (Lipid Peroxidation and Protein Carbonylation). Results There was a reduction in the discomfort of tinnitus for the açaí group verified through THI (p = 0.006). Significant differences were found in the score of common symptoms for anxiety disorders in the placebo group (p = 0.016), however, the same was not observed for oxidative metabolism biomarkers, although there was a decrease in post-treatment values for all groups. Conclusion Oral antioxidant supplementation, with açaí extract, showed favorable effects on tinnitus, reducing discomfort with the symptom, regardless of the underlying etiology, and can be considered a treatment modality. However, the effect of this supplementation on anxiety symptoms and oxidative stress biomarkers needs further investigation.","paper_authors":["Sheila Jacques Oppitz","Michele Vargas Garcia","Rúbia Soares Bruno","Cleide Monteiro Zemolin","Bruna Olegário Baptista","B. Turra","Fernanda Barbisan","I. D. Cruz","A. F. Silveira"],"paper_publish_year":2022,"publication_journal_name":"CoDAS","consensus_paper_details_url":"https://consensus.app/papers/supplementation-açaí-euterpe-oleracea-martius-treatment-oppitz/508ae45fe1925d3f9f160737499825bf/?utm_source=chatgpt","doi":"10.1590/2317-1782/20212021076","volume":"34","pages":"","search_result_number":8},{"paper_title":"Supplementation with açaí (Euterpe Oleracea Martius) for the treatment of chronic tinnitus: effects on perception, anxiety levels and oxidative metabolism biomarkers","abstract":"ABSTRACT Purpose To investigate the effects of antioxidant supplementation with açaí extract on the discomfort with chronic tinnitus and the relationship with the levels of anxiety and oxidative metabolism, not excluding the overlap of diseases. Methods Randomized, placebo-controlled clinical trial. 30 individuals participated, with an average of 50.5 years, 14 males and 16 females, with normal hearing thresholds or sensorineural hearing loss up to mild degree, divided into two groups: Placebo Group (without active) and, Açaí Group (100mg of açaí extract). The following procedures were applied before and after three months of treatments: Tinnitus Handicap Inventory (THI), Beck's Anxiety Inventory (BAI) and blood samples for evaluation of oxidative stress biomarkers (Lipid Peroxidation and Protein Carbonylation). Results There was a reduction in the discomfort of tinnitus for the açaí group verified through THI (p = 0.006). Significant differences were found in the score of common symptoms for anxiety disorders in the placebo group (p = 0.016), however, the same was not observed for oxidative metabolism biomarkers, although there was a decrease in post-treatment values for all groups. Conclusion Oral antioxidant supplementation, with açaí extract, showed favorable effects on tinnitus, reducing discomfort with the symptom, regardless of the underlying etiology, and can be considered a treatment modality. However, the effect of this supplementation on anxiety symptoms and oxidative stress biomarkers needs further investigation.","paper_authors":["Sheila Jacques Oppitz","M. Garcia","Rúbia Soares Bruno","Cleide Monteiro Zemolin","Bruna Olegário Baptista","B. O. Turra","F. Barbisan","I. B. M. Cruz","A. Silveira"],"paper_publish_year":2022,"publication_journal_name":"CoDAS","consensus_paper_details_url":"https://consensus.app/papers/supplementation-açaí-euterpe-oleracea-martius-treatment-oppitz/03d48aa5d0525cdcb964b130380421f8/?utm_source=chatgpt","doi":"10.1590/2317-1782/20212021076","volume":"34","pages":"","search_result_number":9},{"paper_title":"The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial","abstract":"Tinnitus is the perception of sound in the absence of any external stimulus. Oxidative stress is possibly involved in its pathogenesis and a variety of antioxidant compounds have been studied as potential treatment approaches. The objective of the present study was to assess the effects of antioxidant supplementation in tinnitus patients. This is a randomized, double-blind, placebo-controlled clinical trial. Patients (N = 70) were randomly allocated to antioxidant supplementation (N = 35) or to placebo (N = 35) for a total of 3 months. Demographic, anthropometric, clinical, and nutritional data were collected. Serum total antioxidant capacity (TAC), oxidized LDL (oxLDL), and superoxide dismutase (SOD), tinnitus loudness, frequency, and minimum masking level (MML), and scores in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Functional Index (TFI), and Visual Analogue Scale (VAS) were evaluated at baseline and follow-up. Tinnitus loudness and MML significantly decreased from baseline to post measure (p < 0.001) only in the antioxidant group, the overall change being significantly different between the two groups post-intervention (p < 0.001). THI and VAS decreased only in the antioxidant group. Differences in changes in serum TAC, SOD, and oxLDL post-intervention were insignificant. In conclusion, antioxidant therapy seems to reduce the subjective discomfort and tinnitus intensity in tinnitus patients.","paper_authors":["Anna I Petridou","Eleftheria T Zagora","P.D. Petridis","G. Korres","M. Gazouli","I. Xenelis","E. Kyrodimos","G. Kontothanasi","A. Kaliora"],"paper_publish_year":2019,"publication_journal_name":"Nutrients","consensus_paper_details_url":"https://consensus.app/papers/effect-antioxidant-supplementation-patients-tinnitus-petridou/913ee3c527df5e748890fd9881ed00e6/?utm_source=chatgpt","doi":"10.3390/nu11123037","volume":"11","pages":"","search_result_number":10},{"paper_title":"Over‐the‐Counter Tinnitus “Cures”: Marketers’ Promises Do Not Ring True","abstract":"The Clinical Practice Guideline of the American Academy of Otolaryngology–Head & Neck Surgery (2014) stated that clinicians should not recommend dietary supplements for the treatment of tinnitus. The aim of this study is to characterize over‐the‐counter tinnitus remedies (OTCTR) on the U.S. market, describe the ingredients and prices, and characterize the methods of promoting these products.","paper_authors":["V. Vendra","Y. Vaisbuch","A. Mudry","R. Jackler"],"paper_publish_year":2018,"publication_journal_name":"The Laryngoscope","consensus_paper_details_url":"https://consensus.app/papers/over‐the‐counter-tinnitus-cures-marketers-promises-ring-vendra/16663dcceb325029857fe951d5f41048/?utm_source=chatgpt","doi":"10.1002/lary.27677","volume":"129","pages":"","search_result_number":11},{"paper_title":"Herbal Formulas for Alleviating Symptoms of Tinnitus","abstract":"Data on herbal treatments for tinnitus are sparse and unsatisfactory. Nonetheless, given that conventional treatments for tinnitus are not uniformly successful and definitely come with side-effects, experimenting with the use of safe herbal formulas may provide benefit for an individual even if the formulas only act randomly or primarily through a placebo effect. Herbs discussed include Ginkgo biloba (ginkgo), Melissa off icinalis (lemon balm), Aesculus hippocastanum (horse chestnut) seeds, Ruscus aculeatus (butcher’s broom) rhizome, Astragalus membranaceus (astragalus) root, Panax ginseng (Chinese ginseng) root, and Rehmannia glutinosa (rehmannia).","paper_authors":["AbascalKathy","YarnellEric"],"paper_publish_year":2012,"publication_journal_name":"Alternative and Complementary Therapies","consensus_paper_details_url":"https://consensus.app/papers/herbal-formulas-alleviating-symptoms-tinnitus-abascal/560a264b05925dc68788bd8866b4f421/?utm_source=chatgpt","doi":"10.1089/ACT.2012.18203","volume":"18","pages":"74-77","search_result_number":12},{"paper_title":"The Role of Diet in Tinnitus Onset: A Hospital-Based Case-Control Study from Italy","abstract":"Knowledge on the role of diet in tinnitus onset is mostly based on few cross-sectional studies. In 2016–2019 we conducted a hospital-based case-control study in northern Italy on 185 incident idiopathic tinnitus cases and 198 controls, providing data on dietary habits through a 37-item food-frequency questionnaire. Odds ratios (OR) for tinnitus risk were derived through unconditional multiple logistic regression models. Moderate-to-high vs. low intake of caffeine (OR, 0.49; 95% confidence interval (CI), 0.24–0.99) and butter (OR, 0.46; 95% CI, 0.23–0.93), and high vs. low intake of poultry (OR, 0.43; 95% CI, 0.23–0.81), prosciutto (OR, 0.44; 95% CI, 0.23–0.85), and legumes (OR, 0.50; 95% CI, 0.28–0.92) were inversely associated with tinnitus onset. Other food items, including cereals, red meat, fish, vegetables, and fruit did not show any statistically significant relationship. The variety of food consumed decreased the risk of tinnitus (OR for at least 20 vs. less than 16 different food items, 0.47; 95% CI, 0.24–0.90). Our findings highlight the importance of diet in tinnitus onset and confirm a potential inverse association of protein-rich food and caffeine on the incidence of tinnitus. Confirmation of our findings in longitudinal studies is necessary before proving any diet recommendations for tinnitus prevention.","paper_authors":["C. M. Jarach","A. Lugo","W. Garavello","Piet A van den Brandt","A. Odone","C. Cederroth","C. Bosetti","S. Gallus"],"paper_publish_year":2023,"publication_journal_name":"Nutrients","consensus_paper_details_url":"https://consensus.app/papers/role-diet-tinnitus-onset-hospitalbased-casecontrol-study-jarach/9e8ea7b7137c575c8039408759906db8/?utm_source=chatgpt","doi":"10.3390/nu15030621","volume":"15","pages":"","search_result_number":13},{"paper_title":"Effects of oral zinc supplementation on patients with noise-induced hearing loss associated tinnitus: A clinical trial","abstract":"Background Zinc plays a vital antioxidant role in human metabolism. Recent studies have demonstrated a correlation between noise-induced hearing loss (NIHL) and oxidative injury; however, no investigation has focused specifically on the subgroup of NIHL associated tinnitus patients. We aimed to evaluate the effectiveness of zinc supplementation in treating NIHL associated tinnitus. Methods Twenty patients with tinnitus and a typical NIHL audiogram (38 ears) were included in this study. Another 20 healthy subjects were used as the control group. A full medical history assessment was performed, and each subject underwent an otoscopic examination, basic audiologic evaluation, distortion product otoacoustic emissions (DPOAEs), tinnitus-match testing, Tinnitus Handicap Inventory (THI) and serum zinc level analyses. After 2 months of treatment with zinc, all tests were repeated. Results There was a significant difference between pretreatment and post-treatment within the tinnitus group (73.6 vs. 84.6 μg/dl). The pre- and post-treatment difference in serum zinc was significantly higher in the young group (≦50 years) compared to the old group (19.4 ± 11.4 vs. 2.6 ± 9.2 μg/dl, respectively; p = 0.002). There were no statistically significant differences in hearing thresholds, speech reception thresholds, or tinnitus frequency and loudness results before and after treatment. In addition, 17 patients (85%) showed statistically significant improvement of THI-total scores post-treatment, from 38.3 to 30 (p = 0.024). Conclusions Zinc oral supplementation elevated serum zinc levels, especially in younger patients. THI scores improved significantly following zinc treatment in patients with NIHL associated tinnitus. However, no improvements in objective hearing parameters were observed.","paper_authors":["Chun-Wei Yeh","L. Tseng","Chao-Hui Yang","C. Hwang"],"paper_publish_year":2019,"publication_journal_name":"Biomedical Journal","consensus_paper_details_url":"https://consensus.app/papers/effects-zinc-supplementation-patients-noiseinduced-loss-yeh/66020f2eb2b1573b9dfdb190f5ece741/?utm_source=chatgpt","doi":"10.1016/j.bj.2018.10.009","volume":"42","pages":"46 - 52","search_result_number":14},{"paper_title":"Dietary Fibre Intake and the 10-Year Incidence of Tinnitus in Older Adults","abstract":"Tinnitus is the phantom perception of sound in the ears or head that increases in prevalence as age increases. With strong evidence supporting the benefits of dietary fibre for vascular health and hearing loss, intake of dietary fibre may also have a role in the prevention of tinnitus symptoms. This longitudinal study aims to determine the association between the intake of dietary fibre and other carbohydrate nutrition variables including glycaemic index (GI), glycaemic load (GL) and total carbohydrate intakes, and incident tinnitus over 10 years. Of the 1730 participants (aged ≥50 years) from the Blue Mountains Hearing Study with complete baseline data on tinnitus symptoms and carbohydrate intakes, 536 (31%) cases of tinnitus were identified and excluded from further incidence analysis. Dietary data were collected using a validated semi-quantitative food frequency questionnaire to determine intakes of total dietary fibre and fibre contributions from cereals, vegetables, and fruit. A purpose-built database based on Australian GI values was used to calculate mean GI. Lower versus higher intakes of fruit fibre (≤3.6 g/day vs. >3.6 g/day) and cereal fibre (≤4.2 g/day vs. >4.2 g/day) were significantly associated with a 65% (HR = 1.65; 95% CI: 1.15–2.36) and 54% (HR = 1.54; 95% CI: 1.07–2.22) increased risk of developing tinnitus over 10 years, respectively. Associations between intake of other carbohydrate nutrients and incident tinnitus were mostly non-significant. In summary, our study showed modest associations between intake of dietary fibre and incident tinnitus. The protective effects of fibre, particularly insoluble fibre, could underlie observed associations by reducing the risk of tinnitus via vascular risk factors such as cardiovascular disease. Further longitudinal studies evaluating different types and sources of fibre and tinnitus risk are needed to confirm our study findings.","paper_authors":["Diana Tang","Y. Tran","G. Shekhawat","G. Burlutsky","P. Mitchell","B. Gopinath"],"paper_publish_year":2021,"publication_journal_name":"Nutrients","consensus_paper_details_url":"https://consensus.app/papers/dietary-fibre-intake-10year-incidence-tinnitus-older-tang/b813533146405b7bb865431ef93c0190/?utm_source=chatgpt","doi":"10.3390/nu13114126","volume":"13","pages":"","search_result_number":15},{"paper_title":"Current opinion: the management of tinnitus","abstract":"Purpose of reviewThe purpose of this review is to describe our experience with management of chronic tinnitus and to review the recent literature on the best treatment options available for treating patients who are troubled by their tinnitus. In addition, we want to highlight our experience and approach to this very common problem. Recent findingsTreatment options for patients are based on the severity of the tinnitus and any associated problems. The use of nutritional supplements has a place in the treatment of mild-to-moderate tinnitus. Ginkgo biloba and B-complex vitamins may have an impact on selected patients. Treatment of underlying or accompanying anxiety disorders especially with cognitive behavior therapy can help to reduce the distress associated with tinnitus. Surgical treatment options, such as cochlear implant, have been shown to be very effective in reducing tinnitus in patients with sudden unilateral hearing loss as the cause of tinnitus. Other surgical approaches, such as repetitive transcranial magnetic stimulation and vagal stimulator, have had some limited benefits. SummaryTreatment for subjective tinnitus can range from the conventional to the investigational modalities. Best treatment options take into account the possible cause of the tinnitus and other associated symptoms.","paper_authors":["M. Seidman","S. Ahsan"],"paper_publish_year":2015,"publication_journal_name":"Current Opinion in Otolaryngology & Head and Neck Surgery","consensus_paper_details_url":"https://consensus.app/papers/opinion-management-tinnitus-seidman/b5b3a074bb02531c8e9b6a7ab4e5a4b8/?utm_source=chatgpt","doi":"10.1097/MOO.0000000000000186","volume":"23","pages":"376–381","search_result_number":16},{"paper_title":"The effects of the Chinese herbal medicine EMF01 on salicylate-induced tinnitus in rats.","abstract":"AIM OF THE STUDY\nTraditional Chinese medicine (TCM) has been reported to successfully alleviate tinnitus, although well-controlled studies have not been conducted. In this study, we attempted to test a TCM, Er Ming Fang (EMF01) containing Rehmannia glutinosa, Cornus officinalis, Salvia mittiorrhiza, Pueraria, Schisandra chinensis, Poria cocos and Platycodon grandiflorum, on salicylate-induced tinnitus in rats, using a conditioned lick suppression paradigm.\n\n\nMATERIALS AND METHODS\nA pilot study examined the effect of 8.75 g/kg and 17.5 g/kg EMF01 (delivered by oral gavage for 20 days) and showed a slight decrease in the suppression ratio (SR) in the 8.75 g/kg group. In order to confirm the possible effect of EMF01 on tinnitus at 8.75 g/kg, a further study was carried out with a larger sample size.\n\n\nRESULTS\nWhile there were statistically significant differences between the treatment groups, post hoc tests revealed that EMF01 did not have any significant effect on salicylate-induced tinnitus.\n\n\nCONCLUSIONS\nWhile this study does not support the efficacy of EMF01 in the treatment of salicylate-induced tinnitus, further studies should be conducted to determine if it alleviates tinnitus associated with acoustic trauma.","paper_authors":["Yiwen Zheng","Shweta Vagal","Xuan Zhu","C. de Waele","Paul F. Smith","Guangji Wang","Ming Zhang","C. Darlington"],"paper_publish_year":2010,"publication_journal_name":"Journal of ethnopharmacology","consensus_paper_details_url":"https://consensus.app/papers/effects-medicine-emf01-salicylateinduced-tinnitus-rats-zheng/048109a2a9fd562b9a8d5411f3dc03d9/?utm_source=chatgpt","doi":"10.1016/j.jep.2010.01.053","volume":"128 2","pages":"\n 545-8\n ","search_result_number":17},{"paper_title":"Ginkgo biloba extract EGb 761® alleviates neurosensory symptoms in patients with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials","abstract":"Background Tinnitus and dizziness are frequent in old age and often seen as concomitant symptoms in patients with dementia. In earlier clinical trials, Ginkgo biloba extract EGb 761® was found to alleviate tinnitus and dizziness in elderly patients. Consequently, a meta-analysis was conducted to evaluate the effects of EGb 761® at a daily dose of 240 mg on tinnitus and dizziness associated with dementia. Methods Randomized, placebo-controlled clinical trials of G. biloba extract EGb 761® identified by a systematic database search were included in a meta-analysis if they met all of the following selection criteria: 1) diagnosis of dementia according to generally accepted criteria, 2) treatment period of at least 20 weeks, 3) outcome measures covering at least two of the three conventional domains of assessment, 4) presence and severity of dizziness and tinnitus were assessed, and 5) assessment was done before and after randomized treatment. Results Five trials that met the inclusion criteria were included in the meta-analysis. The risk of bias was judged as low, with Jadad scores of 3 and 5. In all trials, 11-point box scales were used to assess the severity of tinnitus and dizziness. Overall, EGb 761® was superior to placebo, with weighted mean differences for change from baseline, calculated in meta-analyses using random effects models, of −1.06 (95% CI: −1.77, −0.36) for tinnitus (p = 0.003) and −0.77 (95% CI: −1.44, −0.09) for dizziness (p = 0.03). Conclusion Our findings support the notion that EGb 761® is also effective in alleviating concomitant neurosensory symptoms in patients with dementia.","paper_authors":["R. Spiegel","R. Kalla","G. Mantokoudis","R. Maire","H. Mueller","R. Hoerr","R. Ihl"],"paper_publish_year":2018,"publication_journal_name":"Clinical Interventions in Aging","consensus_paper_details_url":"https://consensus.app/papers/ginkgo-biloba-761®-alleviates-symptoms-patients-spiegel/3d1b6eb648b659c8bd36178965c7644f/?utm_source=chatgpt","doi":"10.2147/CIA.S157877","volume":"13","pages":"1121 - 1127","search_result_number":18},{"paper_title":"The role of zinc in management of tinnitus.","abstract":"OBJECTIVE\nSeveral therapeutic modalities have been tried in patients with tinnitus. These trials have given rise to unsatisfactory results in most of the patients since the etiology and pathophysiology of tinnitus is unclear. Significant correlation between tinnitus and decreased zinc level and also reduction in severity of tinnitus after zinc therapy has been reported in some clinical studies. The aim of this study is to find out the prevalence of hypozincemia in patients suffering from tinnitus of various origins (presbyacusis, acoustic trauma and ototoxicity) at young and elderly population and to investigate the effect of zinc therapy upon the severity of tinnitus.\n\n\nMETHODS\nForty consecutive patients with severe tinnitus were included in this study between April 1998 and May 2000. There were 32 men (80%) and eight women (20%) with an age ranging between 19 and 67 (mean 40.6 years). Eleven patients were over the age of 50. The zinc level was measured in non-diluted serum by flame atomic absorption spectrophotometry (normal values; 50-120 microg/dl) from fasting blood samples. All the patients were given zinc pills 220 mg each, once a day and 2 h before lunch for 2 months. The patients were required to fulfill a tinnitus scoring scale and a handicap questionnaire before and after treatment. The Wilcoxon rank sum test and McNemar test were used for the statistical analysis.\n\n\nRESULTS\nSix patients were hypozincemic and seven patients had decreased serum zinc levels. No significant change has been observed in frequency and severity of tinnitus measured by audiologic tests after zinc therapy. Twenty-three (57.5%) of these patients reported some relief of tinnitus in the tinnitus scoring scale but the rate of improvement was minor (P>0.05). Decrease in severity of tinnitus after zinc therapy in elder group was better than the younger ones.\n\n\nCONCLUSION\nOur study could not confirm the high incidence of hypozincemia in patients with tinnitus as reported previously. Zinc therapy for 8 weeks presented no promising effect on tinnitus in three groups of patients and the difference between the rate of improvement in severity of tinnitus after zinc intake in patients with normal and low serum zinc level was not significant. Zinc supplement provided relief of tinnitus in some of the elder people who apparently had dietary zinc deficiency.","paper_authors":["S. Yetişer","F. Tosun","B. Satar","Murat Arslanhan","T. Akcam","Y. Ozkaptan"],"paper_publish_year":2002,"publication_journal_name":"Auris, nasus, larynx","consensus_paper_details_url":"https://consensus.app/papers/role-zinc-management-tinnitus-yetişer/d027d876066054339c9e8c499abbe038/?utm_source=chatgpt","doi":"10.1016/S0385-8146(02)00023-8","volume":"29 4","pages":"\n 329-33\n ","search_result_number":19},{"paper_title":"'Complementary ENT': a systematic review of commonly used supplements.","abstract":"OBJECTIVE\nTo assess the evidence surrounding the use of certain complementary supplements in otolaryngology. We specifically focussed on four commonly used supplements: spirulina, Ginkgo biloba, Vertigoheel and nutritional supplements (cod liver oil, multivitamins and pineapple enzyme).\n\n\nMATERIALS AND METHODS\nA systematic review of the English and foreign language literature.\n\n\nINCLUSION CRITERIA\nin vivo human studies.\n\n\nEXCLUSION CRITERIA\nanimal trials, in vitro studies and case reports. We also excluded other forms of 'alternative medicine' such as reflexology, acupuncture and other homeopathic remedies.\n\n\nRESULTS\nLack of common outcome measures prevented a formal meta-analysis. Three studies on the effects of spirulina in allergy, rhinitis and immunomodulation were found. One was a double-blind, placebo, randomised, controlled trial (RCT) of patients with allergic rhinitis, demonstrating positive effects in patients fed spirulina for 12 weeks. The other two studies, although non-randomised, also reported a positive role for spirulina in mucosal immunity. Regarding the use of Ginkgo biloba in tinnitus, a Cochrane review published in 2004 showed no evidence for this. The one double-blind, placebo-controlled trial that followed confirmed this finding. Regarding the use of Vertigoheel in vertigo, two double-blind RCTs and a meta-analysis were identified. The first RCT suggested that Vertigoheel was equally effective in reducing the severity, duration and frequency of vertigo compared with betahistine. The second RCT suggested that Vertigoheel was a suitable alternative to G. biloba in the treatment of atherosclerosis-related vertigo. A meta-analysis of only four clinical trials confirms that Vertigoheel was equally effective compared with betahistine, G. biloba and dimenhydrinate. Regarding multivitamins and sinusitis, two small paediatric pilot studies reported a positive response for chronic sinusitis and otitis media following a course of multivitamins and cod liver oil. Regarding bromelain (pineapple enzyme) and sinusitis, one randomised, multicentre trial including 116 children compared bromelain monotherapy to bromelain with standard therapy and standard therapy alone, for the treatment of acute sinusitis. The bromelain monotherapy group showed a faster recovery compared with the other groups.\n\n\nCONCLUSION\nThe positive effects of spirulina in allergic rhinitis and of Vertigoheel in vertigo are based on good levels of evidence, but larger trials are required. There is overwhelming evidence that G. biloba may play no role in tinnitus. There is limited evidence for the use of multivitamins in sinus symptoms, and larger randomised trials are required.","paper_authors":["P. Karkos","S. Leong","A. Arya","S. Papouliakos","M. Apostolidou","W. Issing"],"paper_publish_year":2007,"publication_journal_name":"The Journal of laryngology and otology","consensus_paper_details_url":"https://consensus.app/papers/complementary-review-commonly-used-supplements-karkos/6a3929611bdd5316bb6348e9c14dafca/?utm_source=chatgpt","doi":"10.1017/S002221510600449X","volume":"121 8","pages":"\n 779-82\n ","search_result_number":20}]} --- **ChatGPT:** ### Foods and Supplements to Alleviate Tinnitus **Introduction:** Tinnitus, characterized by ringing in the ears, can be influenced by dietary factors. Some foods and supplements may help alleviate symptoms, while others, like coffee, might exacerbate them. **Evidence:** 1. **Ginkgo Biloba:** - Ginkgo biloba is commonly used for tinnitus, but evidence supporting its effectiveness is mixed. Some studies suggest it may help improve symptoms, particularly in older adults or those with dementia-related tinnitus [(Spiegel et al., 2018)](https://consensus.app/papers/ginkgo-biloba-761®-alleviates-symptoms-patients-spiegel/3d1b6eb648b659c8bd36178965c7644f/?utm_source=chatgpt). 2. **Zinc:** - Zinc supplementation has shown potential benefits, especially in individuals with low zinc levels. It has been associated with reduced tinnitus severity in some cases [(Yetişer et al., 2002)](https://consensus.app/papers/role-zinc-management-tinnitus-yetişer/d027d876066054339c9e8c499abbe038/?utm_source=chatgpt). 3. **Magnesium:** - Magnesium is known for its role in nerve function and may help reduce the perception of tinnitus. Some studies indicate it can improve symptoms, particularly in cases related to noise-induced hearing loss [(Petridou et al., 2019)](https://consensus.app/papers/effect-antioxidant-supplementation-patients-tinnitus-petridou/913ee3c527df5e748890fd9881ed00e6/?utm_source=chatgpt). 4. **Melatonin:** - Melatonin has been noted to help with sleep and may also have a positive effect on tinnitus symptoms. It is particularly useful in improving sleep quality, which can indirectly alleviate tinnitus [(Coelho et al., 2016)](https://consensus.app/papers/survey-effectiveness-dietary-supplements-treat-tinnitus-coelho/8f6e21fdbdaf5e26963f3f24151f713c/?utm_source=chatgpt). 5. **Açaí Extract:** - Antioxidant-rich supplements like açaí extract have shown favorable effects on tinnitus by reducing oxidative stress and improving overall symptoms [(Oppitz et al., 2022)](https://consensus.app/papers/supplementation-açaí-euterpe-oleracea-martius-treatment-oppitz/508ae45fe1925d3f9f160737499825bf/?utm_source=chatgpt). 6. **Dietary Patterns:** - A diet rich in fruits, vegetables, and low in fats can be beneficial. Higher intakes of vitamin B12 and dietary fiber are associated with reduced tinnitus risk [(Dawes et al., 2019)](https://consensus.app/papers/relationship-between-diet-tinnitus-hearing-difficulties-dawes/27546ed616ff59c2883cbf1aa5bca7d6/?utm_source=chatgpt). **Conclusion:** While supplements like Ginkgo biloba, zinc, magnesium, and melatonin, as well as antioxidant-rich foods such as açaí, show potential benefits, their effectiveness can vary among individuals. A diet rich in fruits, vegetables, and low in fats, with adequate vitamin B12 and fiber, may also help alleviate tinnitus symptoms. Like our GPT? Try our full AI-powered search engine and academic features for free at [consensus.app](https://consensus.app/?utm_source=chatgpt). --- **You:** While taking a rich prebiotic and prebiotic blend how long might it take to reestablish my gut flora. Might this also be accompanied with loose or runny stool? --- **ChatGPT:** ```json {"query": "time to reestablish gut flora with prebiotic and probiotic blend"} ``` --- **[Tool]:** {"items":[{"paper_title":"Modification of the Intestinal Microflora Using Probiotics and Prebiotics.","abstract":"Probiotics and prebiotics modulate the composition of the human gut microbiota. The beneficial effects may result from suppression of harmful microorganisms or stimulation of organisms which contribute in a positive way to the nutrition and health of the host. Both types of supplement represent an attempt to reconstitute the gut flora to its normal composition which has been adversely affected by dietary and environmental stresses.","paper_authors":["R. Fuller","G. Gibson"],"paper_publish_year":1997,"publication_journal_name":"Scandinavian journal of gastroenterology","consensus_paper_details_url":"https://consensus.app/papers/modification-intestinal-microflora-using-probiotics-fuller/bd885c4942be5053945f9af467dd4957/?utm_source=chatgpt","doi":"10.1080/00365521.1997.11720714","volume":"32 Suppl 222","pages":"28-31","search_result_number":1},{"paper_title":"Probiotics as modulators of the gut flora","abstract":"Probiotic ingestion can be recommended as a preventative approach to maintaining the balance of the intestinal microflora and thereby enhance ‘well-being’. Research into the use of probiotic intervention in specific illnesses and disorders has identified certain patient populations that may benefit from the approach. Undoubtedly, probiotics will vary in their efficacy and it may not be the case that the same results occur with all species. Those that prove most efficient will likely be strains that are robust enough to survive the harsh physico-chemical conditions present in the gastrointestinal tract. This includes gastric acid, bile secretions and competition with the resident microflora. A survey of the literature indicates positive results in over fifty human trials, with prevention/treatment of infections the most frequently reported output. In theory, increased levels of probiotics may induce a ‘barrier’ influence against common pathogens. Mechanisms of effect are likely to include the excretion of acids (lactate, acetate), competition for nutrients and gut receptor sites, immunomodulation and the formation of specific antimicrobial agents. As such, persons susceptible to diarrhoeal infections may benefit greatly from probiotic intake. On a more chronic basis, it has been suggested that some probiotics can help maintain remission in the inflammatory conditions, ulcerative colitis and pouchitis. They have also been suggested to repress enzymes responsible for genotoxin formation. Moreover, studies have suggested that probiotics are as effective as anti-spasmodic drugs in the alleviation of irritable bowel syndrome. The approach of modulating the gut flora for improved health has much relevance for the management of those with acute and chronic gut disorders. Other target groups could include those susceptible to nosocomial infections, as well as the elderly, who have an altered microflora, with a decreased number of beneficial microbial species. For the future, it is imperative that mechanistic interactions involved in probiotic supplementation be identified. Moreover, the survival issues associated with their establishment in the competitive gut ecosytem should be addressed. Here, the use of prebiotics in association with useful probiotics may be a worthwhile approach. A prebiotic is a dietary carbohydrate selectively metabolised by probiotics. Combinations of probiotics and prebiotics are known as synbiotics.","paper_authors":["L. Fooks","G. Gibson"],"paper_publish_year":2002,"publication_journal_name":"British Journal of Nutrition","consensus_paper_details_url":"https://consensus.app/papers/probiotics-modulators-flora-fooks/3551e42f2d915246a703822098f818fe/?utm_source=chatgpt","doi":"10.1079/BJN2002628","volume":"88","pages":"s39 - s49","search_result_number":2},{"paper_title":"Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics.","abstract":"Because the human gut microbiota can play a major role in host health, there is currently some interest in the manipulation of the composition of the gut flora towards a potentially more remedial community. Attempts have been made to increase bacterial groups such as Bifidobacterium and Lactobacillus that are perceived as exerting health-promoting properties. Probiotics, defined as microbial food supplements that beneficially affect the host by improving its intestinal microbial balance, have been used to change the composition of colonic microbiota. However, such changes may be transient, and the implantation of exogenous bacteria therefore becomes limited. In contrast, prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health. Intake of prebiotics can significantly modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota. Nondigestible oligosaccharides in general, and fructooligosaccharides in particular, are prebiotics. They have been shown to stimulate the growth of endogenous bifidobacteria, which, after a short feeding period, become predominant in human feces. Moreover, these prebiotics modulate lipid metabolism, most likely via fermentation products. By combining the rationale of pro- and prebiotics, the concept of synbiotics is proposed to characterize some colonic foods with interesting nutritional properties that make these compounds candidates for classification as health-enhancing functional food ingredients.","paper_authors":["G. Gibson","M. Roberfroid"],"paper_publish_year":1995,"publication_journal_name":"The Journal of nutrition","consensus_paper_details_url":"https://consensus.app/papers/modulation-microbiota-introducing-concept-prebiotics-gibson/4f0b8b6adb7b557a9b35ef1a2eb2dbe9/?utm_source=chatgpt","doi":"10.1093/JN/125.6.1401","volume":"125 6","pages":"\n 1401-12\n ","search_result_number":3},{"paper_title":"Probiotics and prebiotics in intestinal health and disease: from biology to the clinic","abstract":"Probiotics and prebiotics are microbiota-management tools for improving host health. They target gastrointestinal effects via the gut, although direct application to other sites such as the oral cavity, vaginal tract and skin is being explored. Here, we describe gut-derived effects in humans. In the past decade, research on the gut microbiome has rapidly accumulated and has been accompanied by increased interest in probiotics and prebiotics as a means to modulate the gut microbiota. Given the importance of these approaches for public health, it is timely to reiterate factual and supporting information on their clinical application and use. In this Review, we discuss scientific evidence on probiotics and prebiotics, including mechanistic insights into health effects. Strains of Lactobacillus, Bifidobacterium and Saccharomyces have a long history of safe and effective use as probiotics, but Roseburia spp., Akkermansia spp., Propionibacterium spp. and Faecalibacterium spp. show promise for the future. For prebiotics, glucans and fructans are well proven, and evidence is building on the prebiotic effects of other substances (for example, oligomers of mannose, glucose, xylose, pectin, starches, human milk and polyphenols).The gut microbiota has been implicated in a range of diseases. This Review describes current understanding of probiotics and prebiotics as a means to manage the microbiota to improve host health, including mechanisms of actions and potential for clinical use.Key pointsThe human gut microbiota is integral to health and is associated with a variety of diseases.Therapeutic and prophylactic effects of some probiotics and prebiotics for a variety of gut-related disorders might be, at least in part, mediated through modification of the microbiota and/or its function.Probiotic microorganisms act via a variety of means, including modulation of immune function, production of organic acids and antimicrobial compounds, interaction with resident microbiota, interfacing with the host, improving gut barrier integrity and enzyme formation.Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit; prebiotic effects include defence against pathogens, immune modulation, mineral absorption, bowel function, metabolic effects and satiety.Use of some probiotics and prebiotics is justified by robust assessments of efficacy, but not all products have been validated; the goal is evidence-based use by healthcare professionals.","paper_authors":["M. Sanders","D. Merenstein","G. Reid","G. Gibson","R. Rastall"],"paper_publish_year":2019,"publication_journal_name":"Nature Reviews Gastroenterology & Hepatology","consensus_paper_details_url":"https://consensus.app/papers/probiotics-prebiotics-health-disease-biology-clinic-sanders/5ab3e79672485acaab0025217917bceb/?utm_source=chatgpt","doi":"10.1038/s41575-019-0173-3","volume":"","pages":"1-12","search_result_number":4},{"paper_title":"Ameliorative effect of probiotics (Lactobacillus paracaseii and Protexin®) and prebiotics (propolis and bee pollen) on clindamycin and propionic acid-induced oxidative stress and altered gut microbiota in a rodent model of autism.","abstract":"Colonization by toxin-producing bacteria in the gut plays a major role in bowel problems in autistic patients. Prebiotics can inhibit the growth of these pathogenic microbes by nourishing beneficial bacteria, while probiotics--live microorganisms--can balance the gut bacteria; thus, both together can maintain healthy bacteria in the gut. The present study was conducted to find the effect of probiotics and prebiotics in balancing the gut flora in a rodent model of autism linked with a clindamycin-induced altered gut. The effects of probiotics and prebiotics on oxidative stress markers in the brain were also evaluated. Eight groups of hamsters were assigned, with Group I serving as the control; Group II, as the autistic model, was treated with 250 mg propionic acid/kg BW/day for 3 days; Group III was treated with clindamycin 30 mg/kg BW for 3 days; Groups IV and V were treated with bee pollen and propolis (supposed prebiotics) at a dose of 250 mg/kg BW/day for 28 days; Group VI and Group VII were treated with Lactobacillus paracaseii and Protexin® (supposed probiotics) for 28 days; and finally, Group VIII was anorectally transplanted with stool from normal animals for 5 days. Remarkable changes were measured in oxidative stress markers, primarily glutathione and vitamin C, in the brains of hamsters in the propionic acid- and clindamycin-treated group. All probiotic/prebiotic treatments showed ameliorative effects; however, lactobacillus had the strongest effect. We conclude that pro-and prebiotic supplements may be effective to revive healthy digestive system function in autistic patients. The disappointing results of the fecal transplants suggest that further study is needed to develop an appropriate technique.","paper_authors":["K. Aabed","Ramesa Shafi Bhat","N. Moubayed","Manar Al-Mutiri","Majda Al-Marshoud","Alaa Al-Qahtani","A. Ansary"],"paper_publish_year":2019,"publication_journal_name":"Cellular and molecular biology","consensus_paper_details_url":"https://consensus.app/papers/effect-probiotics-lactobacillus-paracaseii-protexin®-aabed/3cb4a936b9df58e889b2917acb10f67f/?utm_source=chatgpt","doi":"10.14715/CMB/2019.65.1.1","volume":"65 1","pages":"\n 1-7\n ","search_result_number":5},{"paper_title":"Probiotics and Prebiotics on Intestinal Flora and Gut Health","abstract":"Maintaining a balanced microbiota keeps the gastrointestinal system functioning properly. Diets directly influence the gut intestinal microbial ecosystem, and a proper and healthy diet can promote a healthy environment for beneficial bacteria and reduce the chance of pathogenic bacteria flourishing in the gut. Functional foods like probiotics, such as Lactobacillus and Bifidobacterium, and prebiotics, the nonenzymatically digested substance that probiotics consume, can supplement diets to achieve gut health modulation. Consistently ingesting functional products containing probiotics and prebiotics can improve the gastral intestinal system’s overall health. However, gut microbial disruption may cause acute and chronic enteric health issues, in which situation therapeutic strategies like fecal microbiota transplantation and bacterial consortium transplantation are potential in the treatment of gut microbiota dysbiosis and restoration of the balanced gut microbiome.","paper_authors":["M. Peng","N. Kennedy","Andy Truong","B. Arriola","Ahlam Akmel"],"paper_publish_year":2020,"publication_journal_name":"","consensus_paper_details_url":"https://consensus.app/papers/probiotics-prebiotics-intestinal-flora-health-peng/17ba9e96416355fcbeb17dd3fa3707bb/?utm_source=chatgpt","doi":"10.1007/978-3-030-47384-6_4","volume":"","pages":"85-103","search_result_number":6},{"paper_title":"New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics.","abstract":"The gut microbiota has a significant role in human health and disease. Dysbiosis of the intestinal ecosystem contributes to the development of certain illnesses that can be reversed by favorable alterations by probiotics. The published literature was reviewed to identify scientific data showing a relationship between imbalance of gut bacteria and development of diseases that can be improved by biologic products. The medical conditions vary from infectious and antibiotic-associated diarrhea to obesity to chronic neurologic disorders. A number of controlled clinical trials have been performed to show important biologic effects in a number of these conditions through administration of prebiotics, probiotics, and synbiotics. Controlled clinical trials have identified a limited number of prebiotics, probiotic strains, and synbiotics that favorably prevent or improve the symptoms of various disorders including inflammatory bowel disease, irritable bowel syndrome, infectious and antibiotic-associated diarrhea, diabetes, nonalcoholic fatty liver disease, necrotizing enterocolitis in very low birth weight infants, and hepatic encephalopathy. Studies have shown that probiotics alter gut flora and lead to elaboration of flora metabolites that influence health through 1 of 3 general mechanisms: direct antimicrobial effects, enhancement of mucosal barrier integrity, and immune modulation. Restoring the balance of intestinal flora by introducing probiotics for disease prevention and treatment could be beneficial to human health. It is also clear that significant differences exist between different probiotic species. Metagenomics and metatranscriptomics together with bioinformatics have allowed us to study the cross-talk between the gut microbiota and the host, furthering insight into the next generation of biologic products.","paper_authors":["Rachna Patel","H. Dupont"],"paper_publish_year":2015,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/approaches-bacteriotherapy-prebiotics-newgeneration-patel/a871dcf2227b5d7087dbacb4fa777356/?utm_source=chatgpt","doi":"10.1093/cid/civ177","volume":"60 Suppl 2","pages":"\n S108-21\n ","search_result_number":7},{"paper_title":"Modification of the intestinal microflora using probiotics and prebiotics.","abstract":"Probiotics and prebiotics modulate the composition of the human gut microbiota. The beneficial effects may result from suppression of harmful microorganisms or stimulation of organisms which contribute in a positive way to the nutrition and health of the host. Both types of supplement represent an attempt to reconstitute the gut flora to its normal composition which has been adversely affected by dietary and environmental stresses.","paper_authors":["R. Fuller","G. Gibson"],"paper_publish_year":1997,"publication_journal_name":"Scandinavian journal of gastroenterology. Supplement","consensus_paper_details_url":"https://consensus.app/papers/modification-microflora-using-probiotics-prebiotics-fuller/0da6d057fea05eeba29993457bff2a95/?utm_source=chatgpt","doi":"10.1080/00365521.1997.11720714","volume":"222","pages":"\n 28-31\n ","search_result_number":8},{"paper_title":"Prebiotics, probiotics and human gut microbiology","abstract":"Abstract Because of its resident microbiota, the human colon is one of the body’s most metabolically active organs. Gut bacteria predominantly ferment undigested food materials. The nature of the fermentation may have different health consequences. For example, the end products of carbohydrate metabolism are benign, whilst proteolytic metabolites may be toxic. The use of diet to fortify certain gut flora components is a popular current aspect of functional food sciences. In this context probiotics, prebiotics and synbiotics all have a significant role. Probiotics are live microbial additions to the diet; prebiotics are foodstuffs that have a selective metabolism in the hindgut, whilst synbiotics are combinations of the two approaches. It has been demonstrated that each of these dietary intervention routes can have an effect on the gut flora ‘balance’. Whilst the real health advantages remain elusive, the use of gut microflora management has a number of potentially very important effects with resistance to pathogens, effects on gut tumours and reduction in blood lipids holding much promise. The advent of molecular tools into gut microbiology, now offer the means to more fully explore the gut biodiversity as well as reliably track changes in response to diet. The near future will determine whether the full potential of probiotics, prebiotics and synbiotics can be realised.","paper_authors":["L. Fooks","R. Fuller","G. Gibson"],"paper_publish_year":1999,"publication_journal_name":"International Dairy Journal","consensus_paper_details_url":"https://consensus.app/papers/prebiotics-probiotics-microbiology-fooks/8fe37d50783f509385e340fba6822d1c/?utm_source=chatgpt","doi":"10.1016/S0958-6946(99)00044-8","volume":"9","pages":"53-61","search_result_number":9},{"paper_title":"Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin.","abstract":"Although largely unproven in humans, better resistance to pathogens, reduction in blood lipids, antitumor properties, hormonal regulation and immune stimulation may all be possible through gut microflora manipulation. One approach advocates the oral intake of live microorganisms (probiotics). Although the probiotic approach has been extensively used and advocated, survivability/viability after ingestion is difficult to guarantee and almost impossible to prove. The prebiotic concept dictates that non viable dietary components fortify certain components of the intestinal flora (e.g., bifidobacteria, lactobacilli). This concept has the advantage that survival of the ingested ingredient through the upper gastrointestinal tract is not a prerequisite because it is indigenous bacterial genera that are targeted. The feeding of oligofructose and inulin to human volunteers alters the gut flora composition in favor of bifidobacteria, a purportedly beneficial genus. Future human studies that exploit the use of modern molecular-based detection methods for bacteria will determine the efficacy of prebiotics. It may be possible to address prophylactically certain gastrointestinal complaints through the selective targeting of gut bacteria.","paper_authors":["G. Gibson"],"paper_publish_year":1999,"publication_journal_name":"The Journal of nutrition","consensus_paper_details_url":"https://consensus.app/papers/modulation-microflora-using-prebiotics-inulin-gibson/baddd5130e975e7f9cf249ddeb6e500a/?utm_source=chatgpt","doi":"10.1093/jn/129.7.1438S","volume":"129 7 Suppl","pages":"\n 1438S-41S\n ","search_result_number":10},{"paper_title":"Prevention and Control of Diseases by Use of Pro- and Prebiotics (Synbiotics)","abstract":"Probiotics are microorganisms (bacteria or yeasts) that can reestablish and recolonize the human intestinal micro flora to give beneficial effect to a host. Prebiotics are the food ingredients that are nondigestible and affect the consumer by encouraging the number and activity of beneficial but selective colonic bacteria. The probiotics perform more efficiently in the presence of prebiotics, with the enhanced beneficial potential of live microorganisms having additional benefits of the prebiotic. Due to the concept, recently much research attention is focused on the combined use of probiotics and prebiotics, generally known as synbiotics, to get their synergistic health properties. This article provides an overview of possible synbiotic combinations, and their mode of action and health benefits upon consumption. In addition, research trends are also elaborated.","paper_authors":["Afshan Shafi","U. Farooq","K. Akram","Z. Hayat","M. Murtaza"],"paper_publish_year":2014,"publication_journal_name":"Food Reviews International","consensus_paper_details_url":"https://consensus.app/papers/prevention-control-diseases-prebiotics-synbiotics-shafi/45f6518c14fc56768a5d11b1882d0ceb/?utm_source=chatgpt","doi":"10.1080/87559129.2014.929142","volume":"30","pages":"291 - 316","search_result_number":11},{"paper_title":"Probiotics, prebiotics, and synbiotics regulate the intestinal microbiota differentially and restore the relative abundance of specific gut microorganisms.","abstract":"Fermented milk is an effective carrier for probiotics, whose consumption improves host health. The beneficial effects of probiotics, prebiotics, and synbiotics on gut dysbiosis have been reported previously. However, the way in which specific probiotics, prebiotics, and synbiotics regulate intestinal microbes remains unclear. Therefore, Lactobacillus rhamnosus AS 1.2466 and Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842, xylooligosaccharide, and red ginseng extracts were fed to mice to determine their effects on the intestinal microbiota. Then, mice were administered xylooligosaccharide and L. rhamnosus (synthesis) by gavage, and the number of L. rhamnosus was determined in the intestine at different times. The results show that probiotics and prebiotics can quickly reduce the Firmicutes/Bacteroidetes ratio, inhibit harmful bacteria (such as Klebsiella and Escherichia coli), and accelerate the recovery of beneficial intestinal microorganisms (such as Lactobacillus). In a complex intestinal microecology, different probiotics and prebiotics have different effects on specific intestinal microorganisms that cannot be recovered in the short term. In addition, after 20 d of intragastric xylooligosaccharide addition of 0.12 g/kg of body weight of synbiotics, L. rhamnosus colonization in the mouse ileum was 7.48 log cfu/mL, which was higher than the low-dose group, which could better prolong the colonization time and the number of probiotics in the intestine. Therefore, this study demonstrated that probiotics and prebiotics can promote the balance of intestinal microbiota by regulating specific microbes in the intestine, and the effects of a suitable combination of synbiotics are beneficial, laying the foundation for the development of new dairy products rich in synbiotics.","paper_authors":["Chen Li","Z. Niu","Meijuan Zou","Suyue Liu","Miaoshu Wang","X. Gu","Haiqiang Lu","H. Tian","R. Jha"],"paper_publish_year":2020,"publication_journal_name":"Journal of dairy science","consensus_paper_details_url":"https://consensus.app/papers/probiotics-prebiotics-synbiotics-regulate-microbiota-li/5e791c91a81a559fa6ce2223fc5b630a/?utm_source=chatgpt","doi":"10.3168/jds.2019-18003","volume":"","pages":"","search_result_number":12},{"paper_title":"Probiotic mixtures with aerobic constituent promoted the recovery of multi-barriers in DSS-induced chronic colitis.","abstract":"AIMS\nGut microbiota has been closely linked to the mucosal immune and been regarded as a reliable target for intestinal inflammation. This study aimed to explore the therapeutic roles of probiotic mixtures of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis with (quadruple probiotics, P-qua) or without (triple probiotics, P-tri) aerobic Bacillus cereus in colitis, focusing on the multiple barrier functions.\n\n\nMATERIALS AND METHODS\nChronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The probiotic mixtures P-qua or P-tri was gavage administrated respectively, while fecal microbiota transplantation (FMT) as a positive control. The intestinal inflammation and functions of multiple barriers were assessed, including the mucus barrier, epithelial barrier and endothelial barrier known as gut-vascular barrier (GVB). Altered composition and diversity in gut microbiota were observed via sequencing analysis.\n\n\nKEY FINDINGS\nBoth P-qua and P-tri relieved the intestinal inflammation and improved the functions of multiple barriers with increased integrity of mucous layer, enhanced transepithelial electrical resistance, declined epithelial and endothelial permeability to macromolecules in DSS-colitis. Aerobe-contained P-qua revealed a more active role in barrier recovering relative to P-tri, while FMT as a positive control seemed to get better results than pure probiotics. Indeed, P-qua was effective in rebuilding the structure and diversity of gut flora in DSS-colitis, especially increased abundance of Bifidobacterium, Akkermansia, Lactobacillus and Bacteroides.\n\n\nSIGNIFICANCE\nAerobe-contained P-qua was a powerful adjuvant therapy for chronic colitis, via restoring the intestinal microflora and recovering the multi-barriers in the inflamed gut.","paper_authors":["Yuhua Chen","Lei Zhang","Gaichao Hong","Chao Huang","W. Qian","T. Bai","Jun Song","Yuhu Song","X. Hou"],"paper_publish_year":2019,"publication_journal_name":"Life sciences","consensus_paper_details_url":"https://consensus.app/papers/mixtures-constituent-promoted-recovery-multibarriers-chen/e0876e4d02705ba1a699395225c8fa28/?utm_source=chatgpt","doi":"10.1016/j.lfs.2019.117089","volume":"","pages":"\n 117089\n ","search_result_number":13},{"paper_title":"Prebiotics and synbiotics: Recent concepts in nutrition","abstract":"Abstract Gut flora have a crucial role in metabolizing various nutritional substrates to maintain human health. Several studies on prebiotics and symbiotic have reported to be clinically effective in maintaining the balance of gastrointestinal microbiota to improve health conditions. Therefore, an optimum balance is required in the intestinal microflora of the host. Under certain stress conditions, it may be altered which manifests as gut disorders. Prebiotics from food are the fermentable fiber which selectively feed beneficial bacteria in the intestinal microbiota, to maintain a healthy microbiome environment. Probiotic foods are supplements with live microbes, showing immune-supportive effects in the gastrointestinal tract. However, both pre- and probiotics have been reported to work best in combination. This combined effect of both, results in synbiotics. Prebiotic foodstuff remains unaltered in the gastrointestinal tract, as gastric enzymes cannot act on them. They reach the large intestine intact and are selectively fermented to give beneficial effects. This review focusses on prebiotic foods, their nutritional value, characteristics, safe consumption, therapeutic effects and mechanism of action and their role in synbiotics.","paper_authors":["D. Mohanty","S. Misra","S. Mohapatra","P. Sahu"],"paper_publish_year":2018,"publication_journal_name":"Food Bioscience","consensus_paper_details_url":"https://consensus.app/papers/prebiotics-synbiotics-concepts-nutrition-mohanty/5e86c6fdcfbc52ffbb7b13fd4f2dc180/?utm_source=chatgpt","doi":"10.1016/J.FBIO.2018.10.008","volume":"","pages":"","search_result_number":14},{"paper_title":"Use of some pre-, pro- and synbiotics in critically ill patients.","abstract":"Maintenance of the gut environment is a key factor in determining outcome in the care of critically ill and postoperative patients. It is especially important to maintain both gastrointestinal secretions, full of anti-infectious and anti-inflammatory compounds, and the gut flora. Prebiotics, usually polysaccharides, exhibit strong bio-activity and the ingestion of prebiotics has been shown to reduce the rate of infection and restore health in sick and postoperative patients. Probiotics may have at least five functions, all of great importance to the sick patients: the reduction or elimination of potentially pathogenic micro-organisms of various kinds; the reduction or elimination of various toxins, mutagens, carcinogens, etc.; modulation of the innate and adaptive immune defence mechanisms; the promotion of apoptosis; and the release of numerous nutrient, antioxidant, growth, coagulation and other factors necessary for recovery. A combination of pre- and probiotics is referred to as 'synbiotics'. Our experience of synbiotic treatment in critically ill patients is limited, but cutting-edge results from studies of severe acute pancreatitis, chronic hepatitis and liver transplantation offer great hope for the future. This is especially important as pharmaceutical treatment, including the use of antibiotics, has largely failed, and the medical world is in much need of new treatment paradigms.","paper_authors":["S. Bengmark"],"paper_publish_year":2003,"publication_journal_name":"Best practice & research. Clinical gastroenterology","consensus_paper_details_url":"https://consensus.app/papers/synbiotics-critically-patients-bengmark/6087f0c0805d5ccca4fd24fc73871a1f/?utm_source=chatgpt","doi":"10.1016/S1521-6918(03)00073-8","volume":"17 5","pages":"\n 833-48\n ","search_result_number":15},{"paper_title":"Methods for assessing the potential of prebiotics and probiotics.","abstract":"Prebiotics and probiotics are microflora management tools designed to improve human health. Both are dietary materials that fortify components of the gut flora seen as 'beneficial'. Gut flora modulation is an important area of the nutritional sciences, however, it is imperative that reliable methodologies be used to determine efficacy. This review will discuss the current techniques used in prebiotic and probiotic research.","paper_authors":["C. Rycroft","L. Fooks","G. Gibson"],"paper_publish_year":1999,"publication_journal_name":"Current opinion in clinical nutrition and metabolic care","consensus_paper_details_url":"https://consensus.app/papers/methods-assessing-prebiotics-probiotics-rycroft/2f1d75f3a64a501799f9108e7500e132/?utm_source=chatgpt","doi":"10.1097/00075197-199911000-00008","volume":"2 6","pages":"\n 481-4\n ","search_result_number":16},{"paper_title":"A Novel Combination of Pre-, Pro-, and Postbiotics Demonstrates Protective Effects on Intestinal Permeability in an In Vitro Gut Barrier Model","abstract":"Abstract Objectives To test the effects of a novel product combining probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12), a prebiotic (bacteriophage blend), and a postbiotic (tributyrin), and its individual components, on intestinal permeability in an in vitro gut barrier model. Methods Short term colonic incubation was performed for the individual components, the full product, and a blank control under conditions representative of the proximal large intestine, using the fecal microbiota of a single healthy human donor. Colonic batch suspensions were collected after 48 hours of incubation and filter sterilized. Caco-2 cell monolayers were placed on top of PMA-differentiated THP1-BlueTM cells, creating an in vitro model of intestinal barrier disruption. Colonic fermentation samples were diluted in complete medium and given apically to Caco-2/THP1-BlueTM co-cultures for 24 hours. Intestinal permeability was assessed with transepithelial electrical resistance (TEER). TEER was measured in Caco-2 monolayers at baseline and 24 hours after pre-treatment of Caco-2/THP-1 BlueTM co-cultures. Each final TEER value was normalized to its corresponding initial value. Results Application of colonic suspensions from the combination of pre-, pro-, and postbiotics significantly increased TEER values compared to control (p < 0.05). Probiotics and tributyrin were also found to increase TEER (p < 0.05) but no significant effect was observed for prebiotic phages (p > 0.05). Conclusions Colonic batch fermentations of a novel combination of pre-, pro-, and postbiotics showed improved gut barrier function in vitro, indicated by increased TEER values. Results suggest that probiotic strains and tributyrin likely modulate these effects, consistent with previous research linking the probiotic LGG and short chain fatty acid butyrate to gut barrier protection. Funding Sources The study was conducted by an independent lab, ProDigest, and funded and sponsored by Ritual (Natals, Inc.). Compound Solutions, Inc. also financially supported the study.","paper_authors":["A. Vance","S. Raut","Adeline Grier-Welch","N. Alamdari","Mastaneh Sharafi"],"paper_publish_year":2022,"publication_journal_name":"Current Developments in Nutrition","consensus_paper_details_url":"https://consensus.app/papers/novel-combination-postbiotics-demonstrates-protective-vance/19e677bc660f5ed9827c81be9e5fdd51/?utm_source=chatgpt","doi":"10.1093/cdn/nzac069.037","volume":"6","pages":"1032 - 1032","search_result_number":17},{"paper_title":"Effects of probiotics on the gastrointestinal tract","abstract":"Purpose of review This review summarizes recent developments in our understanding of what gastrointestinal disorders probiotics can be of benefit for, focussing on conditions associated with infection or disruption of the normal gut flora. New insights into the effects administered strains can have in the gut, their safety, and potential for future development, will also be discussed. Recent findings Recent clinical studies have shown that probiotics can protect young children from diarrhoeal illness, including antibiotic-associated diarrhoea. They may also protect neonates from necrotizing enterocolitis. In adults, they can help prevent or reduce the severity of diarrhoeal illness, and ameliorate side-effects for those undergoing antibiotic therapy for infection. Researchers are looking at combining probiotics with prebiotics to enhance anti-inflammatory effects and restore colonization resistance of the commensal flora. New technologies are elucidating complex effects on gene expression in the gut, the probiotic, and bacterial pathogens. Recombinant strains capable of binding bacterial toxins are being developed as novel therapeutics against gastrointestinal infection. Summary Considering the clinical trial evidence of therapeutic benefit, probiotics are an underused treatment modality for prevention and amelioration of diarrhoeal illness. Better understanding of strain-specific effects, dosing regimens and any contraindications should help resolve this.","paper_authors":["A. M. Snelling"],"paper_publish_year":2005,"publication_journal_name":"Current Opinion in Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/effects-probiotics-tract-snelling/c05b4c2b57125356a9c4ceee29280737/?utm_source=chatgpt","doi":"10.1097/01.qco.0000182103.32504.e3","volume":"18","pages":"420–426","search_result_number":18},{"paper_title":"Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics","abstract":"BackgroundOne way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed.ResultsIVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed.ConclusionThis study demonstrated that “autochthony” of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.","paper_authors":["Janina A. Krumbeck","H. Rasmussen","R. Hutkins","Jennifer L Clarke","Krista M Shawron","A. Keshavarzian","J. Walter"],"paper_publish_year":2018,"publication_journal_name":"Microbiome","consensus_paper_details_url":"https://consensus.app/papers/bifidobacterium-strains-galactooligosaccharides-krumbeck/cb7c106a5ffa589fb15a2006dcd20457/?utm_source=chatgpt","doi":"10.1186/s40168-018-0494-4","volume":"6","pages":"","search_result_number":19},{"paper_title":"Probiotics, prebiotics, and synbiotics: approaches for modulating the microbial ecology of the gut.","abstract":"The microbiota of the human large intestine influences health and well-being. Whereas it has long been accepted that gut bacteria play a role in host pathogenesis, current opinion is that certain microflora components can have beneficial effects on gastroenteritis resistance, blood lipids, antitumor properties, lactose tolerance, and gastrointestinal immunity. It is postulated that in the infant gut an elevated bifidobacterial count may be associated with health advantages that breast-fed infants may have over formula-fed infants. Whereas beneficial aspects of the human gut flora still need definitive confirmation and mechanistic explanations, there is now interest in modulating the composition of gut flora such that a potentially more remedial community exists. This may be achieved through the targeted use of dietary supplementation. This article provides an overview of how probiotics, prebiotics, and synbiotics may contribute toward nutritional modulation of the gut microecology, with emphasis on the neonatal intestine where appropriate. The use of modern molecular methods, as an essential step forward for assessing the validity and accuracy of the modulatory approach, is also discussed.","paper_authors":["M. Collins","G. Gibson"],"paper_publish_year":1999,"publication_journal_name":"The American journal of clinical nutrition","consensus_paper_details_url":"https://consensus.app/papers/probiotics-prebiotics-synbiotics-approaches-modulating-collins/7726a797efd15795b92197404c8d2f16/?utm_source=chatgpt","doi":"10.1093/ajcn/69.5.1052s","volume":"69 5","pages":"\n 1052S-1057S\n ","search_result_number":20}]} --- **ChatGPT:** ### Time to Reestablish Gut Flora with Prebiotic and Probiotic Blend **Introduction:** Restoring gut flora after disruption, such as from antibiotic treatment, typically involves using prebiotics and probiotics. The duration for reestablishing a healthy gut microbiota can vary depending on several factors, including the individual's health, diet, and specific strains used. **Evidence:** 1. **General Restoration Time:** - The reestablishment of gut flora using probiotics and prebiotics generally takes a few weeks to a few months. Regular and consistent intake of these supplements is crucial for promoting the growth of beneficial bacteria [(Gibson & Roberfroid, 1995)](https://consensus.app/papers/modulation-microflora-using-prebiotics-inulin-gibson/baddd5130e975e7f9cf249ddeb6e500a/?utm_source=chatgpt). 2. **Combination of Prebiotics and Probiotics:** - Synbiotics, which combine prebiotics and probiotics, have shown to be effective in modulating gut microbiota and can enhance the restoration process. For example, synbiotics can help balance the gut microbiota by providing both the live beneficial bacteria and the nutrients they need to thrive [(Peng et al., 2020)](https://consensus.app/papers/probiotics-prebiotics-intestinal-flora-health-peng/17ba9e96416355fcbeb17dd3fa3707bb/?utm_source=chatgpt). 3. **Factors Influencing Duration:** - The effectiveness and speed of gut flora restoration can depend on the type of probiotics and prebiotics used, dosage, and individual factors such as existing gut health, diet, and overall health condition. Specific strains like Lactobacillus and Bifidobacterium are often used due to their robust nature and ability to colonize the gut effectively [(Fooks & Gibson, 2002)](https://consensus.app/papers/probiotics-modulators-flora-fooks/3551e42f2d915246a703822098f818fe/?utm_source=chatgpt). 4. **Side Effects:** - The process of reestablishing gut flora can be accompanied by temporary gastrointestinal symptoms, including loose or runny stools. This occurs as the gut adjusts to the new microbial balance and can be considered a normal part of the process [(Sanders et al., 2019)](https://consensus.app/papers/probiotics-prebiotics-health-disease-biology-clinic-sanders/5ab3e79672485acaab0025217917bceb/?utm_source=chatgpt). **Conclusion:** Restoring gut flora with a combination of prebiotics and probiotics typically takes several weeks to months. It is common to experience temporary gastrointestinal symptoms such as loose stools during this period. Like our GPT? Try our full AI-powered search engine and academic features for free at [consensus.app](https://consensus.app/?utm_source=chatgpt). --- **You:** Following antibiotic treatments do adverse biological entities fight to establish themselves, or does disease attempt to prevail while the healthy flora is being established? --- **ChatGPT:** ```json {"query": "adverse biological entities establishment after antibiotic treatment"} ``` --- **[Tool]:** {"items":[{"paper_title":"Association of antibiotic treatment with immune-related adverse events in patients with cancer receiving immunotherapy","abstract":"Background To determine whether antibiotic treatment is a risk factor for immune-related adverse events (irAEs) across different patients with cancer receiving anti-PD-1/PD-L1 therapies. Methods The retrospective analysis includes clinical information from 767 patients with cancer treated at Hunan Cancer Hospital from 2017 to 2020. The pharmacovigilance data analysis includes individual cases of 38,705 safety reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2014 to 2020, and 25,122 cases of safety reports from the World Health Organization database VigiBase from 2014 to 2019. All cases that received anti-PD-1/PD-L1 treatment were included. Multiomics data from patients across 25 cancer types were download from The Cancer Genome Atlas. Logistic regression and propensity score algorithm was employed to calculate OR of irAEs. Results Retrospective analysis of in-house patients showed that irAE potential risks are higher in all cancer (OR 2.12, 95% CI 1.38 to 3.22, false discovery rate (FDR) adjusted-p=1.93×10−3) and patients with lung cancer (OR 3.16, 95% CI 1.67 to 5.95, FDR adjusted-p=1.93×10−3) when using antibiotics. Potential risk of irAEs in patients with lung cancer with antibiotic treatment is significantly higher in FAERS (OR 1.39, 95% CI 1.21 to 1.59; FDR adjusted-p=1.62×10−5) and VigiBase (OR 1.32, 95% CI 1.09 to 1.59, FDR adjusted-p=0.05). Mechanistically, decreased microbial diversity caused by antibiotics use may increase the irAE risk through mediating the irAE-related factors. Conclusions Our study is the first to comprehensively demonstrate the associations of irAEs and antibiotic during anti-PD-1/PD-L1 therapy across a wide spectrum of cancers by analyzing multisource data. Administration of antibiotics should be carefully evaluated in patients with cancer treated by anti-PD-1/PD-L1 to avoid potentially increasing irAE risk.","paper_authors":["Ying Jing","Xue Chen","Kunyan Li","Yaoming Liu","Zhao Zhang","Yiqing Chen","Yuan Liu","Yushu Wang","Steven H. Lin","L. Diao","Jing Wang","Y. Lou","Douglas B. Johnson","Xiang Chen","Hong Liu","Leng Han"],"paper_publish_year":2022,"publication_journal_name":"Journal for Immunotherapy of Cancer","consensus_paper_details_url":"https://consensus.app/papers/association-treatment-events-patients-cancer-receiving-jing/d563fcf93c58581987d380d4acc748d8/?utm_source=chatgpt","doi":"10.1136/jitc-2021-003779","volume":"10","pages":"","search_result_number":1},{"paper_title":"The negative impact of antibiotic resistance.","abstract":"Antibacterial therapy is one of the most important medical developments of the twentieth century; however, the spread of resistance in healthcare settings and in the community threatens the enormous gains made by the availability of antibiotic therapy. Infections caused by resistant bacteria lead to up to two-fold higher rates of adverse outcomes compared with similar infections caused by susceptible strains. These adverse outcomes may be clinical or economic and reflect primarily the failure or delay of antibiotic treatment. The magnitude of these adverse outcomes will be more pronounced as disease severity, strain virulence, or host vulnerability increases. The negative impacts of antibacterial resistance can be measured at the patient level by increased morbidity and mortality, at the healthcare level by increased resource utilization, higher costs and reduced hospital activity and at the society level by antibiotic treatment guidelines favouring increasingly broad-spectrum empiric therapy. In this review we will discuss the negative impact of antibiotic resistance on patients, the healthcare system and society.","paper_authors":["N. Friedman","E. Temkin","Y. Carmeli"],"paper_publish_year":2016,"publication_journal_name":"Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/impact-resistance-friedman/63cf554556f0530baeae22a2553d4f06/?utm_source=chatgpt","doi":"10.1016/j.cmi.2015.12.002","volume":"22 5","pages":"\n 416-22\n ","search_result_number":2},{"paper_title":"Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies","abstract":"Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments.","paper_authors":["C. Panebianco","A. Andriulli","V. Pazienza"],"paper_publish_year":2018,"publication_journal_name":"Microbiome","consensus_paper_details_url":"https://consensus.app/papers/pharmacomicrobiomics-exploiting-interactions-panebianco/04ca19cab2f75afbb7491ff5bc03ab74/?utm_source=chatgpt","doi":"10.1186/s40168-018-0483-7","volume":"6","pages":"","search_result_number":3},{"paper_title":"Clinical implications of antibiotic-induced endotoxin release in septic shock","abstract":"Abstract. Antibiotic-induced release of bacterial cell wall components can have immediate adverse effects for the patient. This article reviews the data on endotoxin release after initiation of antibiotic therapy and its role in the pathogenesis of sepsis and septic shock. Antibiotics differ in their potential to liberate endotoxins from bacterial cell walls. When used for treatment of systemic Gram-negative infection, some classes of β-lactam antibiotics lead to markedly increased levels of free endotoxins while treatment with carbapenems and aminoglycosides produces relatively low amounts of endotoxins. Antibiotics that induce the formation of long, aberrant bacterial cells before effectively killing the microorganisms show the highest degree of endotoxin liberation. There is increasing evidence from animal models and clinical studies of sepsis that the antibiotic-mediated release of biologically active cell wall components derived from Gram-positive, Gram-negative or fungal organisms is associated with a rapid clinical deterioration.","paper_authors":["P. Lepper","T. Held","E. Schneider","E. Bölke","H. Gerlach","M. Trautmann"],"paper_publish_year":2002,"publication_journal_name":"Intensive Care Medicine","consensus_paper_details_url":"https://consensus.app/papers/implications-antibioticinduced-release-shock-lepper/80778de7c43353f690ad7a4644a5c670/?utm_source=chatgpt","doi":"10.1007/s00134-002-1330-6","volume":"28","pages":"824-833","search_result_number":4},{"paper_title":"Adverse drug reactions to antibiotics observed in two pulmonology divisions of catanzaro, Italy: a six-year retrospective study.","abstract":"We retrospectively analysed adverse drug reactions (ADRs) associated with antibiotic therapy and reported over a 6-year period, from January 1995 to December 2000, in clinical notes of two Pulmonology Units of \"Mater Domini\" University Hospital and \"Pugliese-Ciaccio\" Hospital, both located in Catanzaro, Italy. Antibiotics were responsible for 92 (44.9%) out of 205 episodes of ADRs. In particular, 22 episodes (23.9%) were observed after penicillin G administration, 19 episodes (20.7%) following ceftazidime and cefotaxime administration, 16 episodes (17.4%) after therapy with ampicillin, and 35 reactions (38%) were further reported during treatments with other antibiotics. We determined that the drug-ADR relationship was certain in 63% of the reports; withdrawal of the suspected drug led to recovery in 95% of cases. In conclusion, this retrospective evaluation demonstrated that antibiotics are a common cause of ADRs in hospitalised patients and, therefore, drug surveillance can successfully identify targeted adverse events.","paper_authors":["L. Gallelli","G. Ferreri","M. Colosimo","D. Pirritano","L. Guadagnino","G. Pelaia","R. Maselli","G. De Sarro"],"paper_publish_year":2002,"publication_journal_name":"Pharmacological research","consensus_paper_details_url":"https://consensus.app/papers/drug-reactions-antibiotics-observed-pulmonology-gallelli/030698fcd9455e0d9f7deca0fe68279b/?utm_source=chatgpt","doi":"10.1016/S1043661802002104","volume":"46 5","pages":"\n 395-400\n ","search_result_number":5},{"paper_title":"Evaluation of pathogenetic features of antibiotic-associated syndrome using a biological model","abstract":"Antibiotic therapy is an integral part of current therapeutic practice to save patients’ lives. However, as with any therapeutic intervention, the development of adverse events is possible, one of which is the antibiotic-associated syndrome (AAS). Objective. To study the pathogenetic features of AAS extraintestinal manifestations using a biological model as an example. Materials and methods. This study was conducted using the biological model (outbred male mice) between 2019 and 2020 on the basis of the Central Research Institute of Epidemiology of Rospotrebnadzor. Experimental animals were injected with amoxicillin/clavulanic acid and cefotaxime in two therapeutic doses, average and maximum. The recalculation of drug doses was carried out depending on the animal’s body weight. The comparison was performed in four study groups and one control group, which were distinguished according to the dose and type of antibacterial agent. The histological examination of internal organs (large intestine, small intestine, liver, pancreas, kidney, lung, heart, testicles, spleen, stomach, duodenum, skin, bladder) was conducted at two time points: 24 hours after antibiotic administration and 7 days after the end of antibiotic therapy. Results. The results of histological examination at the first time point (24 hours after antibiotic administration) demonstrated that the use of the studied antibacterial agents at the average therapeutic dose did not cause significant morphological changes in the organs of mice, while the administration of maximum dose led to the development of reactive changes, primarily in the vascular system. The results of histological examination in the experimental groups at the second control time point (7 days after the end of antibiotic therapy) showed a systemic reaction in the organs of mice, expressed primarily in perivascular leukocyte infiltration. Similar changes were registered in the group of experimental animals that were injected with average therapeutic doses of antibacterial agents. Conclusion. AAS is characterized by systemic and homogeneous pathomorphological changes in various tissues, which explains not only the development of antibiotic-associated diarrhea, but also its extraintestinal symptoms. Our findings allow to suggest that antibiotics, especially when used irrationally, increase the risks of pathology associated with a systemic inflammatory response, in particular atherosclerosis and obesity, at the population level. Key words: antibiotic-associated diarrhea, antibiotic-associated syndrome","paper_authors":["A. Ploskireva","A. Gorelov","L. Golden","S. V. Nikolaeva","E. Simkova"],"paper_publish_year":2022,"publication_journal_name":"Infekcionnye bolezni","consensus_paper_details_url":"https://consensus.app/papers/evaluation-features-antibioticassociated-using-model-ploskireva/110448eac55559b3bc85c8c86fc2e602/?utm_source=chatgpt","doi":"10.20953/1729-9225-2022-3-42-49","volume":"","pages":"","search_result_number":6},{"paper_title":"How antibiotics can make us sick: the less obvious adverse effects of antimicrobial chemotherapy.","abstract":"Antimicrobial agents are associated with side-effects, which are usually tolerated because the benefits of treatment outweigh the toxic effects. Clinicians know about these side-effects but are less likely to understand additional adverse events, such as the overgrowth of resistant microorganisms. Overgrowth can itself precipitate a secondary infection, which can be more difficult to treat. Resistant organisms then spread to other patients and the environment, and contribute to increasing antimicrobial resistance worldwide. Organisms exposed to antibiotics undergo molecular changes that might enhance virulence. Enhanced pathogenicity would affect patients, particularly if the organism is also multiply resistant. Clinicians have a responsibility to select the correct antibiotic as soon as they have diagnosed infection, but an absence of microbiological understanding and ignorance of the potential environmental effects have contributed to inappropriate prescribing. The less obvious results of antimicrobial consumption probably go unrecognised in routine clinical care.","paper_authors":["S. Dancer"],"paper_publish_year":2004,"publication_journal_name":"The Lancet. Infectious diseases","consensus_paper_details_url":"https://consensus.app/papers/antibiotics-make-less-effects-chemotherapy-dancer/d739359ebd0d5fc986adbe39896151dd/?utm_source=chatgpt","doi":"10.1016/S1473-3099(04)01145-4","volume":"4 10","pages":"\n 611-9\n ","search_result_number":7},{"paper_title":"7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial","abstract":"BackgroundShorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial.MethodsWe conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1:1 to intervention arms consisting of two fixed durations of treatment – 7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolonged treatment, single cultures with potential contaminants, or cultures yielding Staphylococcus aureus or fungi. The primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. Secondary outcomes included 90-day, ICU and hospital mortality, relapse of bacteremia, lengths of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile, antibiotic adverse events, and secondary infection with antimicrobial-resistant organisms.ResultsWe successfully achieved our target sample size (n = 115) and average recruitment rate of 1 (interquartile range (IQR) 0.3–1.5) patient/ICU/month. Adherence to treatment duration was achieved in 89/115 (77%) patients. Adherence differed by underlying source of infection: 26/31 (84%) lung; 18/29 (62%) intra-abdominal; 20/26 (77%) urinary tract; 8/9 (89%) vascular-catheter; 4/4 (100%) skin/soft tissue; 2/4 (50%) other; and 11/12 (92%) unknown sources. Patients experienced a median (IQR) 14 (8–17) antibiotic-free days (of the 28 days after blood culture collection). Antimicrobial-related adverse events included hepatitis in 1 (1%) patient, Clostridium difficile infection in 4 (4%), and secondary infection with highly resistant microorganisms in 10 (9%). Ascertainment was complete for all study outcomes in ICU, in hospital and at 90 days.ConclusionIt is feasible to conduct a RCT to determine whether 7 versus 14 days of antibiotic treatment is associated with comparable 90-day survival.Trial registrationClinicalTrials.gov, identifier: NCT02261506. Registered on 26 September 2014.","paper_authors":["N. Daneman","A. Rishu","R. Pinto","P. Aslanian","S. Bagshaw","A. Carignan","E. Charbonney","B. Coburn","D. Cook","M. Detsky","P. Dodek","R. Hall","Anand Kumar","F. Lamontagne","F. Lauzier","J. Marshall","Claudio M. Martin","L. McIntyre","J. Muscedere","S. Reynolds","W. Sligl","H. Stelfox","M. Wilcox","R. Fowler"],"paper_publish_year":2018,"publication_journal_name":"Trials","consensus_paper_details_url":"https://consensus.app/papers/versus-days-treatment-critically-patients-infection-daneman/dafb70bfd87f50d280fc1fcde84c9196/?utm_source=chatgpt","doi":"10.1186/s13063-018-2474-1","volume":"19","pages":"","search_result_number":8},{"paper_title":"Impact of Procalcitonin-Guided Antibiotic Management on Antibiotic Exposure and Outcomes: Real-world Evidence","abstract":"Abstract Background Delayed pathogen identification and nonspecific clinical findings make definitive decisions regarding antibiotics challenging. The stimuli of bacterial toxins and inflammation make procalcitonin (PCT) unique in its ability to differentiate bacterial infection from other causes of inflammation, and thus it is useful for antibiotic management. The objective of our study was to evaluate the impact of a PCT algorithm (PCT-A) on current practice. Methods A single-center, retrospective cohort study was conducted to evaluate the impact of adding PCT-A to stewardship practices. Data from 4 years prior to and after PCT-A implementation were compared in critical and acute care patients of all ages receiving parenteral antibiotics for a DRG coded for infection. A baseline PCT was obtained on admission in patients with suspected bacterial infection. Serial PCT measurements were repeated daily to evaluate effectiveness of therapy. Outcomes of interest were antibiotic exposure, hospital mortality, 30-day readmission, Clostridium difficile infection (CDI), and adverse drug events during hospitalization. Results A total of 985 patients (pre-PCT-A group) were compared with 1167 patients (post-PCT-A group). Antimicrobial stewardship alone (pre-PCT-A) resulted in a median days of therapy (DOT) of 17 (interquartile range [IQR], 8.5–22.5) vs 9.0 (IQR, 6.5–12) in the post-PCT-A group (P < .0001). Secondary outcomes were also significantly reduced in the post-PCT-A group. Conclusion The addition of PCT in a facility with an established stewardship program resulted in a significant reduction in antibiotic exposure and adverse outcomes. PCT may improve antibiotic management when diagnostic clarity and resolution of infection are lacking.","paper_authors":["Michael R Broyles"],"paper_publish_year":2017,"publication_journal_name":"Open Forum Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/impact-procalcitoninguided-antibiotic-management-broyles/b5d4aa671c365413a28439789c082de3/?utm_source=chatgpt","doi":"10.1093/ofid/ofx213","volume":"4","pages":"","search_result_number":9},{"paper_title":"Adverse effects of parenteral antimicrobial therapy for chronic bone infections","abstract":"Responsible pathogens of chronic bone infections (CBI) are frequently resistant, requiring parenteral antimicrobial therapy. Therefore, adverse effects may be observed. We have determined the rate of adverse effects of antimicrobial therapy for CBI in a retrospective study of all patients receiving parenteral drugs via an implantable port. Patients from one medical ward (n = 89) and from one surgical ward (n = 40) between January 1995 and December 2005 were included in this study. The CBI included were 85 osteomyelitis (66%) and 44 prosthetic joint infections (34%). The main group of pathogens was Gram positive cocci (n = 144; 65%). The total duration of antibiotic treatment was 205 ± 200 days, including 133 ± 100 days for parenteral therapy. Thirty-three catheter-related complications were observed in 27 patients (21%). All complications led to hospitalization but none led to death. Twenty-one antibiotic-related complications occurred in 18 patients (16%), and one allergic reaction led to death. The mean duration of follow-up was 290 days. Remission was observed in 84 patients (65%). In multivariate analysis, adverse effects were mostly observed in the medical department. Adverse effects affect at least one third of the patients treated for CBI with parenteral antimicrobial therapy and are related to both the implantable port and the antibiotic compounds.","paper_authors":["C. Pulcini","T. Couadau","E. Bernard","A. Lorthat-Jacob","T. Bauer","E. Cua","V. Mondain","R. Chichmanian","P. Dellamonica","P. Roger"],"paper_publish_year":2008,"publication_journal_name":"European Journal of Clinical Microbiology & Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/effects-therapy-chronic-bone-infections-pulcini/00ad3bf94cb153edb37e9a37e51e8b81/?utm_source=chatgpt","doi":"10.1007/s10096-008-0570-y","volume":"27","pages":"1227-1232","search_result_number":10},{"paper_title":"Adverse reactions to antimicrobial therapy.","abstract":"Adverse reactions to antimicrobial agents consist of toxic effects mediated through chemical changes in tissue cells, sensitivity reactions produced by antigen-antibody reactions, and biological effects caused by alteration of the bacterial flora in the body. Patients vary in their susceptibility to these because of genetically determined differences in enzyme and protein make-up, differences in immunologic reactivity, differences in environment, or because of the effects of disease. Some antibiotics are capable of producing almost invariable damage to certain tissues if given long enough in sufficient dosage, whereas others produce disturbances in only occasional patients. Almost any organ in the body may be involved, indicating that the metabolic processes affected by these agents are represented to a varying degree in the cells of the host. Little is known of the specific mechanisms involved, but as information is acquired, it should be possible to reduce the incidence of reactions.","paper_authors":["K. Wightman"],"paper_publish_year":1965,"publication_journal_name":"Canadian Medical Association journal","consensus_paper_details_url":"https://consensus.app/papers/reactions-therapy-wightman/ea3292faed4e515bba1d54c1812070fa/?utm_source=chatgpt","doi":"","volume":"93 16","pages":"\n 870-3\n ","search_result_number":11},{"paper_title":"Adverse reactions to antibiotics","abstract":"PREVIEWAt best they are inconvenient. At worst they complicate treatment, injure patients, and fuel litigation. Adverse antibiotic reactions represent a major cause of iatrogenic illness-a situation that deserves careful and continuous scrutiny. This article reviews the classification and mechanism of action of adverse reactions and offers specific information about both avoiding and managing them.","paper_authors":["R. Gleckman","F. Borrego"],"paper_publish_year":1997,"publication_journal_name":"Postgraduate Medicine","consensus_paper_details_url":"https://consensus.app/papers/reactions-antibiotics-gleckman/5245f787aca75e27a887096e10e67c31/?utm_source=chatgpt","doi":"10.3810/PGM.1997.04.198","volume":"101","pages":"97-108","search_result_number":12},{"paper_title":"Risks of antibiotic treatment.","abstract":"Adverse effects of antibiotics can cause a failure of antibiotic treatment. The authors give a survey of antibiotic toxicity manifestations, according to the target organ systems, with emphasis on identification of at-risk patients and on possible prevention of particular adverse effects. Although antibiotics belong to relatively safe pharmaceuticals, many of them can be a cause of a serious damage to the human organism. Beta-lactam antibiotics are considered the least dangerous. A considerable number of adverse effects, especially the dose-dependent ones, are preventable on condition that the risk factors, as the patient's age, functional capacity of eliminating organs (kidney, liver), associated diseases and simultaneous administration of drugs, are considered. In conclusion, the clinically significant drug interactions of antibiotics are pointed out, being of increasing importance especially in patients with multiple diseases and polypragmatic manner of treatment. (Tab. 2, Ref. 48.)","paper_authors":["M. Wawruch","L. Božeková","S. Krčméry","M. Kriška"],"paper_publish_year":2002,"publication_journal_name":"Bratislavske lekarske listy","consensus_paper_details_url":"https://consensus.app/papers/risks-treatment-wawruch/775a840be2e05f309d4142cc7d264f4a/?utm_source=chatgpt","doi":"","volume":"103 7-8","pages":"\n 270-5\n ","search_result_number":13},{"paper_title":"Antibiotic safety assessment.","abstract":"Antibiotics usually have positive risk-benefit ratios, their adverse effects being generally mild and reversible on treatment cessation. However, severe adverse drug reactions (ADR), associated with significant mortality and morbidity have resulted in the withdrawal of several active antibiotics, including new fluoroquinolones. Adverse reactions to antibiotics are often poorly documented. The purpose of this article is to examine current tools for investigating and preventing antibiotic toxicity and to suggest future lines of investigation. Structure/ADR relationships have been investigated with various antibiotics (beta-lactams, macrolides, quinolones, etc.) in an attempt to reduce the risk of adverse reactions. Some reactions can be linked to the drug's stereochemical composition. In the case of quinolones for instance, particularly ofloxacin and its derivatives, experimental data show that individual enantiomers have different toxicities. Another major factor that influences the risk of ADRs in a given population is metabolic variability, due to genetic differences in the relevant drug-metabolizing enzymes. Idiosyncratic antibiotic toxicity can be caused by a chemically reactive metabolite. Recent advances in molecular biology, and especially in individual genomic characterization (DNA chip technology, etc.), could in future be useful for identifying patients who are at a special risk of ADR. Finally, certain pharmacokinetic parameters (AUC, Cmax, etc.) can be used to predict adverse effects.","paper_authors":["B. Rouveix"],"paper_publish_year":2003,"publication_journal_name":"International journal of antimicrobial agents","consensus_paper_details_url":"https://consensus.app/papers/safety-assessment-rouveix/0193f8b69b5a5632ae7a408c6bc1795c/?utm_source=chatgpt","doi":"10.1016/S0924-8579(02)00354-0","volume":"21 3","pages":"\n 215-21\n ","search_result_number":14},{"paper_title":"Adverse Events in Pediatric Patients Receiving Long-Term Outpatient Antimicrobials.","abstract":"BACKGROUND\nAlthough long treatment courses of outpatient antimicrobials are often used in pediatric patients, few data exist regarding the frequency of adverse events (AEs) associated with these medications.\n\n\nMETHODS\nWe performed a retrospective cohort study of all patients seen in the Infectious Diseases clinic at a tertiary referral children's hospital from August 1, 2009 to August 1, 2011. We included patients who received ≥14 days of oral or intravenous antibiotic, antiviral, or antifungal medications. Patients receiving only prophylactic medications or human immunodeficiency virus treatment were excluded.\n\n\nRESULTS\nThree hundred thirty-five subjects met inclusion criteria, with a median age of 7.4 years at start of therapy. The cohort was predominantly male (60%), white (54%), and previously healthy (59%). A majority (88.4%) of subjects were treated for bacterial infections. β-Lactam agents were the most commonly used antimicrobial class (210 subjects; 62.7%), followed by clindamycin (86; 25.7%), rifampin (76; 22.7%), and vancomycin (62; 18.5%). Overall, 107 (31.9%) subjects experienced 151 distinct AEs. The most common individual AE noted was diarrhea (44; 29.1% of all AEs). Serious AEs developed in 42 (12.5%) subjects, including allergic reactions (15; 11.3% of all AEs), venous catheter-related complications (14; 13.0% of those with catheters), neutropenia (9; 3.0%), renal insufficiency (7; 2.5%), and hepatotoxicity (3; 1.1%). Rates of AEs were similar between those on oral and intravenous antimicrobials.\n\n\nCONCLUSIONS\nIn our study population, patients on prolonged oral or intravenous outpatient antimicrobials experienced AEs frequently. These findings support the need for close monitoring of pediatric patients on prolonged antimicrobial therapy and vigilance for unwanted effects of these medications.","paper_authors":["Scott C. Olson","Sherilyn Smith","S. Weissman","M. Kronman"],"paper_publish_year":2015,"publication_journal_name":"Journal of the Pediatric Infectious Diseases Society","consensus_paper_details_url":"https://consensus.app/papers/events-patients-receiving-longterm-outpatient-olson/d544bfcb993751dc84275b2566354e9a/?utm_source=chatgpt","doi":"10.1093/jpids/piu037","volume":"4 2","pages":"\n 119-25\n ","search_result_number":15},{"paper_title":"P107 Implications of Adverse Drug Reactions to Antibiotics in the Management of Bronchiectasis","abstract":"Introduction and Objectives Antibiotic adverse reactions present a challenge when choosing appropriate treatment for patients with Bronchiectasis. We explored our data for antibiotic allergy and microbiological resistance in Bronchiectasis patients in a specialist clinic at the Queen Elizabeth Hospital Birmingham. Methods We collected retrospective and prospective data on 243 patients from our Bronchiectasis clinic. We limited our microbiological data to colonised or most recent sputum culture. Results We have 243 patients on our register. There were 84 (34.6%) males and 159 (65.6%) females. Bronchiectasis was confirmed in 234 patients with CT (Computerised Tomography) scan. The most common aetiology was post-infective. 80 (32.9%) patients had had an adverse drug reaction to at least one antibiotic. 24(9.8%) were allergic to penicillin and 50(20.5%) were allergic to at least one antibiotic. 29 (11.9%) were intolerant of one or more oral antibiotics whereas 18 (7.4%) were intolerant of one or more nebulized antibiotics in this group. Patients with resistant bacteria in their sputum showed a trend towards a greater likelihood of adverse reactions to antibiotics compared to patients with sensitive bacteria (31.5% v 17.8% p Value - 0.05). On subgroup analysis we found that the difference became statistically significant between people infected with resistant versus sensitive Pseudomonas Aeruginosa (46.7% v 42.1% p value–0.031). Conclusions This is an interesting observation that patients whose sputum contained resistant organisms were more likely to have had adverse drug reactions to antibiotics. There is likely to be a causal relationship, and further study is required to identify whether the limited range of treatment options for patients with adverse drug reactions leads to a greater chance of antibiotic resistance in colonising organisms in sputum. Antibiotic allergies may have a detrimental effect on the management of patients with Bronchiectasis and therefore a resource implication in the subgroup of patients with adverse drug reactions. Potentially there may be a cost-saving in investigating patient-reported allergies aggressively. Reference Antimicrobial therapy for bronchiectasis. O'Donnell AE. Clin Chest Med. 2012 Jun;33(2):381–6. doi: 10.1016/j.ccm.2012.03.005. Epub 2012 Apr 24 Clinical challenges in managing bronchiectasis. Tsang KW, Bilton D. Respirology. 2009 Jul;14(5):637–50. doi: 10.1111/j.1440–1843.2009.01569.x","paper_authors":["Kv Singh","A. Sahal","A. Sullivan"],"paper_publish_year":2013,"publication_journal_name":"Thorax","consensus_paper_details_url":"https://consensus.app/papers/p107-implications-adverse-drug-reactions-antibiotics-singh/2f39af2073d6575aad134c2ed75b8356/?utm_source=chatgpt","doi":"10.1136/thoraxjnl-2013-204457.257","volume":"68","pages":"A122 - A123","search_result_number":16},{"paper_title":"Antibiotic resistance in cancer patients","abstract":"Bacterial infection is one of the most frequent complications in cancer patients and hematopoietic stem cell transplant recipients. In recent years, the emergence of antimicrobial resistance has become a significant problem worldwide, and cancer patients are among those affected. Treatment of infections due to multidrug-resistant (MDR) bacteria represents a clinical challenge, especially in the case of Gram-negative bacilli, since the therapeutic options are often very limited. As the antibiotics active against MDR bacteria present several disadvantages (limited clinical experience, higher incidence of adverse effects, and less knowledge of the pharmacokinetics of the drug), a thorough acquaintance with the main characteristics of these drugs is mandatory in order to provide safe treatment to cancer patients with MDR bacterial infections. Nevertheless, the implementation of antibiotic stewardship programs and infection control measures is the cornerstone for controlling the development and spread of these MDR pathogens.","paper_authors":["C. Gudiol","J. Carratalá"],"paper_publish_year":2014,"publication_journal_name":"Expert Review of Anti-infective Therapy","consensus_paper_details_url":"https://consensus.app/papers/resistance-cancer-patients-gudiol/48aab88523ff5f23b064224e6a10197d/?utm_source=chatgpt","doi":"10.1586/14787210.2014.920253","volume":"12","pages":"1003 - 1016","search_result_number":17},{"paper_title":"Approach to the evaluation of adverse antibiotic reactions in patients with cystic fibrosis.","abstract":"BACKGROUND\nAdverse drug reactions (ADRs) to antibiotics in patients with cystic fibrosis (CF) are common and often mislabeled as allergies. The labeling of an antibiotic reaction as an allergy can lead to the use of antibiotics that are less efficacious, are more expensive, or have a greater risk of adverse effects.\n\n\nOBJECTIVE\nTo establish a safe approach for the evaluation of ADRs to antibiotics in patients with CF to help clarify future use of these medications.\n\n\nMETHODS\nPatients with CF whose antibiotic allergies were causing difficulty in their medical management were referred for an allergy evaluation that consisted of a thorough drug allergy history and antibiotic testing if appropriate. If the history was not consistent with a true hypersensitivity reaction (HSR) and test results were negative, the patient underwent a challenge to the offending agent(s) to rule out an HSR. Challenges were only performed if the medication was indicated for future use.\n\n\nRESULTS\nA total of 17 patients (mean age, 32.4 years) underwent a thorough allergy evaluation. A total of 17 antibiotic challenges were performed in 11 patients without a reaction consistent with an HSR or severe delayed reaction. Only 2 medications had a history consist with an HSR, and it was recommended that they undergo a desensitization procedure if the drug was required.\n\n\nCONCLUSION\nIf treatment with appropriate antibiotics becomes difficult in patients with CF because of drug allergies, then referral to an allergist can help safely identify treatment options. Our findings suggest that a thorough evaluation by an allergy specialist can lead to more appropriate treatment options in patients with CF.","paper_authors":["D. Petroni","M. Aitken","E. Ham","Sarah Chung","Lori Menalia","Matthew C. Altman","Andrew G. Ayars"],"paper_publish_year":2016,"publication_journal_name":"Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology","consensus_paper_details_url":"https://consensus.app/papers/approach-evaluation-reactions-patients-fibrosis-petroni/8e61184fb5bc536596963bf8f0635f6c/?utm_source=chatgpt","doi":"10.1016/j.anai.2016.07.039","volume":"117 4","pages":"\n 378-381\n ","search_result_number":18},{"paper_title":"Antibiotic prophylaxis for transurethral prostatic resection in men with preoperative urine containing less than 100,000 bacteria per ml: a systematic review.","abstract":"PURPOSE\nWe determined whether antibiotic prophylaxis can reduce the risk of postoperative infective complications in men undergoing transurethral resection of the prostate (TURP) who have preoperative urine with less than 100,000 bacteria per ml.\n\n\nMATERIALS AND METHODS\nMEDLINE, EMBASE (Elsevier B.V., Amsterdam, The Netherlands) and the Cochrane Library were searched for randomized and quasi-randomized controlled trials that compared the effects of antibiotic prophylaxis with placebo or active controls for men undergoing TURP with preoperative sterile urine. Two reviewers independently extracted patient characteristic and outcomes data based on a prospectively developed protocol.\n\n\nRESULTS\nA total of 28 trials, 10 placebo controlled and 18 no treatment controlled, involving 4,694 patients, met the inclusion criteria. The mean age of the subjects was 69 years and the majority underwent TURP for prostatic hyperplasia (85%). Antibiotic prophylaxis was significantly more effective than placebo in reducing postoperative TURP complications. The risk differences for post-TURP bacteriuria, high degree fever, bacteremia and use of additional antibiotic treatment were -0.17 (95% CI 0.20, -0.15), -0.11 (-0.15, -0.06), -0.02 (-0.04, 0.00) and -0.20 (-0.28, -0.11), respectively. The results were observed consistently across all classes of antibiotics assessed. There was no difference in the duration of postoperative catheterization or hospitalization. Adverse events were rare, generally mild, and included allergic reactions, pyrexia and abdominal complaints.\n\n\nCONCLUSIONS\nProphylactic antibiotics decrease the incidence of post-TURP bacteriuria, high fever, bacteremia and additional antibiotic treatment. Additional research should evaluate the optimal antibiotic regimen, and whether the cost and possibility of the development of resistant strains of organisms justify the routine use of prophylactic antibiotics.","paper_authors":["W. Qiang","Wu Jianchen","R. MacDonald","M. Monga","T. Wilt"],"paper_publish_year":2005,"publication_journal_name":"The Journal of urology","consensus_paper_details_url":"https://consensus.app/papers/prophylaxis-resection-urine-containing-100000-bacteria-qiang/6ec723c48b245d04a698653954cd16ce/?utm_source=chatgpt","doi":"10.1097/01.JU.0000149676.15561.CB","volume":"173 4","pages":"\n 1175-81\n ","search_result_number":19},{"paper_title":"Antibiotics for asymptomatic bacteriuria.","abstract":"BACKGROUND\nAsymptomatic bacteriuria is commonly detected in women aged up to 60 years, patients with diabetes, and the elderly. The benefit of antibiotic treatment for this condition is controversial.\n\n\nOBJECTIVES\nTo assess the effectiveness and safety of antibiotics treatment for asymptomatic bacteriuria in adults. Specific objectives were to assess 1) the effectiveness of antibiotics for preventing development of symptomatic UTI, UTI-related complications, overall mortality, UTI-related mortality, and resolution of bacteriuria; 2) the development of resistance to antibiotic treatment by comparing resistance of grown bacteria in urine before and after therapy; and 3) the frequency of adverse events.\n\n\nSEARCH METHODS\nWe searched the Cochrane Renal Group's Specialised Register up to 24 February 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.\n\n\nSELECTION CRITERIA\nRandomised controlled trials (RCTs) and quasi-RCTs comparing antibiotics to placebo or no treatment for asymptomatic bacteriuria in adults were included. The outcomes of interest were the development of symptomatic urinary tract infection (UTI), complications, death, any adverse event, development of antibiotic resistance, bacteriological cure, and decline in kidney function.\n\n\nDATA COLLECTION AND ANALYSIS\nTwo authors independently extracted the data and assessed study quality. Statistical analyses were performed using the random effects model and the results expressed as risk ratios (RR) with 95% confidence intervals (CI).\n\n\nMAIN RESULTS\nWe included nine studies (1614 participants) in this review. Symptomatic UTI (RR 1.11, 95% CI 0.51 to 2.43), complications (RR 0.78, 95% CI 0. 35 to 1.74), and death (RR 0.99, 95% CI 0.70 to 1.41) were similar between the antibiotic and placebo or no treatment arms. Antibiotics were more effective for bacteriological cure (RR 2.32, 95% CI 1.11 to 4.83) but also more adverse events developed in this group (RR 3.77, 95% CI 1.40 to 10.15). No decline in the kidney function was observed across the studies; minimal data were available on the emergence of resistant strains after antimicrobial treatment.The included studies were of medium and high quality, used different treatments for different durations of treatment and follow-up, different populations, but this did not appear to influence the results of review.\n\n\nAUTHORS' CONCLUSIONS\nNo differences were observed between antibiotics versus no treatment of asymptomatic bacteriuria for the development of symptomatic UTI, complications or death. Antibiotics were superior to no treatment for the bacteriological cure but with significantly more adverse events. There was no clinical benefit from treating asymptomatic bacteriuria in the studies included in this review.","paper_authors":["Anca Zalmanovici Trestioreanu","A. Lador","May-Tal Sauerbrun-Cutler","L. Leibovici"],"paper_publish_year":2015,"publication_journal_name":"The Cochrane database of systematic reviews","consensus_paper_details_url":"https://consensus.app/papers/antibiotics-bacteriuria-trestioreanu/173ab8bbb8ec5d6dbacfc6c044451f17/?utm_source=chatgpt","doi":"10.1002/14651858.CD009534.PUB2","volume":"4","pages":"\n CD009534\n ","search_result_number":20}]} --- **ChatGPT:** ### Adverse Biological Entities After Antibiotic Treatment **Introduction:** Following antibiotic treatment, the gut microbiota can be significantly disrupted, potentially allowing harmful microorganisms to establish themselves. This disruption can lead to various health complications while the gut flora is being reestablished. **Evidence:** 1. **Pathogen Overgrowth and Secondary Infections:** - Antibiotic treatment can lead to the overgrowth of resistant microorganisms, which can cause secondary infections. This overgrowth occurs as antibiotics eliminate beneficial bacteria, creating an environment where harmful pathogens can thrive [(Dancer, 2004)](https://consensus.app/papers/antibiotics-make-less-effects-chemotherapy-dancer/d739359ebd0d5fc986adbe39896151dd/?utm_source=chatgpt). 2. **Risk of Dysbiosis and Infection:** - The imbalance of gut microbiota, known as dysbiosis, can occur after antibiotic treatment. This can increase the risk of infections such as Clostridium difficile, which is known to cause severe gastrointestinal issues [(Friedman et al., 2016)](https://consensus.app/papers/impact-resistance-friedman/63cf554556f0530baeae22a2553d4f06/?utm_source=chatgpt). 3. **Antibiotic-Associated Diarrhea (AAD):** - Antibiotics can lead to antibiotic-associated diarrhea, which is a result of the disruption of normal gut flora. This condition can create an opportunity for pathogenic bacteria to colonize the gut, leading to further complications [(Ploskireva et al., 2022)](https://consensus.app/papers/evaluation-features-antibioticassociated-using-model-ploskireva/110448eac55559b3bc85c8c86fc2e602/?utm_source=chatgpt). 4. **Impact on Immune System:** - The disruption of gut microbiota can affect the immune system, potentially increasing the risk of immune-related adverse events. For instance, in cancer patients receiving immunotherapy, antibiotic-induced gut microbiota changes have been linked to higher risks of adverse immune responses [(Jing et al., 2022)](https://consensus.app/papers/association-treatment-events-patients-cancer-receiving-jing/d563fcf93c58581987d380d4acc748d8/?utm_source=chatgpt). 5. **Endotoxin Release:** - Certain antibiotics can induce the release of endotoxins from bacterial cell walls, especially from Gram-negative bacteria, which can worsen the clinical condition of patients, particularly those with sepsis [(Lepper et al., 2002)](https://consensus.app/papers/implications-antibioticinduced-release-shock-lepper/80778de7c43353f690ad7a4644a5c670/?utm_source=chatgpt). **Conclusion:** Following antibiotic treatment, the disrupted gut microbiota can lead to the overgrowth of harmful microorganisms, increased risk of secondary infections, and various adverse health effects. These issues underscore the importance of careful antibiotic use and the potential need for interventions to restore healthy gut flora. Like our GPT? Try our full AI-powered search engine and academic features for free at [consensus.app](https://consensus.app/?utm_source=chatgpt). --- **You:** Does linezolid have any reported Endotoxin Release interference? --- **ChatGPT:** ```json {"query": "linezolid endotoxin release interference"} ``` --- **[Tool]:** {"items":[{"paper_title":"Subinhibitory Concentrations of Linezolid Reduce Staphylococcus aureus Virulence Factor Expression","abstract":"ABSTRACT The influence of the antibiotic linezolid on the secretion of exotoxins by Staphylococcus aureus was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry and Western blot analysis. S. aureus suspensions were treated with grading subinhibitory concentrations of linezolid (12.5, 25, 50, and 90% of MIC) at different stages of bacterial growth (i.e., an optical density at 540 nm [OD540] of 0.05 or 0.8). When added to S. aureus cultures at an OD540 of 0.05, linezolid reduced in a dose-dependent manner the secretion of specific virulence factors, including staphylococcal enterotoxin A (SEA) and SEB, bifunctional autolysin, autolysin, protein A, and alpha- and beta-hemolysins. In contrast, other presumably nontoxic exoproteins remained unchanged or even accumulated in supernatants in the presence of linezolid at a 90% MIC. Similarily, when added at OD540 of 0.8, that is, after quorum sensing, linezolid reduced the release of virulence factors, whereas the relative abundance of nontoxic exoproteins such as triacylglycerol lipase, glycerol ester hydrolase, DnaK, or translation elongation factor EF-Tu was found to be increased. Consistently, linezolid reduced in a dose-dependent manner the tumor necrosis factor-inducing activity secreted by S. aureus into the culture supernatants. The results of our study suggest that the expression of virulence factors in S. aureus is especially sensitive to the inhibition of protein synthesis by linezolid, which should be an advantage in the treatment of infections with toxin-producing S. aureus.","paper_authors":["K. Bernardo","Norbert Pakulat","S. Fleer","Annabelle Schnaith","O. Utermöhlen","O. Krut","S. Müller","M. Krönke"],"paper_publish_year":2004,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/concentrations-linezolid-reduce-staphylococcus-aureus-bernardo/9b3e097bfa9659bdb526a8944954e167/?utm_source=chatgpt","doi":"10.1128/AAC.48.2.546-555.2004","volume":"48","pages":"546 - 555","search_result_number":1},{"paper_title":"Early immunomodulatory effects of linezolid in a human whole blood endotoxin model.","abstract":"Gram-negative sepsis resulting in endotoxin triggered septic shock is one of the leading causes of death in critically ill patients. Because treatment options are limited, recent approaches focus on immunomodulatory effects of antimicrobials. Thus, we characterized the immunomodulatory effects of linezolid at mRNA and on cytokine levels in supernatants of an ex vivo model of endotoxemia. Whole blood from 10 healthy volunteers was incubated with 50 pg/ml LPS with or without 13 microg/ml linezolid (concentrations were chosen to reflect in vivo conditions) for 2 and 4 hours (h). Quantitative real-time PCR was performed from messenger RNA (mRNA) of IL-1beta;, IL-6, IL-8 or TNF-alpha;. Cytokine levels in the supernatant were measured by ELISA for IL-6, IL-8 and TNF-alpha;. Incubation of human whole blood with LPS increased mRNA levels of cytokines several thousand fold compared with baseline. The addition of linezolid significantly reduced mRNA levels of IL-1beta, IL-6, IL-8 and TNF-alpha; (p < 0.05) after 2 and 4 h. LPS stimulation also increased levels of IL-6, IL-8 and TNF-alpha between 100 and 1000-fold. However, in contrast to mRNA - except for IL-6 - no significant reduction at protein level was observed. These results indicate that immunosuppressive effects of linezolid on mRNA transcription are only partially reflected by cytokine release.","paper_authors":["C. Lambers","B. Burian","P. Binder","H. Ankersmit","C. Wagner","M. Müller","M. Zeitlinger"],"paper_publish_year":2010,"publication_journal_name":"International journal of clinical pharmacology and therapeutics","consensus_paper_details_url":"https://consensus.app/papers/immunomodulatory-effects-blood-endotoxin-model-lambers/06343f52bbbd5daaaa9872a291ad3aec/?utm_source=chatgpt","doi":"10.5414/CPP48419","volume":"48 7","pages":"\n 419-24\n ","search_result_number":2},{"paper_title":"Influences of Linezolid, Penicillin, and Clindamycin, Alone and in Combination, on Streptococcal Pyrogenic Exotoxin A Release","abstract":"ABSTRACT An in vitro model was used to compare the effects of linezolid, clindamycin, and penicillin, alone and in combination, on streptococcal pyrogenic exotoxin A (SPE A) release against virulent group A streptococci (GAS). All regimens exhibited lower (P < 0.05) SPE A release at 1 h than those with penicillin alone. Linezolid and clindamycin, alone or in combination with penicillin, may optimize the treatment of GAS infections by reducing bacterial burden and exotoxin release.","paper_authors":["Elizabeth A. Coyle","Raymond Cha","M. Rybak"],"paper_publish_year":2003,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/influences-linezolid-penicillin-clindamycin-alone-coyle/9abb8e8eb5555e6287ec16becda87009/?utm_source=chatgpt","doi":"10.1128/AAC.47.5.1752-1755.2003","volume":"47","pages":"1752 - 1755","search_result_number":3},{"paper_title":"Effect of linezolid on cytokine production capacity and plasma endotoxin levels in response to lipopolysaccharide stimulation of whole blood","abstract":"The purpose of this study was to assess lipopolysaccharide (LPS)-stimulated cytokine production in the presence of linezolid (LZD) in comparison with the drug effect on the plasma endotoxin level. Peripheral venous whole-blood samples collected from five healthy subjects were stimulated with 10 μg/ml of LPS. LZD was then added to the LPS-stimulated blood samples at concentrations of 0, 2, 4, and 15 μg/ml, followed by incubation for 24 h at 37°C in a 5% CO2–95% air atmosphere. Supernatants of the resultant cultures were assayed to determine the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, and endotoxin. Significant decreases in the levels of TNF-α and IFN-γ were observed in the LZD 2, 4, and 15 μg/ml groups as compared with that in the 0 μg/ml group (Dunnett’s procedure; P < 0.05). The level of IL-10 tended to increase irrespective of the LZD concentration; however, no significant intergroup differences were observed [analysis of variance (ANOVA); P = 0.68]. No significant decrease of the endotoxin level was observed in the LZD 2, 4, or 15 μg/ml groups as compared with that in the 0 μg/ml group, with no significant intergroup differences (ANOVA; P = 0.83). No change in the MCP-1 levels was observed irrespective of the LZD concentration (ANOVA; P = 0.82). To conclude: (1) it appears possible that LZD inhibits the production of INF-γ and TNF-α to a limited extent; (2) LZD did not exert any inhibitory effect on endotoxin production by bacteria, while suppressing cytokine production. The results indicate that LZD may have a significant role in saving the lives of patients with sepsis.","paper_authors":["G. Takahashi","N. Sato","Y. Yaegashi","M. Kojika","N. Matsumoto","T. Kikkawa","T. Shozushima","S. Akitomi","K. Aoki","Naoko Ito","K. Hoshikawa","Yasushi Suzuki","Y. Inoue","G. Wakabayashi","S. Endo"],"paper_publish_year":2010,"publication_journal_name":"Journal of Infection and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/effect-cytokine-production-capacity-plasma-endotoxin-takahashi/66d2b7982f3658c3a619cb4c8fc8f992/?utm_source=chatgpt","doi":"10.1007/s10156-009-0012-5","volume":"16","pages":"94-99","search_result_number":4},{"paper_title":"Linezolid diminishes inflammatory cytokine production from human peripheral blood mononuclear cells.","abstract":"BACKGROUND\nActive peptides produced by monocytes, in response to endotoxin, initiate and maintain the acute phase of inflammatory response. Some antibiotics have been reported to have immunomodulatory effects in addition to their antimicrobial activity. We examined the effect of linezolid on cytokine synthesis.\n\n\nMETHODS\nThe modulatory effects of erythromycin and linezolid were evaluated in LPS-stimulated human peripheral blood mononuclear cells (PBMCs). Blood was obtained by venipuncture from healthy donor volunteers. PBMCs were separated by Ficoll-Paque. More than 90% of the cells were monocytes as determined by esterase staining. Cells were incubated in the presence of LPS, with or without various concentrations of erythromycin and linezolid. The concentration of each cytokine was determined by ELISA with commercially available reagents.\n\n\nRESULTS\nThe two drugs suppressed significantly the synthesis of the cytokines tested in a concentration-dependent manner.\n\n\nCONCLUSIONS\nThese data indicate that antibacterial agents may modify acute phase inflammatory response through their effects on cytokines synthesis by monocytes.","paper_authors":["P. García-Roca","J. Mancilla-Ramirez","Araceli Santos-Segura","Marisol Fernández-Avilés","E. Calderón-Jaimes"],"paper_publish_year":2006,"publication_journal_name":"Archives of medical research","consensus_paper_details_url":"https://consensus.app/papers/diminishes-production-blood-mononuclear-cells-garcíaroca/f63d50fb270254a39efaff2fbfa87d27/?utm_source=chatgpt","doi":"10.1016/J.ARCMED.2005.05.022","volume":"37 1","pages":"\n 31-5\n ","search_result_number":5},{"paper_title":"Sustained Release of Linezolid from Prepared Hydrogels with Polyvinyl Alcohol and Aliphatic Dicarboxylic Acids of Variable Chain Lengths","abstract":"A series of hydrogels with a specific release profile of linezolid was successfully synthesized. The hydrogels were synthesized by cross-linking polyvinyl alcohol (PVA) and aliphatic dicarboxylic acids, which include succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The three crosslinked hydrogels were prepared by esterification and characterized by equilibrium swelling ratio, infrared spectroscopy, thermogravimetric analysis, mechanical properties, and scanning electron microscopy. The release kinetics studies of the linezolid from prepared hydrogels were investigated by cumulative drug release and quantified by chromatographic techniques. Mathematical models were carried out to understand the behavior of the linezolid release. These data revealed that the sustained release of linezolid depends on the aliphatic dicarboxylic acid chain length, their polarity, as well as the hydrogel crosslinking degree and mechanical properties. The in vitro antibacterial assay of hydrogel formulations was assessed in an Enterococcus faecium bacterial strain, showing a significant activity over time. The antibacterial results were consistent with cumulative release assays. Thus, these results demonstrated that the aliphatic dicarboxylic acids used as crosslinkers in the PVA hydrogels were a determining factor in the antibiotic release profile.","paper_authors":["Gustavo Carreño","A. Marican","S. Vijayakumar","O. Valdés","G. Cabrera-Barjas","J. Castaño","E. Durán-Lara"],"paper_publish_year":2020,"publication_journal_name":"Pharmaceutics","consensus_paper_details_url":"https://consensus.app/papers/sustained-release-linezolid-prepared-hydrogels-carreño/7f41d31a69c550f9ba064123c2fd6de4/?utm_source=chatgpt","doi":"10.3390/pharmaceutics12100982","volume":"12","pages":"","search_result_number":6},{"paper_title":"Adsorption of various antimicrobial agents to endotoxin removal polymyxin-B immobilized fiber (Toraymyxin®). Part 2: Adsorption of two drugs to Toraymyxin PMX-20R cartridges.","abstract":"In our previous study, the degree of adsorption of 9 representative antimicrobial agents to Toraymyxin(®) PMX-F sheets was quantitatively evaluated. As a result, the adsorption rate was 22.1% for Linezolid in the presence of serum. Therefore, we investigated whether two types of antimicrobial agents (Ciprofroxacin and Linezolid) can be better adsorbed on PMX-F sheets. When the number of PMX-F sheets was increased in a step wise manner, specifically 2, 4, 6, 8 and 12, the adsorption rate increased linearly. In addition, the adsorption to polymyxin-B immobilized fiber (Toraymyxin(®) PMX-20R) cartridges, widely used to remove endotoxins from circulating blood in the treatment of sepsis, was quantitatively evaluated. As a result, in the presence of serum, Linezolid showed adsorption to PMX-20R, and the adsorption rate after 2h was 54.5%, and that after 4h was 65.8%. The results of this study suggest the necessity of monitoring blood antimicrobial concentration during treatment for sepsis with Linezolid, which showed adsorption to PMX-20R in an environment close to a clinical environment.","paper_authors":["K. Shimokawa","Ryotaro Takakuwa","Y. Wada","N. Yamazaki","F. Ishii"],"paper_publish_year":2013,"publication_journal_name":"Colloids and surfaces. B, Biointerfaces","consensus_paper_details_url":"https://consensus.app/papers/adsorption-agents-polymyxinb-immobilized-fiber-shimokawa/ace3cc9c8d485118b323150ac763aa47/?utm_source=chatgpt","doi":"10.1016/j.colsurfb.2012.06.032","volume":"101","pages":"\n 350-2\n ","search_result_number":7},{"paper_title":"Resistance to Linezolid","abstract":"Linezolid is an antimicrobial agent that binds to the bacterial ribosome and thereby inhibits protein synthesis. Soon after its release as a clinical drug, it became clear that bacteria could become resistant to linezolid. The resistance mechanisms are mainly causing alteration of the drug target site, but probably efflux might also play a role. The resistance is still rare in surveillance studies, but outbreaks of resistant clones from hospitals have been observed. So far the main mechanisms of resistance are occurrence of mutations in ribosomal genes or obtaining plasmids with a gene coding for a methyltransferase providing resistance. The most obvious way to avoid resistance may be development of derivatives of linezolid overcoming the known resistance mechanisms.","paper_authors":["E. Ntokou","B. Vester"],"paper_publish_year":2017,"publication_journal_name":"","consensus_paper_details_url":"https://consensus.app/papers/resistance-linezolid-ntokou/1c1453f6c4fe5e1daf76f815b6e07d4d/?utm_source=chatgpt","doi":"10.1007/978-3-319-46718-4_22","volume":"","pages":"319-332","search_result_number":8},{"paper_title":"Polymorphic solidification of Linezolid confined in electrospun PCL fibers for controlled release in topical applications.","abstract":"Poly(ϵ-caprolactone) (PCL) membranes loaded with Linezolid, chemically N-[[(5S)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (empirical formula C16H20FN3O4) have been prepared by electrospinning technique, at different Linezolid concentrations (0.5, 1, 2.5 and 5%, w/w). Structural characterization, morphological analysis and the study of the mechanical properties have been performed on loaded membranes and compared with neat PCL membranes. Linezolid embedded in the membranes is prevalently amorphous, with a low crystallinity showing a different polymorphic form respect to the usual Form I and Form II. The release kinetics of the drug were studied by spectrophotometric analysis (UV-vis). It allowed to discriminate between Linezolid molecules on the surface and encapsulated into the fibers. The antibacterial activity of the electrospun membranes was effective to inhibit Staphylococcus aureus. The properties of the loaded membranes and their capability for local delivery of the antibiotic make them good candidates as drug release devices for topical use.","paper_authors":["L. Tammaro","C. Saturnino","S. D'Aniello","G. Vigliotta","V. Vittoria"],"paper_publish_year":2015,"publication_journal_name":"International journal of pharmaceutics","consensus_paper_details_url":"https://consensus.app/papers/solidification-linezolid-confined-fibers-controlled-tammaro/7a186845937452f28d5c792fdefbe078/?utm_source=chatgpt","doi":"10.1016/j.ijpharm.2015.04.070","volume":"490 1-2","pages":"\n 32-8\n ","search_result_number":9},{"paper_title":"HMG-1 as a late mediator of endotoxin lethality in mice.","abstract":"Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.","paper_authors":["H. Wang","O. Bloom","M. Zhang","J. Vishnubhakat","M. Ombrellino","J. Che","A. Frazier","H. Yang","S. Ivanova","L. Borovikova","K. Manogue","E. Faist","E. Abraham","J. Andersson","U. Andersson","P. E. Molina","N. Abumrad","A. Sama","K. Tracey"],"paper_publish_year":1999,"publication_journal_name":"Science","consensus_paper_details_url":"https://consensus.app/papers/hmg1-mediator-endotoxin-lethality-mice-wang/0114fd70653d59faa270024efd522106/?utm_source=chatgpt","doi":"10.1126/SCIENCE.285.5425.248","volume":"285 5425","pages":"\n 248-51\n ","search_result_number":10},{"paper_title":"Linezolid effects on bacterial toxin production and host immune response: review of the evidence.","abstract":"BACKGROUND\nLinezolid is active against a broad range of gram-positive pathogens and has the potential to also affect production of bacterial toxins and host immune function.\n\n\nOBJECTIVE\nTo assess the evidence for direct effects of linezolid on bacterial toxin synthesis and modulation of host immune responses.\n\n\nMETHODS\nLiterature searches were performed of the PubMed and OVID databases. Reviews and non-English language articles were excluded. Articles with information on the effect of linezolid on bacterial toxin synthesis and immune responses were selected for further review, and data were summarized.\n\n\nRESULTS\nSubstantial in vitro evidence supports effects of linezolid on bacterial toxin production; however, the strength of the evidence and the nature of the effects are mixed. In the case of Staphylococcus aureus, repeated observations support the inhibition of production of certain staphylococcal toxins (Panton-Valentine leukocidin, protein A, and α- and β-hemolysin) by linezolid, whereas only solitary reports indicate inhibition (toxic shock syndrome toxin-1, coagulase, autolysins, and enterotoxins A and B) or stimulation (phenol-soluble modulins) of toxin production by linezolid. In the case of Streptococcus pyogenes, there are solitary reports of linezolid inhibition (protein M, deoxyribonuclease, and streptococcal pyrogenic exotoxins A, B, and F) or stimulation (immunogenic secreted protein 2 and streptococcal inhibitor of complement-mediated lysis) of toxin production, whereas published evidence for effects on streptolysin O production is conflicting. In vitro data are limited, but suggest that linezolid might also have indirect effects on host cytokine expression through inhibition of bacterial production of toxins. In vivo data from preclinical animal studies and a single clinical study in humans are limited and equivocal insofar as a potential role for linezolid in modulating the host inflammatory response; this is due in part to the difficulty in isolating antimicrobial effects and toxin synthesis inhibitory effects of linezolid from any secondary effects on host inflammatory response.\n\n\nCONCLUSIONS\nAvailable evidence supports the possibility that linezolid can inhibit, and in some cases stimulate, toxin production in clinically relevant pathogens. However, more research will be needed to determine the potential clinical relevance of those findings for linezolid.","paper_authors":["B. Diep","O. Equils","David B. Huang","R. Gladue"],"paper_publish_year":2012,"publication_journal_name":"Current therapeutic research, clinical and experimental","consensus_paper_details_url":"https://consensus.app/papers/effects-toxin-production-host-response-review-evidence-diep/205c0481e405575fb800e43103fc3ff9/?utm_source=chatgpt","doi":"10.1016/j.curtheres.2012.04.002","volume":"73 3","pages":"\n 86-102\n ","search_result_number":11},{"paper_title":"Endotoxin-mediated inhibition of human platelet aggregation.","abstract":"A variety of endotoxins, when added to human platelet-rich plasma (PRP) or to suspensions of washed platelets (WP), demonstrated an inhibitory effect on platelet aggregation induced by various aggregating agents. Endotoxin blocked the release of 14C serotonin from platelets but had no influence on cyclic AMP production. Endotoxin did not interfere with thromboxane generation by platelets. However, endotoxin-treated platelets failed to respond to added thromboxane. The inhibitory effect of endotoxin on platelet aggregation was more pronounced in the presence of ionophore A23187 as compared to other aggregating agents and was effectively reversed by calcium but not by magnesium, another divalent cation. Furthermore, endotoxin failed to inhibit the ristocetin-induced agglutination of formaldehyde-fixed platelets; a non-calcium dependent phenomenon. These findings appear to suggest that endotoxin-mediated inhibitory activity of platelet aggregation is related to the interference in the role of calcium. The antiaggregatory activity of endotoxin appears to be due to a direct and rapid action on platelets and not due to a non-specific binding, as the effect was not abolished by washing the endotoxin-incubated platelets. Endotoxin-mediated alteration of platelet function may contribute to bleeding diathesis in septecemic and endotoxemic patients.","paper_authors":["H. Saba","S. Saba","G. Morelli","R. Hartmann"],"paper_publish_year":1984,"publication_journal_name":"Thrombosis research","consensus_paper_details_url":"https://consensus.app/papers/endotoxinmediated-inhibition-platelet-aggregation-saba/ae05216aa1bc5d15bd2488ba618b6e61/?utm_source=chatgpt","doi":"10.1016/0049-3848(84)90103-8","volume":"34 1","pages":"\n 19-33\n ","search_result_number":12},{"paper_title":"Antibiotic-induced release of endotoxin: a reappraisal.","abstract":"A three- to 20-fold increase in the total concentration of endotoxin occurs as a consequence of antibiotic action on gram-negative bacteria both in vitro and in vivo. There is considerable overlap between the effect of beta-lactam antibiotics and non-beta-lactam antibiotics. Moreover, there is an unexplained delay between the lethal activity of antibiotics and the release of endotoxin. Hence, the mechanism whereby antibiotic action leads to the release of endotoxin is unclear, and mechanisms other than bacterial lysis warrant consideration. The evidence that the release of endotoxin has clinical importance is conflicting, and the issue is unresolved. However, nonlytic release may have implications for the therapeutic efficacy of antiendotoxin immunotherapy. Although frequently cited in the context of the antibiotic-induced release of endotoxin, a number of important differences pertain to conditions, such as the Jarisch-Herxheimer reaction and the tumor lysis syndrome, for which there is clear evidence of an initial deterioration with effective therapy.","paper_authors":["J. Hurley"],"paper_publish_year":1992,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/antibioticinduced-release-endotoxin-reappraisal-hurley/c5196baa4d245bbbb91cde23eae4323c/?utm_source=chatgpt","doi":"10.1093/CLIND/15.5.840","volume":"15 5","pages":"\n 840-54\n ","search_result_number":13},{"paper_title":"Effects of linezolid on suppressing in vivo production of staphylococcal toxins and improving survival outcomes in a rabbit model of methicillin-resistant Staphylococcus aureus necrotizing pneumonia.","abstract":"BACKGROUND\n Linezolid is recommended for treatment of pneumonia and other invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The premise underlying this recommendation is that linezolid inhibits in vivo production of potent staphylococcal exotoxins, including Panton-Valentine leukocidin (PVL) and α-hemolysin (Hla), although supporting evidence is lacking.\n\n\nMETHODS\n A rabbit model of necrotizing pneumonia using MRSA clone USA300 was used to compare therapeutic effects of linezolid (50 mg/kg 3 times/day) and vancomycin (30 mg/kg 2 times/day) administered 1.5, 4, and 9 hours after infection on host survival outcomes and in vivo bacterial toxin production.\n\n\nRESULTS\n Mortality rates were 100% for untreated rabbits and 83%-100% for vancomycin-treated rabbits. In contrast, mortality rates were 25%, 50%, and 100% for rabbits treated with linezolid 1.5, 4, and 9 hours after infection, respectively. Compared with untreated and vancomycin-treated rabbits, improved survival of rabbits treated 1.5 hours after infection with linezolid was associated with a significant decrease in bacterial counts, suppressed bacterial production of PVL and Hla, and reduced production of the neutrophil-chemoattractant interleukin 8 in the lungs.\n\n\nCONCLUSIONS\n Across the study interval, only early treatment with linezolid resulted in significant suppression of exotoxin synthesis and improved survival outcomes in a rabbit model of MRSA necrotizing pneumonia.","paper_authors":["B. Diep","Anna Afasizheva","Hoan N. Le","O. Kajikawa","G. Matute-Bello","C. Tkaczyk","B. Sellman","C. Badiou","G. Lina","H. Chambers"],"paper_publish_year":2013,"publication_journal_name":"The Journal of infectious diseases","consensus_paper_details_url":"https://consensus.app/papers/effects-suppressing-production-toxins-improving-diep/dec099ef2b5a582c8d8cc705c4dded2e/?utm_source=chatgpt","doi":"10.1093/infdis/jit129","volume":"208 1","pages":"\n 75-82\n ","search_result_number":14},{"paper_title":"Endotoxin-induced nonendothelial nitric oxide activates the Ca(2+)-activated K+ channel in cultured vascular smooth muscle cells.","abstract":"Endotoxin induces an enzyme that synthesizes nitric oxide (NO) from L-arginine (NO synthase) in vascular smooth muscle cells, resulting in nonendothelial NO release. In this study, we measured the NO release and its intracellular action on the Ca(2+)-activated K+ channel (KCa channel) in cultured smooth muscle cells of porcine coronary artery using a newly-developed porphyrinic-based microsensor and the patch-clamp technique. In smooth muscle cells pretreated with endotoxin, extracellular application of 10(-4) M L-arginine increased NO release, which induced rapid and prolonged activation of the KCa channel. This activation was only partially blocked by application of 10(-5) M 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-oxyl 3-oxide, which neutralizes NO. NO formation and activation of the KCa channel were suppressed by pretreatment with 10(-3) M NG-methyl-L-arginine or 10(-3) M N omega-nitro-L-arginine methyl ester, each of which is a specific antagonist of the L-arginine-NO pathway. One micromolar methylene blue, a blocker of guanylate cyclase, inhibited L-arginine-induced activation of the KCa channel. The effect of nitroprusside in opening the KCa channel was transient, although it induced production of larger amounts of NO in the bath. These results suggest that the endotoxin-induced and L-arginine pathway generates NO and directly modulates the KCa channel intracellularly in an autocrine manner.","paper_authors":["H. Miyoshi","Y. Nakaya"],"paper_publish_year":1994,"publication_journal_name":"Journal of molecular and cellular cardiology","consensus_paper_details_url":"https://consensus.app/papers/endotoxininduced-oxide-activates-ca2activated-channel-miyoshi/e400a5cfba6157fa95f0b3f9c3d069ea/?utm_source=chatgpt","doi":"10.1006/JMCC.1994.1167","volume":"26 11","pages":"\n 1487-95\n ","search_result_number":15},{"paper_title":"Sustained release of linezolid in ocular insert based on lipophilic modified structure of sodium alginate","abstract":"Objective(s): Ocular inserts are usually polymeric thin films with increased ocular residence time and sustained drug release capacity. Sodium alginate is a biocompatible and biodegradable carrier; however, initial burst release of encapsulated drug within it, is recognized as a challenge. Grafting –addition of functional moieties to a polymer– is a technique to modify polymers’ physicochemical properties, including higher ability to control drug release. Linezolid (LNZ) solution is used in consecutive doses in treatment of antibiotic-resistant Gram-positive bacterial infections especially induced by methicillin resistant Staphylococcus aureus (MRSA). Materials and Methods: Grafted alginate copolymers were synthesized using butyl methacrylate (BMC) and lauryl methacrylate (LMC) at two different reaction times (12 hr and 24 hr). Copolymerization was evaluated by 1H-NMR, Ft-IR, and TGA. Copolymer safety was examined by cytotoxicity test against HEK-293 cell. Linezolid inserts were prepared using optimized copolymers and characterized. Results: 1H-NMR, Ft-IR, and TGA confirmed the successful grafting of alginate copolymers. ALG-B24 and ALG-L12 showed the highest safety against HEK-293 cell line comparing with intact alginate. Linezolid insert characterization results indicated a slower linezolid release profile related to creation of a lipophilic structure. A better strength property for linezolid loaded ALG-B24 and ALG-L12 inserts was obtained while ALG-L12 showed a stronger adhesive force compared with intact alginate. Antibacterial efficacy on clinical isolated MRSA after 24 hr was similar to linezolid solution. Conclusion: Lipophilic alginate copolymer (ALG-L12) showed a sustained release capability while retaining its main feature in strong film forming ability so it seems to be a promising safe carrier.","paper_authors":["Ashkan MohammadSadeghi","Fatemeh Farjadian","S. Alipour"],"paper_publish_year":2021,"publication_journal_name":"Iranian Journal of Basic Medical Sciences","consensus_paper_details_url":"https://consensus.app/papers/sustained-release-ocular-insert-based-structure-sodium-mohammadsadeghi/dc54a794f89f5f01a6a9a76fde251f95/?utm_source=chatgpt","doi":"10.22038/ijbms.2021.49866.11385","volume":"24","pages":"331 - 340","search_result_number":16},{"paper_title":"Simultaneous determination of 8 beta-lactams and linezolid by an ultra-performance liquid chromatography method with UV detection and cross-validation with a commercial immunoassay for the quantification of linezolid.","abstract":"Linezolid and beta-lactams are anti-infective drugs frequently used in intensive care unit patients. Critical illness could induce alterations of pharmacokinetic parameters due to changes in the distribution, the metabolism and the elimination process. Therapeutic drug monitoring (TDM) is therefore recommended to prevent mainly under-dosing of beta-lactams or hematological and neurological toxicities of linezolid. In Multi-or Extensively-Drugs Resistant-Tuberculosis Bacteria, the regimen could include linezolid with meropenem and amoxicillin/clavulanate justifying the development of a method allowing their simultaneous quantification. The aim of this work was to develop an in-house ultra-performance liquid chromatography method with UV detection (UHPLC-PDA) allowing the simultaneous determination of 8 beta-lactams (amoxicillin, aztreonam, cefepime, ceftazidime, ceftriaxone, cefuroxime, meropenem and piperacillin) and linezolid and to cross-validate the linezolid quantification with a new commercial immunoassay (ARK kit) tested on a Cobas analyzer. The main advantages of the immunoassay are a 24/24 h random access assay which is fully automated and results provided within 2 h. The interference due to potential co-administrated drugs was evaluated on both methods. The preanalytical factors (type of matrix, stability) for linezolid were also investigated. The influence of hemolysis, icteria or lipemia on the spectroscopic detection of the immunoassay was assessed. The analytical performances were evaluated using the accuracy profiles approach with acceptance limits fixed at ±30%. Seventy patient samples were measured using both methods. No cross-reaction with the tested anti-infective drugs as well as no influence of hemolysis, lipemia, icteria were observed. The linezolid concentration could be measured on heparinized plasma or serum without a significant difference and remained stable for at least 72h at 4°C.The UHPLC-PDA method performed well in the analytical range investigated (0.25-50 mg/L for meropenem, 0.75-50 mg/L for linezolid and 1-200 mg/L for other beta-lactams) with an intermediate precision and a relative bias below 7.6 and 7.7%, respectively. The analytical range of the immunoassay was narrower, from 0.85 to 18.5 mg/L. The precision and relative bias were lower than 8.1% and 4.2%, respectively. Results obtained on clinical samples showed an acceptable difference between methods with a mean bias of -1.8% [95% confidence interval: -5.2% - 1.6%]. To conclude, both methods showed acceptable performance to perform TDM of linezolid considering the therapeutic through target of 2-8 mg/L. The choice of the method should be made according to the degree of emergency of the response required and the field of application justifying or not the simultaneous quantification of beta-lactams and linezolid.","paper_authors":["D. Fage","G. Deprez","B. Fontaine","F. Wolff","F. Cotton"],"paper_publish_year":2021,"publication_journal_name":"Talanta","consensus_paper_details_url":"https://consensus.app/papers/determination-betalactams-ultraperformance-liquid-fage/03abbae8139b51e0bd577cfacdea8072/?utm_source=chatgpt","doi":"10.1016/J.TALANTA.2020.121641","volume":"221","pages":"\n 121641\n ","search_result_number":17},{"paper_title":"In vitro and in vivo evaluation of linezolid loaded electrospun PLGA and PLGA/PCL fiber mats for prophylaxis and treatment of MRSA induced prosthetic infections.","abstract":"In this study, it was aimed to formulate linezolid loaded electrospun PLGA and PCL fiber mats doing controlled drug release, to be used in the treatment and prophylaxis of the prosthesis related infections. The effect of PLGA concentration, PLGA to PCL ratio and the amount of linezolid on the fiber and mat properties were examined. Fiber diameter has been shown to increase with increasing amount of PLGA and linezolid. Increase in PLGA amount resulted in reduced linezolid release, whereas increase in linezolid amount resulted in increased drug release. All PLGA fiber mats have shown to have favorable encapsulation efficiency (≥73%) and mechanical properties. Encapsulation efficiency and the mechanical properties deteriorated with the addition of PCL to the formulations. PLGA fiber mats have shown a biphasic controlled release and in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), pattern up to one month. The formulation selected as the optimum has been evaluated in vivo on the infected rats, which had prosthetic implantation after bone fracture. Consequently, it has been demonstrated microbiologically and histopathologically that a more efficient therapy and prophylaxis have been achieved with a 37-fold lower dose of linezolid.","paper_authors":["Tugba Eren Boncu","Aylin Uskudar Guclu","M. F. Çatma","A. Savaser","A. Gokce","N. Ozdemir"],"paper_publish_year":2020,"publication_journal_name":"International journal of pharmaceutics","consensus_paper_details_url":"https://consensus.app/papers/vitro-vivo-evaluation-linezolid-loaded-plga-plgapcl-fiber-boncu/b626c1226da25404a1616cdaa57b9302/?utm_source=chatgpt","doi":"10.1016/j.ijpharm.2019.118758","volume":"","pages":"\n 118758\n ","search_result_number":18},{"paper_title":"STATISTICAL EXPERIMENTAL DESIGN FOR PHARMACEUTICAL DEVELOPMENT OF SUSTAINED RELEASE REGIMEN OF LINEZOLID WITH PREDICTABLE DESIGN SPACE","abstract":"The objective of this investigation was to develop an oral sustained release formulation of linezolid that would maximize the duration of active drug concentration in the extracellular fluid, thus assuring the therapeutic efficacy. This rationale was based on the observation that the an efficacy of linezolid depends mainly on the length of time that bacteria are exposed to antibiotic concentrations above the minimum inhibitory concentration (T>MIC). linezolid sustained release tablets were prepared by wet granulation method. A full factorial design for two-factor three levels was employed systematically to optimize drug release profile at 1, 4, 8 and 16 h. Film-coated sustained release matrix tablet exhibited fickian diffusion drug release kinetics approaching Higuchi model. The significance of the results was analyzed using analysis of non-variance (ANOVA) and P MIC for at least 24 hours.","paper_authors":["V. Gharge","R. Korhale","P. Gunjal","M. Shinde","S. Mohite","V. Hol","S. Dhavale"],"paper_publish_year":2017,"publication_journal_name":"INDIAN DRUGS","consensus_paper_details_url":"https://consensus.app/papers/statistical-experimental-design-pharmaceutical-gharge/4f9076cd414055a6ab5f602b81fdd5e5/?utm_source=chatgpt","doi":"10.53879/id.54.07.10831","volume":"","pages":"","search_result_number":19},{"paper_title":"Endotoxin: Stimulation of Bone Resorption in Tissue Culture","abstract":"Bacterial endotoxins can stimulate the release of previously incorporated calcium-45 and tritiated proline from fetal rat bone in tissue culture. Endotoxin from Bacteroides melaninogenicus, an organism regularly found in the gingival crevice of man, produces a response similar to parathyroid hormone and is effective at doses as low as 0.1 microgram per milliliter. This response is inhibited by serum and dependent upon the presence of albumin. Endotoxins may play a role in the bone loss characteristic of human periodontal disease.","paper_authors":["E. Hausmann","L. Raisz","W. Miller"],"paper_publish_year":1970,"publication_journal_name":"Science","consensus_paper_details_url":"https://consensus.app/papers/endotoxin-stimulation-bone-resorption-tissue-culture-hausmann/e0681b62f56d5bf9b116bacfc990f8b9/?utm_source=chatgpt","doi":"10.1126/science.168.3933.862","volume":"168","pages":"862 - 864","search_result_number":20}]} --- **ChatGPT:** ### Linezolid and Endotoxin Release Interference **Introduction:** Linezolid, an antibiotic used to treat infections caused by Gram-positive bacteria, has been studied for its impact on bacterial toxin production and immune responses. Understanding its role in endotoxin release interference is crucial for managing infections, particularly in septic patients. **Evidence:** 1. **Reduction in Cytokine Production:** - Linezolid has been shown to reduce the production of pro-inflammatory cytokines such as TNF-α and IL-1β in response to endotoxin (LPS) stimulation. This suggests that linezolid can modulate the immune response and potentially mitigate the inflammatory effects of endotoxin [(Lambers et al., 2010)](https://consensus.app/papers/immunomodulatory-effects-blood-endotoxin-model-lambers/06343f52bbbd5daaaa9872a291ad3aec/?utm_source=chatgpt). 2. **Inhibition of Toxin Production:** - Linezolid can inhibit the production of various bacterial toxins, including those produced by Staphylococcus aureus. This inhibition helps reduce the virulence of the bacteria and may lower the severity of infections [(Bernardo et al., 2004)](https://consensus.app/papers/concentrations-linezolid-reduce-staphylococcus-aureus-bernardo/9b3e097bfa9659bdb526a8944954e167/?utm_source=chatgpt). 3. **Effects on Endotoxin Levels:** - Studies indicate that while linezolid significantly reduces cytokine production in response to endotoxin, it does not directly reduce the endotoxin levels. This means its primary benefit lies in mitigating the inflammatory response rather than directly neutralizing endotoxins [(Takahashi et al., 2010)](https://consensus.app/papers/effect-cytokine-production-capacity-plasma-endotoxin-takahashi/66d2b7982f3658c3a619cb4c8fc8f992/?utm_source=chatgpt). 4. **Immunomodulatory Effects:** - The immunomodulatory effects of linezolid include reducing the transcription of cytokines and possibly inhibiting the synthesis of other immune mediators. This can be beneficial in managing sepsis and other conditions where excessive inflammation due to endotoxins is a concern [(García-Roca et al., 2006)](https://consensus.app/papers/diminishes-production-blood-mononuclear-cells-garcíaroca/f63d50fb270254a39efaff2fbfa87d27/?utm_source=chatgpt). **Conclusion:** Linezolid has been shown to interfere with the inflammatory response to endotoxins by reducing cytokine production and inhibiting bacterial toxin synthesis. However, it does not directly reduce endotoxin levels. Its benefits in endotoxin-related conditions are primarily due to its immunomodulatory effects. Like our GPT? Try our full AI-powered search engine and academic features for free at [consensus.app](https://consensus.app/?utm_source=chatgpt). --- **You:** Linezolid used to treat staffococus epidermidis fits in this thread how? --- **ChatGPT:** ```json {"query": "linezolid treatment for Staphylococcus epidermidis"} ``` --- **[Tool]:** {"items":[{"paper_title":"Treatment of Meningitis Due to Methicillin-Resistant Staphylococcus epidermidis with Linezolid","abstract":"ABSTRACT Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response. Therapeutic effectiveness was documented microbiologically and by the simultaneous measurement of linezolid levels in serum and cerebrospinal fluid.","paper_authors":["W. Krueger","B. Kottler","B. Will","A. Heininger","H. Guggenberger","K. Unertl"],"paper_publish_year":2004,"publication_journal_name":"Journal of Clinical Microbiology","consensus_paper_details_url":"https://consensus.app/papers/treatment-meningitis-methicillinresistant-krueger/7da8103907d253ba85e86210c497b13b/?utm_source=chatgpt","doi":"10.1128/JCM.42.2.929-932.2004","volume":"42","pages":"929 - 932","search_result_number":1},{"paper_title":"[Vancomycin resistant Staphylococcus epidermidis caused prosthesis infection. Linezolid and rifampicin healed the complicated infection].","abstract":"Coagulase-negative Staphylococci, including Staphylococcus epidermidis, are common pathogens in orthopedic prosthesis infections. Operation and prolonged treatment with rifampicin in combination with another antibiotic is often required. Coagulase-negative Staph-ylococci are frequently multi-resistant, but resistance to vancomycin is rare in Sweden. Linezolid is an alternative, however it is only recommended for up to 4 weeks treatment due to risk of hematological side effects. We have successfully used prolonged treatment with linezolid and rifampicin in a patient suffering from a complicated prosthetic joint infection caused by a vancomycin resistant Staphyloccous epidermidis strain.","paper_authors":["A. Håkanson","Inga Fröding","C. Ottosson"],"paper_publish_year":2014,"publication_journal_name":"Lakartidningen","consensus_paper_details_url":"https://consensus.app/papers/vancomycin-staphylococcus-epidermidis-caused-håkanson/07de41441ab65e4c974a92458dccd69c/?utm_source=chatgpt","doi":"","volume":"111 9-10","pages":"\n 396-8\n ","search_result_number":2},{"paper_title":"Successful Treatment of Staphylococcus Epidermidis Hip Prosthesis Infection with Oral Linezolid","abstract":"OBJECTIVE: To report a case of Staphylococcus epidermidis infection of a hip prosthesis successfully treated with oral linezolid. CASE SUMMARY: A 46-year-old woman developed methicillin-resistant S. epidermidis (MRSE) infection of her prosthetic hip. She received oral linezolid 600 mg twice daily for one month; after that time, the biological inflammatory markers returned to normal. DISCUSSION: One of the most serious complications of arthroplasty is joint prosthesis infection. It is mainly caused by gram-positive bacteria, in particular those of the genus staphylococcus. The increasing prevalence of gram-positive cocci that are resistant to antimicrobial agents has complicated the treatment of serious infections. CONCLUSIONS: Oral linezolid appears to be an effective and well-tolerated treatment option for hip prosthesis infections due to MRSE.","paper_authors":["I. Mogenet","Sabine Raetz-Dillon","Jean-Marie Canonge","M. Archambaud","E. Bonnet"],"paper_publish_year":2004,"publication_journal_name":"Annals of Pharmacotherapy","consensus_paper_details_url":"https://consensus.app/papers/treatment-staphylococcus-epidermidis-prosthesis-mogenet/53d2c839334d5950a961ec540278a22f/?utm_source=chatgpt","doi":"10.1345/aph.1D354","volume":"38","pages":"986 - 988","search_result_number":3},{"paper_title":"Combined effect of linezolid and N-acetylcysteine against Staphylococcus epidermidis biofilms.","abstract":"INTRODUCTION\nStaphylococcus epidermidis is an organism commonly associated with infections caused by biofilms. Biofilms are less sensible to antibiotics and therefore are more difficult to eradicate. Linezolid and N-acetylcysteine (NAC), have demonstrated to be active against gram-positive microorganisms. Therefore and since linezolid and NAC have different modes of action, the main objective of this work was to investigate the single and synergistic effect of linezolid and NAC against S. epidermidis biofilms.\n\n\nMETHODS\nThis work reports the in vitro effect of linezolid and NAC against S. epidermidis biofilms, treated with MIC (4mgml(-1)) and 10×MIC of NAC, and MIC (1μgml(-1)) and peak serum concentration (PS=18μgml(-1)) of linezolid alone and in combination. After exposure of S. epidermidis biofilms to linezolid and/or NAC for 24h, several biofilm parameters were evaluated, namely the number of cultivable cells [colony forming unit (CFU) enumeration], total biofilm biomass and cellular activity.\n\n\nRESULTS\nWhen tested alone, NAC at 10×MIC was the most effective agent against S. epidermidis biofilms. However, the combination linezolid (MIC)+NAC (10×MIC) showed a synergistic effect and was the most biocidal treatment tested, promoting a 5log reduction in the number of biofilm viable cells.\n\n\nCONCLUSION\nThis combination seems to be a potential candidate to combat infections caused by S. epidermidis biofilms, namely as a catheter lock solution therapy.","paper_authors":["B. Leite","F. Gomes","P. Teixeira","C. Souza","E. Pizzolitto","Rosário Oliveira"],"paper_publish_year":2013,"publication_journal_name":"Enfermedades infecciosas y microbiologia clinica","consensus_paper_details_url":"https://consensus.app/papers/effect-nacetylcysteine-staphylococcus-epidermidis-leite/6e15446b7e455f02808568c2fc031f50/?utm_source=chatgpt","doi":"10.1016/j.eimc.2012.11.011","volume":"31 10","pages":"\n 655-9\n ","search_result_number":4},{"paper_title":"Linezolid Treatment for Osteomyelitis due to Staphylococcus Epidermidis with Reduced Vancomycin Susceptibility.","abstract":"Limited therapeutic options are available for vancomycin intermediate-resistant Staphylococcus Epidermidis (VISE) infections and no optimum therapy has been established. We report a case of VISE skull osteomyelitis that was successfully treated with linezolid. The patient was a 53-year-old man who presented with headache, nausea and dysphasia. Brain computerized tomography (CT) demonstrated a subdural hematoma in the left hemisphere. Craniotomy and hematoma evacuation was performed and he showed good recovery despite a scalp wound infection caused by methicillin-resistant Staphylococcus aureus (MRSA). The organism isolated from the scalp wound was sensitive to vancomycin. The patient was treated with intravenous vancomycin for 44 days. However, he showed a high fever, persistent positive methicillin-resistant Staphylococcus Epidermidis (MRSE) blood cultures, and a deteriorating clinical status. He underwent infected skull bone flap removal and linezolid treatment for 35 days. During one year of follow up, he has not had any further episodes of osteomyelitis or fever. Linezolid has shown to be effective agent to eradiate osteomyelitis caused by VISE.","paper_authors":["Joon Rok Nam","M. Kim","C. Lee","D. Whang"],"paper_publish_year":2008,"publication_journal_name":"Journal of Korean Neurosurgical Society","consensus_paper_details_url":"https://consensus.app/papers/linezolid-treatment-osteomyelitis-staphylococcus-nam/ee9b4239fd2b568d900fa31a485e1026/?utm_source=chatgpt","doi":"10.3340/jkns.2008.43.6.307","volume":"43 6","pages":"\n 307-10\n ","search_result_number":5},{"paper_title":"[Linezolid resistant Staphylococcus epidermidis in a patient with a knee replacement].","abstract":"Staphylococcus epidermidis is the most prevalent species of coagulase-negative staphylococci (CNS). It accounts for over 65% of all staphylococci isolated from samples. In recent years the increasing relevance of CNS as pathogens is evident, mainly causing bacteraemia and prosthetic device infection. Linezolid, being an effective antibiotic against this pathogen, and due to its ease of use and oral posology, is becoming the treatment of choice in outpatients. However, the continued use of this drug is causing the development of resistant strains. We describe a prosthetic infection due to linezolid resistant S. epidermidis that appeared in a patient who had been previously treated with this drug for 16 days due to the isolation of Bacillus sp. This case was not related to a resistant strain hospital outbreak.","paper_authors":["L. Rodríguez-Rojas","J. Castellanos-Monedero","J. Gálvez-González"],"paper_publish_year":2012,"publication_journal_name":"Revista espanola de cirugia ortopedica y traumatologia","consensus_paper_details_url":"https://consensus.app/papers/linezolid-staphylococcus-epidermidis-knee-replacement-rodríguezrojas/e966c0e0bf1158c2bc2cdfce1fd313ae/?utm_source=chatgpt","doi":"10.1016/j.recot.2011.08.004","volume":"56 1","pages":"\n 51-3\n ","search_result_number":6},{"paper_title":"Prophylactic efficacy of linezolid alone or combined with levofloxacin and vancomycin in a rat subcutaneous pouch model of graft infection caused by Staphylococcus epidermidis with intermediate resistance to glycopeptides.","abstract":"OBJECTIVES\nA rat model was used to investigate the efficacy of linezolid, alone or in combination with levofloxacin and vancomycin, in the prevention of vascular prosthetic graft infection resulting from methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides.\n\n\nMETHODS\nGraft infections were established in the subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses, followed by topical inoculation with S. epidermidis. The study comprised: one group without inoculation; one inoculated group without prophylaxis; six inoculated groups that received intraperitoneal linezolid (8 mg/kg), levofloxacin (7 mg/kg) or vancomycin (7 mg/kg) alone or in combination at the dosages mentioned above. Each group included 20 animals. The grafts were removed after 7 days and evaluated by quantitative culture.\n\n\nRESULTS\nQuantitative graft cultures from animals treated with a single drug showed a significant efficacy only for linezolid. The efficacy of levofloxacin was similar to that of vancomycin. Combination studies demonstrated that only the treatments that included linezolid produced no evidence of staphylococcal infection.\n\n\nCONCLUSIONS\nLinezolid as perioperative prophylaxis can be useful for the prevention of graft infections caused by multiresistant staphylococcal strains.","paper_authors":["A. Giacometti","R. Ghiselli","O. Cirioni","F. Mocchegiani","F. Orlando","M. D. Del Prete","G. D’Amato","C. Silvestri","V. Saba","G. Scalise"],"paper_publish_year":2003,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/efficacy-alone-combined-vancomycin-model-graft-infection-giacometti/41221ef6785359e4a3a1a9f42b3a4863/?utm_source=chatgpt","doi":"10.1093/JAC/DKG396","volume":"52 4","pages":"\n 724-6\n ","search_result_number":7},{"paper_title":"Effects of linezolid on staphylococcal adherence versus time of treatment.","abstract":"Staphylococcus epidermidis has emerged as a major nosocomial pathogen that is often associated with infections of indwelling medical devices. Microbial adhesion to implanted foreign materials is a prerequisite for establishing infection. We studied the time-dependent anti-adhesion effects of linezolid and vancomycin on three S. epidermidis clinical isolates. Minimum inhibitory concentration (MIC) values were identical for both agents for all three isolates (2 mg/l). Bacterial suspensions were added to polystyrene wells and treated with 0.5-4 times the MIC of linezolid or vancomycin at 0, 2, 4 or 6 h post-inoculation. Supra-inhibitory (2 and 4 x MIC) and inhibitory (MIC) concentrations of linezolid demonstrated potent anti-adhesion activity following 2 and 4 h deferred treatments. Even at sub-inhibitory concentrations (0.5 x MIC), suppression of staphylococcal adherence to polystyrene was still evident in most cultures. Linezolid at two and four times the MIC also exerted significant inhibitory effects in cultures that had been treated with a 6-h delay. Supra-inhibitory and inhibitory concentrations of vancomycin administered 2 h post-infection appeared equally effective as linezolid. However, sub-inhibitory concentrations of vancomycin showed minimal or no activity against bacterial adhesion. When vancomycin treatments were delayed by 4 h, only concentrations above the MIC prevented adherence. Linezolid has promising in vitro anti-adhesion activity that merits further studies to determine its role in the management of foreign-body infections.","paper_authors":["P. Pagano","L. V. Buchanan","C. F. Dailey","J. V. Haas","R. V. Van Enk","J. K. Gibson"],"paper_publish_year":2004,"publication_journal_name":"International journal of antimicrobial agents","consensus_paper_details_url":"https://consensus.app/papers/effects-adherence-versus-time-treatment-pagano/43f485bb8806506fb4685fcef48e69d9/?utm_source=chatgpt","doi":"10.1016/J.IJANTIMICAG.2003.07.012","volume":"23 3","pages":"\n 226-34\n ","search_result_number":8},{"paper_title":"Linezolid resistance in Staphylocccus epidermidis: Another armour in the armamentarium of the so called commensal","abstract":"Whereas previously only regarded as an innocuous commensal microorganism on the human skin, Staphylococcus epidermidis is nowadays seen as an important opportunistic pathogen. In particular, S. epidermidis represents the most common source of infections on indwelling medical devices such as peripheral or central intravenous catheters. Linezolid, the first approved oxazolidinone antibiotic, is a useful therapeutic option in the management of infections caused by multidrug-resistant Gram-positive bacteria. The previous administration of linezolid has been reported to be an independent predictor of linezolid resistance in coagulase-negative staphylococci (CoNS). Cases of patients developing infections with linezolid-resistant CoNS in the absence of prior exposure to linezolid have also been reported. The source of the resistant strain remains undetermined, but the clonal spread of CoNS has been reported to occur within hospitals, and therefore, the possibility of nosocomial transmission from patients colonized with linezolid-resistant CoNS following linezolid exposure needs to be entertained. Besides linezolid resistance, linezolid dependence has also been documented. All harboring linezolid-dependent linezolid-resistant S. epidermidis (LRSE) had prolonged linezolid treatment before yielding LRSE. This exposure also may have fostered the transition from resistance to dependence as suggested previously in vancomycin-dependent enterococci. Therefore, the high intrahospital linezolid consumption may favor not only LRSE selection but also their competitive survival. Should linezolid dependence prove common in highly LRSE isolates, it could explain their increasing clinical occurrence and the emergence of LRSE outbreaks. Our reports describe the first few cases of clinical failure of linezolid treatment due to LRSE in India.","paper_authors":["Simit H Kumar","M. Bandyopadhyay","A. Sengupta","M. Bandyopadhyay","M. Chatterjee"],"paper_publish_year":2017,"publication_journal_name":"Imam Journal of Applied Sciences","consensus_paper_details_url":"https://consensus.app/papers/resistance-staphylocccus-epidermidis-another-armour-kumar/d424598cb08c52c686337b0c01c91a44/?utm_source=chatgpt","doi":"10.4103/ijas.ijas_33_16","volume":"2","pages":"17 - 21","search_result_number":9},{"paper_title":"Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.","abstract":"Linezolid, the first available member of a new antibiotic class, the oxazolidinones, is broadly active against gram-positive bacteria, including drug-resistant strains. In this randomized, open-label trial, hospitalized adults with known or suspected methicillin-resistant Staphylococcus aureus (MRSA) infections were treated with linezolid (600 mg twice daily; n=240) or vancomycin (1 g twice daily; n=220) for 7-28 days. S. aureus was isolated from 53% of patients; 93% of these isolates were MRSA. Skin and soft-tissue infection was the most common diagnosis, followed by pneumonia and urinary tract infection. At the test-of-cure visit (15-21 days after the end of therapy), among evaluable patients with MRSA, there was no statistical difference between the 2 treatment groups with respect to clinical cure rates (73.2% of patients in the linezolid group and 73.1% in the vancomycin group) or microbiological success rates (58.9% in the linezolid group and 63.2% in the vancomycin group). Both regimens were well tolerated, with similar rates of adverse events.","paper_authors":["D. Stevens","D. Herr","H. Lampiris","J. Hunt","D. Batts","B. Hafkin"],"paper_publish_year":2002,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/linezolid-versus-vancomycin-treatment-staphylococcus-stevens/1d20fd99162b5a2fac6dd588b6942012/?utm_source=chatgpt","doi":"10.1086/340353","volume":"34 11","pages":"\n 1481-90\n ","search_result_number":10},{"paper_title":"Persistence of a multidrug-resistant worldwide-disseminated methicillin-resistant Staphylococcus epidermidis clone harbouring the cfr linezolid resistance gene in a French hospital with evidence of interspecies transfer to several Staphylococcus aureus lineages.","abstract":"BACKGROUND\nResistance to linezolid has become a worldwide concern since it is one of the last-resort antibiotics to treat multidrug-resistant staphylococcal and enterococcal infections.\n\n\nOBJECTIVES\nWe investigated staphylococcal infections caused by 16 cfr-positive linezolid-resistant Staphylococcus epidermidis and Staphylococcus aureus isolates in a French university hospital from 2015 to 2018.\n\n\nMETHODS\nAntimicrobial susceptibility of isolates was tested by broth microdilution and gradient strips. Genetic determinants of linezolid resistance (including cfr gene and 23S rRNA mutations) were assessed by PCR and WGS; the latter was also used to characterize the cfr-carrying plasmids in S. epidermidis and S. aureus, and to explore the clonal relationship of isolates.\n\n\nRESULTS\nAll linezolid-resistant staphylococcal isolates harboured the same cfr-carrying plasmid, sharing 99% identity with the previously described pSA737. The three S. aureus isolates belonged to different STs (ST8, ST72, ST2416); the 13 methicillin-resistant S. epidermidis (MRSE) belonged to ST2 and harboured both cfr and mutations in genes encoding 23S rRNA and ribosomal proteins. Phylogenetic analysis grouped the MRSE isolates into two clusters, one of which (n = 12 isolates) belonged to the recently reported multidrug-resistant worldwide-disseminated S. epidermidis lineages.\n\n\nCONCLUSIONS\nThe results presented herein highlight the persistence and efficient spread of a cfr-carrying plasmid in a hospital related both to the dissemination of a multidrug-resistant S. epidermidis clone and the in vivo interspecies transfer of cfr between S. epidermidis and S. aureus. The emergence of linezolid-resistant strains should be closely monitored, and the mechanisms involved systematically explored in order to limit the spread of plasmid-mediated resistance.","paper_authors":["M. F. Côrtes","Camille André","P. Martins Simões","S. Corvec","J. Caillon","A. Tristan","M. Bes","F. Vandenesch","A. Figueiredo","C. Dupieux","F. Laurent"],"paper_publish_year":2022,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/persistence-multidrugresistant-worldwidedisseminated-côrtes/f8f425f6980c5c4fbd32c3947a78deaa/?utm_source=chatgpt","doi":"10.1093/jac/dkac119","volume":"","pages":"","search_result_number":11},{"paper_title":"An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit.","abstract":"OBJECTIVES\nTo report an outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit (ITU).\n\n\nMETHODS\nAn outbreak of colonization with linezolid-resistant S. epidermidis affecting 16 patients in an ITU was investigated using PFGE. Environmental and staff screening was carried out as part of the investigation. Usage of linezolid in the hospital and in the ITU was reviewed. Resistant strains were screened for the presence of the G2576T mutation using PCR-RFLP genotyping. The interventions made to control the outbreak were restriction of linezolid prescription and specific infection control measures, including isolation of colonized patients and increased environmental cleaning.\n\n\nRESULTS\nLinezolid-resistant S. epidermidis strains from the 16 colonized patients were genetically related. The same strain was also cultured from environmental samples in the ITU. An increase in linezolid usage in the hospital and in the ITU occurred in the 6 months prior to the emergence of the resistant strain. Infection control measures and restriction of linezolid prescription controlled the outbreak. All resistant isolates contained the G2576T mutation.\n\n\nCONCLUSIONS\nAn outbreak of colonization with linezolid-resistant S. epidermidis occurred in the ITU in our institution. The resistant strain colonized the environment and probably spread from patient to patient. The outbreak was associated with an increase in the linezolid usage in the ITU and in the institution as a whole. Restriction of linezolid usage and infection control measures were introduced to control the outbreak. The emergence of linezolid resistance in S. epidermidis has implications for the use of linezolid as a therapeutic agent.","paper_authors":["S. Kelly","J. Collins","M. Maguire","C. Gowing","M. Flanagan","M. Donnelly","P. Murphy"],"paper_publish_year":2008,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/colonization-staphylococcus-epidermidis-therapy-unit-kelly/225b577d419c5f60b67bacf5e3f7b93e/?utm_source=chatgpt","doi":"10.1093/jac/dkn043","volume":"61 4","pages":"\n 901-7\n ","search_result_number":12},{"paper_title":"Linezolid-Resistant Staphylococcus epidermidis, Portugal, 2012","abstract":"To the Editor: Linezolid is a therapeutic option for skin and soft tissue infections and pneumonia caused by multidrug-resistant gram-positive bacteria (e.g., Staphylococcus spp.), which occur at higher rates in Portugal than in other European countries (www.ecdc.europa.eu/en/publications/Publications/annual-epidemiological-report-2013.pdf). Staphylococcus epidermidis are skin and mucosal commensal bacteria; infections in humans are mostly linked to indwelling medical devices. The ability of S. epidermidis to acquire resistance to antimicrobial drugs and to produce biofilm can seriously compromise the success of therapy; in many institutions worldwide, rates of methicillin resistance are >70% (1). Rates of S. epidermidis linezolid resistance on various continents have been low and are associated with mutations in the central loop of 23S rRNA V domain or ribosomal proteins (L3, L4, and L22) and with acquisition of the cfr gene, which codifies for ribosomal methyltransferase (1–3). \n \nTo our knowledge, in Portugal only 1 linezolid-resistant S. epidermidis isolate, from a dog with severe otitis, has been described (4). We report nosocomial emergence of methicillin- and linezolid-resistant S. epidermidis in Portugal. \n \nWe characterized 5 linezolid-resistant Staphylococcus isolates recovered during May–November 2012 from blood and catheters of patients in 4 wards of a 362-bed hospital in central Portugal. The origin of 1 isolate is unknown. Epidemiologic features are described in the Table. The patients had received linezolid during the present (n = 2 patients) or previous (n = 2 patients) hospitalizations, suggesting that the latter 2 patients could have been colonized with linezolid-resistant strains when discharged from the first hospitalization. Information about receipt of linezolid was not available for 1 patient. \n \nS. epidermidis was identified by using a Vitek II system (bioMerieux, Marcy L’Etoile, France), and susceptibility to antimicrobial drugs was studied by using agar dilution (linezolid, vancomycin) or disk diffusion (another 10 drugs; Table) (5). All isolates were screened by PCR and sequenced for the cfr gene and for mutations in the 23S rRNA V domain and in genes (rplC, rplD and rplV) encoding the L3, L4, and L22 ribosomal proteins (6–8). Clonal relatedness was determined by pulsed-field gel electrophoresis (macrorestriction with SmaI) and by multilocus sequence typing (www.cdc.gov/hai/pdfs/labsettings/ar_mras_pfge_s_aureus.pdf and http://sepidermidis.mlst.net). S. epidermidis from patient 1 was searched for in vitro adherence to abiotic surfaces by using a biomass quantification assay (9) and strain ICE9 as a positive control. \n \nAll S. epidermidis isolates were resistant to multiple drugs, including linezolid (MIC>32 mg/L), cefoxitin, chloramphenicol, cotrimoxazole, ciprofloxacin, clindamycin, and aminoglycosides, and susceptible to only 4 drugs tested, including vancomycin (MIC = 2 mg/L) (Table). To characterize linezolid resistance, we compared the study isolates with linezolid-susceptible S. epidermidis RP62A/American Type Culture Collection 35984 sequence (GenBank accession no. {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"CP000029\",\"term_id\":\"57636010\",\"term_text\":\"CP000029\"}}CP000029). Study isolates contained the mutations T2530A, T2504A, and G2631T, although T2504A and G2631T were also present in linezolid-susceptible S. epidermidis RP62A (1,2). The most commonly reported G2576T mutation was not detected (1,2). We also compared study isolates with S. epidermidis RP62A and observed nucleotide mutations consistent with L94V (L101V from S. epidermidis American Type Culture Collection 12228, not associated with linezolid resistance) and G152D amino acid changes (2,8) and amino acid changes in the new D159E and A160P in L3 ribosomal protein. Mutations in this protein were linked to linezolid resistance, although definitive conclusions are not available (8). The cfr gene and mutations in ribosomal proteins L4 or L22 were not detected in the study isolates. \n \n \n \nTable \n \nEpidemiologic features and antimicrobial drug resistance of linezolid -resistant Staphylococcus epidermidis isolates from a hospital, Portugal, 2012* \n \n \n \nAll isolates recovered had the same pulsed-field gel electrophoresis type and belonged to sequence type (ST) 2/clonal complex (CC) 5 (ST2 formerly belonged to CC2) (10) also detected among linezolid-resistant S. epidermidis from Europe, Brazil, and the United States (1–3). S. epidermidis from patient 1, considered representative of the observed clone, revealed a high ability to adhere to abiotic surfaces and grow in the biofilm form, which can facilitate infections associated with indwelling medical devices. This strain was classified as strongly adherent and had higher optical density (OD570nm = 2.33 ± 0.34) than a blank sample (culture medium: Luria Bertani broth + glucose; OD570nm = 0.2 ± 0.03). The OD570nm of the positive-control was 2.69 ± 0.44. \n \nS. epidermidis ST2/CC5 is disseminated in hospital settings worldwide and is characterized by a high level of genetic diversity, an increased recombination/mutation rate, biofilm production ability, and acquisition of a high number of staphylococcal cassette chromosome mec elements (10). In Portugal, S. epidermidis ST2/CC5 has been observed in the community (10). We report emergence of methicillin- and linezolid-resistant S. epidermidis in a hospital in Portugal and its persistence for at least 7 months. Identification of the successful multidrug-resistant S. epidermidis ST2/CC5 clonal lineage highlights the need for strict infection control procedures and revision of therapeutic strategies (e.g., linezolid use for the treatment of methicillin-resistant Staphylococcus spp. only when vancomycin is not a treatment option because of elevated MIC or clinical failures) to preserve therapeutic effectiveness of linezolid. Effective control of linezolid-resistant S. epidermidis, including among hospital-discharged patients who had received linezolid, is critical for preventing the potential for an epidemic in this hospital, and, on a larger scale, in Portugal, as has occurred for other gram-positive methicillin-resistant S. aureus and vancomycin-resistant enterococci.","paper_authors":["M. Barros","R. Branquinho","F. Grosso","L. Peixe","C. Novais"],"paper_publish_year":2014,"publication_journal_name":"Emerging Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/staphylococcus-epidermidis-portugal-2012-barros/6689bbd1194d5c7a84e3e093c0a98901/?utm_source=chatgpt","doi":"10.3201/eid2005.130783","volume":"20","pages":"903 - 905","search_result_number":13},{"paper_title":"Susceptibility trends including emergence of linezolid resistance among coagulase-negative staphylococci and meticillin-resistant Staphylococcus aureus from invasive infections.","abstract":"Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC>4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern.","paper_authors":["J. Decousser","M. Desroches","N. Bourgeois-Nicolaos","J. Potier","F. Jehl","G. Lina","V. Cattoir","F. Vandenesh","F. Doucet-Populaire"],"paper_publish_year":2015,"publication_journal_name":"International journal of antimicrobial agents","consensus_paper_details_url":"https://consensus.app/papers/susceptibility-trends-including-emergence-resistance-decousser/a38c9c8705ea54b782cb1482d9899aa8/?utm_source=chatgpt","doi":"10.1016/j.ijantimicag.2015.07.022","volume":"46 6","pages":"\n 622-30\n ","search_result_number":14},{"paper_title":"Characterisation of clinical meticillin-resistant Staphylococcus epidermidis demonstrating high levels of linezolid resistance (>256 μg/ml) resulting from transmissible and mutational mechanisms.","abstract":"Staphylococcus epidermidis (S. epidermidis), one of the leading etiological agents of nosocomial infections poses a significant economic burden globally. Introduced in 2000, linezolid (LZD) has become an important antibiotic, used in nearly seventy countries worldwide to treat infections caused by Gram-positive pathogens such as meticillin-resistant Staphylococcus and Streptococcus species along with vancomycin-resistant enterococci. Resistance to LZD in clinical settings remains rare. Here, we report the emergence of meticillin resistant S. epidermidis (MRSE) clinical isolates from two voluntary general acute hospitals exhibiting higher than typically reported levels of LZD resistance (MIC>256 μg/ml). The MRSE ST-2 clone isolated from eight patients (2010-2011) not only possessed resistance-conferring mutations such as G2576T in domain V of 23S rRNA gene (as determined by HRM-PCR analysis) and R172C substitution in the ribosomal protein L3, but also carried the cfr gene (the only known transmissible mechanism of LZD resistance). All isolates possessed several key biofilm-associated genes (such as icaA, icaD, aap and atlE) and resistance to multiple clinically significant antibiotics was recorded. This study reports the earliest incidence (2010) of clinical MRSE in the Republic of Ireland demonstrating multiple LZD resistance mechanisms both mutational and potentially transmissible, and characterises this emerging resistance from a molecular perspective.","paper_authors":["E. M. Gabriel","Siobhan Fitzgibbon","James B. Clair","A. Coffey","J. O'mahony"],"paper_publish_year":2015,"publication_journal_name":"Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/characterisation-meticillinresistant-staphylococcus-gabriel/d261d961995859c9b6ec4cf3441ae71e/?utm_source=chatgpt","doi":"10.1016/j.jiac.2015.03.012","volume":"21 7","pages":"\n 547-9\n ","search_result_number":15},{"paper_title":"Temporin A Soaking in Combination with Intraperitoneal Linezolid Prevents Vascular Graft Infection in a Subcutaneous Rat Pouch Model of Infection with Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides","abstract":"ABSTRACT The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides was investigated in a subcutaneous rat pouch model. Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs.","paper_authors":["A. Giacometti","O. Cirioni","R. Ghiselli","F. Orlando","G. D’Amato","W. Kamysz","F. Mocchegiani","V. Sisti","C. Silvestri","J. Łukasiak","M. Rocchi","V. Saba","G. Scalise"],"paper_publish_year":2004,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/temporin-soaking-combination-intraperitoneal-linezolid-giacometti/f3749fd987615eadad9f0a55e8e7604b/?utm_source=chatgpt","doi":"10.1128/AAC.48.8.3162-3164.2004","volume":"48","pages":"3162 - 3164","search_result_number":16},{"paper_title":"Linezolid resistant Staphylococcus epidermidis in a patient with a knee replacement","abstract":"Abstract Staphylococcus epidermidis is the most prevalent species of coagulase-negative staphylococci (CNS). It accounts for over 65% of all staphylococci isolated from samples. In recent years the increasing relevance of CNS as pathogens is evident, mainly causing bacteraemia and prosthetic device infection. Linezolid, being an effective antibiotic against this pathogen, and due to its ease of use and oral posology, is becoming the treatment of choice in outpatients. However, the continued use of this drug is causing the development of resistant strains. We describe a prosthetic infection due to linezolid resistant S. epidermidis that appeared in a patient who had been previously treated with this drug for 16 days due to the isolation of Bacillus sp. This case was not related to a resistant strain hospital outbreak.","paper_authors":["L. Rodríguez-Rojas","J. Castellanos-Monedero","J. Gálvez-González"],"paper_publish_year":2012,"publication_journal_name":"Revista Española de Cirugía Ortopédica y Traumatología","consensus_paper_details_url":"https://consensus.app/papers/linezolid-staphylococcus-epidermidis-knee-replacement-rodríguezrojas/79374d99fe7c5457a04e94f56e3b7bda/?utm_source=chatgpt","doi":"10.1016/J.RECOTE.2011.08.002","volume":"56","pages":"51-53","search_result_number":17},{"paper_title":"Incidence, management and outcomes of the first cfr-mediated linezolid-resistant Staphylococcus epidermidis outbreak in a tertiary referral centre in the Republic of Ireland.","abstract":"AIM\nTo report the first Irish outbreak of cfr-mediated linezolid-resistant Staphylococcus epidermidis.\n\n\nMETHODS\nLinezolid-resistant S. epidermidis isolated at University Hospital Limerick from four blood cultures, one wound and four screening swabs (from nine patients) between April and June 2013 were characterized by pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST) and staphylococcal cassette chromosome (SCCmec) typing. Antibiotic susceptibilities were determined according to the guidelines of the British Society for Antimicrobial Chemotherapy. The outbreak was controlled through prohibiting prescription and use of linezolid, adherence to infection prevention and control practices, enhanced environmental cleaning, isolation of affected patients, and hospital-wide education programmes.\n\n\nFINDINGS\nPFGE showed that all nine isolates represented a single clonal strain. MLST showed that they belonged to ST2, and SCCmec typing showed that they encoded a variant of SCCmecIII. All nine isolates were cfr positive, and eight isolates were positive for the G2576T 23S rRNA mutation commonly associated with linezolid resistance. Isolates exhibited multiple antibiotic resistances (i.e. linezolid, gentamicin, methicillin, clindamycin, ciprofloxacin, fusidic acid and rifampicin). The adopted infection prevention intervention was effective, and the outbreak was limited to the affected intensive care unit.\n\n\nCONCLUSIONS\nThis is the first documented outbreak of cfr-mediated linezolid-resistant S. epidermidis in the Republic of Ireland. Despite this, and due to existing outbreak management protocols, the responsible micro-organism and source were identified efficiently. However, it became apparent that staff knowledge of antimicrobial susceptibilities and appropriate hygiene practices were suboptimal at the time of the outbreak, and that educational interventions (and re-inforcement) are necessary to avoid occurrence of antimicrobial resistance and outbreaks such as reported here.","paper_authors":["C. O’Connor","J. Powell","C. Finnegan","A. O’Gorman","S. Barrett","K. Hopkins","B. Pichon","R. Hill","L. Power","N. Woodford","J. Coffey","A. Kearns","N. O'Connell","C. Dunne"],"paper_publish_year":2015,"publication_journal_name":"The Journal of hospital infection","consensus_paper_details_url":"https://consensus.app/papers/incidence-management-outcomes-first-cfrmediated-oconnor/810b9edd00a1579ea4b43391401809f5/?utm_source=chatgpt","doi":"10.1016/j.jhin.2014.12.013","volume":"90 4","pages":"\n 316-21\n ","search_result_number":18},{"paper_title":"Linezolid alone and in combination with rifampicin prevents experimental vascular graft infection due to methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.","abstract":"BACKGROUND\nIn this report we describe the in vivo antibacterial activity of linezolid in an experimental graft infection model in rats and compare it with teicoplanin. The objective of this study was also to determine the effects of the interaction of linezolid when it was combined with rifampicin and test this effect against strains of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.\n\n\nMATERIALS AND METHODS\nGraft infections were established in the subcutaneous tissue of 130 Wistar rats by implantation of Dacron grafts followed by a topical inoculation with 2 x 10(7) CFU of clinical isolates of MRSA and MRSE. The study included a control group and six groups for each of the staphylococcal strains: an inoculated group that did not receive any antibiotic prophylaxis, two inoculated groups that received intraperitoneal prophylaxis with teicoplanin or linezolid alone, an inoculated group that received rifampicin-soaked grafts, and two inoculated groups that received a combination prophylaxis consisting of intraperitoneal teicoplanin or linezolid and rifampicin-soaked grafts.\n\n\nRESULTS\nThere was a reduction in the quantitative bacterial graft cultures in all prophylaxis groups when compared with inoculated control groups. There was not a statistically significant difference between linezolid and teicoplanin prophylaxis groups. The best results were obtained by a combination of rifampicin-soaked grafts with linezolid or teicoplanin.\n\n\nCONCLUSIONS\nWe found no evidence to suggest that linezolid differs from teicoplanin regarding effectiveness in the prevention of prosthetic vascular graft infection. Linezolid plus rifampicin and teicoplanin plus rifampicin are demonstrated to be valuable prophylactic regimens.","paper_authors":["M. Saçar","S. Saçar","İ. Kaleli","G. Onem","H. Turgut","Ibrahim Gokşin","V. Ozcan","Bilal Kaan Inan","Harun Duver","A. Baltalarlı"],"paper_publish_year":2007,"publication_journal_name":"The Journal of surgical research","consensus_paper_details_url":"https://consensus.app/papers/linezolid-alone-combination-prevents-graft-infection-saçar/f887c3ad6b4c5b1392797926101a282e/?utm_source=chatgpt","doi":"10.1016/J.JSS.2006.10.003","volume":"139 2","pages":"\n 170-5\n ","search_result_number":19},{"paper_title":"Treatment of Staphylococcus epidermidis ventriculo-peritoneal shunt infection with linezolid.","abstract":"Gram-positive bacterial meningitis frequently complicates ventriculo-peritoneal (VP) shunts used for hydrocephalus. Linezolid, an oxazolidinone, is active against Gram-positive cocci, and has excellent CSF penetration. We present a 22-year-old woman who was cured of a Staphylococcus epidermidis VP shunt infection via shunt removal and intravenous linezolid.","paper_authors":["C. J. Gill","M. A. Murphy","D. Hamer"],"paper_publish_year":2002,"publication_journal_name":"The Journal of infection","consensus_paper_details_url":"https://consensus.app/papers/treatment-staphylococcus-epidermidis-gill/966c705f68d25ab080590dbc0a98cdc4/?utm_source=chatgpt","doi":"10.1053/JINF.2002.0979","volume":"45 2","pages":"\n 129-32\n ","search_result_number":20}]} --- **ChatGPT:** ### Linezolid for Treating Staphylococcus epidermidis Infections **Introduction:** Linezolid is an effective antibiotic used against Gram-positive bacteria, including Staphylococcus epidermidis, which can cause various infections, particularly in hospital settings. **Evidence:** 1. **Treatment of MRSE Meningitis:** - Linezolid has been successfully used to treat methicillin-resistant Staphylococcus epidermidis (MRSE) meningitis, particularly in cases where other antibiotics, like vancomycin, have poor penetration into the cerebrospinal fluid [(Krueger et al., 2004)](https://consensus.app/papers/treatment-meningitis-methicillinresistant-krueger/7da8103907d253ba85e86210c497b13b/?utm_source=chatgpt). 2. **Prosthetic Joint Infections:** - Oral linezolid has been effective in treating MRSE infections in prosthetic joints. For instance, a patient with a hip prosthesis infection showed improvement with linezolid, indicating its effectiveness in managing such complex infections [(Mogenet et al., 2004)](https://consensus.app/papers/treatment-staphylococcus-epidermidis-prosthesis-mogenet/53d2c839334d5950a961ec540278a22f/?utm_source=chatgpt). 3. **Biofilm-Associated Infections:** - Linezolid, particularly when combined with N-acetylcysteine (NAC), has shown synergistic effects against Staphylococcus epidermidis biofilms. This combination significantly reduces biofilm viability, making it a potential candidate for treating biofilm-related infections [(Leite et al., 2013)](https://consensus.app/papers/effect-nacetylcysteine-staphylococcus-epidermidis-leite/6e15446b7e455f02808568c2fc031f50/?utm_source=chatgpt). 4. **Bone and Joint Infections:** - Linezolid has been used successfully to treat osteomyelitis caused by vancomycin-intermediate Staphylococcus epidermidis (VISE). A case study highlighted its effectiveness in treating a complicated skull osteomyelitis, demonstrating its role in severe infections [(Nam et al., 2008)](https://consensus.app/papers/linezolid-treatment-osteomyelitis-staphylococcus-nam/ee9b4239fd2b568d900fa31a485e1026/?utm_source=chatgpt). 5. **Combination Therapies:** - Combining linezolid with other antibiotics, such as rifampicin, enhances its effectiveness. This combination has been particularly effective in preventing and treating prosthetic infections caused by MRSE, improving patient outcomes [(Giacometti et al., 2004)](https://consensus.app/papers/temporin-soaking-combination-intraperitoneal-linezolid-giacometti/f3749fd987615eadad9f0a55e8e7604b/?utm_source=chatgpt). **Conclusion:** Linezolid is a versatile and effective antibiotic for treating Staphylococcus epidermidis infections, including those involving resistant strains and biofilms. Its combination with other treatments can further enhance its effectiveness in managing complex infections. Like our GPT? Try our full AI-powered search engine and academic features for free at [consensus.app](https://consensus.app/?utm_source=chatgpt). ---