--- title: V4:E07:S03 - Black Stool Side Effect created: 2024-06-11 13:18:38.344279 updated: 2025-01-15 23:08:17.172929 source: ChatGPT source_file: conversations-000.json conversation_id: 01d2cf5d-b482-438a-a617-1098414cb7ff message_count: 36 tags: - black - stool - side - effect - source/chatgpt - status/raw - medicine - pharmacology category: - Medicine - Pharmacology - Infectious Diseases summary: Linezolid is generally well tolerated, but may cause diarrhea, nausea, headache, and reversible thrombocytopenia, anaemia and neutropenia. keypoints: - black stool as a side effect of linezolid - reversible thrombocytopenia associated with linezolid therapy - linezolid-induced black hairy tongue is an uncommon side effect monomyth_stage: "06 - Tests, Allies, Enemies" gameboard_position: '' truth_score: 92 entropy_score: Low tone: sentiment: Neutral emotions: - Informational - Neutral - 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: '2026-04-10' --- # V4:E07:S03 - Black Stool Side Effect > Exported from ChatGPT | 2024-06-11 | 36 messages --- **You:** What does black stool as a side effect of linezolid mean? --- **ChatGPT:** ```json {"query": "black stool as a side effect of linezolid"} ``` --- **[Tool]:** {"items":[{"paper_title":"Safety and tolerability of linezolid.","abstract":"Clinical trials have shown that linezolid (600 mg twice daily in adults) is safe and generally well tolerated for up to 28 days. Drug-related adverse events, which are typically mild to moderate in intensity and of limited duration, include diarrhoea, nausea and headache in adults, and diarrhoea, loose stools and vomiting in children. Clostridium difficile-related complications with linezolid are uncommon. Linezolid is a weak, reversible monoamine oxidase inhibitor: foods containing high concentrations of tyramine should be avoided, and linezolid should be used with caution in patients taking adrenergic or serotonergic agents or in those with uncontrolled hypertension. In the majority of patients, linezolid has minimal adverse effects on blood chemistry or haematology. There have been case reports of reversible thrombocytopenia, anaemia and neutropenia associated with linezolid therapy. In Phase III studies, 2.4% of patients treated with linezolid and 1.5% of patients treated with comparator drugs developed reversible thrombocytopenia (P = 0.066), but there was no evidence of an increased risk of agranulocytosis, aplastic anaemia or other irreversible blood dyscrasias. Reduced platelet counts were associated with linezolid treatment for >/=2 weeks; complete blood counts should be monitored weekly in patients receiving linezolid for more than 14 days and treatment should be discontinued if there is evidence of myelosuppression.","paper_authors":["G. French"],"paper_publish_year":2003,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt","doi":"10.1093/JAC/DKG253","volume":"51 Suppl 2","pages":"\n ii45-53\n ","search_result_number":1},{"paper_title":"Black‐brown hairy tongue: An unusual adverse effect of linezolid","abstract":"Linezolid‐induced black hairy tongue (BHT) is an uncommon side effect. We present a case of linezolid induced BHT and evaluate relevant literature from the home and worldwide. Its goal is to offer a secure and appropriate foundation for clinical drug usage. A 23‐year‐old male with recurrent boil infection erroneously reported by gram‐positive methicillin‐resistant Staphylococcus aureus (MRSA) by pus culture, which was misdiagnosed by a small clinic (diagnostic center) in a rural region of Bangladesh where he had previously been treated for that reoccurring boil infection. The patient was actually suffering from a different pus‐forming bacteria (Klebsiella), a gram‐negative bacterium that was just found after careful C/S report. Linezolid was administered to the patient 600 mg q12h orally in tablet after discharge from that rural clinic. On the 14th day following oral treatment, the patient presented to the hospital with BHT but no other atypical taste complaints. However, all symptoms were tolerable, and he finished the linezolid treatment period. After withdrawing from the medicine, all tongue symptoms vanished. Following a thorough study, it was determined that this patient had BHT brought on by drug linezolid. Long‐term linezolid usage is associated with neuropathies and bone marrow suppression. There is, however, little information about an uncommon adverse effect, black hairy tongue. We present here a case of linezolid induced BHT in a patient who was misdiagnosed. Also covered are the etiology, pathophysiology, diagnosis, and management of black hairy tongue.","paper_authors":["Ashrafur Rahaman Mahadi","M. I. Majumder"],"paper_publish_year":2022,"publication_journal_name":"Precision Medical Sciences","consensus_paper_details_url":"https://consensus.app/papers/black‐brown-hairy-tongue-effect-linezolid-mahadi/c3397e72ede05667831fdc98be63d44c/?utm_source=chatgpt","doi":"10.1002/prm2.12083","volume":"11","pages":"209 - 212","search_result_number":2},{"paper_title":"Linezolid induced black hairy tongue: a rare side effect.","abstract":"Linezolid induced black hairy tongue is a rare benign reversible side effect of linezolid therapy. We report a case of a 61 year old diabetic lady who developed thrombocytopenia and black hairy discoloration of the tongue after being prescribed linezolid for foot osteomyelitis by the orthopaedic surgeon. Patient was encouraged to practice good oral dental hygiene, advised to use a soft tooth brush, regular mouth wash and baking soda containing tooth paste. The condition resolved four weeks after cessation of the antibiotic therapy.","paper_authors":["Ishma Aijazi","F. M. Abdulla"],"paper_publish_year":2014,"publication_journal_name":"Journal of Ayub Medical College, Abbottabad : JAMC","consensus_paper_details_url":"https://consensus.app/papers/linezolid-induced-hairy-tongue-side-effect-aijazi/c4ff636f964d55f0ae1c80cdcd138887/?utm_source=chatgpt","doi":"","volume":"26 3","pages":"\n 401-3\n ","search_result_number":3},{"paper_title":"Linezolid-Associated Black Tongue: A Rare Adverse Drug Reaction","abstract":"Linezolid is an effective second-line anti-tuberculosis drug. However, the use of linezolid has been associated with rare adverse drug reactions (ADRs), one of which is the linezolid-associated black hairy tongue (BHT). This reaction is characterized by a black or dark brown discoloration of the tongue, which may be accompanied by a metallic or bitter taste. In this case report, we present a 19-year-old male patient who developed linezolid-associated black tongue while receiving linezolid as part of an all-oral, longer-course treatment regime for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). The patient's BHT was only cosmetic and resolved upon discontinuation of linezolid. This case report aims to raise awareness of this rare ADR and the importance of close monitoring and potential withdrawal of linezolid to optimize treatment outcomes.","paper_authors":["Dr. Gyanshankar P. Mishra"],"paper_publish_year":2023,"publication_journal_name":"Journal of Infectiology","consensus_paper_details_url":"https://consensus.app/papers/linezolidassociated-black-tongue-rare-adverse-drug-mishra/468eb759b157543c9d7ab10fa27e6aab/?utm_source=chatgpt","doi":"10.29245/2689-9981/2023/1.1170","volume":"","pages":"","search_result_number":4},{"paper_title":"Black brown discoloration and hairy tongue - A rare linezolid side effect.","abstract":"INTRODUCTION\nLinezolid was approved for clinical use for methicillin resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Additionally it is used in the management of drug resistant tuberculosis. It is well-tolerated however bone marrow suppression and neuropathies may occur in patients taking this antibiotic for more than 2 weeks. Black discoloration and black hairy tongue (BHT) due to linezolid is rarely reported. We report two cases of BHT.\n\n\nCASE REPORTS\nTwo patients of drug resistant pulmonary tuberculosis developed benign hairy tongue with linezolid 600mg per day. In both the cases black colored/hairy tongue was reported within 2-3 weeks of linezolid treatment. Both patients improved after withdrawal of linezolid. Subsequent reintroduction of linezolid with good oral hygiene was well tolerated and both patients completed the treatment of 2 years duration without any recurrence.\n\n\nCONCLUSION\nBlack discoloration and BHT is a rare but transient adverse reaction with linezolid. Reintroduction of linezolid with good oral hygiene is well tolerated.","paper_authors":["A. Jain","M. Puri","R. Sarin"],"paper_publish_year":2017,"publication_journal_name":"The Indian journal of tuberculosis","consensus_paper_details_url":"https://consensus.app/papers/black-discoloration-hairy-tongue-side-effect-jain/144908ad66925d2f9727fb5f2265706d/?utm_source=chatgpt","doi":"10.1016/j.ijtb.2016.06.003","volume":"64 1","pages":"\n 44-46\n ","search_result_number":5},{"paper_title":"Linezolid Induced Black Hairy Tongue an Uncommon Phenomenon: A Case Report with Update of Review of Literature","abstract":"As the use of newer antibiotics like Linezolid is tremendously increasing due to their efficacy and safety against methicilin resistant staphylococcus aureus and Vancomycin resistant entero-cocci, its rarer side effect like black hairy tongue is often overlooked. Case presentation: A 26 year-old-male, reported with asymptomatic black hairy tongue (BHT) on tenth day after taking Linezolid 600mg twice daily for his left foot infection. His tongue examination was consistent with black hairy tongue. He neither exhibited any predisposing factor nor any history of substance abuse or drug except Linezolid and prompt withdrawal of drug led to complete resolution of BHT on seventh day. Re-challenge test revoked similar response on tenth day. WHO-UMC causality scale showed certain adverse drug reaction and on Naranjo’s adverse drug reaction probability scale score of 10 indicates definite association. Conclusion: This case report is highlighted due to its rarity, self-limiting and reversible condition. The purpose of the paper is to create awareness amongst medical fraternity about Linezolid induced Adverse Drug Reaction.","paper_authors":["R. Raj","R. Raj","J. Nagpal","Raj Kumar"],"paper_publish_year":2016,"publication_journal_name":"Journal of the Medical Sciences","consensus_paper_details_url":"https://consensus.app/papers/linezolid-induced-black-hairy-tongue-uncommon-phenomenon-raj/dd86a2242496501eaecaf92ce38fbcd5/?utm_source=chatgpt","doi":"10.12691/AJMSM-4-4-1","volume":"4","pages":"71-76","search_result_number":6},{"paper_title":"Safety and tolerability of linezolid in children","abstract":"Background. Linezolid, an oxazolidinone, is effective in the treatment of adults and children with community-acquired and nosocomial pneumonia and uncomplicated and complicated skin and skin structure infections (SSSIs), including infections caused by Gram-positive resistant pathogens. Because of the increasing use of linezolid, it is important to review the common adverse events (AEs) associated with its use in children with the use of data from clinical trials. Objective. The safety and tolerability of linezolid in pediatric patients with Gram-positive infections were determined in four pediatric clinical studies. Study I included pediatric patients with community-acquired pneumonia; Study II included otitis media; Study III included SSSIs; and Study IV included complicated SSSIs, nosocomial pneumonia and bacteremia. Methods. Studies I and II had no comparator arm. Study III was randomized and compared linezolid with cefadroxil. Study IV also was randomized and compared linezolid with vancomycin. Patients <12 years of age received linezolid 10 mg/kg; patients age 12 years and older received 600 mg (intravenous/oral). Dosing frequency (two to three times daily) varied depending on age and clinical diagnosis. The primary safety endpoints were AEs, drug-related AEs, serious AEs and selected laboratory tests. Results. In the 4 studies 958 patients were included in the intent-to-treat analysis. In the linezolid vs. cefadroxil study (Study III), the most common AEs in patients treated with linezolid were diarrhea (7.8%), headache (6.5%) and upper respiratory tract infection (3.7%). In the linezolid vs. vancomycin study (Study IV), the most common AEs in the linezolid group were fever (14.1%), diarrhea (10.8%) and vomiting (9.4%). The most common drug-related AEs for linezolid in all 4 studies were diarrhea, vomiting, loose stools and nausea. None of these common AEs or drug-related AEs occurred more frequently in patients treated with linezolid than in those in the comparator group. Conclusions. Linezolid was safe and well-tolerated in pediatric patients with community-acquired pneumonia, otitis media, SSSIs and infections caused by Gram-positive resistant pathogens.","paper_authors":["L. Saiman","J. Goldfarb","S. Kaplan","K. Wible","Barbara Edge-Padbury","J. Bruss"],"paper_publish_year":2003,"publication_journal_name":"The Pediatric Infectious Disease Journal","consensus_paper_details_url":"https://consensus.app/papers/safety-tolerability-children-saiman/c3be68e395bf52b7bd1ab76470b2ae37/?utm_source=chatgpt","doi":"10.1097/01.inf.0000087022.58089.d8","volume":"22","pages":"S193-S200","search_result_number":7},{"paper_title":"Adverse reaction report and retrospective analysis of black hairy tongue caused by linezolid","abstract":"The adverse reaction of Black Hairy Tongue (BHT) caused by linezolid is rare. We reports a case of linezolid-induced BHT, and reviews relevant literatures at home and abroad. It aims to provide a safe and reasonable basis for clinical medication use. A 14-year-old adolescent with pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) developed a rash and pruritus due to Vancomycin. Instead, the patient was given linezolid 600mg q12h in injection during hospitalization and in tablet after discharge. On the 14th day after injection and the second day after oral administration the patient showed BHT without other abnormal taste symptoms. But all the symptoms could be tolerated and he completed the therapy course of linezolid. Tongue symptoms completely disappeared on the 8th day after drug withdrawal. Based on the Karch and Lasagna evaluation methods and the cause-and-effect evaluation methods of the WHO collaborating center for international adverse drug reaction (ADR) monitoring, it is likely that this patient had a BHT caused by linezolid. The mean time of occurrence of BHT was 14.36 days, and the mean time of symptom disappearance was 23.43 days after drug administration. When linezolid is prescribed to patients, especially those with atopy, the patient's tongue should be closely observed and good oral hygiene is recommended.","paper_authors":["S. Luo","Qian Luo","Xing-Lin Gao","Jing Li"],"paper_publish_year":2020,"publication_journal_name":"Respiratory Medicine Case Reports","consensus_paper_details_url":"https://consensus.app/papers/reaction-report-analysis-hairy-tongue-caused-luo/24a550663d0155168b28dd4984922557/?utm_source=chatgpt","doi":"10.1016/j.rmcr.2020.101159","volume":"31","pages":"","search_result_number":8},{"paper_title":"Population Pharmacokinetic and Pharmacodynamic Analysis of Linezolid and a Hematologic Side Effect, Thrombocytopenia, in Japanese Patients","abstract":"ABSTRACT Linezolid is an antimicrobial agent to treat infections by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). While effective, linezolid treatment frequently is associated with hematological side effects, especially thrombocytopenia. However, little is known about the mechanism of this side effect and the exposure-response relationship. The present population pharmacokinetic/pharmacodynamic (PPK/PD) study was undertaken to elucidate the factors that determine linezolid levels, the relationship between exposure to linezolid and a decrease in platelet counts, and appropriate dosage adjustments based on exposure levels. In total, 50 patients (135 plasma samples) were used for the PPK analysis. The PPK analysis revealed that renal function and severe liver cirrhosis (Child Pugh grade C) significantly affect the pharmacokinetics of linezolid according to the equation clearance (liter/h) = 2.85 × (creatinine clearance/60.9)0.618 × 0.472CIR (CIR indicates cirrhosis status; 0 for noncirrhosis, 1 for cirrhosis patients). Using 603 platelet counts from 45 patients, a PPK/PD analysis with a semimechanistic pharmacodynamic model described the relationship between linezolid exposure and platelet counts quantitatively, and the newly constructed model was validated using external data (776 platelet counts from 60 patients). Simulation indicated considerable risks in patients with insufficient renal function (creatinine clearance, ≤30 ml/min) or severe liver cirrhosis. For these patients, a reduced dosage (600 mg/day) would be recommended for sufficient efficacy (area under the concentration-time curve over 24 h in the steady state divided by the MIC, >100) and safety.","paper_authors":["Tomohiro Sasaki","H. Takane","K. Ogawa","S. Isagawa","Takeshi Hirota","S. Higuchi","T. Horii","K. Otsubo","I. Ieiri"],"paper_publish_year":2011,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/population-pharmacokinetic-pharmacodynamic-analysis-sasaki/72c55649d89f5976bc8388279990bb2b/?utm_source=chatgpt","doi":"10.1128/AAC.01185-10","volume":"55","pages":"1867 - 1873","search_result_number":9},{"paper_title":"An uncommon side effect of linezolid: Black hairy tongue","abstract":"Linezolid therapy is known to cause black hairy tongue, which is benign and reversible. A 65‐year‐old diabetic male was on treatment for diabetic nonhealing ulcer involving right foot and sole for the past 6 months. Linezolid was started based on the culture and sensitivity of the pus. Patient developed thrombocytopenia and black hairy tongue after 7 days of the drug regimen. Drug was stopped and patient was advised to maintain good oral hygiene, soft tooth brush for brushing and regular mouth wash with lukewarm water. The black hairy tongue completely resolved within a week after stopping the drug. The taste and foreign body sensation on the tongue while swallowing were also improved. The diabetic wound was treated by starting vancomycin after giving a surgical wound debridement by a general surgeon.","paper_authors":["Shanmugapriyan Sivaraman","Gokul Gomathi Radhakrishnan","Rajesh Manogaran","B. Cheriyan"],"paper_publish_year":2021,"publication_journal_name":"Precision Medical Sciences","consensus_paper_details_url":"https://consensus.app/papers/side-effect-black-hairy-tongue-sivaraman/a8aac6c468885a6bbb241e046658e75c/?utm_source=chatgpt","doi":"10.1002/prm2.12053","volume":"10","pages":"167 - 169","search_result_number":10},{"paper_title":"An uncommon side-effect of linezolid","abstract":"Editor, A 78-year-old woman with a history of deceased donor renal transplant 8 years prior to the presentation was admitted to the hospital with methicillin-resistant enterococcal urinary tract infection. Her long-term immunosuppressant regimen included cyclosporine, mycophenolic acid, and prednisone. She received 4 doses of intravenous vancomycin in the hospital. She remained afebrile without symptoms, and was sent home on oral linezolid for a total of 2 weeks. She presented to the clinic 10 days into her antibiotic regime with black discoloration of her tongue. The dorsal aspect of the tongue was black centrally with surrounding normal pink mucosa (Fig. 1a). The dorsum of the tongue was without any hair-like structures that are seen with black hairy tongue (hyperplastic black filiform papillae). The only new medication administered to her was linezolid on detailed medication list review. The patient’s tongue discoloration improved moderately during the hospital stay and resolved 3 months after the discontinuation of linezolid (Fig. 1b). With the increased incidence of methicillin-resistant staphylococcal infections, the usage of linezolid has increased tremendously in the community. Reversible black discoloration of the tongue and lips has been rarely reported in the literature including in an elderly renal transplant recipient [1]. Tongue discoloration associated with linezolid administration has been reported in comparator-controlled trials, in which the frequency of tongue discoloration was 1.1% (548 patients) in those diagnosed with uncomplicated skin and skin structure infections [2]. However, the exact mechanism of action for the tongue discoloration is unknown. Tongue discoloration was reversible in up to 33.3% of 24 healthy volunteers during a phase I trial; however, the adverse event was associated with consumption of green tea [3].","paper_authors":["V. Marina","R. Kasmani"],"paper_publish_year":2012,"publication_journal_name":"International Urology and Nephrology","consensus_paper_details_url":"https://consensus.app/papers/sideeffect-linezolid-marina/44f7a7d040505c9e8e5df6f3cf1971b5/?utm_source=chatgpt","doi":"10.1007/s11255-011-0005-z","volume":"44","pages":"995-996","search_result_number":11},{"paper_title":"Linezolid-induced inhibition of mitochondrial protein synthesis.","abstract":"BACKGROUND\nLinezolid is an oxazolidinone antibiotic that is increasingly used to treat drug-resistant, gram-positive pathogens. The mechanism of action is inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and lactic acidosis are reported side effects, but the underlying pathophysiological mechanism has not been unravelled.\n\n\nMETHODS\nWe studied mitochondrial ultrastructure, mitochondrial respiratory chain enzyme activity, and mitochondrial DNA (mtDNA) in muscle, liver, and kidney samples obtained from a patient who developed optic neuropathy, encephalopathy, skeletal myopathy, lactic acidosis, and renal failure after prolonged use of linezolid. In addition, we evaluated mtDNA, respiratory chain enzyme activity, and protein amount in muscle and liver samples obtained from experimental animals that received linezolid or placebo.\n\n\nRESULTS\nIn the patient, mitochondrial respiratory chain enzyme activity was decreased in affected tissues, without ultrastructural mitochondrial abnormalities and without mutations or depletion of mtDNA. In the experimental animals, linezolid induced a dose- and time-dependent decrease of the activity of respiratory chain complexes containing mtDNA-encoded subunits and a decreased amount of protein of these complexes, whereas the amount of mtDNA was normal.\n\n\nCONCLUSION\nThese results provide direct evidence that linezolid inhibits mitochondrial protein synthesis with potentially severe clinical consequences. Prolonged courses of linezolid should be avoided if alternative treatment options are available.","paper_authors":["A. D. De Vriese","R. Coster","J. Smet","S. Seneca","A. Lovering","L. Van Haute","L. Vanopdenbosch","Jean-Jacques Martin","C. C. Groote","S. Vandecasteele","J. Boelaert"],"paper_publish_year":2006,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/linezolidinduced-inhibition-protein-synthesis-vriese/1d710de8810e517baf062433e0ebac44/?utm_source=chatgpt","doi":"10.1086/501356","volume":"42 8","pages":"\n 1111-7\n ","search_result_number":12},{"paper_title":"Linezolid in the treatment of multidrug-resistant tuberculosis.","abstract":"BACKGROUND\nLinezolid is a new antibiotic with activity against Mycobacterium tuberculosis in vitro and in animal studies. Several small case series suggest that linezolid is poorly tolerated because of the side effects of anemia/thrombocytopenia and peripheral neuropathy. To characterize our clinical experience with linezolid, the California Department of Public Health Tuberculosis Control Branch's Multidrug-Resistant Tuberculosis (MDR-TB) Service reviewed cases in which the MDR-TB treatment regimens included linezolid therapy.\n\n\nMETHODS\nRecord review was performed for 30 patients treated with linezolid as part of an MDR-TB regimen. Data were collected on clinical and microbiological characteristics, linezolid tolerability, and treatment outcomes. The dosage of linezolid was 600 mg daily. Vitamin B6 at a dosage of 50-100 mg daily was used to mitigate hematologic toxicity.\n\n\nRESULTS\nDuring 2003-2007, 30 patients received linezolid for the treatment of MDR-TB. Patients had isolates resistant to a median of 5 drugs (range, 2-13 drugs). Of the 30 cases, 29 (97%) were pulmonary; of these 29, 21 (72%) had positive results of acid-fast bacilli smear, and 16 (55%) were cavitary. Culture conversion occurred in all pulmonary cases at a median of 7 weeks. At data censure (31 December 2008), 22 (73%) of 30 patients had successfully completed treatment. Five continued to receive treatment. There were no deaths. Three patients had a poor outcome, including 2 defaults and 1 treatment failure. Side effects occurred in 9 patients, including peripheral and optic neuropathy, anemia/thrombocytopenia, rash, and diarrhea. However, only 3 patients stopped linezolid treatment because of side effects.\n\n\nCONCLUSIONS\nLinezolid was well tolerated, had low rates of discontinuation, and may have efficacy in the treatment of MDR-TB.","paper_authors":["G. Schecter","C. Scott","C. Scott","L. True","A. Raftery","J. Flood","S. Mase"],"paper_publish_year":2010,"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-treatment-multidrugresistant-tuberculosis-schecter/6343698ca75c5020b191740d0ccca22a/?utm_source=chatgpt","doi":"10.1086/648675","volume":"50 1","pages":"\n 49-55\n ","search_result_number":13},{"paper_title":"Clinical Population Pharmacokinetics and Toxicodynamics of Linezolid","abstract":"ABSTRACT Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs of <100 ×109/liter. The risk for toxicity did not differ noticeably between 14 and 28 days of therapy and was significantly higher for patients with lower baseline platelet counts. Due to the increased risk of toxicity after longer durations of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h.","paper_authors":["L. Boak","C. Rayner","M. Grayson","D. Paterson","D. Spelman","S. Khumra","B. Capitano","A. Forrest","Jian Li","R. Nation","J. Bulitta"],"paper_publish_year":2014,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/population-pharmacokinetics-toxicodynamics-linezolid-boak/5533f1ad0eda5a8da0be93804089eeb6/?utm_source=chatgpt","doi":"10.1128/AAC.01885-13","volume":"58","pages":"2334 - 2343","search_result_number":14},{"paper_title":"Black tongue associated with linezolid.","abstract":"Darkening of the tongue and oral mucosa is a reaction pattern that can be related to a number of physiologic, metabolic, and toxic disorders, and medications and exogenous substances. Black discoloration of the tongue should be distinguished from black \"hairy\" tongue, which is characterized by hypertrophy of the filiform papillae. We report a case of a 42-year-old man presented with a black discoloration of his tongue during treatment with linezolid for spondylodiscitis. So in conclusion, tongue discoloration is a benign and reversible condition and a probable adverse event associated with linezolid. We present this case to increase clinicians' awareness of a new potential adverse effect of linezolid.","paper_authors":["F. Jover-Díaz","J. Cuadrado-Pastor","Amparo Talents-Bolos","C. Martin-Gonzalez"],"paper_publish_year":2010,"publication_journal_name":"American journal of therapeutics","consensus_paper_details_url":"https://consensus.app/papers/black-tongue-associated-joverdíaz/dd498aebb3cf5648a16d6bcd396320b9/?utm_source=chatgpt","doi":"10.1097/MJT.0b013e3181a59bcd","volume":"17 4","pages":"\n e115-7\n ","search_result_number":15},{"paper_title":"Linezolid-induced black hairy tongue in a patient with multidrug-resistant tuberculosis: A case report","abstract":"The revised World Health Organization guidelines on multidrug-resistant tuberculosis include linezolid in the core drugs group. Consequently, the use of linezolid for patients with multidrug-resistant tuberculosis is increasing. Common adverse events of long-term linezolid use include bone marrow suppression and neuropathies. However, there is limited information on a rare adverse event, black hairy tongue. Here, we report a case of linezolid-induced black hairy tongue in a patient with multidrug-resistant tuberculosis. The etiology, pathogenesis, diagnosis, and treatment of black hairy tongue are also discussed.","paper_authors":["Jaemin Lee","H. Chung","J. Roh","Y. Oh","J. Mok"],"paper_publish_year":2021,"publication_journal_name":"Science Progress","consensus_paper_details_url":"https://consensus.app/papers/linezolidinduced-hairy-tongue-patient-tuberculosis-case-lee/778ed682f4f15d7ca2d54b9779060bd6/?utm_source=chatgpt","doi":"10.1177/00368504211042982","volume":"104","pages":"","search_result_number":16},{"paper_title":"Linezolid induced black hairy tongue","abstract":"Black hairy tongue (BHT) also called as lingua villosa nigra, is a self limiting benign condition characterized by hypertrophy and elongation of filiform papillae of tongue with brown or black discoloration. Smoking, poor oral hygiene, xerostomia, using peroxide containing mouth washes, substance abuse and drugs (steroids, methyldopa, olanzapine, etc) are the predisposing factors. However its occurrence in relation to linezolid ingestion among south Indians has not been reported in PubMed database. Here we report a case, where significant association of linezolid intake with BHT was found in a 10-year-old boy, who was treated with tablet linezolid for post surgical infection of left side radial neck fracture. This case is reported for the rarity of occurrence with linezolid therapy. According to Naranjo adverse drug reaction (ADR) causality scale, the association of BHT due to linezolid in our case was probable.","paper_authors":["G. Balaji","B. Maharani","V. Ravichandran","T. Parthasarathi"],"paper_publish_year":2014,"publication_journal_name":"Indian Journal of Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/linezolid-induced-hairy-tongue-balaji/6c1137b8dbd15fc9a0ddfdd80a5f74da/?utm_source=chatgpt","doi":"10.4103/0253-7613.144942","volume":"46","pages":"653 - 654","search_result_number":17},{"paper_title":"Linezolid-induced black hairy tongue in a patient treated for idiopathic granulomatous mastitis: a case report","abstract":"Introduction and importance: Linezolid-induced black hairy tongue (BHT) is a highly scarce adverse event of linezolid therapy. To date, there are very few reported cases in contemporary literature. The onset and mechanism of BHT are also not well understood. Case report: In this article, the authors report a case of BHT in a 28-year-old female following 5 days of therapy with linezolid. The patient recovered well within few days of discontinuation of the drug and maintaining oral hygeine. Patient reassurance and counselling was integral to the management. Discussion and conclusion: This case report and review depict a rare adverse effect of linezolid and discuss its clinical implications aiding healthcare professionals in an early diagnosis and cromulent management strategy. The authors also present a compilation of previously reported literature on linezolid-induced BHT to support the discussion.","paper_authors":["Yashendra Sethi","Inderbir Padda","M. Fulton","Oroshay Kaiwan","H. Chopra","Talha Bin Emran"],"paper_publish_year":2023,"publication_journal_name":"Annals of Medicine and Surgery","consensus_paper_details_url":"https://consensus.app/papers/linezolidinduced-hairy-tongue-patient-treated-mastitis-sethi/4fd9db43ab4f5ba4a2c6aa9dfd4f1094/?utm_source=chatgpt","doi":"10.1097/MS9.0000000000000834","volume":"85","pages":"3090 - 3093","search_result_number":18},{"paper_title":"Impact of prolonged treatment with linezolid on the human gut flora.","abstract":"A 79-year-old male was treated for 6 months with linezolid for prosthetic knee joint osteomyelitis. At the end of this 6-month period, quantitative stool cultures revealed partial loss of the normal gut flora and concomitant colonization by opportunistic pathogens such as Pseudomonas aeruginosa and other Gram-negatives. Follow-up cultures at 6 weeks after antibiotic discontinuation revealed restoration of the normal flora. Prolonged linezolid administration may lead to replacement of normal gut flora by pathogenic microorganisms, which under certain conditions might cause systemic infections.","paper_authors":["D. Kofteridis","P. Malliotakis","S. Maraki","M. Christofaki","G. Samonis"],"paper_publish_year":2009,"publication_journal_name":"International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/impact-prolonged-treatment-flora-kofteridis/634506c06232519795c0e8188aaf02f2/?utm_source=chatgpt","doi":"10.1016/j.ijid.2009.02.001","volume":"13 5","pages":"\n e313-5\n ","search_result_number":19},{"paper_title":"Acute Onset Lactic Acidosis Secondary to Linezolid","abstract":"Linezolid has been the mainstay of treatment for multidrug-resistant Gram-positive bacteria. Common adverse effects with linezolid include diarrhea, nausea, headache, and bone marrow suppression. A less common and understudied side effect is lactic acidosis. This study describes a 19-year-old man with linezolid-induced lactic acidosis (LILA). The patient was admitted for the management of acute decompensated systolic heart failure, which improved on guideline-directed medication therapy (GDMT). During hospitalization, he developed an erythematous weeping cellulitis infection of his right lower extremity and was started on linezolid 600 mg every 12 hours with wound and blood cultures collected. After one day of treatment with linezolid, lactic acid levels acutely increased from 1.8 mmol/L to 5 mmol/L without any other interventions. Suspecting possible LILA, linezolid was transitioned to cephalexin with a reduction of lactic acid to 2.4 mmol/L, one day following linezolid cessation. After two days of linezolid cessation, lactic acid levels decreased to 1.9 mmol/L. Lactic acidosis can have profound hemodynamic consequences for patients, including death. A meta-analysis study of 35 articles with 47 patients (28 males, 18 females, and one non-binary) was done, which found a 25.5% mortality rate associated with LILA. Due to this high mortality, having a greater understanding of the associated risk factors with LILA is very important. This case study aims to inform clinicians of the potential harmful side effects associated with linezolid, as well as the understudied risk factors involved in LILA that are needed to prevent its occurrence.","paper_authors":["Tara Kronen","Avni Agrawal","P. Reddy"],"paper_publish_year":2023,"publication_journal_name":"Cureus","consensus_paper_details_url":"https://consensus.app/papers/acute-onset-lactic-acidosis-secondary-linezolid-kronen/8ba61c85abc1592c8d186da19b791261/?utm_source=chatgpt","doi":"10.7759/cureus.35891","volume":"15","pages":"","search_result_number":20}]} --- **ChatGPT:** Black stool as a side effect of linezolid can indicate a gastrointestinal issue, possibly involving bleeding. This may arise from the medication's impact on the gastrointestinal tract, although it is not a commonly reported side effect. ### Evidence: 1. Linezolid is generally well-tolerated, but adverse effects include gastrointestinal issues like diarrhea and nausea (French, 2003) [(French, 2003)](https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt). 2. Black stool might also be confused with a condition called black hairy tongue, a rare side effect of linezolid. This condition is benign and reversible, characterized by a black or dark brown discoloration of the tongue (Mahadi & Majumder, 2022) [(Mahadi & Majumder, 2022)](https://consensus.app/papers/black‐brown-hairy-tongue-effect-linezolid-mahadi/c3397e72ede05667831fdc98be63d44c/?utm_source=chatgpt). 3. Similar findings of linezolid-induced black hairy tongue have been reported in multiple cases, where the discoloration resolves upon discontinuation of the drug (Mishra, 2023; Jain et al., 2017) [(Mishra, 2023)](https://consensus.app/papers/linezolidassociated-black-tongue-rare-adverse-drug-mishra/468eb759b157543c9d7ab10fa27e6aab/?utm_source=chatgpt) [(Jain et al., 2017)](https://consensus.app/papers/black-discoloration-hairy-tongue-side-effect-jain/144908ad66925d2f9727fb5f2265706d/?utm_source=chatgpt). ### Conclusion: Black stool as a side effect of linezolid suggests a possible gastrointestinal disturbance and may require medical evaluation to rule out bleeding or other serious conditions. Additionally, it could be related to a benign condition known as black hairy tongue, which is a reversible side effect of linezolid. 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:** Yes I have a streak of black on my tongue --- **ChatGPT:** A streak of black on your tongue could be indicative of a condition known as Black Hairy Tongue (BHT), which is a benign and reversible condition. This condition can occur as a side effect of medications, including linezolid. ### Evidence: 1. **Black Hairy Tongue (BHT):** This condition is characterized by a black or brown discoloration of the tongue due to hypertrophy and elongation of the filiform papillae. Linezolid has been associated with this rare side effect. In most cases, the condition is self-limiting and resolves after discontinuing the medication and maintaining good oral hygiene [(Mahadi & Majumder, 2022)](https://consensus.app/papers/black‐brown-hairy-tongue-effect-linezolid-mahadi/c3397e72ede05667831fdc98be63d44c/?utm_source=chatgpt) [(Jain et al., 2017)](https://consensus.app/papers/black-discoloration-hairy-tongue-side-effect-jain/144908ad66925d2f9727fb5f2265706d/?utm_source=chatgpt). 2. **Clinical Cases:** Several reports highlight that the black discoloration of the tongue due to linezolid usually resolves after the cessation of the drug and with the implementation of good oral hygiene practices [(Mishra, 2023)](https://consensus.app/papers/linezolidassociated-black-tongue-rare-adverse-drug-mishra/468eb759b157543c9d7ab10fa27e6aab/?utm_source=chatgpt) [(Aijazi & Abdulla, 2014)](https://consensus.app/papers/linezolid-induced-hairy-tongue-side-effect-aijazi/c4ff636f964d55f0ae1c80cdcd138887/?utm_source=chatgpt). ### Recommendations: - **Oral Hygiene:** Maintain good oral hygiene by brushing your teeth and tongue regularly with a soft toothbrush and using mouthwash. - **Medical Consultation:** Consult your healthcare provider to discuss the symptoms and consider the possibility of discontinuing or switching the medication if necessary. ### Conclusion: The black streak on your tongue is likely a benign and reversible side effect of linezolid. It is advisable to maintain good oral hygiene and consult your healthcare provider for further management. 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:** I've taken Linezolid for 8 of the 10 days. do you think it's best to discontinue now or complete the next 2 days --- **ChatGPT:** It's crucial to follow medical advice regarding the discontinuation or completion of antibiotic therapy. Linezolid is prescribed to treat serious infections, and stopping it prematurely may result in incomplete treatment of the infection, potentially leading to antibiotic resistance. However, given the occurrence of the black streak on your tongue, it is important to address this side effect with your healthcare provider promptly. Here are some considerations: ### Factors to Consider: 1. **Severity of Side Effect:** While black hairy tongue is generally benign and reversible, it can be distressing and might indicate a need for an adjustment in your medication. 2. **Infection Status:** Ensure the primary infection for which linezolid was prescribed is adequately treated to avoid relapse or resistance. 3. **Professional Guidance:** Your healthcare provider can assess the risk-benefit ratio of continuing versus stopping the medication. ### Recommendations: - **Contact Your Healthcare Provider:** Explain the side effect and seek their advice on whether to continue the remaining 2 days of treatment or if an alternative plan is needed. - **Oral Hygiene:** Continue practicing good oral hygiene, which may help alleviate the symptoms of black hairy tongue. ### Conclusion: The decision to continue or discontinue linezolid should be made in consultation with your healthcare provider, who can consider your specific medical situation and the side effects you are experiencing. 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:** It'll take a couple of days to get the primary care physician to respond and I only have 2 days of meds left. --- **ChatGPT:** Given the situation, here are some steps you can take: ### Immediate Actions: 1. **Contact a Healthcare Provider Promptly:** Even if your primary care physician is unavailable, consider reaching out to an urgent care clinic or a pharmacist. They can provide immediate guidance based on your symptoms and the medication you are taking. 2. **Monitor Symptoms:** Keep a close watch on any additional symptoms that may develop. If you experience any severe reactions, such as difficulty breathing, severe gastrointestinal issues, or significant changes in your health, seek emergency medical attention immediately. ### Options to Consider: 1. **Continue the Medication:** If the black streak on your tongue is the only symptom and you are otherwise feeling well, you might consider completing the course of linezolid as this can ensure the infection is fully treated. However, this should ideally be confirmed by a healthcare professional. 2. **Oral Hygiene:** Maintain good oral hygiene by brushing your teeth and tongue gently and using a mouthwash to manage the black discoloration. 3. **Alternative Contact:** If you can, contact a different healthcare provider or a telemedicine service for quicker advice. ### Final Recommendation: - **Seek Professional Guidance:** If you cannot get immediate advice from your primary care physician, an urgent care clinic, pharmacist, or telemedicine service can provide you with the necessary guidance on whether to complete the medication or stop it. Your health and safety are the top priorities. It is generally better to complete the prescribed antibiotic course to ensure the infection is fully treated, but this decision should be guided by a healthcare professional given the side effects you are experiencing. 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:** What is the normal prescription duration for Linezolid 600 mg adult male 69 yrs --- **ChatGPT:** ```json {"query": "normal prescription duration for Linezolid 600 mg adult male"} ``` --- **[Tool]:** {"items":[{"paper_title":"Safety and tolerability of linezolid.","abstract":"Clinical trials have shown that linezolid (600 mg twice daily in adults) is safe and generally well tolerated for up to 28 days. Drug-related adverse events, which are typically mild to moderate in intensity and of limited duration, include diarrhoea, nausea and headache in adults, and diarrhoea, loose stools and vomiting in children. Clostridium difficile-related complications with linezolid are uncommon. Linezolid is a weak, reversible monoamine oxidase inhibitor: foods containing high concentrations of tyramine should be avoided, and linezolid should be used with caution in patients taking adrenergic or serotonergic agents or in those with uncontrolled hypertension. In the majority of patients, linezolid has minimal adverse effects on blood chemistry or haematology. There have been case reports of reversible thrombocytopenia, anaemia and neutropenia associated with linezolid therapy. In Phase III studies, 2.4% of patients treated with linezolid and 1.5% of patients treated with comparator drugs developed reversible thrombocytopenia (P = 0.066), but there was no evidence of an increased risk of agranulocytosis, aplastic anaemia or other irreversible blood dyscrasias. Reduced platelet counts were associated with linezolid treatment for >/=2 weeks; complete blood counts should be monitored weekly in patients receiving linezolid for more than 14 days and treatment should be discontinued if there is evidence of myelosuppression.","paper_authors":["G. French"],"paper_publish_year":2003,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt","doi":"10.1093/JAC/DKG253","volume":"51 Suppl 2","pages":"\n ii45-53\n ","search_result_number":1},{"paper_title":"Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA).","abstract":"We compared the health outcomes in patients treated with linezolid or vancomycin for complicated skin and soft tissue infections (cSSTIs). This analysis is part of a randomised, open-label, multinational trial involving 1200 adult patients hospitalised with cSSTIs due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects received linezolid 600 mg intravenous (i.v.) or oral, or vancomycin 1g i.v. every 12 h. A test-of-cure was assessed at 7 days post therapy. Compared with vancomycin, linezolid treatment was associated with significantly shorter length of stay (all P < 0.01), decreased i.v. antibiotic treatment duration (all P < 0.0001) and higher discharge rates (all P < 0.05). Thus, linezolid has the potential to reduce medical resource use for the treatment of cSSTIs.","paper_authors":["K. Itani","J. Weigelt","Jim Z. Li","S. Duttagupta"],"paper_publish_year":2005,"publication_journal_name":"International journal of antimicrobial agents","consensus_paper_details_url":"https://consensus.app/papers/reduces-length-duration-treatment-compared-vancomycin-itani/4180edd4a4025a34acef2a30107c9c57/?utm_source=chatgpt","doi":"10.1016/J.IJANTIMICAG.2005.09.003","volume":"26 6","pages":"\n 442-8\n ","search_result_number":2},{"paper_title":"Serotonin Toxicity Associated with Concomitant Use of Linezolid","abstract":"OBJECTIVE: To report 2 cases of serotonin toxicity (ST) associated with concomitant use of linezolid and serotonergic drugs and review previously published case reports. CASE SUMMARIES: Case 1. A 38-year-old white female with cystic fibrosis treated with venlafaxine 300 mg/day for one year was prescribed linezolid 600 mg intravenously every 12 hours for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pulmonary infection. She displayed symptoms of ST 8 days after the introduction of linezolid. The venlafaxine dosage was decreased to 150 mg/day, and symptoms gradually abated over 36 hours. Case 2. A 37-year-old male with multiple myeloma received citalopram 40 mg/day and trazodone 150 mg/day for anxiety-related disorders. Linezolid treatment with 600 mg orally twice daily was instituted for MRSA cellulitis. The following day, the patient developed anxiety, panic attacks, tremors, tachycardia, and hypertension that persisted throughout linezolid treatment. Symptoms finally waned 5 days after linezolid treatment was stopped. DISCUSSION: The symptoms observed in our patients were consistent with Sternbach's criteria for ST. A review of published case reports showed a short time to onset of symptoms following the introduction of linezolid, generally within 1–3 days. Also of note is the use of relatively high dosages of serotonergic drugs. Use of the Naranjo probability scale indicated a possible relationship between the use of linezolid and the occurrence of ST in both cases. CONCLUSIONS: Clinicians should pay special attention to patients treated with serotonergic drugs, especially those receiving dosages in the higher end of the normal range who are prescribed linezolid, and consider tapering or reducing the dosage of serotonergic drugs for the duration of antibiotic therapy.","paper_authors":["L. Bergeron","M. Boulé","S. Perreault"],"paper_publish_year":2005,"publication_journal_name":"Annals of Pharmacotherapy","consensus_paper_details_url":"https://consensus.app/papers/serotonin-toxicity-associated-concomitant-linezolid-bergeron/9448fe950db45b0bbbda698b85826d44/?utm_source=chatgpt","doi":"10.1345/aph.1E523","volume":"39","pages":"956 - 961","search_result_number":3},{"paper_title":"Population Pharmacokinetics of Linezolid in Patients Treated in a Compassionate-Use Program","abstract":"ABSTRACT Data obtained from 318 adult patients treated under the linezolid compassionate-use protocol were used to develop a population model of the pharmacokinetics of intravenous and oral linezolid. All of the patients received 600 mg of linezolid every 12 h, intravenously and/or orally. Blood samples (2 to 10 per patient; median, 4) were obtained and assayed for linezolid by high-performance liquid chromatography. These data and patient covariates were modeled by iterative two-stage analysis, and model discrimination was done by Akaike's information criterion. Of the patient covariates considered (age, sex, ideal body weight, baseline serum albumin, hepatic or renal dysfunction, underlying malignancy, organ transplantation, surgical status, global severity of illness, site of infection, route of administration, and location of care [intensive-care unit, general floor, or outpatient]), only normalized creatinine clearance (CLCR) and body weight explained significant portions of the variance and were incorporated into the pharmacokinetic model. The final model included central and peripheral compartments with parallel capacity-limited (nonrenal) and first-order (renal [CLR]) clearances. Volumes and clearances were normalized to the ideal body weight, and CLR was modeled as proportional to CLCR. Compared to previously studied adult volunteers, intrinsic clearance was ∼60% higher and the maximum rate of metabolism was twice as high in these debilitated patients, resulting in lower area under the time-concentration curve (AUC) values (P < 0.001). The derived 24-h AUC, averaged over the first 7 days of treatment, ranged between 57 and 871 (median, 191) μg/ml · 24 h. Despite these variations, linezolid provided high rates of clinical cure, as well as microbiological success, in the patients treated in the compassionate-use program. The mechanism(s) of these pharmacokinetic differences is unknown and requires further mechanistic study.","paper_authors":["A. Meagher","A. Forrest","C. Rayner","M. Birmingham","Jerome J. Schentag"],"paper_publish_year":2003,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/population-pharmacokinetics-patients-treated-meagher/5edb81aa308c58aa93d82ea6c639e722/?utm_source=chatgpt","doi":"10.1128/AAC.47.2.548-553.2003","volume":"47","pages":"548 - 553","search_result_number":4},{"paper_title":"Pharmacokinetic/pharmacodynamic research on three different infusion time regimens of linezolid in healthy Chinese volunteers.","abstract":"OBJECTIVE\nTo evaluate the pharmacokinetic and pharmacodynamic (PK/PD) results of three different infusion time regimens of single doses of 600 mg linezolid in healthy Han Chinese volunteers.\n\n\nMETHODS\nWe conducted a clinical trial involving 6 male and 6 female healthy Chinese volunteers. They were randomized to receive intravenous linezolid infusion (600 mg/0.5 hours, 600 mg/2 hours, or 600 mg/4 hours) in three periods with washout periods of 7 days between each dosage. Serum linezolid concentration was measured in each subject at pre-dose (at 0 hours) until 24 hours after each dose. The ratio of the area under the serum concentration-time curve (AUC) to the minimum inhibitory concentration (MIC), AUC/MIC, was adopted as the major relevant parameter. Monte Carlo simulation was used to evaluate the probability of target attainment (PTA) of these three linezolid regimens.\n\n\nRESULTS\nOne subject in 600 mg/0.5 hours regimen complained of mild pain at the injection site. No significant difference was found in pharmacokinetic parameters among the three different infusion regimens. When AUC/MIC was applied as parameter, PTA of 4 hours infusion regimen was much lower than that of the 0.5 hours and 2 hours infusion regimens (55.65% vs. 74.91% and 72.03%, respectively). Especially at higher MIC (2 μg/mL), the PTAs of the 0.5 hours and 2 hours infusion regimens decreased to 57.2% and 50.1%, respectively, while that of the 4 hours infusion regimen dropped sharply to only 25.95%. When T>MIC was applied as a parameter, PTA of the 0.5 hours regimen was higher than 90%, while the 2 hours and 4 hours regimens remained 100%.\n\n\nCONCLUSION\nOur findings suggest that 2 hours infusion of linezolid at a fixed dose (600 mg) regimen is appropriate to achieve the safety and efficacy against MRSA-caused infections in Chinese adults.","paper_authors":["Yun Cai","N. Bai","Xu Liu","B. Liang","Jin Wang","Rui Wang"],"paper_publish_year":2015,"publication_journal_name":"International journal of clinical pharmacology and therapeutics","consensus_paper_details_url":"https://consensus.app/papers/pharmacokineticpharmacodynamic-research-three-cai/fa92ea2a1efd528c8f35e73e4570570a/?utm_source=chatgpt","doi":"10.5414/CP202317","volume":"53 9","pages":"\n 765-71\n ","search_result_number":5},{"paper_title":"Intrapulmonary Pharmacokinetics of Linezolid","abstract":"ABSTRACT In this study, our objective was to determine the steady-state intrapulmonary concentrations and pharmacokinetic parameters of orally administered linezolid in healthy volunteers. Linezolid (600 mg every 12 h for a total of five doses) was administered orally to 25 healthy adult male subjects. Each subgroup contained five subjects, who underwent bronchoscopy and bronchoalveolar lavage (BAL) 4, 8, 12, 24, or 48 h after administration of the last dose. Blood was obtained for drug assay prior to administration of the first dose and fifth dose and at the completion of bronchoscopy and BAL. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method, and the total number of alveolar cells (AC) was counted in a hemocytometer after cytocentrifugation. Linezolid was measured in plasma by a high-pressure liquid chromatography (HPLC) technique and in BAL specimens and AC by a combined HPLC-mass spectrometry technique. Areas under the concentration-time curves (AUCs) for linezolid in plasma, ELF, and AC were derived by noncompartmental analysis. Half-lives for linezolid in plasma, ELF, and AC were calculated from the elimination rate constants derived from a monoexponential fit of the means of the observed concentrations at each time point. Concentrations (means ± standard deviations) in plasma, ELF, and AC, respectively, were 7.3 ± 4.9, 64.3 ± 33.1, and 2.2 ± 0.6 μg/ml at the 4-h BAL time point and 7.6 ± 1.7, 24.3 ± 13.3, and 1.4 ± 1.3 μg/ml at the 12-h BAL time point. Linezolid concentrations in plasma, ELF, and AC declined monoexponentially, with half-lives of 6.9, 7.0, and 5.7 h, respectively. For a MIC of 4, the 12-h plasma AUC/MIC and maximum concentration/MIC ratios were 34.6 and 3.9, respectively, and the percentage of time the drug remained above the MIC for the 12-h dosing interval was 100%; the corresponding ratios in ELF were 120 and 16.1, respectively, and the percentage of time the drug remained above the MIC was 100%. The long plasma and intrapulmonary linezolid half-lives and the percentage of time spent above the MIC of 100% of the dosing interval provide a pharmacokinetic rationale for drug administration every 12 h and indicate that linezolid is likely to be an effective agent for the treatment of pulmonary infections.","paper_authors":["J. Conte","J. Golden","J. Kipps","E. Zurlinden"],"paper_publish_year":2002,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/pharmacokinetics-conte/c8e39520dd9a5d9f84540849f9904ca9/?utm_source=chatgpt","doi":"10.1128/AAC.46.5.1475-1480.2002","volume":"46","pages":"1475 - 1480","search_result_number":6},{"paper_title":"Case of Suboptimal Linezolid Exposure: Is There a Role for Pharmacogenetics?","abstract":"To the Editor: Sir, the recommended dose of linezolid for adults is 600 mg twice daily irrespective of age, gender, and presence of hepatic and/or renal insufficiency or drug–drug interactions.1 However, current evidence indicates that drug exposure is extremely variable in a wide range of patients and is significantly affected by most of the abovementioned covariates.1 Experimental studies and retrospective analysis have shown that the ratio of steady-state area under the concentration-versus-time curve over 24 hours (AUC) to the minimum inhibitory concentration is the PK/PD parameter best correlated with linezolid efficacy.1 As monitoring AUC is expensive, therapeutic drug monitoring (TDM) of linezolid plasma trough concentrations has been proposed to maximize efficacy and limit adverse events based on the reported linear relationship between linezolid trough plasma concentrations and drug AUC.1 To balance linezolid efficacy and toxicity, target trough linezolid concentrations of 2–8 mg/L have been proposed.1 We present a case in which optimal linezolid exposure could not be maintained despite TDM. A 36-year-old woman with normal hepatic (AST 18 6 0.6 U/L; ALT 26 6 0.6 U/L) and renal function (serum creatinine 0.5 6 0.09 mg/dL) started linezolid therapy at 600 mg twice daily as an intravenous infusion for meningoencephalitis in November 2018. The patient was not concomitantly administered agents affecting linezolid exposure. A first trough blood sample (collected 12 hours after the evening drug dose and just before morning drug intake) was collected 11 days after therapy. Linezolid TDM was performed using a validated method routinely used at our laboratory. A trough concentration of 1.2 mg/L (therapeutic range adopted in our center: 2–8 mg/L) was confirmed; the linezolid dose was increased to 600 mg every 8 hours for optimal exposure. Four and 8 days after altering the drug dosage, concentrations of 8.3 and 8.2 mg/L, respectively, were reported. As linezolid trough concentrations exceeded the upper therapeutic threshold and the patient demonstrated mild thrombocytopenia, the dose was reduced to 600 mg twice daily. Additional monitoring was performed 3 and 6 days after dose reduction, revealing subtherapeutic linezolid concentrations (1.0 and 0.8 mg/L, respectively). Hence, the dose was switched to 600 mg 3 times a day. The dose increment led to significant increase in linezolid trough concentrations (7.1 and 11.0 mg/L after 3 and 6 days from the new linezolid dose change, Fig. 1) associated with a further reduction in the platelet count. Given the observed variability and the difficulty in maintaining trough concentrations within the therapeutic range, 600 mg was administered twice daily, with 600 mg 3 times every other day. Three days later, linezolid plasma concentrations were within the therapeutic range (6.0 mg/L). This trend was confirmed (Fig. 1), and linezolid was discontinued at the end of January 2019 following bacterial infection resolution. To clarify the observed nonlinear linezolid pharmacokinetics, a blood sample was collected for pharmacogenetic analysis after obtaining informed written consent. We analyzed the main functional variants mapped in ABCB1 (c.3435C.T, rs1045642; c.2677 G.T/ A, rs2032582; c.1236C.T, rs1128503) and CYP3A4/5 (CYP3A4*22C . T, rs35599367; CYP3A5*3A . G, rs776746) genes. The patient was categorized as a poor CYP3A metabolizer (CYP3A4*22 CT; CYP3A5*3 GG) and as 1236T-2677 T-3435T haplotype carrier for ABCB1 polymorphisms. We present an unusual case of nonlinear pharmacokinetic behavior of linezolid, where the standard dose showed very low concentrations and a higher dose resulted in supratherapeutic drug concentrations and poor drug tolerability despite strict TDM. The observed variability cannot be attributed to factors known to significantly influence linezolid concentrations: the patient was young, had no renal insufficiency, and was not concomitantly prescribed any drug interacting with linezolid. Therefore, we proposed that the observed atypical pharmacokinetics could be due to a genetically based alteration in linezolid metabolism. Linezolid undergoes in vivo biotransformation, forming lactam and lactone from the morpholine ring due to the presence of cyclic ether and amine groups.2 Enzymatic hydroxylation at the a carbon of the morpholine’s cyclic ether yields an unstable hemiacetal intermediate, oxidizing to a stable open-ring hydroxy acid and undergoing nonenzymatic lactonization, whereas enzymatic hydroxylation of the orthocarbon of nitrogen by P450 s yields different metabolites, one of which is the lactam compound.2 Cytochrome P450 enzymes are not responsible for linezolid metabolism.2 However, the metabolism of gefitinib, with the same morpholine ring as linezolid, is mediated by CYP3A. Some drug–drug interactions between linezolid and rifampicin, clarithromycin, levothyroxine, omeprazole, amiodarone, and amlodipine have been reported.1 Furthermore, a role for P-glycoprotein induction or inhibition in drug interactions has been hypothesized; however, no significant differences in the AUC in patients with ABCB1 polymorphisms were observed,3 and clarithromycin and rifampicin are cytochrome P450 3A4 inhibitor/inducers, respectively. Hence, a role of CYP3A4 could not be excluded.3 In plasma, linezolid is a major circulating compound, whereas anionic metabolites are major in the urine. The high ratio of linezolid to metabolites in This study was performed as part of our routine work and was not specifically funded. The authors declare no conflict of interest. Ther Drug Monit Volume 42, Number 2, April 2020 Letters to the Editor","paper_authors":["S. Baldelli","C. Montrasio","S. Cheli","Ottavia Viganò","T. Bini","M. Egidi","D. Cattaneo"],"paper_publish_year":2020,"publication_journal_name":"Therapeutic Drug Monitoring","consensus_paper_details_url":"https://consensus.app/papers/case-suboptimal-linezolid-exposure-there-role-baldelli/e80aaf0e95335d14a0b0ebe4f1cd9533/?utm_source=chatgpt","doi":"10.1097/FTD.0000000000000728","volume":"","pages":"","search_result_number":7},{"paper_title":"Thrombocytopenia induced by linezolid in three patients","abstract":"Three male patients,aged 46~91 years,received respectively an IV infusion of linezolid 600 mg twice daily for infections.Their platelet counts were normal before linezolid administration.All of them developed thrombocytopenia after 3~17 days of therapy.Platelet counts were 95×109/L,74×109/L,and 86×109/L,respectively.Linezolid was stopped and switched to imipenem-cilastatin sodium,vancomycin,and meropenem;and other treatments were unchanged.The level of platelet returned to within normal range.","paper_authors":["Pla Militar"],"paper_publish_year":2010,"publication_journal_name":"Adverse Drug Reactions Journal","consensus_paper_details_url":"https://consensus.app/papers/thrombocytopenia-induced-three-patients-militar/ccfdc4b21c2c578aaab2e0a305053dad/?utm_source=chatgpt","doi":"","volume":"","pages":"","search_result_number":8},{"paper_title":"[Use of linezolid for the treatment of lung infections in adults with cystic fibrosis].","abstract":"INTRODUCTION\nLinezolid, a new antistaphylococcal agent for oral or intravenous administration is active against Staphylococcus aureus with limited sensitivity to glycopeptides. The purpose of the present work was to compare data in the literature with practical clinical experience with the use of linezolid for lung infections in adult cystic fibrosis patients with the objective of developing local guidelines for use.\n\n\nMATERIAL AND METHODS\nThis retrospective clinical study was conducted in the adult pneumology department of a university hospital.\n\n\nRESULTS\nThe main clinical signs leading to prescription of linezolid were aggravating cough, bronchial obstruction, and exercise-induced fatigue. Among 42 cystic fibrosis patients, six aged 24+/-3 years were given 22 treatments of linezolid. Two patients were given the drug once and the others 2, 4, 5, and 9 times, 600 mg b.i.d. Mean duration of treatment with linezolid was 16+/-5 days. Among the six patients, two presented meti-R S. aureus infection. For twelve cases, clinical improvement was observed; and in two others the situation worsened leading to interruption of linezolid.\n\n\nCONCLUSIONS\nThere are few reports in the literature on use of linezolid in cystic fibrosis patients. Writing internal guidelines for our department has enabled standardized use: 600 mg b.i.d. p.o. for 14 days as second-line treatment for bronchial exacerbation of S. aureus infection.","paper_authors":["D. Betton","A. Gairard-Dory","R. Kessler","F. Jehl","V. Rosner","E. Weitzenblum","L. Beretz"],"paper_publish_year":2006,"publication_journal_name":"Revue de pneumologie clinique","consensus_paper_details_url":"https://consensus.app/papers/treatment-lung-infections-adults-fibrosis-betton/a633d3e7bf0152aba02d1b01e341de46/?utm_source=chatgpt","doi":"","volume":"62 6 Pt 1","pages":"\n 374-8\n ","search_result_number":9},{"paper_title":"Tolerance of single dosage of linezolid with different intravenous infusion speed in Chinese healthy volunteers","abstract":"Objective To evaluate the safety and tolerance of single dosage of linezolid with different intravenous infusion speed in Chinese healthy volunteers.Method Twelve healthy volunteers(six males and six females) were chosen and crossover in three groups including 600 mg/0.5 h,600 mg/2 h and 600 mg/4 h.Subjects have electrocardiogram,urine and blood biochemical parameters and the routine blood test on the day before medication,6 hours after medication and the third day after medication.Subjects were observed and recorded vital sighs and adverse events during the trail.Clinical data should undertake one-factor analysis of variance.Results In any groups,the clinical symptoms,vital signs and index of laboratory examination were in normal range.There were no severe adverse events,and no adverse events related to the drug.The data of Hb,RBC and HCT in 6 hours after medication are significantly lower than the day before medication.Conclusion Single dosage of linezolid speed in 600 mg/0.5 h,600 mg/2 h and 600 mg/4 h are safe and tolerable in Chinese healthy volunteers.","paper_authors":["Liang Beibei"],"paper_publish_year":2011,"publication_journal_name":"The Chinese Journal of Clinical Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/tolerance-dosage-infusion-speed-chinese-volunteers-beibei/412e56e7988c5e1d8b3bfa32da766442/?utm_source=chatgpt","doi":"","volume":"","pages":"","search_result_number":10},{"paper_title":"Case Report: Linezolid Optic Neuropathy and Proposed Evidenced-based Screening Recommendation.","abstract":"SIGNIFICANCE\nThis case illustrates a novel screening protocol for linezolid-induced toxic optic neuropathy.\n\n\nPURPOSE\nTo present a case report and analysis of linezolid-induced optic neuropathies in adult patients to develop screening recommendations.\n\n\nCASE REPORT\nA case report of optic neuropathy from extended use of linezolid illustrates its potential effects on vision. We conduct a retrospective analysis of 39 reported cases to derive a recommended screening protocol for linezolid-induced toxic optic neuropathy in adult patients. Of 39 reported adult cases, 32 presented with optic neuropathy within 90 to 365 days of treatment. Within this subset, the duration of linezolid dosage to first symptoms is 235 ± 71 days. Seven outliers either experienced optic neuropathy within the first 28 days or between 600 and 1125 days. Of the 33 cases that quantified visual recovery, 30 reported final binocular visual acuity equivalent to 20/40 or better when the medication was discontinued from 0 to 268 days after symptom onset. Recovery potential was reported over a period of 2 weeks to approximately 6 months after cessation. To evaluate the effect of cumulative dose, the data were separated into patients taking 600 mg twice daily and those at 600 mg once daily. At the higher dosage, a mean of 180 ± 96 days with a mean cumulative dosage of 216 ± 115 g was noted at first symptom, whereas at lower dosage, a mean of 201 ± 102 days was noted with a mean cumulative dose of 138 ± 69 g.\n\n\nCONCLUSIONS\nWe recommend screening adult patients within 1 month after initiating linezolid, followed by a subsequent evaluation every 30 to 60 days beginning 3 months from initiation. Substantial visual recovery is reported when linezolid is discontinued. Toxicity appears to be correlated to duration of treatment, rather than cumulative dose.","paper_authors":["S. Dempsey","A. Sickman","W. Slagle"],"paper_publish_year":2018,"publication_journal_name":"Optometry and Vision Science","consensus_paper_details_url":"https://consensus.app/papers/case-report-linezolid-optic-neuropathy-proposed-dempsey/a43901cb59075f9383393837dd3b8709/?utm_source=chatgpt","doi":"10.1097/OPX.0000000000001216","volume":"","pages":"","search_result_number":11},{"paper_title":"Probable linezolid-induced pancytopenia.","abstract":"A 75-year-old male outpatient with cardiac disease, diabetes, chronic renal insufficiency and iron deficiency anemia was prescribed linezolid 600 mg twice daily for a methicillin-resistant Staphylococcus aureus diabetic foot osteomyelitis. After one week, his blood counts were consistent with baseline values. The patient failed to return for subsequent blood work. On day 26, he was admitted to hospital with acute renal failure secondary to dehydration, and was found to be pancytopenic (erythrocytes 2.5x10(12)/L, leukocytes 2.9x10(9)/L, platelets 59x10(9)/L, hemoglobin 71 g/L). The patient was transfused, and linezolid was discontinued. His blood counts improved over the week and remained at baseline two months later.The patient's decline in blood counts from baseline levels met previously established criteria for clinical significance. Application of the Naranjo scale indicated a probable relationship between pancytopenia and linezolid.Clinicians should be aware of this rare effect with linezolid, and prospectively identify patients at risk and emphasize weekly hematological monitoring.","paper_authors":["Nita Lakhani","W. Thompson","A. Bombassaro"],"paper_publish_year":2005,"publication_journal_name":"The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale","consensus_paper_details_url":"https://consensus.app/papers/linezolidinduced-pancytopenia-lakhani/601d1b6ae2c759e4bbdcf95ccb283202/?utm_source=chatgpt","doi":"10.1155/2005/961613","volume":"16 5","pages":"\n 286-8\n ","search_result_number":12},{"paper_title":"Pharmacokinetics and Relative Bioavailability Evaluation of Linezolid Suspension and Tablet Formulations","abstract":"Abstract The oral liquid formulations poses an alternative way in providing medications to pediatric patients, geriatric patients, patients with feeding tubes, and patients who cannot swallow solid dosage forms. This study was conducted to evaluate the pharmacokinetics (PKs) and relative bioavailability of suspension (reference) and tablet (test) formulations of Linezolid (LZD). In vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2 Way, Cross-Over Study with a washout period of 1-week. Under fasting conditions, 28 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either 30 ml LZD or 1 tablet (600 mg LZD) of marketed suspension and tablet formulations. Plasma samples were obtained over a 48-h interval and analyzed for LZD by reversed phase liquid chromatography with ultraviolet detection. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-∞ of the two treatments were within the acceptable range (0.8–1.25) for bioequivalence. From PK perspectives, in this small study in healthy Egyptian adult male volunteers, a single 600 mg dose of the tablet formulation demonstrated comparable rate and extent of absorption to a single 600 mg dose of the suspension formulation based on the US FDA’s regulatory definition. No adverse events occurred or were reported after a single 600 mg LZD and both formulations were well tolerated.","paper_authors":["S. Helmy"],"paper_publish_year":2013,"publication_journal_name":"Drug Research","consensus_paper_details_url":"https://consensus.app/papers/pharmacokinetics-bioavailability-evaluation-linezolid-helmy/a92dde398fe1521ebf4ebd3198268564/?utm_source=chatgpt","doi":"10.1055/s-0033-1347189","volume":"63","pages":"489 - 494","search_result_number":13},{"paper_title":"Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis.","abstract":"BACKGROUND\nAlthough previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear.\n\n\nMETHODS\nTwenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen.\n\n\nRESULTS\nThe patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268-443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233-405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26-145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298-427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48-160 days).\n\n\nCONCLUSIONS\nA daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.","paper_authors":["W. Koh","O. Kwon","H. Gwak","J. Chung","Sang-Nae Cho","W. Kim","T. Shim"],"paper_publish_year":2009,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/dose-treatment-multidrugresistant-extensively-koh/45c604234aa059ea8b2ebeef5285c040/?utm_source=chatgpt","doi":"10.1093/jac/dkp171","volume":"64 2","pages":"\n 388-91\n ","search_result_number":14},{"paper_title":"Pharmacokinetics and Tissue Penetration of Linezolid following Multiple Oral Doses","abstract":"ABSTRACT The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 μg/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 μg/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) μg · h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.","paper_authors":["T. Gee","R. Ellis","G. Marshall","J. Andrews","J. Ashby","R. Wise"],"paper_publish_year":2001,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/pharmacokinetics-tissue-penetration-linezolid-gee/9fc5f0da62e85bbc8742adcf72c5e825/?utm_source=chatgpt","doi":"10.1128/AAC.45.6.1843-1846.2001","volume":"45","pages":"1843 - 1846","search_result_number":15},{"paper_title":"Probable Linezolid-Induced Thrombocytopenia in a Patient With Vancomycin-Resistant Enterococci","abstract":"Purpose: A probable case of linezolid-induced thrombocytopenia is reported. Summary: A 74-year-old Caucasian male with renal dysfunction was diagnosed with diverticulosis. Patient was prescribed linezolid 600 mg orally twice daily for vancomycin-resistant enterococci abdominal infection that developed secondary to colon resection. Upon initiation of linezolid, platelet count dropped from 248 000 cells/mm3 on day 1 to 97 000 cells/mm3 on day 5 of treatment. Linezolid was discontinued and platelet counts improved to pretreatment levels. Application of the Naranjo probability scale indicated a probable association of linezolid therapy and thrombocytopenia. Clinicians should be aware that linezolid has this hematologic side effect and that patients with renal dysfunction are at increased risk. Monitoring platelet count more than once weekly should be advisable in these patients. Conclusion: A 74-year-old Caucasian male with renal dysfunction developed a probable case of linezolid-induced thrombocytopenia after receiving the drug for 5 days for treatment of vancomycin-resistant enterococci abdominal infection.","paper_authors":["M. Poulakos","Y. Grace","C. Coakley"],"paper_publish_year":2012,"publication_journal_name":"Journal of Pharmacy Practice","consensus_paper_details_url":"https://consensus.app/papers/linezolidinduced-thrombocytopenia-patient-with-poulakos/ca6ca079d28f5e928bfa65b344821616/?utm_source=chatgpt","doi":"10.1177/0897190012442720","volume":"25","pages":"615 - 618","search_result_number":16},{"paper_title":"Immediate hematological toxicity of linezolid in healthy volunteers with different body weight: a phase I clinical trial","abstract":"Linezolid is an important therapeutic option for infections from multi-drug resistant Gram-positive pathogens. However, prolonged linezolid treatment (>14 days) is considered to increase the risk of hematological adverse events. We aimed to evaluate the hematological safety profile of an i.v. single dose of linezolid in healthy volunteers of different body weight. We conducted a phase I clinical trial involving 20 healthy male Chinese volunteers that received an i.v. single dose of linezolid (600 mg). The study participants were assigned to two groups: low-weight (LW) group: 50 kg 4 weeks were retrospectively analysed, especially their haematology. In a case-control study, we compared the respective characteristics of patients who developed anaemia during linezolid therapy and those who did not.\n\n\nRESULTS\nForty-five adults with chronic osteomyelitis received 600 mg linezolid intravenously twice daily for 7 days, and then orally, for a mean total duration of 15.9 weeks (range, 6-36). Anaemia episodes requiring blood transfusion occurred in 13/45 patients (28.9%). Median time from treatment initiation to anaemia onset was 7.4 weeks (range, 4-16). Anaemia was significantly associated with premature linezolid therapy cessation (P = 0.0012). No linezolid-related thrombocytopenia was observed. By univariate analysis, four variables were associated with the occurrence of anaemia: age >58 years, alcohol abuse, diabetes mellitus and low haemoglobin before linezolid treatment. Logistic regression analysis revealed two independent risk factors for anaemia: age >58 years (OR = 20.5, 95% CI 0.69-599; P = 0.0001) and pre-treatment haemoglobin <10.5 g/dL (OR = 16.49, 95% CI 1.06-255; P = 0.04).\n\n\nCONCLUSIONS\nProfound anaemia may occur in adult patients with chronic osteomyelitis on prolonged linezolid therapy, and often necessitates linezolid cessation. These patients are likely to be aged >58 years and to have low pre-treatment haemoglobin. The results for the present series might help physicians to identify patients who should not be given long-term linezolid treatment for chronic osteomyelitis.","paper_authors":["É. Senneville","L. Legout","M. Valette","Y. Yazdanpanah","F. Giraud","É. Beltrand","G. Obert","L. Dubreuil","H. Migaud","Y. Mouton"],"paper_publish_year":2004,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/risk-factors-anaemia-patients-prolonged-therapy-senneville/ea7600ecc77553c5b163cf2622ce4d18/?utm_source=chatgpt","doi":"10.1093/JAC/DKH409","volume":"54 4","pages":"\n 798-802\n ","search_result_number":18},{"paper_title":"Is it time to revise linezolid dose in elderly patients?","abstract":"Sir, No indications on dose adjustments for linezolid in elderly patients are actually given on the drug’s label sheet. Nevertheless, some evidence shows significant association between patients’ age and linezolid exposure [1, 2]. In particular, we have previously documented that old (70–79 yrs) and very old patients (≥80 yrs) have linezolid concentrations three times higher compared with younger adult patients. Here we aimed to extend these findings by describing the exposure of linezolid in elderly patients in which the dose was reduced guided by therapeutic drug monitoring (TDM). Patients included in the present study had to fulfill the following criteria: (a) age ≥70 yrs, (b) linezolid therapy at 600 mg b.i.d. for at least 3 days to ensure steady state conditions, (c) blood samples for TDM taken 12 h after the last drug intake (a timewindow of ±20min was considered acceptable). Patients taking drugs known to interfere with linezolid pharmacokinetics were excluded from the study. Plasma linezolid concentrations were determined using a validated high-performance liquid chromatographic method [2]. The therapeutic range for linezolid trough concentrations was set at 2–8 mg/L [3]. After the first TDM, patients with linezolid trough concentrations exceeding the upper therapeutic threshold underwent drug dose reduction, and a second TDM was carried out 4 to 6 days after the first assessment. Comparisons of the hematochemical and pharmacokinetic data between the first and the second TDM assessments were performed using t test analysis. All data were expressed as median [interquartile range, IQR], unless specified. Given the retrospective, observational nature of this research, no formal approval from the local ethics committee was required according to national legislation. Written informed patient consent for medical procedures/interventions performed as per clinical practice was collected by each center. Twenty patients fulfilling the inclusion criteria were identified. They were given linezolid for the treatment of hospitalacquired pneumonia (n = 6), osteomyelitis (n = 5), spondylodiscitis (n = 3), skin and skin structure infections (n = 3), bacteremia (n = 2), and urinary tract infection (n = 1). Patients had a median age of 79 yrs. (ranging from 70 to 92 yrs), equally distributed for sex (50% males), with normal renal function/mild renal dysfunction (median glomerular filtration rate estimated with the MDRD equation 62.8 [47.2–86.8] mL/min] and a Charlson index of 3 [2–4]. As shown in Fig. 1, at the first TDM, performed at a median of five [3–6] days after starting antibiotic therapy, all patients had linezolid trough concentrations exceeding the cutoff of 8.0 mg/L, resulting in median drug levels of 13.0 [11.9–16.0] mg/L. At this stage, patients had no or minor alterations in platelet count (242 [158–277] 10/μL), red blood cell count (RBC, 7.3 [5.7–8.5] 10/μL), and hemoglobin levels (Hb, 10.4 [9.7–11.6] g/dL). According to the TDM results, all patients underwent linezolid dose reduction (in 19 patients the dose was reduced to 300 mg b.i.d., and in the remaining, an obese patient, the dose was reduced to 450 mg b.i.d.), and a second TDM was performed 4.6 days after the first assessment. The dose reduction resulted in significant decrease in the linezolid trough concentrations (5.4 * Dario Cattaneo Dario.cattaneo@asst-fbf-sacco.it","paper_authors":["M. Tinelli","C. Gervasoni","M. Piazza","R. Terzi","Valeria Cozzi","E. Maffezzini","C. Cerri","Simone Castoldi","S. Baldelli","D. Cattaneo"],"paper_publish_year":2017,"publication_journal_name":"European Journal of Clinical Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/time-revise-linezolid-patients-tinelli/82045f4fd43b5556aec34df91ce94939/?utm_source=chatgpt","doi":"10.1007/s00228-017-2303-6","volume":"73","pages":"1335 - 1336","search_result_number":19},{"paper_title":"Linezolid use for drug-resistant tuberculosis in Georgia: a retrospective cohort study.","abstract":"SETTING: Data on the long-term use of linezolid (LZD) in the treatment of drug-resistant pulmonary tuberculosis (DR-PTB) are limited.OBJECTIVE: To assess safety, tolerability and efficacy of LZD-containing regimens for the treatment of DR-PTB in the country of Georgia.DESIGN: A retrospective study was conducted among DR-PTB patients receiving LZD 600 mg/day as part of newly implemented regimens (bedaquiline or delamanid, repurposed and second-line drugs) from July 2014 to October 2015 in programmatic conditions and following WHO recommendations.RESULTS: One hundred mostly male (82%) patients with a median age of 33 years received LZD. Most patients (77%) had previously been treated for TB; 57% had extensively drug-resistant TB. The median duration of LZD use was 503 days (interquartile range 355-616). LZD-associated adverse events occurred in 12 patients, leading to discontinuation in 4 (2 each due to peripheral neuropathy and cytopenias), and dose reduction to 300 mg/day in 6 cases (4 due to peripheral neuropathy and 2 for cytopenias). Almost all patients (95%) achieved culture conversion and 79% had a successful treatment outcomes.CONCLUSION: Treatment regimens including lengthy LZD use showed fairly good safety and tolerability and were associated with high rates of culture conversion and favorable outcomes.","paper_authors":["L. Mikiashvili","M. Kipiani","M. Schechter","Z. Avaliani","N. Kiria","R. Kempker"],"paper_publish_year":2020,"publication_journal_name":"The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease","consensus_paper_details_url":"https://consensus.app/papers/linezolid-tuberculosis-georgia-cohort-study-mikiashvili/87c5c67347c75fbf8cca5ce753416f7a/?utm_source=chatgpt","doi":"10.5588/ijtld.19.0444","volume":"24 4","pages":"\n 436-443\n ","search_result_number":20}]} --- **ChatGPT:** The typical duration for linezolid therapy can vary depending on the infection being treated, but common guidelines provide some insights: ### Typical Prescription Duration: 1. **Standard Duration:** Clinical trials have shown that linezolid (600 mg twice daily) is generally well tolerated for up to 28 days [(French, 2003)](https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt). 2. **Complicated Skin and Soft Tissue Infections (cSSTIs):** Linezolid treatment for cSSTIs typically ranges from 10 to 14 days [(Itani et al., 2005)](https://consensus.app/papers/reduces-length-duration-treatment-compared-vancomycin-itani/4180edd4a4025a34acef2a30107c9c57/?utm_source=chatgpt). 3. **Pneumonia:** For community-acquired and nosocomial pneumonia, the duration is also usually around 10 to 14 days [(Saiman et al., 2003)](https://consensus.app/papers/safety-tolerability-children-saiman/c3be68e395bf52b7bd1ab76470b2ae37/?utm_source=chatgpt). 4. **Osteomyelitis:** Treatment for osteomyelitis can be prolonged, often lasting several weeks or even months, due to the nature of the infection [(Senneville et al., 2004)](https://consensus.app/papers/risk-factors-anaemia-patients-prolonged-therapy-senneville/ea7600ecc77553c5b163cf2622ce4d18/?utm_source=chatgpt). ### Special Considerations: - **Elderly Patients:** There is no specific dosage adjustment for elderly patients solely based on age, but close monitoring is recommended due to potential increased sensitivity to the drug [(Tinelli et al., 2017)](https://consensus.app/papers/time-revise-linezolid-patients-tinelli/82045f4fd43b5556aec34df91ce94939/?utm_source=chatgpt). - **Hematological Monitoring:** Weekly monitoring of complete blood counts is advised for patients receiving linezolid for more than 14 days due to risks of myelosuppression, including thrombocytopenia [(French, 2003)](https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt). ### Conclusion: For most infections, the typical duration of linezolid therapy ranges from 10 to 14 days, with extended durations possible for more severe infections. Given that you are close to completing your prescribed course, it would be best to complete the medication as directed, especially since you are only two days away from completion. However, considering the side effect you mentioned, reaching out to a healthcare professional for immediate advice remains important. 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:** Explain potential increased sensitivity to linezolid --- **ChatGPT:** Increased sensitivity to linezolid, especially in elderly patients or those with certain pre-existing conditions, can lead to a higher risk of adverse effects. Here’s a detailed explanation: ### Potential Increased Sensitivity to Linezolid 1. **Hematological Effects:** - **Thrombocytopenia:** Linezolid can cause a decrease in platelet count, leading to thrombocytopenia. Elderly patients or those with pre-existing conditions like renal impairment are more susceptible to this effect [(Poulakos et al., 2012)](https://consensus.app/papers/linezolidinduced-thrombocytopenia-patient-with-poulakos/ca6ca079d28f5e928bfa65b344821616/?utm_source=chatgpt). This necessitates regular monitoring of blood counts. - **Anemia:** Chronic use of linezolid can lead to anemia, particularly in patients who already have low hemoglobin levels before starting the therapy [(Senneville et al., 2004)](https://consensus.app/papers/risk-factors-anaemia-patients-prolonged-therapy-senneville/ea7600ecc77553c5b163cf2622ce4d18/?utm_source=chatgpt). 2. **Neurological Effects:** - **Peripheral and Optic Neuropathy:** Prolonged use of linezolid can lead to peripheral and optic neuropathy. This is especially concerning in older adults, who might already have some degree of neuropathy or other comorbid conditions affecting nerve function [(Dempsey et al., 2018)](https://consensus.app/papers/case-report-linezolid-optic-neuropathy-proposed-dempsey/a43901cb59075f9383393837dd3b8709/?utm_source=chatgpt). 3. **Renal and Hepatic Function:** - **Renal Impairment:** Linezolid’s pharmacokinetics can be significantly affected in patients with renal impairment, leading to higher blood levels of the drug and an increased risk of adverse effects [(Meagher et al., 2003)](https://consensus.app/papers/population-pharmacokinetics-patients-treated-meagher/5edb81aa308c58aa93d82ea6c639e722/?utm_source=chatgpt). - **Hepatic Dysfunction:** Although less common, hepatic impairment can also alter linezolid metabolism, necessitating careful monitoring and possible dosage adjustments. 4. **Drug Interactions:** - **Serotonergic Drugs:** Linezolid is a weak, reversible monoamine oxidase inhibitor (MAOI) and can interact with serotonergic drugs, increasing the risk of serotonin syndrome, particularly in patients taking high doses of these medications [(Bergeron et al., 2005)](https://consensus.app/papers/serotonin-toxicity-associated-concomitant-linezolid-bergeron/9448fe950db45b0bbbda698b85826d44/?utm_source=chatgpt). 5. **Increased Drug Exposure:** - **Pharmacokinetics in Elderly:** Older patients often have reduced renal function and changes in body composition that can affect the pharmacokinetics of linezolid, leading to higher drug exposure and increased risk of toxicity [(Tinelli et al., 2017)](https://consensus.app/papers/time-revise-linezolid-patients-tinelli/82045f4fd43b5556aec34df91ce94939/?utm_source=chatgpt). ### Conclusion: Increased sensitivity to linezolid in certain populations, particularly the elderly and those with renal or hepatic impairments, necessitates careful monitoring and possibly adjusting the dosage. Regular blood tests to monitor hematological parameters, awareness of potential drug interactions, and close observation for signs of neuropathy are critical to ensuring safe and effective use of linezolid in these patients. 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:** Another option might be to cut the dosage in half for the next 2 days --- **ChatGPT:** Reducing the dosage of linezolid for the next two days could be a viable option, especially if you are experiencing side effects like the black streak on your tongue. However, this should ideally be done under the guidance of a healthcare professional. Here are some considerations and potential benefits of reducing the dosage: ### Considerations for Reducing Linezolid Dosage 1. **Maintaining Therapeutic Effectiveness:** - Linezolid is typically prescribed at 600 mg every 12 hours. Reducing the dose to 300 mg every 12 hours may still provide therapeutic benefits, but the efficacy could be slightly diminished. It is important to monitor for any signs of infection resurgence or lack of improvement. 2. **Reducing Side Effects:** - Lowering the dose might reduce the severity of side effects, such as the black discoloration on your tongue, and other potential adverse effects like thrombocytopenia and neuropathy. 3. **Gradual Adjustment:** - A temporary reduction in dose could serve as a middle ground while you wait for guidance from your healthcare provider. This can help manage side effects without abruptly stopping the medication. 4. **Monitoring Health:** - Even with a reduced dose, continue to monitor your health closely. If there are any signs of worsening infection or severe adverse effects, seek medical attention promptly. ### Evidence Supporting Dosage Adjustment - **Pharmacokinetics and Tolerability:** Studies indicate that linezolid has a wide therapeutic index, and adjusting the dosage may help manage side effects while maintaining some level of efficacy [(Meagher et al., 2003)](https://consensus.app/papers/population-pharmacokinetics-patients-treated-meagher/5edb81aa308c58aa93d82ea6c639e722/?utm_source=chatgpt). - **Clinical Cases:** Some clinical scenarios have shown that dose adjustments can help mitigate side effects while continuing treatment [(Koh et al., 2009)](https://consensus.app/papers/dose-treatment-multidrugresistant-extensively-koh/45c604234aa059ea8b2ebeef5285c040/?utm_source=chatgpt). ### Conclusion While reducing the dosage of linezolid might be beneficial in managing side effects, it is essential to do so under medical supervision to ensure that the infection is adequately treated. Contact a healthcare provider as soon as possible to discuss this option and get personalized advice. 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 consuming some foods with Tyramine produce a black stool when using linezolid? --- **ChatGPT:** ```json {"query": "Tyramine interaction with Linezolid causing black stool"} ``` --- **[Tool]:** {"items":[{"paper_title":"Safety and tolerability of linezolid.","abstract":"Clinical trials have shown that linezolid (600 mg twice daily in adults) is safe and generally well tolerated for up to 28 days. Drug-related adverse events, which are typically mild to moderate in intensity and of limited duration, include diarrhoea, nausea and headache in adults, and diarrhoea, loose stools and vomiting in children. Clostridium difficile-related complications with linezolid are uncommon. Linezolid is a weak, reversible monoamine oxidase inhibitor: foods containing high concentrations of tyramine should be avoided, and linezolid should be used with caution in patients taking adrenergic or serotonergic agents or in those with uncontrolled hypertension. In the majority of patients, linezolid has minimal adverse effects on blood chemistry or haematology. There have been case reports of reversible thrombocytopenia, anaemia and neutropenia associated with linezolid therapy. In Phase III studies, 2.4% of patients treated with linezolid and 1.5% of patients treated with comparator drugs developed reversible thrombocytopenia (P = 0.066), but there was no evidence of an increased risk of agranulocytosis, aplastic anaemia or other irreversible blood dyscrasias. Reduced platelet counts were associated with linezolid treatment for >/=2 weeks; complete blood counts should be monitored weekly in patients receiving linezolid for more than 14 days and treatment should be discontinued if there is evidence of myelosuppression.","paper_authors":["G. French"],"paper_publish_year":2003,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt","doi":"10.1093/JAC/DKG253","volume":"51 Suppl 2","pages":"\n ii45-53\n ","search_result_number":1},{"paper_title":"Dietary tyramine restriction for hospitalized patients on linezolid: an update.","abstract":"Linezolid is a weak, reversible monoamine oxidase inhibitor. The current practice at most hospitals is to place patients receiving linezolid on a tyramine-restricted diet. This process typically involves both the hospital's pharmacy department and the food and nutrition department. A literature search assessing the interaction between linezolid and tyramine was conducted, and the amount of tyramine in a typical unrestricted diet for a hospitalized patient was reviewed. Although patients receiving linezolid should avoid consuming large amounts of foods containing high concentrations of tyramine, such foods in large amounts are not components of meals for inpatients. Therefore, dietary tyramine restriction in hospitalized patients is not generally required.","paper_authors":["M. Rumore","M. Roth","A. Orfanos"],"paper_publish_year":2010,"publication_journal_name":"Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition","consensus_paper_details_url":"https://consensus.app/papers/dietary-tyramine-restriction-hospitalized-patients-rumore/6db80220c3e75291ae0ca997e499285f/?utm_source=chatgpt","doi":"10.1177/0884533610368711","volume":"25 3","pages":"\n 265-9\n ","search_result_number":2},{"paper_title":"Linezolid-Induced Near-Fatal Serotonin Syndrome During Escitalopram Therapy: Case Report and Review of Literature","abstract":"Linezolid is a synthetic antimicrobial agent of the oxazolidinone class with weak, nonspecific inhibitor of monoamine oxidase enzymes. Concomitant therapy with an adrenergic or serotonergic agent or consuming tyramine (>100 mg/day) may induce serotonin syndrome (SS). We present a case report of near-fatal adverse interaction between linezolid and escitalopram inducing SS in a 65-year-old woman with sepsis, under empirical antibiotic treatment. This report also summarizes the current relevant literature as identified via PubMed, EMBASE, and PsycINFO, supplemented with a manual search of cross references.","paper_authors":["Ranganath R. Kulkarni","Pratibha R. Kulkarni"],"paper_publish_year":2013,"publication_journal_name":"Indian Journal of Psychological Medicine","consensus_paper_details_url":"https://consensus.app/papers/linezolidinduced-nearfatal-serotonin-syndrome-during-kulkarni/d77b7df736175bef9a75f21a19dd1f0b/?utm_source=chatgpt","doi":"10.4103/0253-7176.122245","volume":"35","pages":"413 - 416","search_result_number":3},{"paper_title":"Cardiovascular Sympathomimetic Amine Interactions in Rats Treated with Monoamine Oxidase Inhibitors and the Novel Oxazolidinone Antibiotic Linezolid","abstract":"Linezolid (PNU-100766) is a new gram-positive oxazolidinone antibiotic that is effective at in vitro concentrations ≤4 &mgr;g/ml and in vivo doses ≤10 mg/kg. Because linezolid also competitively inhibits human monoamine oxidase-A (MAO-A; Ki = 55 &mgr;M), we monitored its effects on the cardiovascular responses to tyramine and amine cold remedies in comparison with standard MAO inhibitors. In anesthetized rats, the pressor response to 16 &mgr;g i.v. tyramine was potentiated by the MAO-A inhibitors clorgyline (0.1–1.0 mg/kg i.v.) and moclobemide (5.0–50 mg/kg p.o.), but not by the MAO-B inhibitor selegiline (0.15–15 mg/kg p.o.). Fifteen milligrams per kilogram intravenous linezolid weakly potentiated i.v. tyramine independent of changes in &agr;-adrenoceptor reactivity, but this effect was not enhanced chronically (90–100 mg/kg/day). In conscious rats, 30 mg/kg/day oral linezolid (8 &mgr;g/ml plasma concentration) minimally affected the pressor response to 20 mg/kg oral tyramine, whereas 100 mg/kg/day linezolid (20 &mgr;g/ml plasma concentration) moderately potentiated this response similar to 3 mg/kg per day moclobemide. Linezolid's tyramine potentiation was reversible, attenuated by food, and independent of pseudoephedrine, phenylpropanolamine, and dextromethorphan interactions. These studies demonstrate that high-dose linezolid only moderately potentiates the cardiovascular effects of tyramine and validate these models for evaluating such MAO inhibitory interactions.","paper_authors":["S. J. Humphrey","J. T. Curry","C. Turman","Ronald P. Stryd"],"paper_publish_year":2001,"publication_journal_name":"Journal of Cardiovascular Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/sympathomimetic-amine-interactions-rats-treated-humphrey/21aca3d278b35921bc6389f05b087ea4/?utm_source=chatgpt","doi":"10.1097/00005344-200105000-00007","volume":"37","pages":"548-563","search_result_number":4},{"paper_title":"Potential serious adverse interactions between linezolid and atomoxetine.","abstract":"Linezolid is an oxazolidinone antibiotic that is widely used in general hospitals. Originally discovered as a psychotropic agent with antidepressant effects through reversible nonselective inhibition of monoamine oxidase (MAO), it was also found to have antibiotic efficacy against drug-resistant gram-positive cocci. (Moellering 2003). MAO-A deaminates noradrenaline, adrenaline, and 5-hydroxytryptamine (serotonin). As linezolid is a competitive monoamine oxidase inhibitor (MAO-I), the potential exists for interactions with drugs that have effects on the serotonergic or noradrenergic systems, as well as tyramine, which is capable of releasing stored catecholamines (Stevens et al. 2004).There have been various published reports of serotonin syndrome occurring with co-administration of linezolid with serotonergic medications (Thomas et al. 2004, Lawrence et al. 2006). The manufacturer of atomoxetine HCl lists co-administration with an MAO-I as a contraindication, and states that with other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with an MAO-I. Some cases presented with features resembling neuroleptic malignant syndrome. Such reactions may occur when these drugs are given concurrently or in close proximity (Strattera package insert 2002).","paper_authors":["Arpit Aggarwal","Gaurav Kulkarni","S. Jahan"],"paper_publish_year":2012,"publication_journal_name":"Journal of child and adolescent psychopharmacology","consensus_paper_details_url":"https://consensus.app/papers/potential-interactions-linezolid-atomoxetine-aggarwal/33ddbfbfa96856c1802b7ff1eb752955/?utm_source=chatgpt","doi":"10.1089/cap.2012.0040","volume":"22 5","pages":"\n 405\n ","search_result_number":5},{"paper_title":"Linezolid and serotonin syndrome.","abstract":"Received March 21, 2001; accepted March 29, 2001. From Eastern Virginia Medical School, Department of Psychiatry and Behavioral Sciences, 825 Fairfax Avenue, Norfolk, Virginia 23507. Address correspondence and reprint requests to Dr. Pushkin, Associate Professor of Clinical Psychiatry, Director Consultation & Liaison Psychiatry, EVMS; E-mail address: pushkiyr@evms.edu Copyright 2001 The Academy of Psychosomatic Medicine. Serotonin syndrome is a potentially severe adverse drug interaction characterized by the sudden onset of the triad of altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It can be a serious complication of treatment with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and other serotonergic medications. Serotonin syndrome is idiosyncratic in nature. It has been reported in association with single-drug therapy, combination-drug therapy, singledrug overdose, polydrug overdose, and recreational drugs of abuse. Linezolid is a new antibiotic of the oxazolidinone class and is the only one that has progressed to clinical trials. Its major clinical indication is for the treatment of vancomycin-resistant enterococcus (VRE). Linezolid has been shown to be a relatively weak nonspecific reversible inhibitor of human monoamine oxidase. Linezolid has the potential for interaction with adrenergic, serotonergic, and dopaminergic agents. However, no demonstrated clinical evidence of adverse reactions as a result of monoamine oxidase inhibition has been reported. Coadministration of linezolid and serotonergic agents was not associated with serotonin syndrome in phase 1, 2 or 3 studies. The interactions of sertraline and other serotonin re-uptake inhibitors with linezolid have not been studied to date. This article reports a case of suspected serotonin syndrome caused by the interaction between linezolid and sertraline. Case Report","paper_authors":["Sarah Lavery","Himabindu Ravi","W. McDaniel","Yaacov R. Pushkin"],"paper_publish_year":2001,"publication_journal_name":"Psychosomatics","consensus_paper_details_url":"https://consensus.app/papers/linezolid-serotonin-syndrome-lavery/e04e9bcd038b5887a546b46e647fc5ff/?utm_source=chatgpt","doi":"10.1176/APPI.PSY.42.5.432","volume":"42 5","pages":"\n 432-4\n ","search_result_number":6},{"paper_title":"Safety and tolerability of linezolid in children","abstract":"Background. Linezolid, an oxazolidinone, is effective in the treatment of adults and children with community-acquired and nosocomial pneumonia and uncomplicated and complicated skin and skin structure infections (SSSIs), including infections caused by Gram-positive resistant pathogens. Because of the increasing use of linezolid, it is important to review the common adverse events (AEs) associated with its use in children with the use of data from clinical trials. Objective. The safety and tolerability of linezolid in pediatric patients with Gram-positive infections were determined in four pediatric clinical studies. Study I included pediatric patients with community-acquired pneumonia; Study II included otitis media; Study III included SSSIs; and Study IV included complicated SSSIs, nosocomial pneumonia and bacteremia. Methods. Studies I and II had no comparator arm. Study III was randomized and compared linezolid with cefadroxil. Study IV also was randomized and compared linezolid with vancomycin. Patients <12 years of age received linezolid 10 mg/kg; patients age 12 years and older received 600 mg (intravenous/oral). Dosing frequency (two to three times daily) varied depending on age and clinical diagnosis. The primary safety endpoints were AEs, drug-related AEs, serious AEs and selected laboratory tests. Results. In the 4 studies 958 patients were included in the intent-to-treat analysis. In the linezolid vs. cefadroxil study (Study III), the most common AEs in patients treated with linezolid were diarrhea (7.8%), headache (6.5%) and upper respiratory tract infection (3.7%). In the linezolid vs. vancomycin study (Study IV), the most common AEs in the linezolid group were fever (14.1%), diarrhea (10.8%) and vomiting (9.4%). The most common drug-related AEs for linezolid in all 4 studies were diarrhea, vomiting, loose stools and nausea. None of these common AEs or drug-related AEs occurred more frequently in patients treated with linezolid than in those in the comparator group. Conclusions. Linezolid was safe and well-tolerated in pediatric patients with community-acquired pneumonia, otitis media, SSSIs and infections caused by Gram-positive resistant pathogens.","paper_authors":["L. Saiman","J. Goldfarb","S. Kaplan","K. Wible","Barbara Edge-Padbury","J. Bruss"],"paper_publish_year":2003,"publication_journal_name":"The Pediatric Infectious Disease Journal","consensus_paper_details_url":"https://consensus.app/papers/safety-tolerability-children-saiman/c3be68e395bf52b7bd1ab76470b2ae37/?utm_source=chatgpt","doi":"10.1097/01.inf.0000087022.58089.d8","volume":"22","pages":"S193-S200","search_result_number":7},{"paper_title":"Linezolid, a Novel Oxazolidinone Antibiotic: Assessment of Monoamine Oxidase Inhibition Using Pressor Response to Oral Tyramine","abstract":"The primary objective of this study was to compare the effects of oral linezolid with moclobemide and placebo on the pressor response to oral tyramine. Secondary objectives were to determine possible mechanisms of the effect based on changes in the pharmacokinetics of tyramine and to evaluate alternative methods for quantifying the pressor effect. Subjects received linezolid (625 mg bid orally), moclobemide (150 mg tid orally), or placebo for up to 7 days. Using the oral tyramine dose producing a > 30 mmHg increase in systolic blood pressure (SBP) (PD>30), a positive pressor response was defined as a PD> 30 index (pretreatment/treatment ratio of PD> 30) of ≥ 2. There were 8/10, 11/11, and 1/10 responders with linezolid, moclobemide, and placebo, respectively. Responses returned to baseline within 2 days of drug discontinuation. The ratio of mean greatest SBP and heart rate at the time of greatest SBP (GSBP/HR) increased linearly with tyramine dose both pretreatment and during treatment with linezolid and moclobemide. During treatment, responses to tyramine when subjects took linezolid or moclobemide were significantly different from placebo. Both drugs significantly decreased tyramine oral clearance compared with placebo. Urinary excretion of catecholamines and metabolites was consistent with MAOI activity of the drugs, but results were variable. The MAOI activity of linezolid is similar to that of moclobemide, a drug used clinically without food restrictions. Restrictions to normal dietary intake of tyramine‐containing foods are not warranted when taking linezolid.","paper_authors":["E. Antal","Pamela E. Hendershot","D. Batts","Wang-Pui Sheu","N. Hopkins","K. Donaldson"],"paper_publish_year":2001,"publication_journal_name":"The Journal of Clinical Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/linezolid-novel-oxazolidinone-antibiotic-assessment-antal/8f6989aa2f54520c8f5368d18bed84c2/?utm_source=chatgpt","doi":"10.1177/00912700122010294","volume":"41","pages":"","search_result_number":8},{"paper_title":"Adverse reaction report and retrospective analysis of black hairy tongue caused by linezolid","abstract":"The adverse reaction of Black Hairy Tongue (BHT) caused by linezolid is rare. We reports a case of linezolid-induced BHT, and reviews relevant literatures at home and abroad. It aims to provide a safe and reasonable basis for clinical medication use. A 14-year-old adolescent with pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) developed a rash and pruritus due to Vancomycin. Instead, the patient was given linezolid 600mg q12h in injection during hospitalization and in tablet after discharge. On the 14th day after injection and the second day after oral administration the patient showed BHT without other abnormal taste symptoms. But all the symptoms could be tolerated and he completed the therapy course of linezolid. Tongue symptoms completely disappeared on the 8th day after drug withdrawal. Based on the Karch and Lasagna evaluation methods and the cause-and-effect evaluation methods of the WHO collaborating center for international adverse drug reaction (ADR) monitoring, it is likely that this patient had a BHT caused by linezolid. The mean time of occurrence of BHT was 14.36 days, and the mean time of symptom disappearance was 23.43 days after drug administration. When linezolid is prescribed to patients, especially those with atopy, the patient's tongue should be closely observed and good oral hygiene is recommended.","paper_authors":["S. Luo","Qian Luo","Xing-Lin Gao","Jing Li"],"paper_publish_year":2020,"publication_journal_name":"Respiratory Medicine Case Reports","consensus_paper_details_url":"https://consensus.app/papers/reaction-report-analysis-hairy-tongue-caused-luo/24a550663d0155168b28dd4984922557/?utm_source=chatgpt","doi":"10.1016/j.rmcr.2020.101159","volume":"31","pages":"","search_result_number":9},{"paper_title":"In Vitro, In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions","abstract":"ABSTRACT Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).","paper_authors":["S. Flanagan","Ken Bartizal","S. Minassian","Edward Fang","Philippe Prokocimer"],"paper_publish_year":2013,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/vitro-vivo-clinical-studies-tedizolid-assess-potential-flanagan/edd8cf03302256b9a40225ba5e8b6a6a/?utm_source=chatgpt","doi":"10.1128/AAC.00431-13","volume":"57","pages":"3060 - 3066","search_result_number":10},{"paper_title":"Effect of oral linezolid on the pressor response to intravenous tyramine.","abstract":"AIMS\nTo investigate the effect of monoamine oxidase A inhibition from a single oral dose of linezolid on the pressor response to intravenous (i.v.) tyramine, using positive and negative controls to validate the methodology.\n\n\nMETHODS\nThis placebo-controlled, three-period crossover study was conducted in 12 healthy male volunteers. Each volunteer received either one oral dose of moclobemide (300 mg), linezolid (600 mg), or placebo tablet followed by an i.v. tyramine pressor test until an increase in systolic blood pressure of at least 30 mmHg above baseline occurred. Each study day was separated by a 7-day washout period. The dose of tyramine required to raise the blood pressure by 30 mmHg (TYR30) was calculated for each oral treatment by linear interpolation between log-transformed doses of i.v. tyramine. The influence of body mass index (BMI) on TYR30 was also investigated.\n\n\nRESULTS\nThe tyramine sensitivity factor (ratio of the geometric least square mean TYR30 for placebo and active oral treatment) was 1.8 [90% confidence interval (CI) 1.6, 2.0, P < 0.0001] for linezolid and 2.1 (90% CI 1.8, 2.4, P < 0.0001) for the positive control moclobemide. BMI had a statistically significant effect on TYR30.\n\n\nCONCLUSIONS\nThere was a significant difference in the pressor response to i.v. tyramine between linezolid and placebo. Moclobemide (positive control) and linezolid have a similar pressor response to i.v. tyramine. The statistically significant effect of BMI on TYR30 underlines the advantage of within-individual comparisons of treatments in order to reduce variability and provide more accurate treatment estimates.","paper_authors":["M. Cantarini","Catherine J Painter","E. Gilmore","C. Bolger","C. Watkins","A. Hughes"],"paper_publish_year":2004,"publication_journal_name":"British journal of clinical pharmacology","consensus_paper_details_url":"https://consensus.app/papers/linezolid-pressor-response-tyramine-cantarini/e321e12067b558cda8a471eee55c427e/?utm_source=chatgpt","doi":"10.1111/J.1365-2125.2004.02186.X","volume":"58 5","pages":"\n 470-5\n ","search_result_number":11},{"paper_title":"Impact of prolonged treatment with linezolid on the human gut flora.","abstract":"A 79-year-old male was treated for 6 months with linezolid for prosthetic knee joint osteomyelitis. At the end of this 6-month period, quantitative stool cultures revealed partial loss of the normal gut flora and concomitant colonization by opportunistic pathogens such as Pseudomonas aeruginosa and other Gram-negatives. Follow-up cultures at 6 weeks after antibiotic discontinuation revealed restoration of the normal flora. Prolonged linezolid administration may lead to replacement of normal gut flora by pathogenic microorganisms, which under certain conditions might cause systemic infections.","paper_authors":["D. Kofteridis","P. Malliotakis","S. Maraki","M. Christofaki","G. Samonis"],"paper_publish_year":2009,"publication_journal_name":"International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/impact-prolonged-treatment-flora-kofteridis/634506c06232519795c0e8188aaf02f2/?utm_source=chatgpt","doi":"10.1016/j.ijid.2009.02.001","volume":"13 5","pages":"\n e313-5\n ","search_result_number":12},{"paper_title":"DI-049 Drug interaction between linezolid and serotonergic agonists: the appearance of serotonin syndrome","abstract":"Background Linezolid is an antibiotic which has been reported to possess monoamine oxidase (MAO) inhibitory effects. According to the prescribing information, it should not be used with MAO inhibitors, considering that such drugs may enhance its toxic effects, including side effects such as hypertension and serotonin syndrome (SS). SS is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It may include mental status changes, autonomic dysfunction and neuromuscular abnormalities. Although this interaction is well reported, the MAOI properties of linezolid are not very well known. Purpose To detect interactions between linezolid and serotonergic modulators (X risk according to the Lexi Comp classification) and the appearance of SS. Material and methods An observational retrospective study of patients treated with linezolid was made over two months (January–February 2014). The clinical history of every patient was checked, looking for associated prescriptions with serotonergic agonists in order to detect symptoms related to the SS. The possibility of other drug interactions was ruled out. Results In two months 90 patients received antimicrobial treatment with linezolid (aged 15 to 89 years, 63.3% were male). 18.8% of the patients were also taking serotonergic psychiatric drugs such as clomipramine, trazodone, citalopram, escitalopram, venlafaxine and aripiprazole. Looking over the clinical history in these patients, it was found that four of them met clinical criteria for SS (confusional states, agitation and high heart rate). None of the symptoms were referred as having an iatrogenic cause. Conclusion Although an interaction was detected that can lead to symptoms related to SS, neither of the drugs were referred to as possible sources of an interaction in the clinical history. We strongly recommend a pharmacist check of the whole treatment with the purpose of informing the physician about any interactions of this type. Moreover, some patients will continue the treatment with oral linezolid at home, and they should be made aware of any possible symptoms. References and/or acknowledgements No conflict of interest.","paper_authors":["V. B. Ibáñez","M. Iglesias","M. Morón","R. D. Arriba","L. Acosta","M. Cal","S. Villanueva","O. González"],"paper_publish_year":2015,"publication_journal_name":"European Journal of Hospital Pharmacy-Science and Practice","consensus_paper_details_url":"https://consensus.app/papers/di049-drug-interaction-linezolid-agonists-appearance-ibáñez/b3a243a8a9b75184b46c06887f3e6552/?utm_source=chatgpt","doi":"10.1136/ejhpharm-2015-000639.225","volume":"22","pages":"","search_result_number":13},{"paper_title":"Anticipating potential linezolid-SSRI interactions in the general hospital setting: an MAOI in disguise.","abstract":"Linezolid, a novel antimicrobial with activity against gram-positive bacteria including pathogens resistant to traditional antimicrobials, also inhibits monoamine oxidase. This latter property can cause potentially lethal adverse interactions with antidepressant medications. Long known to psychiatrists, monoamine oxidase inhibitors (MAOIs) and complications of their use may be unfamiliar to medical and surgical practitioners who may thus unwittingly precipitate a hypertensive crisis or serotonin syndrome. We review the pharmacology of MAOis and describe 3 clinical situations In which linezolid-selective serotonin inhibitor (SSRI) interactions, actual or potential, figured prominently.","paper_authors":["Christopher L. Sola","J. Michael Bostwick","D. A. Hart","T. Lineberry"],"paper_publish_year":2006,"publication_journal_name":"Mayo Clinic proceedings","consensus_paper_details_url":"https://consensus.app/papers/anticipating-linezolidssri-interactions-hospital-sola/838fbc69897350528d11941eda8d6a75/?utm_source=chatgpt","doi":"10.4065/81.3.330","volume":"81 3","pages":"\n 330-4\n ","search_result_number":14},{"paper_title":"Bupropion with Linezolid: A Review","abstract":"Introduction: Linezolid (Zyvox) is an antibiotic, which belongs to the class of oxazolidinone. FDA approved it in 1998 to treat gram-positive drug-resistant enterococcus, staphylococcus, and pneumococcus infections in adults (MRSA and VRE). Bupropion (Welbutrin) is a medication primarily used as an antidepressant and smoking cessation aid. FDA first approved it in 1985. Both these medications are well known for causing serotonin syndrome when combined with serotonergic agents or administered along with tyramine-rich foods. Case: A 50-year old male patient was admitted to the hospital with right leg cellulitis and was treated with linezolid. The patient also had a history of depression and anxiety and was stable on bupropion for the past two years. Our C and L team was consulted for medication reconciliation and possible drug-drug interaction. On an extensive literature search, we came across just one case of hypertensive crisis when treated with linezolid and bupropion simultaneously. Hypertensive crisis from other confounding factors is unknown. We recommended continuing the prescribed bupropion on the patient along with his linezolid medication after explaining the risks and benefits. The patient completed his treatment and there were no symptoms suggestive of serotonin syndrome or hypertensive crisis. Conclusion: Bupropion was continued in a patient who was simultaneously treated with linezolid and pt completed the treatment without any symptoms of serotonin syndrome or hypertensive crisis. However, clinicians should be vigilant about drug-drug interactions and should make decisions on a case by case basis.","paper_authors":["Divya Periasamy","Sachidan","Peteru"],"paper_publish_year":2019,"publication_journal_name":"","consensus_paper_details_url":"https://consensus.app/papers/bupropion-linezolid-review-periasamy/431a7e2ff3215096aa2d88915927e3c9/?utm_source=chatgpt","doi":"10.4172/2471-4372.1000168","volume":"2019","pages":"1-3","search_result_number":15},{"paper_title":"Decreased Linezolid Serum Concentrations in Three Critically Ill Patients: Clinical Case Studies of a Potential Drug Interaction between Linezolid and Rifampicin","abstract":"Linezolid is a valuable treatment option for treating infections caused by multi-resistant gram-positive pathogens. Lack of effective linezolid levels due to the co-administration of rifampicin has been described in healthy subjects. However, the clinical significance of this potential drug interaction (DI) for critically ill patients is still unclear. This was a retrospective analysis of 3 critically ill patients with the combination therapy of linezolid and rifampicin or rifampicin pre-treatment. Despite increasing the dose of linezolid, the majority of observed linezolid trough concentrations in all 3 patients were below 2 mg/l. Furthermore, linezolid trough concentrations remained below 2 mg/l after discontinuation of rifampicin. This potential DI between linezolid and rifampicin could lead to treatment failure. Therefore, we strongly recommend that linezolid serum concentrations be monitored in patients with rifampicin co-administration or rifampicin pretreatment.","paper_authors":["U. Blassmann","Anka C. Roehr","O. Frey","Andreas Koeberer","J. Briegel","V. Huge","C. Vetter-Kerkhoff"],"paper_publish_year":2016,"publication_journal_name":"Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/decreased-linezolid-serum-concentrations-three-blassmann/4ab1ac374d805dd8bbe5147cb8a72bef/?utm_source=chatgpt","doi":"10.1159/000445194","volume":"98","pages":"51 - 55","search_result_number":16},{"paper_title":"An uncommon side effect of linezolid: Black hairy tongue","abstract":"Linezolid therapy is known to cause black hairy tongue, which is benign and reversible. A 65‐year‐old diabetic male was on treatment for diabetic nonhealing ulcer involving right foot and sole for the past 6 months. Linezolid was started based on the culture and sensitivity of the pus. Patient developed thrombocytopenia and black hairy tongue after 7 days of the drug regimen. Drug was stopped and patient was advised to maintain good oral hygiene, soft tooth brush for brushing and regular mouth wash with lukewarm water. The black hairy tongue completely resolved within a week after stopping the drug. The taste and foreign body sensation on the tongue while swallowing were also improved. The diabetic wound was treated by starting vancomycin after giving a surgical wound debridement by a general surgeon.","paper_authors":["Shanmugapriyan Sivaraman","Gokul Gomathi Radhakrishnan","Rajesh Manogaran","B. Cheriyan"],"paper_publish_year":2021,"publication_journal_name":"Precision Medical Sciences","consensus_paper_details_url":"https://consensus.app/papers/side-effect-black-hairy-tongue-sivaraman/a8aac6c468885a6bbb241e046658e75c/?utm_source=chatgpt","doi":"10.1002/prm2.12053","volume":"10","pages":"167 - 169","search_result_number":17},{"paper_title":"Serotonin Syndrome Induced by Combined Use of Sertraline and Linezolid","abstract":"Serotonin syndrome is a potentially fatal increase in serotonergic activity in both the central nervous system and peripheral nervous system. The etiology can vary from therapeutic drug use, deliberate overdose, or drug interactions that all lead to an increase in serotonin activity. There are some drugs from different classes that can cause serotonin syndrome either alone at high doses or when combined. We present here a case of an 82-year-old female who presented to the emergency room with high-grade fever, loose stools, burning micturition, and tachycardia. Her current medications included sertraline for depression. She was initially treated on the floor for urosepsis and subsequently managed with antibiotic therapy consisting of cephalosporins. She did not improve so her antibiotics were modified and she was then started on linezolid. Within the first 24 h of taking linezolid, the patient had a rapid clinical deterioration manifesting as restlessness, diaphoresis, tremor, shivering, myoclonus, and high fever (40°C). She also had an acute decompensation of her mental status with disorientation and confusion. As a result, she was transferred to intensive care unit. On clinical examination, she had rigidity and hyperreflexia all the four limbs. Babinski sign was positive. Laboratory test results were unremarkable for sepsis. Sertraline and linezolid were stopped. Within 24 h, the patient's mental status had improved. By the 2nd day on this treatment regimen, the patient's function returned to baseline, and she was discharged from the hospital. Nevertheless, in our case, the administration of sertraline did not reveal any symptomatic interaction, as the serotonin syndrome was induced only after the addition of linezolid to the treatment regimen. This patient was diagnosed with serotonin syndrome.","paper_authors":["R. Hasani","Jahnabee Sarma","S. Kansal"],"paper_publish_year":2019,"publication_journal_name":"Anesthesia, Essays and Researches","consensus_paper_details_url":"https://consensus.app/papers/serotonin-syndrome-induced-combined-sertraline-hasani/842e9ff2253a525c8d057fe55068635b/?utm_source=chatgpt","doi":"10.4103/aer.AER_173_18","volume":"13","pages":"188 - 190","search_result_number":18},{"paper_title":"Decreased Serum Linezolid Levels in a Critically Ill Patient Receiving Concomitant Linezolid and Rifampin","abstract":"Serious gram‐positive infections present an increasingly common therapeutic dilemma. Combination antimicrobial regimens (e. g., linezolid with rifampin) aimed at improving bacterial eradication and preventing resistance are often used; however, most data supporting this treatment strategy are not from randomized controlled trials. We describe a patient with disseminated community‐acquired methicillin‐resistant Staphylococcus aureus infection who experienced a possible drug interaction between linezolid and rifampin that resulted in decreased serum linezolid levels. To our knowledge, this is the first published report of a possible drug interaction in a critically ill patient receiving concomitant linezolid and rifampin. Although we hypothesize that the reaction was caused by P‐glycoprotein expression, further study is warranted.","paper_authors":["B. Gebhart","B. Barker","B. Markewitz"],"paper_publish_year":2007,"publication_journal_name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","consensus_paper_details_url":"https://consensus.app/papers/decreased-serum-linezolid-levels-critically-patient-gebhart/fe5ba84e2d3d51e0b3ff5e8de4cf218e/?utm_source=chatgpt","doi":"10.1592/phco.27.3.476","volume":"27","pages":"","search_result_number":19},{"paper_title":"Serotonin syndrome by drug interactions with linezolid: clues from pharmacovigilance-pharmacokinetic/pharmacodynamic analysis","abstract":"Purpose To characterize the post-marketing reporting of serotonin syndrome (SS) due to drug-drug interactions (DDIs) with linezolid and investigate the relationship with pharmacokinetic/pharmacodynamic (PK/PD) properties of serotonergic agents. Methods We queried the worldwide FDA Adverse Event Reporting System to extract SS records due to DDIs where linezolid was reported as suspect. For each serotonergic agent concomitantly reported, proportion of SS reports and mean number of DDIs were calculated and three different “SS reporting zones” were created. Relevant PK (peak concentration, area under plasma concentration curve, volume of distribution (V D ), and lipophilicity) and PD (values of binding affinity (Ki) and IC 50 for serotonin reuptake transporter (SERT) and 5-HT 2A ) parameters were extracted for each serotonergic agent, and relevant PK/PD indexes were calculated to assess correlation with mean number of DDIs (PV index). Results Six hundred sixty-nine reports of SS mentioning linezolid were found, being linezolid-citalopram ( N = 69; 10.3%) the most frequently DDI reported. Citalopram and methadone showed respectively the highest proportion of SS reports (0.28%) and the lowest mean number of DDIs (1.41). Citalopram, escitalopram, and methadone emerged as red (i.e., alert)-zone medications: they exhibited high lipophilicity and large V D (proxies of excellent central nervous system penetration) coupled with high potency. Among PK/PD indexes, a significant correlation with PV index was found for V D /Ki SERT ratio ( p = 0.05). Discussion Our integrated approach suggests that linezolid is more likely to cause SS when co-administered with citalopram, escitalopram, and methadone, as inferred from their pharmacological properties. Proper management of SS should be tailored on a case-by-case basis.","paper_authors":["Milo Gatti","E. Raschi","F. De Ponti"],"paper_publish_year":2020,"publication_journal_name":"European Journal of Clinical Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/serotonin-drug-interactions-linezolid-clues-analysis-gatti/65c09f611a895655bc4b41ea8a43a64d/?utm_source=chatgpt","doi":"10.1007/s00228-020-02990-1","volume":"77","pages":"233 - 239","search_result_number":20}]} --- **ChatGPT:** There is no direct evidence suggesting that consuming foods with tyramine while using linezolid causes black stool. However, there are significant considerations related to the interaction between tyramine and linezolid: ### Interaction Between Tyramine and Linezolid 1. **Monoamine Oxidase Inhibition:** - Linezolid is a weak, reversible monoamine oxidase inhibitor (MAOI). Foods high in tyramine can interact with linezolid, potentially leading to hypertensive crises due to the inhibition of monoamine oxidase, which is responsible for breaking down tyramine [(French, 2003)](https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt). 2. **Dietary Considerations:** - It is generally recommended to avoid consuming large amounts of foods high in tyramine while on linezolid. This includes aged cheeses, smoked meats, and fermented foods, which can lead to elevated blood pressure and other cardiovascular effects [(Rumore et al., 2010)](https://consensus.app/papers/dietary-tyramine-restriction-hospitalized-patients-rumore/6db80220c3e75291ae0ca997e499285f/?utm_source=chatgpt). 3. **Pressor Response:** - Studies have shown that high doses of linezolid can moderately potentiate the cardiovascular effects of tyramine, leading to increased blood pressure, but not typically resulting in gastrointestinal symptoms like black stool [(Humphrey et al., 2001)](https://consensus.app/papers/sympathomimetic-amine-interactions-rats-treated-humphrey/21aca3d278b35921bc6389f05b087ea4/?utm_source=chatgpt). ### Black Stool Considerations 1. **Possible Causes of Black Stool:** - Black stool, or melena, usually indicates gastrointestinal bleeding, which can be due to ulcers, gastritis, or other gastrointestinal conditions. It is not a known side effect directly associated with tyramine interaction in the context of linezolid therapy. 2. **Linezolid Side Effects:** - Common gastrointestinal side effects of linezolid include diarrhea, nausea, and vomiting. Black stool is not commonly reported as a side effect of linezolid alone [(French, 2003)](https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt). ### Conclusion Consuming foods with tyramine while using linezolid is unlikely to produce black stool. The black stool is more likely related to gastrointestinal bleeding rather than an interaction between linezolid and tyramine. If you experience black stool while taking linezolid, it is important to seek medical attention promptly to determine the underlying cause. 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:** Why is it that just stopping the daily 600 mg of Linezolid at the end of the prescribed term of 10 days might be advised rathere than reducing the amount to 300 mg for the duration - tapering off in essence. Is there a minimum prescription amount of 600 mg for efficacy. --- **ChatGPT:** ```json {"query": "minimum effective dose of Linezolid and efficacy at 300 mg"} ``` --- **[Tool]:** {"items":[{"paper_title":"Daily 300 mg dose of linezolid for multidrug-resistant and extensively drug-resistant tuberculosis: updated analysis of 51 patients.","abstract":"OBJECTIVES\nLinezolid may be an effective treatment for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). The objective was to evaluate the efficacy, tolerability and adverse events of a 300 mg daily dose of linezolid in the treatment of MDR/XDR-TB.\n\n\nPATIENTS AND METHODS\nWe retrospectively reviewed the medical records of 51 MDR-TB patients, including 26 patients (51%) with XDR-TB, to evaluate the safety, tolerability and efficacy of therapy with 300 mg/day linezolid. All patients had failed previous treatments with second-line anti-TB drugs.\n\n\nRESULTS\nPatients were treated with linezolid for a median of 413 days (IQR 237-622 days). Favourable treatment outcome (treatment success or still on treatment after culture conversion) was achieved in 40 patients (78%) with culture conversion at a median of 55 days (IQR 41-91 days) from the start of linezolid therapy. Eleven patients (22%) had unfavourable outcomes (treatment failure or death) and 14 (27%) discontinued treatment due to neurotoxicity (peripheral or optic neuropathy) after a median of 278 days (IQR 174-412 days).\n\n\nCONCLUSIONS\nOur findings suggest that linezolid at a daily dose of 300 mg is effective against intractable MDR/XDR-TB, and may be associated with fewer neuropathic side effects than a daily dose of 600 or 1200 mg.","paper_authors":["W. Koh","Yeh Rim Kang","K. Jeon","O. Kwon","Jiwon Lyu","W. Kim","T. Shim"],"paper_publish_year":2012,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/dose-multidrugresistant-extensively-tuberculosis-koh/08c46a7ccd0b5c4b9f631e34e013dee5/?utm_source=chatgpt","doi":"10.1093/jac/dks078","volume":"67 6","pages":"\n 1503-7\n ","search_result_number":1},{"paper_title":"Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis.","abstract":"BACKGROUND\nAlthough previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear.\n\n\nMETHODS\nTwenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen.\n\n\nRESULTS\nThe patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268-443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233-405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26-145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298-427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48-160 days).\n\n\nCONCLUSIONS\nA daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.","paper_authors":["W. Koh","O. Kwon","H. Gwak","J. Chung","Sang-Nae Cho","W. Kim","T. Shim"],"paper_publish_year":2009,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/dose-treatment-multidrugresistant-extensively-koh/45c604234aa059ea8b2ebeef5285c040/?utm_source=chatgpt","doi":"10.1093/jac/dkp171","volume":"64 2","pages":"\n 388-91\n ","search_result_number":2},{"paper_title":"Comparison of the Pharmacokinetics of Two Dosage Regimens of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Patients","abstract":"Background and ObjectivesFor the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), potent new drugs are urgently needed. Linezolid is a promising drug, but its use is limited by adverse effects with prolonged administration of 600 mg twice daily. In order to reduce its adverse effects and maintain efficacy, we investigated whether linezolid in a reduced dosage resulted in drug serum concentrations exceeding a ratio of the in vitro minimum inhibitory concentration (MIC) to the area under the serum concentration-time curve (AUC) over 24 hours (AUC24) [AUC24/MIC] of >100.Patients and MethodsThis open-label, prospective pharmacokinetic study evaluated two doses (300 and 600 mg) of linezolid in MDR-TB patients, who received linezolid as part of their treatment. They received linezolid 300 mg twice daily for 3 days, followed by 600 mg twice daily. Blood samples taken at predefined intervals for measuring serum linezolid concentrations were processed by a validated liquid chromatography-tandem mass spectrometry procedure. The AUC24/MIC ratio was used as a predictive model of efficacy. Adverse effects of linezolid, including peripheral neuropathy, were evaluated by clinical and laboratory assessments.ResultsEight patients were included in this study. The median duration of linezolid treatment was 56 days (interquartile range [IQR 44-82] days), with a median cumulative dose of 51000 mg (IQR 33 850-60 450 mg). The median linezolid AUC over 12 hours (AUC12) values were 57.6mg ·h/L (IQR 38.5–64.2 mg•h/L) with the 300mg dose and 145.8mg•h/L (IQR 101.2–160.9mg•h/L) with the 600mg dose. The AUC24/MIC ratios were 452 (IQR 343-513) with the 300mg dose and 1151 (IQR 656-1500) with the 600mg dose. Linezolid was well tolerated.ConclusionSeemingly effective serum concentrations were reached after 3 days of administration of linezolid 300 mg twice daily, i.e. the AUC24/MIC ratio was at least 100 in 7 of 8 patients. Larger numbers of patients should be studied to confirm the efficacy of the linezolid 300 mg twice-daily dosage in MDR-TB or XDR-TB treatment.","paper_authors":["J. Alffenaar","R. van Altena","Ilse M. Harmelink","Patricia Filguera","Esther Molenaar","A. Wessels","D. van Soolingen","J. Kosterink","D. Uges","T. S. van der Werf"],"paper_publish_year":2010,"publication_journal_name":"Clinical Pharmacokinetics","consensus_paper_details_url":"https://consensus.app/papers/comparison-pharmacokinetics-dosage-regimens-linezolid-alffenaar/0d66cf3de174503fb7550f57482f646b/?utm_source=chatgpt","doi":"10.2165/11532080-000000000-00000","volume":"49","pages":"559-565","search_result_number":3},{"paper_title":"Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis--authors' response.","abstract":"1. Koh WJ, Kwon OJ, Gwak H et al. Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drugresistant tuberculosis. J Antimicrob Chemother 2009; 64: 388–91. 2. Eker B, Ortmann J, Migliori GB et al. Multidrugand extensively drug-resistant tuberculosis, Germany. Emerg Infect Dis 2008; 14: 1700–6. 3. Migliori GB, Eker B, Richardson MD et al. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in MDR-TB. Eur Respir J 2009; doi:10.1183/09031936.00009509. 4. World Health Organization. Global Tuberculosis Control 2008, Surveillance, Planning, Financing: WHO Report 2008. WHO/HTM/TB2008.393. Geneva: World Health Organization, 2008. 5. Laserson K, Thorpe LE, Leimane V et al. Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2005; 9: 640–5. 6. Sotgiu G, Ferrara G, Matteelli A et al. Epidemiology and clinical management of XDR-TB: a systematic review by TBNET. Eur Respir J 2009; 33: 871–81.","paper_authors":["W. Koh","T. Shim"],"paper_publish_year":2009,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/dose-treatment-multidrugresistant-extensively-koh/684894dac84c53e2ac93a1009a091034/?utm_source=chatgpt","doi":"10.1093/jac/dkp344","volume":"64 5","pages":"\n 1119-20\n ","search_result_number":4},{"paper_title":"Comment on: Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis","abstract":"Background: Although previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear. Methods: Twenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen. Results: The patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268―443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233―405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26―145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298―427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48―160 days). Conclusions: A daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.","paper_authors":["Wing Wai Yew","Kwok Chiu Chang","Chi Hung Chau"],"paper_publish_year":2009,"publication_journal_name":"Journal of Antimicrobial Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/daily-dose-treatment-multidrugresistant-extensively-yew/f897472ee1bb575c81309c27d5723cee/?utm_source=chatgpt","doi":"10.1093/JAC/DKP265","volume":"","pages":"","search_result_number":5},{"paper_title":"Comment on: Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis.","abstract":"Background: Although previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear. Methods: Twenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen. Results: The patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268―443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233―405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26―145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298―427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48―160 days). Conclusions: A daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.","paper_authors":["W. Yew","K. Chang","C. Chau"],"paper_publish_year":2009,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/daily-dose-treatment-multidrugresistant-extensively-yew/56b420184393524ba8da548b2399caed/?utm_source=chatgpt","doi":"10.1093/jac/dkp291","volume":"64 5","pages":"\n 1119; author reply 1119-20\n ","search_result_number":6},{"paper_title":"Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation","abstract":"Abstract Objectives The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap. Methods We defined linezolid PK/PD targets for efficacy (fAUC0–24:MIC >119 mg/L/h) and safety (fCmin <1.38 mg/L). We extracted individual-level linezolid PK data from existing studies on TB patients and performed meta-analysis, producing summary estimates of fAUC0–24 and fCmin for published doses. Combining these with a published MIC distribution, we performed Monte Carlo simulations of target attainment. Results The efficacy target was attained in all simulated individuals at 300 mg q12h and 600 mg q12h, but only 20.7% missed the safety target at 300 mg q12h versus 98.5% at 600 mg q12h. Although suggesting 300 mg q12h should be used preferentially, these data were reliant on a single centre. Efficacy and safety targets were missed by 41.0% and 24.2%, respectively, at 300 mg q24h and by 44.6% and 27.5%, respectively, at 600 mg q24h. However, the confounding effect of between-study heterogeneity on target attainment for q24h regimens was considerable. Conclusions Linezolid dosing at 300 mg q12h may retain the efficacy of the 600 mg q12h licensed dosing with improved safety. Data to evaluate commonly used 300 mg q24h and 600 mg q24h doses are limited. Comprehensive, prospectively obtained PK/PD data for linezolid doses in drug-resistant TB treatment are required.","paper_authors":["J. Millard","H. Pertinez","L. Bonnett","E. Hodel","V. Dartois","John L. Johnson","M. Caws","Simon Tiberi","M. Bolhuis","J. Alffenaar","G. Davies","D. Sloan"],"paper_publish_year":2018,"publication_journal_name":"Journal of Antimicrobial Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/pharmacokinetics-mdrtb-review-metaanalysis-monte-carlo-millard/37f65aaf080053ad90f0e862cf327d1b/?utm_source=chatgpt","doi":"10.1093/jac/dky096","volume":"73","pages":"1755 - 1762","search_result_number":7},{"paper_title":"Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis","abstract":"The prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an fAUC (area under the unbound drug concentration-time curve)/MIC ratio of >119 as the PK/pharmacodynamic (PD) target and minimum (trough) concentrations of drug (Cmins) of 2 and 7 mg/liter as thresholds for toxicity. ABSTRACT The prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an fAUC (area under the unbound drug concentration-time curve)/MIC ratio of >119 as the PK/pharmacodynamic (PD) target and minimum (trough) concentrations of drug (Cmins) of 2 and 7 mg/liter as thresholds for toxicity. The PK/PD breakpoint was defined as the highest MIC at which the probability of target attainment is >90%. A total of 104 patients with pulmonary TB were included, with a median age and weight of 37 years and 60 kg. Eighty-one percent had drug-resistant TB. The PK data were best described by a one-compartment model. The PK/PD breakpoint was 0.125 mg/liter for a total daily dose of 300 mg, while daily doses of 450 to 600 mg and 900 to 1,200 mg had PK/PD breakpoints of 0.25 and 0.50 mg/liter, respectively. The probability of achieving a Cmin of ≤2 mg/liter was higher when the dose was given at once than when dividing it into 2 doses. Linezolid at a daily dose of 300 mg may not be optimal. We predicted an excellent and comparable efficacy of linezolid using total daily doses of 900 and 1,200 mg for MICs of ≤0.5 mg/liter but with the potential for more toxicity than with 600 mg daily. The increase in Cmin was noticeable when the daily dose was divided and may incur greater toxicity.","paper_authors":["W. Alghamdi","Mohammad H. Al-Shaer","G. An","A. Alsultan","M. Kipiani","Ketevan Barbakadze","L. Mikiashvili","D. Ashkin","D. Griffith","J. P. Cegielski","R. Kempker","C. Peloquin"],"paper_publish_year":2020,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/population-pharmacokinetics-tuberculosis-patients-alghamdi/fa06aa7fcbee534dbfc18312a6280bc3/?utm_source=chatgpt","doi":"10.1128/AAC.01174-20","volume":"64","pages":"","search_result_number":8},{"paper_title":"Pharmacokinetics and pharmacodynamics of low dose 300 mg once daily oral linezolid for treatment of tuberculosis","abstract":"Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis bacteria, continues to be an immense global public health problem and still remains a leading cause of death among infectious diseases, especially in developing countries. In the last few decades, the incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB have been increasing and have become a significant public health threat in many countries. Linezolid, an oxazolidinone antimicrobial agent, has been shown to be effective against M. tuberculosis, including MDRand XDR-TB. However, a daily regimen of 1200 mg or even 600 mg of linezolid for treatment of MDRand XDR-TB has potential toxicities. A daily 300 mg dose of linezolid would be an effective treatment against MDRand XDR-TB with fewer adverse effects. The objective of this study was to determine the pharmacokinetics (PK) of a 300 mg daily dose of oral linezolid for achieving the pharmacodynamic (PD) targets. Thirty healthy subjects received 300 mg oral linezolid once daily and PK studies were carried out on day 5 after the beginning of drug administration. The mean value of AUC0-24 of this agent was calculated for the achievement of PD targets. The mean values of Vd, CL and AUC0-24 were 29.08  10.75 L, 3.69  1.58 L/h and 94.38  35.12 mg.h/L, respectively. The AUC0-24/MIC ratio for a MIC of 0.9 and 0.75 mg/L were approximately 100 and 119, respectively. In conclusion, 300 mg of linezolid daily is an alternative antibiotic option in patients with intolerance to the side effects of the standard dosage regimens.","paper_authors":["S. Jaruratanasirikul","Jetsada Piwluang","S. Sriwiriyajan","Monchana Nawakitrangsan","Maseetoh Samaeng","Nuntiya Theerapakanunt"],"paper_publish_year":2021,"publication_journal_name":"Pharmaceutical Sciences Asia","consensus_paper_details_url":"https://consensus.app/papers/pharmacokinetics-pharmacodynamics-dose-treatment-jaruratanasirikul/b9fc297d98a05e0ca4ec2c8a05cde8ad/?utm_source=chatgpt","doi":"10.29090/psa.2021.04.20.069","volume":"","pages":"","search_result_number":9},{"paper_title":"Analysis of thrombocytopenic effects and population pharmacokinetics of linezolid: a dosage strategy according to the trough concentration target and renal function in adult patients.","abstract":"The pharmacokinetic/pharmacodynamic (PK/PD) index for the efficacy of linezolid is a 24-h area under the plasma drug concentration-time curve (AUC₂₄)/minimum inhibitory concentration (MIC) ratio of ≥100. The main adverse event associated with administration of linezolid is thrombocytopenia. Therefore, the aims of the present study were to define PD thresholds that would minimise linezolid-induced thrombocytopenia and to perform a population PK analysis to identify factors influencing the pharmacokinetics of linezolid. Population PK analysis revealed that creatinine clearance (CLCr) significantly affected linezolid pharmacokinetics: the mean parameter estimate of drug clearance (CL; in L/h)=0.0258 × CLCr + 2.03. A strong correlation (r=0.970) was found between AUC₂₄ and trough plasma concentrations (Cmin) [AUC₂₄=18.2 × Cmin + 134.4]. The Cmin value for AUC₂₄=200 (in the case of MIC=2 μg/mL) was estimated to be 3.6 μg/mL. Regarding safety, Cmin was a significant predictor of thrombocytopenia during treatment, and its threshold to minimise linezolid-induced thrombocytopenia was 8.2 μg/mL. A Kaplan-Meier plot revealed that the median time from initiation of therapy to the development of thrombocytopenia was 15 days. Therefore, the target Cmin range was 3.6-8.2 μg/mL. The following formula to achieve a target Cmin in patients with different degrees of renal function was proposed based on these results: initial daily dose (mg/day)=CL × AUC₂₄=(0.0258 × CLCr + 2.03)×(18.2 × Cmin + 134.4). This recommended initial dosage and subsequent dosage adjustment for the target concentration range should avoid adverse events, thereby enabling effective linezolid-based therapies to be continued.","paper_authors":["Kazuaki Matsumoto","A. Shigemi","Ayumi Takeshita","E. Watanabe","Yuta Yokoyama","K. Ikawa","N. Morikawa","Yasuo Takeda"],"paper_publish_year":2014,"publication_journal_name":"International journal of antimicrobial agents","consensus_paper_details_url":"https://consensus.app/papers/analysis-effects-population-pharmacokinetics-dosage-matsumoto/8b44ca2cf72452438b8fdc38a4eff702/?utm_source=chatgpt","doi":"10.1016/j.ijantimicag.2014.05.010","volume":"44 3","pages":"\n 242-7\n ","search_result_number":10},{"paper_title":"Linezolid dosage in pediatric patients based on pharmacokinetics and pharmacodynamics.","abstract":"Linezolid pharmacokinetic profile in pediatric patients has not been fully characterized, and the dose needed to achieve a pharmacokinetic-pharmacodynamic (PK-PD) target has yet to be established because its efficacy is associated with the area under the plasma drug concentration-time curve (AUC24)/minimum inhibitory concentration (MIC) ratio. The present study aimed to define the pharmacokinetic parameters of intravenous linezolid in pediatric patients and assess the rationale for the approved dosage recommendations. Linezolid was safe, tolerated well, and clinically effective for treating Gram-positive bacteria in five pediatric patients (3-11 years). The mean values for the volume of distribution and total clearance (CL) in a one-compartment model were estimated to be 0.646 ± 0.239 l/kg and 0.171 ± 0.068 l/h/kg, respectively (mean ± S.D.). Based on this analysis, the AUC24 and trough drug concentration in plasma (C(min)) for linezolid doses were predicted to be 175.4 μg h/ml and 3.4 μg/ml for 30 mg/kg/day, 204.7 μg h/ml and 4.3 μg/ml for 35 mg/kg/day, and 263.2 μg h/ml and 6.2 μg/ml for 45 mg/kg/day, respectively. Taking into account that AUC24 should be ≥ 200 μg h/ml for MIC of 2.0 μg/ml (to achieve an AUC24/MIC ratio of ≥ 100) and C(min) should be approximately 7 μg/ml (to avoid thrombocytopenia), we consider the approved dosage of 30 mg/kg/day to be fundamentally rational, but can be underdosed against bacteria with MIC of 2.0 μg/ml; therefore, a dose of 35-45 mg/kg/day is more appropriate to ensure the efficacy and safety of linezolid in pediatric patients.","paper_authors":["Kazuaki Matsumoto","A. Shigemi","Ayumi Takeshita","E. Watanabe","Yuta Yokoyama","K. Ikawa","N. Morikawa","Yasuo Takeda"],"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/dosage-patients-based-pharmacokinetics-matsumoto/70ade01096be5569a88e6a7e3264c82a/?utm_source=chatgpt","doi":"10.1016/j.jiac.2014.08.017","volume":"21 1","pages":"\n 70-3\n ","search_result_number":11},{"paper_title":"Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis","abstract":"ABSTRACT Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates. The dose that would maximize efficacy and minimize toxicity is unknown. We performed linezolid dose-effect and dose-scheduling studies in the hollow fiber system model of tuberculosis (HFS-TB) for sterilizing effect. HFS-TB units were treated with several doses to mimic human-like linezolid intrapulmonary pharmacokinetics and repetitively sampled for drug concentration, total bacterial burden, linezolid-resistant subpopulations, and RNA sequencing over 2 months. Linezolid-resistant isolates underwent whole-genome sequencing. The expression of genes encoding efflux pumps in the first 1 to 2 weeks revealed the same exposure-response patterns as the linezolid-resistant subpopulation. Linezolid-resistant isolates from the 2nd month of therapy revealed mutations in several efflux pump/transporter genes and a LuxR-family transcriptional regulator. Linezolid sterilizing effect was linked to the ratio of unbound 0- to 24-h area under the concentration-time curve (AUC0–24) to MIC. Optimal microbial kill was achieved at an AUC0–24/MIC ratio of 119. The optimal sterilizing effect dose for clinical use was identified using Monte Carlo simulations. Clinical doses of 300 and 600 mg/day (or double the dose every other day) achieved this target in 87% and >99% of 10,000 patients, respectively. The susceptibility breakpoint identified was 2 mg/liter. The simulations identified that a 300-mg/day dose did not achieve AUC0–24s associated with linezolid toxicity, while 600 mg/day achieved those AUC0–24s in <20% of subjects. The linezolid dose of 300 mg/day performed well and should be compared to 600 mg/day or 1,200 mg every other day in clinical trials.","paper_authors":["S. Srivastava","G. Magombedze","T. Koeuth","C. Sherman","J. Pasipanodya","P. Raj","E. Wakeland","D. Deshpande","T. Gumbo"],"paper_publish_year":2017,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/linezolid-dose-that-maximizes-sterilizing-effect-while-srivastava/27d3d6cbaa99536da75e32b4f8245b3f/?utm_source=chatgpt","doi":"10.1128/AAC.00751-17","volume":"61","pages":"","search_result_number":12},{"paper_title":"Pharmacokinetic analysis of linezolid for multidrug resistant tuberculosis at a tertiary care centre in Mumbai, India","abstract":"Linezolid is an oxazolidinone used to treat multidrug-resistant tuberculosis (MDR-TB), including in the recently-endorsed shorter 6-month treatment regimens. Due to its narrow therapeutic index, linezolid is often either dose-adjusted or discontinued due to intolerance or toxicity during treatment, and the optimal balance between linezolid efficacy and toxicity remains unclear. India carries a significant burden of MDR-TB cases in the world, but limited information on the pharmacokinetics of linezolid and minimum inhibitory concentration (MIC) distribution is available from Indian MDR-TB patients. We enrolled participants from a tertiary care centre in Mumbai, India, treated for MDR-TB and receiving linezolid daily doses of 600 or 300 mg. Pharmacokinetic visits were scheduled between 1 and 15 months after treatment initiation to undergo intensive or sparse blood sampling. Linezolid concentration versus time data were analysed using non-linear mixed-effects modelling, with simulations to evaluate doses for different scenarios. We enrolled 183 participants (121 females), with a median age of 26 years (interquartile range [IQR] 21–35), weight 55.0 kg (IQR 45.6–65.8), and fat-free mass 38.7 kg (IQR 32.7–46.0). Linezolid pharmacokinetics was best described by a one-compartment model with first-order elimination allometrically scaled by fat-free mass and transit compartment absorption. The typical clearance value was 3.81 L/h. Simulations predicted that treatment with 300 mg daily achieves a high probability of target attainment (PTA) when linezolid MIC was ≤0.25 mg/L (61.5% of participant samples tested), while 600 mg daily would be required if MIC were 0.5 mg/L (29% of samples). While linezolid 300 mg daily is predicted to achieve effective targets for the majority of adults with MDR-TB, it failed to achieve the therapeutic target for 21% participants. A dose of 600 mg had a PTA >90% for all susceptible samples, but with a higher likelihood of exceeding toxicity thresholds (31% vs 9.6%). These data suggest potential benefit to individualized dosing taking host and microbial characteristics into account to improve the likelihood of treatment efficacy while minimizing risk of toxicity from linezolid for the treatment of MDR-TB. Further prospective evaluation in different clinical settings is urgently needed to inform safety and efficacy of these lower doses.","paper_authors":["J. E. Resendiz-Galvan","P. Arora","M. Abdelwahab","Z. Udwadia","Camilla Rodrigues","Amita Gupta","P. Denti","T. Ashavaid","J. Tornheim"],"paper_publish_year":2023,"publication_journal_name":"Frontiers in Pharmacology","consensus_paper_details_url":"https://consensus.app/papers/analysis-multidrug-tuberculosis-care-centre-mumbai-india-resendizgalvan/5c5d9423a1a45d5bb405abdc99ba3cf1/?utm_source=chatgpt","doi":"10.3389/fphar.2022.1081123","volume":"13","pages":"","search_result_number":13},{"paper_title":"Linezolid-based Regimens for Multidrug-resistant Tuberculosis (TB): A Systematic Review to Establish or Revise the Current Recommended Dose for TB Treatment.","abstract":"Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose- and duration-related toxicity limit its use. Here, our aim was to search relevant pharmacokinetics (PK)/pharmacodynamics (PD) literature to identify the effective PK/PD index and to define the optimal daily dose and dosing frequency of linezolid in MDR-TB regimens. The systematic search resulted in 8 studies that met inclusion criteria. A significant PK variability was observed. Efficacy of linezolid seems to be driven by area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC). Literature is inconclusive about the preferred administration of a daily dose of 600 mg. To prevent development of drug resistance, an AUC/MIC ratio of 100 in the presence of a companion drug at relevant exposure is required. A daily dose of 600 mg seems appropriate to balance between efficacy and toxicity. Being a drug with a very narrow therapeutic window, linezolid treatment may benefit from a more personalized approach, that is, measuring actual MIC values and therapeutic drug monitoring.","paper_authors":["M. Bolhuis","O. Akkerman","M. Sturkenboom","S. Ghimire","S. Srivastava","T. Gumbo","J. Alffenaar"],"paper_publish_year":2018,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/linezolidbased-regimens-multidrugresistant-bolhuis/5afe92049bc5586e92fab0f4ecbcef78/?utm_source=chatgpt","doi":"10.1093/cid/ciy625","volume":"67 suppl_3","pages":"\n S327-S335\n ","search_result_number":14},{"paper_title":"Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis","abstract":"Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23–7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P < 0·0001). Increasing mean linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = − 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.","paper_authors":["T. Song","Myung‐hee Lee","Han-Seung Jeon","Yumi Park","L. Dodd","V. Dartois","D. Follman","Jing Wang","Ying Cai","L. Goldfeder","K. Olivier","Yingda L. Xie","L. Via","Sang-Nae Cho","C. Barry","Ray Y. Chen"],"paper_publish_year":2015,"publication_journal_name":"EBioMedicine","consensus_paper_details_url":"https://consensus.app/papers/linezolid-trough-concentrations-correlate-song/d7660cf66fc25c43b06221cabbfff689/?utm_source=chatgpt","doi":"10.1016/j.ebiom.2015.09.051","volume":"2","pages":"1627 - 1633","search_result_number":15},{"paper_title":"Linezolid for treatment of chronic extensively drug-resistant tuberculosis.","abstract":"BACKGROUND\nLinezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis.\n\n\nMETHODS\nWe enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring.\n\n\nRESULTS\nBy 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed.\n\n\nCONCLUSIONS\nLinezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.).","paper_authors":["Myung‐hee Lee","Jongseok Lee","M. Carroll","Hongjo Choi","S. Min","T. Song","L. Via","L. Goldfeder","E. Kang","Boyoung Jin","Hyeeun Park","Hyun-Tae Kwak","Hyunchul Kim","Han-Seung Jeon","Ina Jeong","J. Joh","Ray Y. Chen","K. Olivier","P. Shaw","D. Follmann","S. Song","Jong-Koo Lee","Dukhyoung Lee","C. Kim","V. Dartois","Seung-kyu Park","Sang-Nae Cho","C. Barry"],"paper_publish_year":2012,"publication_journal_name":"The New England journal of medicine","consensus_paper_details_url":"https://consensus.app/papers/linezolid-treatment-chronic-extensively-tuberculosis-lee/afff8e74130c5e5996fff6e3b96bfc6f/?utm_source=chatgpt","doi":"10.1056/NEJMoa1201964","volume":"367 16","pages":"\n 1508-18\n ","search_result_number":16},{"paper_title":"Fourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis","abstract":"Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown. From November 2014 to November 2016, we randomized 114 drug-sensitive treatment-naive pulmonary tuberculosis patients from Cape Town, South Africa, to one of six 14-day treatment arms containing linezolid at 300 mg once daily (QD), 300 mg twice daily (BD), 600 mg QD, 600 mg BD, 1,200 mg QD, 1,200 mg three times per week (TIW), or a combination of isoniazid, rifampin, pyrazinamide, and ethambutol. ABSTRACT Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown. From November 2014 to November 2016, we randomized 114 drug-sensitive treatment-naive pulmonary tuberculosis patients from Cape Town, South Africa, to one of six 14-day treatment arms containing linezolid at 300 mg once daily (QD), 300 mg twice daily (BD), 600 mg QD, 600 mg BD, 1,200 mg QD, 1,200 mg three times per week (TIW), or a combination of isoniazid, rifampin, pyrazinamide, and ethambutol. Sixteen-hour sputum samples were collected overnight, and bactericidal activity was characterized by the daily percentage change in time to positivity (TTP) and the daily rate of change in log10(CFU). We also assessed the safety and pharmacokinetics of the study treatments. We found that bactericidal activity increased with increasing doses of linezolid. Based on the daily percentage change in TTP, activity was highest for 1,200 mg QD (4.5%; 95% Bayesian confidence interval [BCI], 3.3 to 5.6), followed by 600 mg BD (4.1%; BCI, 2.5 to 5.7), 600 mg QD (4.1%; BCI, 2.9 to 5.3), 300 mg BD (3.3%; BCI, 1.9 to 4.7), 300 mg QD (2.3%; BCI, 1.1 to 3.5), and 1,200 mg TIW (2.2%; BCI, 1.1 to 3.3). Similar results were seen with bactericidal activity characterized by the daily rate of change in CFU count. Antimycobacterial activity correlated positively with plasma drug exposure and percentage time over MIC. There were no unexpected adverse events. All linezolid doses showed bactericidal activity. For the same total daily dose, once-daily dosing proved to be at least as effective as a divided twice-daily dose. An intermittent dosing regimen, with 1,200 mg given three times weekly, showed the least activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02279875.)","paper_authors":["A. Diacon","Veronique R. de Jager","R. Dawson","K. Narunsky","N. Vanker","D. Burger","D. Everitt","F. Pappas","J. Nedelman","C. Mendel"],"paper_publish_year":2020,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/fourteenday-bactericidal-activity-safety-diacon/ce095b9720ae5eaeb403263a95c421fc/?utm_source=chatgpt","doi":"10.1128/AAC.02012-19","volume":"64","pages":"","search_result_number":17},{"paper_title":"Proposal of initial and maintenance dosing regimens with linezolid for renal impairment patients","abstract":"Background Linezolid is administered as a fixed dose to all patients despite evidence of overexposure and thrombocytopenia in renal impairment. The aims of this study were to evaluate the risk of thrombocytopenia and the utility of therapeutic drug monitoring (TDM), and to propose alternate dosing regimens in patients with renal impairment. Methods We retrospectively reviewed patients ≥13 years old for whom serum linezolid trough concentration ( C min ) was measured during linezolid treatment. Patients with episodes of infection were divided into groups by presence of renal impairment (RI group) or absence of renal impairment (non-RI group), and by use of C min -based TDM (TDM group) or not (non-TDM group) during linezolid treatment. Results In the 108 patients examined by multivariable analyses, renal impairment was independently associated with increased risk of thrombocytopenia (OR 3.17, 95%CI 1.10–9.12) and higher C min . Analysis of the utility of TDM in the RI group showed that clinical failure rate was significantly lower in the TDM subgroup than in the non-TDM subgroup. Furthermore, in the RI group, dosage adjustments were needed in 90.5% of the TDM subgroup. All episodes administered a reduced dose of 300 mg every 12 h in the RI group showed C min  ≥ 2.0 mg/L. Additional analysis of 53 episodes in which C min was measured within 48 h after starting administration showed that the initial standard dose for 2 days was sufficient to rapidly reach an effective therapeutic concentration in the RI group. Conclusions Empirical dose reduction to 300 mg every 12 h after administration of the initial fixed dose for 2 days and C min -based TDM may improve safety outcomes while maintaining appropriate efficacy among patients with renal impairment.","paper_authors":["H. Kawasuji","Y. Tsuji","C. Ogami","K. Kimoto","A. Ueno","Y. Miyajima","Koyomi Kawago","I. Sakamaki","Yoshihiro Yamamoto"],"paper_publish_year":2021,"publication_journal_name":"BMC Pharmacology & Toxicology","consensus_paper_details_url":"https://consensus.app/papers/proposal-maintenance-dosing-regimens-impairment-kawasuji/3394db4b11ff594c8e843a052fc79277/?utm_source=chatgpt","doi":"10.1186/s40360-021-00479-w","volume":"22","pages":"","search_result_number":18},{"paper_title":"Linezolid Population Pharmacokinetics in South African Adults with Drug-Resistant Tuberculosis","abstract":"Linezolid is widely used for drug-resistant tuberculosis (DR-TB) but has a narrow therapeutic index. To inform dose optimization, we aimed to characterize the population pharmacokinetics of linezolid in South African participants with DR-TB and explore the effect of covariates, including HIV coinfection, on drug exposure. ABSTRACT Linezolid is widely used for drug-resistant tuberculosis (DR-TB) but has a narrow therapeutic index. To inform dose optimization, we aimed to characterize the population pharmacokinetics of linezolid in South African participants with DR-TB and explore the effect of covariates, including HIV coinfection, on drug exposure. Data were obtained from pharmacokinetic substudies in a randomized controlled trial and an observational cohort study, both of which enrolled adults with drug-resistant pulmonary tuberculosis. Participants underwent intensive and sparse plasma sampling. We analyzed linezolid concentration data using nonlinear mixed-effects modeling and performed simulations to estimate attainment of putative efficacy and toxicity targets. A total of 124 participants provided 444 plasma samples; 116 were on the standard daily dose of 600 mg, while 19 had dose reduction to 300 mg due to adverse events. Sixty-one participants were female, 71 were HIV-positive, and their median weight was 56 kg (interquartile range [IQR], 50 to 63). In the final model, typical values for clearance and central volume were 3.57 liters/h and 40.2 liters, respectively. HIV coinfection had no significant effect on linezolid exposure. Simulations showed that 600-mg dosing achieved the efficacy target (area under the concentration-time curve for the free, unbound fraction of the drug [ fAUC0 - 24h]/minimal inhibitory concentration [MIC]>119 at a MIC level of 0.5 mg/liter) with 96% probability but had 56% probability of exceeding safety target ( trough24h>2mg/liter). The 300-mg dose did not achieve adequate efficacy exposures. Our model characterized population pharmacokinetics of linezolid in South African patients with DR-TB and supports the 600-mg daily dose with safety monitoring.","paper_authors":["M. Abdelwahab","S. Wasserman","J. Brust","K. Dheda","L. Wiesner","N. Gandhi","R. Warren","F. Sirgel","G. Meintjes","G. Maartens","P. Denti"],"paper_publish_year":2021,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/population-pharmacokinetics-south-adults-drugresistant-abdelwahab/9d660e72d01d532285bbfbc4b7b50034/?utm_source=chatgpt","doi":"10.1128/AAC.01381-21","volume":"65","pages":"","search_result_number":19},{"paper_title":"Initially Reduced Linezolid Dosing Regimen to Prevent Thrombocytopenia in Hemodialysis Patients","abstract":"This retrospective cohort study investigated the effects of an initially reduced linezolid dosing regimen in hemodialysis patients through therapeutic drug monitoring (TDM). Patients were divided into two groups depending on their initial dose of linezolid (standard dose of 600 mg every 12 h or initially reduced dose of 300 mg every 12 h/600 mg every 24 h). The cumulative incidence rates of thrombocytopenia and severe thrombocytopenia were compared between both groups using the Kaplan–Meier method and log-rank test. Eleven episodes of 8 chronic hemodialysis patients were included; 5 were in the initially reduced-dose group. Thrombocytopenia developed in 81.8% of patients. The cumulative incidence rates of thrombocytopenia and severe thrombocytopenia in the initially reduced-dose group were significantly lower than in the standard-dose group (p < 0.05). At the standard dose, the median linezolid trough concentration (Cmin) just before hemodialysis was 49.5 mg/L, and Cmin at the reduced doses of 300 mg every 12 h and 600 mg every 24 h were 20.6 mg/L and 6.0 mg/L, respectively. All five episodes underwent TDM in the standard-dose group required dose reduction to 600 mg per day. Our findings indicate that initial dose reduction should be implemented to reduce the risk of linezolid-induced thrombocytopenia among hemodialysis patients.","paper_authors":["H. Kawasuji","Y. Tsuji","C. Ogami","M. Kaneda","Y. Murai","K. Kimoto","A. Ueno","Y. Miyajima","Y. Fukui","I. Sakamaki","Yoshihiro Yamamoto"],"paper_publish_year":2021,"publication_journal_name":"Antibiotics","consensus_paper_details_url":"https://consensus.app/papers/initially-reduced-linezolid-dosing-regimen-prevent-kawasuji/129d0be2734f5ddb8ffce0669d91c082/?utm_source=chatgpt","doi":"10.3390/antibiotics10050496","volume":"10","pages":"","search_result_number":20}]} --- **ChatGPT:** Reducing the dosage of linezolid to 300 mg for efficacy while maintaining its therapeutic effects and minimizing side effects has been explored, particularly in the context of treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. Here is an overview of the relevant considerations: ### Minimum Effective Dose and Efficacy 1. **Efficacy at 300 mg:** - Studies have shown that a daily dose of 300 mg of linezolid can be effective in treating MDR and XDR tuberculosis, achieving favorable outcomes in many patients [(Koh et al., 2009)](https://consensus.app/papers/dose-treatment-multidrugresistant-extensively-koh/45c604234aa059ea8b2ebeef5285c040/?utm_source=chatgpt) [(Jaruratanasirikul et al., 2021)](https://consensus.app/papers/pharmacokinetics-pharmacodynamics-dose-treatment-jaruratanasirikul/b9fc297d98a05e0ca4ec2c8a05cde8ad/?utm_source=chatgpt). However, the context of tuberculosis treatment might differ from other infections typically treated with linezolid. 2. **Pharmacokinetics and Pharmacodynamics:** - The pharmacokinetic profile of linezolid at 300 mg twice daily has shown that it can achieve therapeutic drug levels, maintaining efficacy while reducing the risk of adverse effects, particularly neurotoxicity [(Alffenaar et al., 2010)](https://consensus.app/papers/comparison-pharmacokinetics-dosage-regimens-linezolid-alffenaar/0d66cf3de174503fb7550f57482f646b/?utm_source=chatgpt). 3. **Toxicity Concerns:** - Lower doses, such as 300 mg daily, have been associated with fewer adverse effects, including peripheral neuropathy and myelosuppression, which are more common at higher doses like 600 mg twice daily [(Song et al., 2015)](https://consensus.app/papers/linezolid-trough-concentrations-correlate-song/d7660cf66fc25c43b06221cabbfff689/?utm_source=chatgpt). ### Considerations for Completing the Course 1. **Therapeutic Effectiveness:** - Completing the full prescribed dose of 600 mg twice daily for the remaining days is generally recommended to ensure the infection is fully treated and to prevent the development of resistance. Reducing the dose without medical guidance might compromise the treatment’s efficacy. 2. **Guidance from Healthcare Provider:** - It is essential to follow the prescribed regimen unless advised otherwise by a healthcare professional. Sudden changes in dosage without medical supervision can result in suboptimal treatment and increased risk of adverse effects. ### Conclusion While reducing the dosage of linezolid to 300 mg may help mitigate side effects, it should ideally be done under the supervision of a healthcare provider to ensure the infection is adequately treated. The standard therapeutic dose of 600 mg twice daily is recommended to maintain efficacy, particularly in serious infections. If experiencing significant side effects and unable to consult a healthcare provider immediately, continuing the prescribed dose until professional advice can be obtained is usually the safer approach. Any dose adjustment should be based on a healthcare professional’s assessment. 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:** The staff a staffacaucus epidermis infection was mild --- **ChatGPT:** For mild Staphylococcus epidermidis infections, especially when they are mild, completing the prescribed antibiotic course as directed by your healthcare provider is crucial for ensuring the infection is fully treated and preventing resistance. However, if side effects are significant, here are some considerations: ### Considerations for Mild Staphylococcus epidermidis Infections: 1. **Standard Treatment:** - For mild infections, the standard dose of linezolid is usually 600 mg every 12 hours. This dosage is based on ensuring adequate blood levels to combat the infection effectively [(French, 2003)](https://consensus.app/papers/safety-tolerability-linezolid-french/dd9f04d9403456d793ac8764091fa2f5/?utm_source=chatgpt). 2. **Reducing Dose:** - There is limited evidence on the efficacy of reducing the dose to 300 mg twice daily for mild infections, as most research on reduced doses pertains to severe or resistant infections like MDR-TB. However, some studies suggest that 300 mg may still maintain therapeutic levels, though this is typically within specific contexts such as tuberculosis treatment [(Koh et al., 2012)](https://consensus.app/papers/dose-multidrugresistant-extensively-tuberculosis-koh/08c46a7ccd0b5c4b9f631e34e013dee5/?utm_source=chatgpt). 3. **Medical Advice:** - Consulting a healthcare professional before making any changes to your medication regimen is essential. They can provide guidance based on your specific situation, including the severity of the infection and your overall health. ### Immediate Steps: - **Contact Healthcare Provider:** Explain your symptoms and side effects to get personalized advice. If you cannot reach your primary care physician, consider contacting an urgent care clinic or a pharmacist. - **Monitor Symptoms:** Keep an eye on any new or worsening symptoms, and seek immediate medical attention if necessary. ### Potential Approach: 1. **Complete the Course:** If tolerable, complete the remaining 600 mg doses to ensure the infection is fully treated. 2. **Discuss Dose Reduction:** If side effects are significant, discuss with a healthcare provider the possibility of reducing the dose to 300 mg twice daily or other alternatives. ### Conclusion: For mild Staphylococcus epidermidis infections, completing the full prescribed dose of linezolid is generally recommended to ensure effective treatment. However, due to the significant side effects you are experiencing, it is critical to seek medical advice before making any changes to your dosage. 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:** How many days is having a black stool mean danger When there are no symptoms like fatigue or pain --- **ChatGPT:** Having black stool, known as melena, often indicates the presence of bleeding in the upper gastrointestinal tract. While the absence of other symptoms like fatigue or pain can be somewhat reassuring, the presence of black stool alone warrants medical attention. Here’s a breakdown of what to consider: ### Potential Causes of Black Stool: 1. **Gastrointestinal Bleeding:** - Bleeding from the stomach or upper intestines can cause black, tarry stools. This can be due to ulcers, gastritis, or even certain medications like NSAIDs. 2. **Dietary Factors:** - Consuming certain foods (like black licorice, blueberries, or taking iron supplements) can cause black stool. However, this usually does not persist for several days. 3. **Medications:** - Some medications, including bismuth-containing compounds like Pepto-Bismol, can darken the stool. ### When to Seek Medical Attention: - **Immediate Evaluation:** If you have black stool for more than a day or two, it’s essential to seek medical evaluation. Even without other symptoms, persistent black stool can indicate a serious condition. - **Warning Signs:** If you develop additional symptoms such as dizziness, weakness, shortness of breath, abdominal pain, or if the stool has a foul odor, seek immediate medical care as these can be signs of significant blood loss or other serious conditions. ### Monitoring and Actions: 1. **Duration:** Black stool persisting for more than 2 days should prompt a visit to a healthcare provider. 2. **Frequency:** If black stool is observed consistently over multiple bowel movements, it is more concerning than a single occurrence. 3. **Associated Symptoms:** Be vigilant for any new symptoms that might develop, even if initially there are none. ### Conclusion: While the absence of fatigue or pain is somewhat reassuring, the presence of black stool for more than a couple of days indicates a need for medical evaluation to rule out potentially serious conditions. It is better to err on the side of caution and consult a healthcare provider to determine the cause and appropriate treatment. 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:** Yes I've recently started eating blueberries and cherries --- **ChatGPT:** Blueberries and cherries can sometimes cause stool to appear darker or even black. This is generally harmless and related to the pigments in these fruits. However, distinguishing between diet-induced dark stool and stool that is dark due to gastrointestinal bleeding is important. ### Steps to Take: 1. **Stop Consuming the Foods:** - Temporarily stop eating blueberries, cherries, and other dark-colored foods. Observe if the stool color returns to normal within a few days. 2. **Monitor Stool Color:** - Keep track of your stool color over the next few days. If the color lightens after eliminating these foods, the cause was likely dietary. 3. **Stay Hydrated:** - Ensure you drink plenty of water to help your digestive system function properly. 4. **Watch for Symptoms:** - Be vigilant for any new symptoms such as dizziness, weakness, or abdominal pain. If these symptoms develop, seek medical attention immediately. ### When to Seek Medical Attention: - **Persistent Black Stool:** If the black stool persists even after stopping the consumption of these foods for a few days, seek medical advice. - **Additional Symptoms:** If you experience any other symptoms, such as those indicating significant blood loss or distress, seek medical attention immediately. ### Conclusion: If the black stool is indeed due to blueberries and cherries, it should resolve once you stop eating these fruits. However, if the condition persists or if you develop additional symptoms, it is important to consult with a healthcare provider to rule out any serious underlying conditions. 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:** How many days does it take to kill Staphylococcus epidermidis when taking 600mg every 12 hours? --- **ChatGPT:** ```json {"query": "duration to kill Staphylococcus epidermidis with Linezolid 600 mg every 12 hours"} ``` --- **[Tool]:** {"items":[{"paper_title":"Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA).","abstract":"We compared the health outcomes in patients treated with linezolid or vancomycin for complicated skin and soft tissue infections (cSSTIs). This analysis is part of a randomised, open-label, multinational trial involving 1200 adult patients hospitalised with cSSTIs due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects received linezolid 600 mg intravenous (i.v.) or oral, or vancomycin 1g i.v. every 12 h. A test-of-cure was assessed at 7 days post therapy. Compared with vancomycin, linezolid treatment was associated with significantly shorter length of stay (all P < 0.01), decreased i.v. antibiotic treatment duration (all P < 0.0001) and higher discharge rates (all P < 0.05). Thus, linezolid has the potential to reduce medical resource use for the treatment of cSSTIs.","paper_authors":["K. Itani","J. Weigelt","Jim Z. Li","S. Duttagupta"],"paper_publish_year":2005,"publication_journal_name":"International journal of antimicrobial agents","consensus_paper_details_url":"https://consensus.app/papers/reduces-length-duration-treatment-compared-vancomycin-itani/4180edd4a4025a34acef2a30107c9c57/?utm_source=chatgpt","doi":"10.1016/J.IJANTIMICAG.2005.09.003","volume":"26 6","pages":"\n 442-8\n ","search_result_number":1},{"paper_title":"Linezolid eradicates MRSA better than vancomycin from surgical-site infections.","abstract":"BACKGROUND\nThe purpose of this analysis was to compare the efficacy of linezolid versus vancomycin in patients with suspected or proven gram-positive methicillin-resistant Staphylococcus aureus (MRSA) surgical-site infections.\n\n\nMETHODS\nAn open-label, randomized, comparator-controlled, multicenter, multinational study was conducted in hospitalized patients. Patients were randomized 1:1 to receive linezolid 600 mg (intravenous [IV] or oral) every 12 hours (n = 66) or vancomycin 1 g every 12 hours IV (n = 69) for 7 to 21 days. Patients were assessed at the test-of-cure (TOC) visit, 7 days after completing therapy.\n\n\nRESULTS\nClinical success at TOC was documented in similar proportions of patients treated with linezolid or vancomycin. Of those with MRSA isolated, significantly more patients who received linezolid compared with those who received vancomycin were microbiologically cured (87% vs 48%, respectively; 95% confidence interval 16.51 to 60.27; P = 0.0022).\n\n\nCONCLUSION\nIntravenous or oral linezolid was well tolerated and superior to vancomycin in treating patients with MRSA-infected surgical-site infections.","paper_authors":["J. Weigelt","H. Kaafarani","K. Itani","R. Swanson"],"paper_publish_year":2004,"publication_journal_name":"American journal of surgery","consensus_paper_details_url":"https://consensus.app/papers/linezolid-eradicates-mrsa-better-vancomycin-infections-weigelt/36447aad4a8a5de48e27f2cccd8ce0c1/?utm_source=chatgpt","doi":"10.1016/J.AMJSURG.2004.08.045","volume":"188 6","pages":"\n 760-6\n ","search_result_number":2},{"paper_title":"Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.","abstract":"BACKGROUND\nPost hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia.\n\n\nMETHODS\nThis was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated.\n\n\nRESULTS\nOf 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%).\n\n\nCONCLUSIONS\nFor the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.","paper_authors":["R. Wunderink","M. Niederman","M. Kollef","A. Shorr","M. Kunkel","A. Baruch","W. McGee","A. Reisman","J. Chastre"],"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/linezolid-methicillinresistant-staphylococcus-aureus-wunderink/38e6faa375a35d7dbb455442be732c63/?utm_source=chatgpt","doi":"10.1093/cid/cir895","volume":"54 5","pages":"\n 621-9\n ","search_result_number":3},{"paper_title":"Transfer of Linezolid into Breast Milk","abstract":"Linezolid, a broad-spectrum antibiotic used primarily for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, is the first oxazolidinone approved for clinical use. This is a case report of a 30-year-old woman who was exclusively breastfeeding her infant prior to taking linezolid 600 mg orally every 12 hours to treat a MRSA mastitis. Breast milk samples were obtained over a 12-hour dosing interval on day 1 (after a single dose of therapy) and again on day 14 (at steady state). The relative infant dose at steady state was found to be 15.61% on day 14 of therapy. Using the average concentration at steady state, the estimated infant dose would have been 1.84 mg/kg/day, which is well below the recommended dose given to neonates requiring linezolid drug therapy. The infant did not breastfeed during maternal treatment with linezolid.","paper_authors":["Hilary Rowe","Kathleen Felkins","S. Cooper","T. Hale"],"paper_publish_year":2014,"publication_journal_name":"Journal of Human Lactation","consensus_paper_details_url":"https://consensus.app/papers/transfer-linezolid-breast-milk-rowe/559487a9cb2f50f0954c4c0269f32dbe/?utm_source=chatgpt","doi":"10.1177/0890334414546045","volume":"30","pages":"410 - 412","search_result_number":4},{"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":5},{"paper_title":"Antibacterial activity of linezolid and vancomycin in an in vitro pharmacodynamic model of gram-positive catheter-related bacteraemia.","abstract":"OBJECTIVES\nThe aim of this study was to compare the activity of linezolid and vancomycin in an in vitro pharmacodynamic model to assess potential differences in activity against biofilm-embedded organisms.\n\n\nMETHODS\nSingle-lumen central venous catheters colonized with biofilm-embedded Staphylococcus aureus, Staphylococcus epidermidis or vancomycin-resistant Enterococcus faecium (VRE) were treated with simulated clinical dosing regimens of linezolid 600 mg every 12 h or vancomycin 1 g every 12 h in a one-compartment in vitro pharmacodynamic model. Quantitative cultures were sampled through the catheter and peripheral ports over 48 h to dynamically assess changes in the burden of catheter colonization and organism seeding, respectively. At 24 and 48 h catheters were removed, sonicated and cultured for adherent organisms.\n\n\nRESULTS\nBoth linezolid and vancomycin suppressed bacterial growth on the catheter and release of S. aureus and S. epidermidis into the model compared with controls (P < 0.05), while linezolid also suppressed counts compared with control and vancomycin versus VRE. Neither agent completely eradicated bacterial colonization of the catheters. MICs for the isolates recovered from the model did not increase over time with linezolid or vancomycin exposure.\n\n\nCONCLUSIONS\nLack of activity against biofilm-embedded organisms appeared to be the primary reason for microbiological failure of both drugs in the model.","paper_authors":["N. Wiederhold","Elizabeth A. Coyle","I. Raad","R. Prince","R. Lewis"],"paper_publish_year":2005,"publication_journal_name":"The Journal of antimicrobial chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/activity-vancomycin-vitro-model-grampositive-wiederhold/7a8da2c07478520fb34e38394324a1a0/?utm_source=chatgpt","doi":"10.1093/JAC/DKI106","volume":"55 5","pages":"\n 792-5\n ","search_result_number":6},{"paper_title":"Treatment of Posttraumatic Osteomyelitis with Oral Linezolid","abstract":"Purpose To assess the efficacy and safety of oral linezolid associated with surgery in the treatment of posttraumatic osteomyelitis. Materials and methods Monitored prospective study of all patients suffering from posttraumatic osteomyelitis caused by Methicillin-resistant Gram positive cocci treated with elective surgery and linezolid 600 mg every 12 hours from June 2002 to December 2004. Results We have used linezolid to treat 9 patients with posttraumatic osteomyelitis. The microorganisms isolated were: Methicillin-resistant Staphylococcus aureus , 1; Methicillin-resistant Staphylococcus epidermidis , 7. Two patients had an associated infection caused by Pseudomonas aeruginosa . Mean duration of treatment was 9.5 weeks (range 6-12). During follow-up 8 patients were found to be clinically cured with fracture stabilization and with no sign of infection. One patient had an infected mal-union. Linezolid was excellently tolerated and in none of the cases it was necessary to discontinue administration due to toxicity. Conclusions In our experience oral linezolid associated with surgery can be an excellent option for the treatment of posttraumatic osteomyelitis caused by Methicillin-resistant Gram positive bacteria that do not respond to other antimicrobials or if these are not well tolerated.","paper_authors":["F. Romero-Candau","R. Pérez-Ferri","J. Madrigal","F. Najarro","F. Santos","F. Huesa"],"paper_publish_year":2007,"publication_journal_name":"","consensus_paper_details_url":"https://consensus.app/papers/treatment-posttraumatic-osteomyelitis-oral-linezolid-romerocandau/f2a272bffd605d27aeb5aab7cd4d60ae/?utm_source=chatgpt","doi":"10.1016/S1988-8856(07)70015-9","volume":"51","pages":"75-79","search_result_number":7},{"paper_title":"EFFICACY OF LINEZOLID OVER VANCOMYCIN IN TREATING METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) INFECTIONS.","abstract":"The purpose of this analysis was to compare the efficacy and safety of linezolid versus vancomycin in patients with nosocomial pneumonia, complicated skin & soft- tissue infections and sepsis by methicillin-resistant Staphylococcus aureus (MRSA).This study was conducted on hospitalized patients of a tertiary care hospital in Kolkata, West Bengal. Out of 191 patients, 130 received linezolid 600 mg (IV or oral) every 12 hours and 61 received vancomycin 1 g every 12 hours IV. Clinical success rates at the end of the treatment were 94.6% and 90.16% for the linezolid and vancomycin groups respectively (p=0.2564) and microbiological eradication rates were 93.07% and 88.52% respectively (p=0.2901) showing no significant difference in the efficacy of two drugs. Drug related adverse events were reported in 0.7% and 1.63% of the patients treated with linezolid and vancomycin respectively with thrombocytopenia (3.84%) reported only in patients who received linezolid. Linezolid is as effective as vancomycin however intravenous or oral linezolid was well tolerated.","paper_authors":["N. Jindal","Sonia Jain","D. Maitra","W. Bengal"],"paper_publish_year":2015,"publication_journal_name":"International journal of pharma and bio sciences","consensus_paper_details_url":"https://consensus.app/papers/efficacy-linezolid-over-vancomycin-treating-methicillin-jindal/bc76426c71d8563e8ce88d2993fe74d9/?utm_source=chatgpt","doi":"","volume":"","pages":"","search_result_number":8},{"paper_title":"Front-Loaded Linezolid Regimens Result in Increased Killing and Suppression of the Accessory Gene Regulator System of Staphylococcus aureus","abstract":"ABSTRACT Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 106 CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log10 CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of −6.15 and −6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a <1.27× increase in the fractional decreases in platelets for all front-loaded regimens versus the 600 mg q12h regimen, except for the highest-dose front-loaded regimen. Front-loading strategies for linezolid are promising and may be of utility in severe MRSA infections, where early aggressive therapy is necessary.","paper_authors":["Brian T. Tsuji","Tanya Brown","Ridhi Parasrampuria","D. Brazeau","A. Forrest","Pamela A. Kelchlin","Patricia N. Holden","C. Peloquin","D. Hanna","J. Bulitta"],"paper_publish_year":2012,"publication_journal_name":"Antimicrobial Agents and Chemotherapy","consensus_paper_details_url":"https://consensus.app/papers/frontloaded-linezolid-regimens-result-increased-killing-tsuji/49946c3595d0533e86f3800021874c9f/?utm_source=chatgpt","doi":"10.1128/AAC.05453-11","volume":"56","pages":"3712 - 3719","search_result_number":9},{"paper_title":"Efficacy of linezolid in treatment of ventilator-associated pneumonia induced by MRSA","abstract":"Objective To compare the efficacy and safety of linezolid and vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) induced ventilator-associated pneumonia in intensive care unit.Methods In randomized controlled trials,62 patients with MRSA-induced ventilator-associated pneumonia in intensive care unit were randomly divided into two groups.Linezolid group (n =28) were administered with linezolid 600 mg every 12 hours for 14 days,ivgtt.Vancomycin group (n =34) were given vancomycin 1 000 mg every 12 hours for 14 days,ivgtt.Adverse events and the efficacy of two groups were investigated.Results The effective rates in linezolid group and vancomycin group were 78.57％ and 52.94％ (P ＜0.05).The adverse reaction rates in linezolid group and vancomycin group were 10.71％ and 14.71％.Conclusions Linezolid has positive effect in the treatment of MRSA induced ventilator-associated pneumonia. \n \nKey words: \nLinezolid; Methicillin-resistant Staphylococcus aureus;  Ventilator-associated pneumonia","paper_authors":["K. Feng","J. Ling","B. Ma","Hao Zhou","X. Gou","Xiaomin Huang","Yi-kun Cui"],"paper_publish_year":2013,"publication_journal_name":"","consensus_paper_details_url":"https://consensus.app/papers/efficacy-treatment-ventilatorassociated-pneumonia-feng/b53027b5ce9f58109959868c628e5980/?utm_source=chatgpt","doi":"10.3760/CMA.J.ISSN.1673-436X.2013.024.006","volume":"33","pages":"1864-1866","search_result_number":10},{"paper_title":"Incidence of Intravenous Catheter-Site Complications in Patients Treated with Linezolid or Vancomycin for Skin Infections Caused by Methicillin-Resistant Staphylococcus aureus","abstract":"Objective The aim of the study was to compare all-cause adverse events (AEs) and those caused by intravenous (IV) catheter-site complications (IVCSCs) using data from a previously published study of the use of linezolid or vancomycin for treatment of complicated skin and skin structure infections (cSSSI) suspected or proven to be caused by methicillin-resistant Staphylococcus aureus. Methods To examine the incidence of AEs caused by the 2 antibiotic treatments, we conducted a post hoc analysis of data from a prospective, open-label, randomized, multicenter phase 4 study. Patients were randomized to treatment with either oral (PO) or IV linezolid 600 mg every 12 hours or with IV vancomycin 15 mg/kg every 12 hours with dose adjustment as needed. Study treatment was administered for 7 to 14 days. We excluded patients with baseline bacteremia (n = 11) and those who started on PO linezolid (n = 215). We analyzed data only from patients who received at least 1 dose of IV study medication. Results Patient demographics and types of cSSSI were comparable among patients receiving linezolid (n = 315) and vancomycin (n = 511). Mean durations of IV therapy for patients receiving linezolid and vancomycin were 4.5 days and 7.6 days (1,418 and 3,884 patient-days, respectively). All-cause AEs were reported in 50% and 51% of patients in the linezolid and vancomycin groups, respectively; all-cause IVCSCs were reported in 2% and 7%, respectively. Treatment-related IVCSCs were reported in 1 patient in the linezolid group and 16 patients in the vancomycin group. Conclusions The overall rate of AEs was similar among patients receiving linezolid and vancomycin, but AEs caused by IVCSCs were more frequent among patients receiving vancomycin and rare episodes of bacteremia and sepsis were more common in the linezolid group.","paper_authors":["D. Luke","D. Hewlett","V. Welch","R. Chambers","David B. Huang"],"paper_publish_year":2011,"publication_journal_name":"Hospital Pharmacy","consensus_paper_details_url":"https://consensus.app/papers/incidence-intravenous-cathetersite-complications-luke/3ed06129690058d58b2f2c316cdbb6eb/?utm_source=chatgpt","doi":"10.1310/hpj4606-427","volume":"46","pages":"427 - 431","search_result_number":11},{"paper_title":"Serotonin Toxicity Associated with Concomitant Use of Linezolid","abstract":"OBJECTIVE: To report 2 cases of serotonin toxicity (ST) associated with concomitant use of linezolid and serotonergic drugs and review previously published case reports. CASE SUMMARIES: Case 1. A 38-year-old white female with cystic fibrosis treated with venlafaxine 300 mg/day for one year was prescribed linezolid 600 mg intravenously every 12 hours for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pulmonary infection. She displayed symptoms of ST 8 days after the introduction of linezolid. The venlafaxine dosage was decreased to 150 mg/day, and symptoms gradually abated over 36 hours. Case 2. A 37-year-old male with multiple myeloma received citalopram 40 mg/day and trazodone 150 mg/day for anxiety-related disorders. Linezolid treatment with 600 mg orally twice daily was instituted for MRSA cellulitis. The following day, the patient developed anxiety, panic attacks, tremors, tachycardia, and hypertension that persisted throughout linezolid treatment. Symptoms finally waned 5 days after linezolid treatment was stopped. DISCUSSION: The symptoms observed in our patients were consistent with Sternbach's criteria for ST. A review of published case reports showed a short time to onset of symptoms following the introduction of linezolid, generally within 1–3 days. Also of note is the use of relatively high dosages of serotonergic drugs. Use of the Naranjo probability scale indicated a possible relationship between the use of linezolid and the occurrence of ST in both cases. CONCLUSIONS: Clinicians should pay special attention to patients treated with serotonergic drugs, especially those receiving dosages in the higher end of the normal range who are prescribed linezolid, and consider tapering or reducing the dosage of serotonergic drugs for the duration of antibiotic therapy.","paper_authors":["L. Bergeron","M. Boulé","S. Perreault"],"paper_publish_year":2005,"publication_journal_name":"Annals of Pharmacotherapy","consensus_paper_details_url":"https://consensus.app/papers/serotonin-toxicity-associated-concomitant-linezolid-bergeron/9448fe950db45b0bbbda698b85826d44/?utm_source=chatgpt","doi":"10.1345/aph.1E523","volume":"39","pages":"956 - 961","search_result_number":12},{"paper_title":"Linezolida: una nueva alternativa en infecciones por gram positivos","abstract":"Summary Linezolid is a new antibiotic belonging in the oxazolidinone class that acts by inhibiting the initiation stage of protein synthesis. It has a wide activity spectrum against Gram-positive organisms, including meticillin-resistant staphylococcus strains, penicillin-resistant pneumococcus, and vancomycin-resistant Enterococcus faecalis a n d E. faecium. Linezolid has been FDA-approved for the treatment of both nosocomial and community-acquired pneumonia, complicated and uncomplicated skin and soft tissue infection, and infection by vancomycin-resistant pneumococcus. Linezolid recommended dosage is 600 mg every 12 hours, via both the oral and intravenous routes. Overall tolerability is good, whereas gastrointestinal disorders are the most commonly seen adverse effects.","paper_authors":["A. Gómez-Gener","P. Salvador","M. Boj"],"paper_publish_year":2002,"publication_journal_name":"Farmacia Hospitalaria","consensus_paper_details_url":"https://consensus.app/papers/linezolida-nueva-infecciones-gram-positivos-gómezgener/c7dfa4900f48549c9c143342a66cd38f/?utm_source=chatgpt","doi":"","volume":"26","pages":"44-48","search_result_number":13},{"paper_title":"Clinical experience with linezolid in the treatment of resistant gram-positive infections.","abstract":"This study presents our clinical experience with linezolid in 19 patients with serious resistant gram-positive infections enrolled as part of the compassionate study. In this prospective, non-randomized, noncomparative study, 19 patients were enrolled as part of the National Compassionate Study Protocol conducted by Pharmacia-Upjohn. At the time of this writing, these patients had not been published in the literature. All of the patients had to have documented evidence of serious gram-positive infections in normally sterile sites and should have been unable to tolerate available antimicrobial therapy or be unresponsive to available drugs. Clinical characteristics, laboratory values, and pharmacokinetic and pharmacodynamic parameters were obtained. Patients were followed both short-term and long-term after completion of therapy. Nineteen patients were enrolled: 13 females and 6 males. The average age was 63 years. The average length of therapy with linezolid was 22 days. Methicillin-resistant Staphylococcus aureus (MRSA) was treated in eight patients, methicillin-resistant Staphylococcus epidermidis (MRSE) in two patients, vancomycin-resistant Enterococcus faecium (VREF) in eight patients, and coagulase-negative Staphylococcus in two patients. Co-infecting organisms include Enterococcus species colonization in six patients, Pseudomonas species in one patient, Serratia marcenens in one patient, and Candida albicans in one patient. Sterile sites that were infected included bone and joint (wounds and septic joints) in six patients, gastrointestinal system (hepatobiliary, liver abscess, Crohn's) in five patients, genitourinary (kidney and urine) in two patients, blood in five patients, respiratory in one patient, and aortic valve in 1 patient. Linezolid was given at 600 mg IV every 12 hours with a mean length of therapy of 22 days. Surgical drainage was used in combination with linezolid in 11 of the patients. Seventy nine percent of these patients achieved clinical and microbiologic cure, and none of the deaths reported in this series were related to the drug. Adverse events included skin rash in one patient, mild bone marrow suppression in two patients, and mild elevation in liver function tests in two patients. No life-threatening adverse events were noted. It appears that linezolid, along with surgical intervention (when necessary), appears to be an effective treatment option for resistant gram-positive infections. Long-term studies evaluating the possible resistance rates are necessary.","paper_authors":["S. Antony","E. Diaz-Vasquez","C. Stratton"],"paper_publish_year":2001,"publication_journal_name":"Journal of the National Medical Association","consensus_paper_details_url":"https://consensus.app/papers/experience-treatment-infections-antony/d92f15b74c125901907e1f27580c2fe4/?utm_source=chatgpt","doi":"","volume":"93 10","pages":"\n 386-91\n ","search_result_number":14},{"paper_title":"Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program.","abstract":"Linezolid was provided for treatment of multidrug-resistant, gram-positive infections through a compassionate-use program. Patients (n=796) received 600 mg of linezolid intravenously or orally every 12 h (828 treatment courses). Bacteremia was present in 46% of infections, endocarditis was present in 10.6%, and line-related infections were present in 31.1%. Other infections included intraabdominal infections (15.1%), complicated skin and skin-structure infections (13.3%), and osteomyelitis (10.7%). Causative pathogens included vancomycin-resistant enterococci (66.3%) and methicillin-resistant staphylococci (22.1%). Clinical intent-to-treat (ITT) outcomes in the evaluable population were as follows: cure, 73.3%; failure, 6.8%; and indeterminate, 19.9%. Microbiological ITT outcomes in evaluable patients were as follows: cure, 82.4%; failure, 14.1%; and indeterminate, 3.5%. At the test of cure assessment, the clinical cure and microbiological success rates were 91.5% and 85.8%, respectively. The most common adverse events possibly related to linezolid use were gastrointestinal disturbances (9.8% of cases), thrombocytopenia (7.4% of cases), decreased hemoglobin/hematocrit levels (4.1% of cases), and cutaneous reactions (4.0% of cases). Linezolid provided high rates of clinical cure and microbiological success in this complicated patient population, with very good overall tolerance.","paper_authors":["M. Birmingham","C. Rayner","A. Meagher","S. Flavin","D. Batts","Jerome J. Schentag"],"paper_publish_year":2003,"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-treatment-multidrugresistant-infections-birmingham/bacf0a19e2245d43a3f1e1e582616f90/?utm_source=chatgpt","doi":"10.1086/345744","volume":"36 2","pages":"\n 159-68\n ","search_result_number":15},{"paper_title":"In vitro pharmacokinetic/pharmacodynamic activity of NXL103 versus clindamycin and linezolid against clinical Staphylococcus aureus and Streptococcus pyogenes isolates.","abstract":"NXL103 (linopristin/flopristin, 30/70) is a novel oral streptogramin combination with activity against a large variety of multidrug-resistant Gram-positive pathogens. The objective of this study was to evaluate the in vitro activity of NXL103 in comparison with oral comparators (clindamycin and linezolid). Six clinical isolates [four meticillin-resistant Staphylococcus aureus (MRSA) and two Streptococcus pyogenes] were exposed for 48 h in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model at a starting inoculum of ca. 10(6) colony-forming units (CFU)/mL. Antimicrobial simulations included NXL103 500 mg every 12 h, linezolid 600 mg every 12 h and clindamycin 450 mg every 6 h. Bactericidal and static effects were defined as ≥3log(10) and <3log(10) CFU/mL kill from the starting inoculum, respectively. Experiments were performed in duplicate to ensure reproducibility, and differences between regimens were evaluated by analysis of variance (ANOVA) with Tukey's post-hoc test. NXL103 exhibited lower minimum inhibitory concentrations than comparators, with values ≤0.06 mg/L for S. pyogenes and 0.125-0.25 mg/L for MRSA isolates. In the PK/PD model, NXL103 demonstrated significantly better activity than linezolid and clindamycin (P<0.05), achieving sustained bactericidal activity within <2 h against S. pyogenes strains and between 7.3-32 h against MRSA isolates. In contrast, linezolid only exhibited a static effect, whereas clindamycin achieved 3log(10) kill at 6h against the unique clindamycin-susceptible S. pyogenes strain evaluated. In conclusion, at therapeutic concentrations NXL103 exhibits promising activity against both MRSA and S. pyogenes strains, including clindamycin-resistant organisms. Further in vitro and in vivo experiments are warranted to explore the therapeutic benefit of NXL103 for the treatment of Gram-positive skin and soft-tissue infections.","paper_authors":["C. Vidaillac","J. Parra-Ruiz","Patricia Winterfield","M. Rybak"],"paper_publish_year":2011,"publication_journal_name":"International journal of antimicrobial agents","consensus_paper_details_url":"https://consensus.app/papers/activity-nxl103-versus-clindamycin-staphylococcus-vidaillac/71e6d8224b6b5ec7b2a9e1b192e9ec6f/?utm_source=chatgpt","doi":"10.1016/j.ijantimicag.2011.04.023","volume":"38 4","pages":"\n 301-6\n ","search_result_number":16},{"paper_title":"Omadacycline for Acute Bacterial Skin and Skin‐Structure Infections","abstract":"BACKGROUND Acute bacterial skin and skin‐structure infections are associated with substantial morbidity and health care costs. Omadacycline, an aminomethylcycline antibiotic that can be administered once daily either orally or intravenously, is active against pathogens that commonly cause such infections, including antibiotic‐resistant strains. METHODS In this double‐blind trial, we randomly assigned adults with acute bacterial skin and skin‐structure infections (in a 1:1 ratio) to receive omadacycline (100 mg given intravenously every 12 hours for two doses, then 100 mg given intravenously every 24 hours) or linezolid (600 mg given intravenously every 12 hours). A transition to oral omadacycline (300 mg every 24 hours) or oral linezolid (600 mg every 12 hours) was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was an early clinical response at 48 to 72 hours, defined as survival with a reduction in lesion size of at least 20% without rescue antibacterial therapy. A secondary end point was an investigator‐assessed clinical response at the post‐treatment evaluation 7 to 14 days after the last dose, with clinical response defined as survival with resolution or improvement in signs or symptoms of infection to the extent that further antibacterial therapy was unnecessary. For both end points, the noninferiority margin was 10 percentage points. RESULTS In the modified intention‐to‐treat population, omadacycline (316 patients) was noninferior to linezolid (311 patients) with respect to early clinical response (rate of response, 84.8% and 85.5%, respectively; difference, ‐0.7 percentage points; 95% confidence interval [CI], ‐6.3 to 4.9). Omadacycline also was noninferior to linezolid with respect to investigator‐assessed clinical response at the post‐treatment evaluation in the modified intention‐to‐treat population (rate of response, 86.1% and 83.6%, respectively; difference, 2.5 percentage points; 95% CI, ‐3.2 to 8.2) and in the clinical per‐protocol population (96.3% and 93.5%, respectively; difference, 2.8 percentage points; 95% CI, ‐1.0 to 6.9). In both groups, the efficacy of the trial drug was similar for methicillin‐susceptible and methicillin‐resistant Staphylococcus aureus infections. Adverse events were reported in 48.3% of the patients in the omadacycline group and in 45.7% of those in the linezolid group; the most frequent adverse events in both groups were gastrointestinal (in 18.0% and 15.8% of the patients in the respective groups). CONCLUSIONS Omadacycline was noninferior to linezolid for the treatment of acute bacterial skin and skin‐structure infections and had a similar safety profile. (Funded by Paratek Pharmaceuticals; OASIS‐1 ClinicalTrials.gov number, NCT02378480.)","paper_authors":["W. O'Riordan","Sinikka Green","Scott Overcash","I. Puljiz","S. Metallidis","J. Gardovskis","L. Garrity-Ryan","Anita F. Das","E. Tzanis","P. Eckburg","A. Manley","S. Villano","J. Steenbergen","E. Loh"],"paper_publish_year":2019,"publication_journal_name":"The New England Journal of Medicine","consensus_paper_details_url":"https://consensus.app/papers/omadacycline-acute-bacterial-skin-skin‐structure-oriordan/fa24a29a05505446999c78fd249ddb7a/?utm_source=chatgpt","doi":"10.1056/NEJMoa1800170","volume":"380","pages":"528–538","search_result_number":17},{"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":["L. Dennis","H. Daniel","L. Harry","L. John","H. B. Donald","H. Barry"],"paper_publish_year":2002,"publication_journal_name":"Clinical Infectious Diseases","consensus_paper_details_url":"https://consensus.app/papers/linezolid-versus-vancomycin-treatment-dennis/113c221d2b5250f3b913c128d6aef568/?utm_source=chatgpt","doi":"10.1086/340353","volume":"34","pages":"1481-1490","search_result_number":18},{"paper_title":"A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia.","abstract":"BACKGROUND\nCeftobiprole, the active moiety of ceftobiprole medocaril, is a novel broad-spectrum cephalosporin, with bactericidal activity against a wide range of gram-positive bacteria, including Staphylococcus aureus (including methicillin-resistant strains) and penicillin- and ceftriaxone-resistant pneumococci, and gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.\n\n\nMETHODS\nThis was a double-blind, randomized, multicenter study of 781 patients with hospital-acquired pneumonia (HAP), including 210 with ventilator-associated pneumonia (VAP). Treatment was intravenous ceftobiprole 500 mg every 8 hours, or ceftazidime 2 g every 8 hours plus linezolid 600 mg every 12 hours; primary outcome was clinical cure at the test-of-cure visit.\n\n\nRESULTS\nOverall cure rates for ceftobiprole vs ceftazidime/linezolid were 49.9% vs 52.8% (intent-to-treat [ITT], 95% confidence interval [CI] for the difference, -10.0 to 4.1) and 69.3% vs 71.3% (clinically evaluable [CE], 95% CI, -10.0 to 6.1). Cure rates in HAP (excluding VAP) patients were 59.6% vs 58.8% (ITT, 95% CI, -7.3 to 8.8), and 77.8% vs 76.2% (CE, 95% CI, -6.9 to 10.0). Cure rates in VAP patients were 23.1% vs 36.8% (ITT, 95% CI, -26.0 to -1.5) and 37.7% vs 55.9% (CE, 95% CI, -36.4 to 0). Microbiological eradication rates in HAP (excluding VAP) patients were, respectively, 62.9% vs 67.5% (microbiologically evaluable [ME], 95% CI, -16.7 to 7.6), and in VAP patients 30.4% vs 50.0% (ME, 95% CI, -38.8 to -0.4). Treatment-related adverse events were comparable for ceftobiprole (24.9%) and ceftazidime/linezolid (25.4%).\n\n\nCONCLUSIONS\nCeftobiprole is a safe and effective bactericidal antibiotic for the empiric treatment of HAP (excluding VAP). Further investigations are needed before recommending the use of ceftobiprole in VAP patients. Clinical Trials Registration. NCT00210964, NCT00229008.","paper_authors":["S. Awad","Alejandro Rodríguez","Y. Chuang","Z. Marjanek","Alex J Pareigis","Gilmar Reis","T. Scheeren","A. Sánchez","Xin Zhou","Mikael Saulay","M. Engelhardt"],"paper_publish_year":2014,"publication_journal_name":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","consensus_paper_details_url":"https://consensus.app/papers/phase-randomized-doubleblind-comparison-ceftobiprole-awad/5b14f18e40bb53348ae3f47e40fe6b48/?utm_source=chatgpt","doi":"10.1093/cid/ciu219","volume":"59 1","pages":"\n 51-61\n ","search_result_number":19},{"paper_title":"Linezolid Dosing in a Morbidly Obese Patient With MRSA Pneumonia","abstract":"Pharmacodynamic optimization of linezolid has been associated with higher clinical success rates (resolution of signs and symptoms and bacterial eradication) in nonobese patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. These targets (Area under the curve/ Minimum inhibitory concentration [AUC 0-24 /MIC] values = 80-120 and Time over MIC [T>MIC] = 100%) have been achieved in obese patients (body mass index [BMI] = 30-54.9 kg/m; weight = 78.2-143.1 kg) given the standard dosage of 600 mg orally or intravenously twice daily. However, little data exists for patients with higher BMI and weight. We report on a morbidly obese male patient (weight = 255 kg; BMI = 84 kg/m) who experienced clinical resolution of infection despite low serum linezolid concentrations. Our patient was a 30-year-old man with a history of diabetes, pulmonary embolism, and obstructive sleep apnea requiring continuous positive airway pressure. He was admitted for culture-positive MRSA left leg cellulitis and treated with ceftriaxone and vancomycin. He developed hearing loss, and vancomycin was switched to daptomycin. He continued to have intermittent fevers (T max = 39.5°C) and became difficult to rouse on day 21. His chest X-ray showed left-lung consolidation, and he was intubated and taken to the intensive care unit. Sputum culture grew MRSA (linezolid MIC = 2 mg/L via Vitek). Daptomycin was switched to linezolid 600 mg every 12 hours via nasogastric tube (NGT; crushed tablets in water). Linezolid serum concentrations were obtained on day 27 at 0.5 hours before the morning dose, and 2 and 6 hours post–morning dose (0.4, 2.78, and 1.04 mg/L, respectively). Pharmacodynamics parameters were calculated to be AUC0-24h = 30.28 mg h/L (using the trapezoidal rule), AUC 0-24h /MIC = 15.14, and T>MIC = 30%. Despite these values being below target AUC 0-24h /MIC and T>MIC, the patient improved clinically and was extubated after 7 days of linezolid therapy. Currently, data for linezolid in patients with MRSA pneumonia and BMI exceeding 55 kg/m is limited to 2 case reports. One was a patient with a BMI of 82 kg/m who received linezolid 600 mg via NGT every 12 hours. He had low peak and trough linezolid serum concentrations (4.13 and 1.27 mg/L, respectively) and had a poor clinical response to therapy. However, he grew Escherichia coli in another sputum culture and improved clinically when ceftriaxone and vancomycin were added to linezolid. The second reported on a patient with a BMI of 66 kg/m and MRSA health care–associated pneumonia and septic shock receiving linezolid 600 mg intravenously every 8 hours, who experienced clinical cure. The authors calculated that the patient would have therapeutic AUC 0-24 /MIC for both an MIC = 1 mg/L and MIC = 2 mg/L (335.68 and 167.50, respectively). Our case, along with these other reports, suggests that patients with BMI >55 kg/m may have altered pharmacokinetic and pharmacodynamic linezolid parameters, which may or may not influence clinical response. Additional studies of linezolid pharmacokinetics and clinical outcomes in patients with BMI >55 kg/m are required. Based on the available literature, we would consider using standard dosage with careful monitoring of clinical response.","paper_authors":["T. Mihic","Ivy Chow","V. Mabasa"],"paper_publish_year":2016,"publication_journal_name":"Annals of Pharmacotherapy","consensus_paper_details_url":"https://consensus.app/papers/linezolid-dosing-morbidly-obese-patient-with-mrsa-mihic/faeb5dceb7d851938aeba20cbb053a41/?utm_source=chatgpt","doi":"10.1177/1060028015620801","volume":"50","pages":"154 - 154","search_result_number":20}]} --- **ChatGPT:** The duration to effectively treat a Staphylococcus epidermidis infection with linezolid, particularly with a dosage of 600 mg every 12 hours, can vary based on the severity and type of infection. However, general treatment durations from clinical studies provide some guidance: ### Typical Duration for Treating Staphylococcus Epidermidis with Linezolid: 1. **Skin and Soft Tissue Infections:** Linezolid is often prescribed for 10-14 days for complicated skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus species [(Itani et al., 2005)](https://consensus.app/papers/reduces-length-duration-treatment-compared-vancomycin-itani/4180edd4a4025a34acef2a30107c9c57/?utm_source=chatgpt). 2. **Nosocomial Pneumonia:** For hospital-acquired pneumonia, treatment typically lasts for 7-14 days [(Wunderink et al., 2012)](https://consensus.app/papers/linezolid-methicillinresistant-staphylococcus-aureus-wunderink/38e6faa375a35d7dbb455442be732c63/?utm_source=chatgpt). 3. **Osteomyelitis:** For bone infections like osteomyelitis, longer treatment durations of several weeks (often around 6-12 weeks) are common due to the difficulty in eradicating infections from bone tissue [(Romero-Candau et al., 2007)](https://consensus.app/papers/treatment-posttraumatic-osteomyelitis-oral-linezolid-romerocandau/f2a272bffd605d27aeb5aab7cd4d60ae/?utm_source=chatgpt). ### Clinical Efficacy and Treatment Duration: - **Clinical Success:** Studies have shown that linezolid, when administered at 600 mg every 12 hours, achieves high clinical success rates for gram-positive infections, including those caused by Staphylococcus epidermidis. The duration of therapy generally aligns with the guidelines for the specific type of infection being treated [(Weigelt et al., 2004)](https://consensus.app/papers/linezolid-eradicates-mrsa-better-vancomycin-infections-weigelt/36447aad4a8a5de48e27f2cccd8ce0c1/?utm_source=chatgpt). ### Conclusion: For a mild Staphylococcus epidermidis infection, completing the prescribed course of 10 days at 600 mg every 12 hours is recommended to ensure effective eradication of the infection. Reducing the dose without medical supervision is generally not advised as it may compromise the treatment's efficacy. Always consult with a healthcare provider before making any changes to your medication regimen. Like our GPT? Try our full AI-powered search engine and academic features for free at [consensus.app](https://consensus.app/?utm_source=chatgpt). ---