{"doi":"10.1093/jac/dkac019","title":"Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study","abstract":"BACKGROUND: Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescribers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. PATIENTS AND METHODS: We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifampicin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. RESULTS: One hundred and fifty-one participants, 63% HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21%) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14%) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95% CI 0.02-0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin >2 g/dL. Trough linezolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemoglobin and treatment-emergent anaemia (adjusted OR 2.9; 95% CI 1.3-6.8). SNPs 2706A > G and 3010G > A in mitochondrial DNA were not associated with linezolid toxicity. CONCLUSIONS: Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.","journal":"Journal of Antimicrobial Chemotherapy","year":2022,"id":241952,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308894,"name":"James C.M. Brust","orcid":"0000-0003-3362-1818","position":1,"is_corresponding":false},{"id":308892,"name":"Mahmoud Tareq Abdelwahab","orcid":"0000-0002-2134-8749","position":2,"is_corresponding":false},{"id":403920,"name":"Francesca Little","orcid":"0000-0002-5917-9928","position":3,"is_corresponding":false},{"id":308900,"name":"Paolo Denti","orcid":"0000-0001-7494-079X","position":4,"is_corresponding":false},{"id":308898,"name":"Lubbe Wiesner","orcid":"0000-0002-9070-8699","position":5,"is_corresponding":false},{"id":308895,"name":"Neel R. Gandhi","orcid":"0000-0002-1665-299X","position":6,"is_corresponding":false},{"id":292884,"name":"Graeme Meintjes","orcid":"0000-0003-1196-4414","position":7,"is_corresponding":false},{"id":110248,"name":"Gary Maartens","orcid":"0000-0003-3080-6606","position":8,"is_corresponding":false},{"id":308893,"name":"Sean Wasserman","orcid":"0000-0002-3508-6719","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:23:00.865267Z","pmid":"35134182","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}