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Journal Article > Review

The safety and tolerability of linezolid in novel short-course regimens containing bedaquiline, pretomanid, and linezolid to treat rifampicin-resistant tuberculosis: An individual patient data meta-analysis

Hasan T, Medcalf E, Nyang'wa BT, Egizi E, Berry C, Dodd M, Foraida S, Gegia M, Li M, Mirzayev F, Morgan H, Motta I, Nguyen L, Schumacher S, Schlub T, Fox G
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Abstract
BACKGROUND
Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials.

METHODS
A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment-related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid.

RESULTS
Data from 3 clinical trials investigating 8 unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200 mg linezolid, 68 of 195 (35%) experienced a grade 3–4 adverse event versus 89 of 396 (22%) patients receiving BPaL-containing regimens containing 600 mg linezolid.

CONCLUSIONS
Regimens containing BPaL were relatively well tolerated when they included a daily linezolid dose of 600 mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Countries
BelarusGeorgiaMoldovaSouth AfricaUzbekistan
Subject Area
tuberculosisantimicrobial resistance
DOI
10.1093/cid/ciad653
Published Date
20-Mar-2024
PubMed ID
37874021
Languages
English
Journal
Clinical Infectious Diseases
Volume / Issue / Pages
Volume 78, Issue 3, Pages 730-741
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