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

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...

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Vydáno v:Clinical infectious diseases Ročník 78; číslo 3; s. 730 - 741
Hlavní autoři: Hasan, Tasnim, Medcalf, Ellie, Nyang'wa, Bern-Thomas, Egizi, Erica, Berry, Catherine, Dodd, Matthew, Foraida, Salah, Gegia, Medea, Li, Mengchun, Mirzayev, Fuad, Morgan, Hannah, Motta, Ilaria, Nguyen, Linh, Schumacher, Samuel, Schlub, Tim, Fox, Greg
Médium: Journal Article
Jazyk:angličtina
Vydáno: US Oxford University Press 20.03.2024
Témata:
Antitubercular Agents - adverse effects
Diarylquinolines - therapeutic use
Humans
Linezolid - adverse effects
Nitroimidazoles
Randomized Controlled Trials as Topic
Rifampin - pharmacology
Tuberculosis - drug therapy
Tuberculosis, Multidrug-Resistant - drug therapy
severe adverse events
linezolid
multidrug-resistant tuberculosis
BPaL
ISSN:1058-4838, 1537-6591, 1537-6591
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Shrnutí: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 Methods A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB.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. Different bedaquiline, pretomanid, and linezolid–containing regimens from recently published clinical trials for the treatment of drug-resistant tuberculosis are compared. Different linezolid doses and durations were used in these regimens, allowing for an assessment of the safety of linezolid.
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ISSN:1058-4838
1537-6591
1537-6591
DOI:10.1093/cid/ciad653