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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, 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.
Affiliation
  • Hasan T; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
  • Medcalf E; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
  • Nyang'wa BT; Public Health Department, Médecins sans Frontières, Amsterdam, The Netherlands.
  • Egizi E; Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
  • Berry C; TB Alliance Research and Development, New York City, USA.
  • Dodd M; Manson Unit, Médecins sans Frontières, London, United Kingdom.
  • Foraida S; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
  • Gegia M; TB Alliance Research and Development, New York City, USA.
  • Li M; Global Tuberculosis Program, World Health Organization, Geneva, Switzerland.
  • Mirzayev F; TB Alliance Research and Development, New York City, USA.
  • Morgan H; Global Tuberculosis Program, World Health Organization, Geneva, Switzerland.
  • Motta I; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
  • Nguyen L; Manson Unit, Médecins sans Frontières, London, United Kingdom.
  • Schumacher S; Global Tuberculosis Program, World Health Organization, Geneva, Switzerland.
  • Schlub T; Global Tuberculosis Program, World Health Organization, Geneva, Switzerland.
  • Fox G; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Clin Infect Dis ; 78(3): 730-741, 2024 03 20.
Article in En | MEDLINE | ID: mdl-37874021
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.
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Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Tuberculosis / Tuberculosis, Multidrug-Resistant / Linezolid Type of study: Systematic_reviews Limits: Humans Language: En Journal: Clin Infect Dis Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Tuberculosis / Tuberculosis, Multidrug-Resistant / Linezolid Type of study: Systematic_reviews Limits: Humans Language: En Journal: Clin Infect Dis Year: 2024 Document type: Article