Sputum culture reversion in longer treatments with bedaquiline, delamanid, and repurposed drugs for drug-resistant tuberculosis

Nat Commun. 2024 May 9;15(1):3927. doi: 10.1038/s41467-024-48077-8.

Abstract

Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate the frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced culture conversion. We also conduct Cox proportional hazard regression analyses to identify factors associated with reversion, including comorbidities, previous treatment, cavitary disease at conversion, low body mass index (BMI) at conversion, time to conversion, and number of likely-effective drugs. Of 1,286 patients, 54 (4.2%) experienced reversion, a median of 173 days (97-306) after conversion. Cavitary disease, BMI < 18.5, hepatitis C, prior treatment with second-line drugs, and longer time to initial culture conversion were positively associated with reversion. Reversion was uncommon. Those with cavitary disease, low BMI, hepatitis C, prior treatment with second-line drugs, and in whom culture conversion is delayed may benefit from close monitoring following conversion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Multicenter Study

MeSH terms

  • Adult
  • Antitubercular Agents* / pharmacology
  • Antitubercular Agents* / therapeutic use
  • Diarylquinolines* / pharmacology
  • Diarylquinolines* / therapeutic use
  • Drug Repositioning
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Nitroimidazoles* / pharmacology
  • Nitroimidazoles* / therapeutic use
  • Oxazoles* / therapeutic use
  • Prospective Studies
  • Sputum* / microbiology
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / microbiology

Substances

  • bedaquiline
  • Antitubercular Agents
  • Diarylquinolines
  • Oxazoles
  • OPC-67683
  • Nitroimidazoles