A Bedaquiline, Pyrazinamide, Levofloxacin, Linezolid, and Clofazimine Second-line Regimen for Tuberculosis Displays Similar Early Bactericidal Activity as the Standard Rifampin-Based First-line Regimen

J Infect Dis. 2024 Aug 16;230(2):e447-e456. doi: 10.1093/infdis/jiad564.

Abstract

Background: In 2018 the World Health Organization recommended a switch to an all oral bedaquiline-based second-line regimen for treatment of drug-resistant tuberculosis (DR-TB). How these new second-line regimens fare in comparison to first-line regimens for treatment of drug-sensitive tuberculosis (DS-TB) is not well known.

Methods: In this study, we contemporaneously enrolled subjects with DS-TB (n = 31) or DR-TB (n = 23) and assessed their response to therapy with first-line (rifampin, isoniazid, ethambutol, pyrazinamide) or second-line (bedaquiline, pyrazinamide, levofloxacin, linezolid, clofazimine) regimens, respectively.

Results: We found that the early bactericidal activity of first- and second-line regimens was similar during the first 2 weeks of therapy as determined by BACTEC MGIT, colony-forming units, and a liquid limiting dilution assay capable of detecting differentially detectable/culturable Mycobacterium tuberculosis. Furthermore, an identical percentage (77.8%) of subjects from the DS-TB and DR-TB cohorts converted to culture negative after 2 months of therapy.

Conclusions: Despite presenting with more advanced disease at time of treatment, subjects with DR-TB receiving an all oral bedaquiline-based second-line treatment regimen displayed a similar microbiological response to therapy as subjects with DS-TB receiving a first-line treatment regimen.

Keywords: EBA; MDR; diarylquinoline; fluoroquinolone; treatment shortening.

MeSH terms

  • Adult
  • Aged
  • Antitubercular Agents* / administration & dosage
  • Antitubercular Agents* / pharmacology
  • Antitubercular Agents* / therapeutic use
  • Clofazimine* / pharmacology
  • Clofazimine* / therapeutic use
  • Diarylquinolines* / pharmacology
  • Diarylquinolines* / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Humans
  • Levofloxacin* / pharmacology
  • Levofloxacin* / therapeutic use
  • Linezolid* / pharmacology
  • Linezolid* / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mycobacterium tuberculosis* / drug effects
  • Pyrazinamide* / therapeutic use
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Young Adult

Substances

  • Antitubercular Agents
  • bedaquiline
  • Linezolid
  • Clofazimine
  • Diarylquinolines
  • Pyrazinamide
  • Levofloxacin
  • Rifampin