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

• Published in: The Journal of infectious diseases Vol. 230; no. 2; pp. e447 - e456
• Main Authors: Zainabadi, Kayvan, Vilbrun, Stalz Charles, Mathurin, Laurent Daniel, Walsh, Kathleen Frances, Pape, Jean William, Fitzgerald, Daniel W, Lee, Myung Hee
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 16.08.2024
• Subjects: Adult; Aged; Antibiotics; Antitubercular Agents - administration & dosage; Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Bactericidal activity; Clofazimine; Clofazimine - pharmacology; Clofazimine - therapeutic use; Diarylquinolines - pharmacology; Diarylquinolines - therapeutic use; Drug resistance; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Levofloxacin; Levofloxacin - pharmacology; Levofloxacin - therapeutic use; Linezolid; Linezolid - pharmacology; Linezolid - therapeutic use; Major; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium tuberculosis - drug effects; Pyrazinamide; Pyrazinamide - therapeutic use; Rifampin; Rifampin - pharmacology; Rifampin - therapeutic use; Treatment Outcome; Tuberculosis; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - microbiology; Young Adult; diarylquinoline; MDR; EBA; fluoroquinolone; treatment shortening
• ISSN: 0022-1899; 1537-6613; 1537-6613
• 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. This study reports that the early bactericidal activity of a bedaquiline-based second-line regimen for drug-resistant tuberculosis (TB) is similar to that of the standard rifampin-based first-line regimen for drug-sensitive TB.