Safety, efficacy and feasibility of preventive treatment for drug-resistant tuberculosis with moxifloxacin or bedaquiline

IntroductionRates of drug-resistant tuberculosis (TB) are increasing worldwide. TB preventive treatment (TPT) for contacts of active TB patients is essential to halt infection progression and transmission. While newer TPT regimens for drug-sensitive strains are expanding, optimal treatment for contacts exposed to drug-resistant TB (DR-TB) remains unclear. In 2019-2020, Vladimir City, Russia, introduced moxifloxacin and bedaquiline-based TPT regimens to prevent disease development in contacts exposed to DR-TB. MethodsWe conducted a retrospective cohort study using medical records data that included adult TB contacts, people experiencing homelessness, and persons with HIV who received TPT in Vladimir City, Russia, between 2019 and 2020. Those without TB disease but with indications for TPT were offered one of six regimens, based on drug-susceptible testing results of index patient: Rifapentine/Isoniazid (3HP), Isoniazid (6H), Rifabutin/Isoniazid (3HRb), Rifampicin (4R), Moxifloxacin (4Mfx), or Bedaquiline (3Bdq). Adverse drug reactions (ADRs) were monitored with monthly lab tests and ECGs. ResultsOver 24 months, 403 people started TPT. No life-threatening ADRs or deaths occurred. The lowest ADR rate and significantly higher completion rate was observed in 3Bdq (n=20, 95.2%) compared to 3HP (n=192, 75.9%, Mid-P exact = .03). The rate of TB disease per 1,000 person-years of observation was four times higher in individuals eligible for TPT who did not start it compared to those who initiated TPT. ConclusionTreatment for the prevention of DR-TB, including forms resistant to rifampicin and fluoroquinolones, is feasible, effective and safe. This study introduces a novel paradigm for TB prevention in high-burden DR-TB settings, offering a promising strategy to protect contacts and reduce transmission. Key pointsMoxifloxacin and bedaquiline are safe, effective, and feasible agents for preventive therapy among contacts of individuals with drug-resistant tuberculosis (TB) and can be used as part of the comprehensive search-treat-prevent approach for TB elimination.