New preventive drugs curb drug-resistant tuberculosis spread

Drug-resistant tuberculosis (DR-TB) is rising worldwide, and preventing infection from becoming active disease is a critical public health challenge. Contacts of people with active TB are at particularly high risk, and tuberculosis preventive treatment (TPT) for those contacts is essential to stop progression and transmission. While newer preventive regimens are expanding for drug-sensitive TB, the best approach for people exposed to DR-TB has been unclear. In 2019–2020, Vladimir City, Russia, launched an effort to offer preventive treatment tailored to the resistance profile of the source patient, and a team led by corresponding author Salmaan Keshavjee evaluated the outcomes. The program included adult TB contacts, people experiencing homelessness, and persons with HIV who had indications for TPT but did not have active TB disease. By introducing regimens based on the index patient’s drug-susceptibility testing, the city aimed to protect exposed people from developing DR-TB. The study reviewed medical records from this program to assess whether moxifloxacin and bedaquiline, two drugs used against resistant strains, could be used safely and effectively as part of a prevention strategy.

Researchers carried out a retrospective cohort study using medical records from Vladimir City for 2019–2020. People without TB disease but eligible for TPT were offered one of six regimens, selected according to the index patient’s drug-susceptible testing results: Rifapentine/Isoniazid (3HP), Isoniazid (6H), Rifabutin/Isoniazid (3HRb), Rifampicin (4R), Moxifloxacin (4Mfx), or Bedaquiline (3Bdq). Adverse drug reactions (ADRs) were tracked with monthly lab tests and ECGs. Over 24 months, 403 people started TPT under this program. Importantly, no life-threatening ADRs or deaths occurred. The regimen Bedaquiline (3Bdq) showed the lowest ADR rate and a significantly higher completion rate: 3Bdq (n=20) had a 95.2% completion rate compared with 3HP (n=192) at 75.9% (Mid-P exact = .03). Finally, the rate of TB disease per 1,000 person-years was four times higher among people who were eligible for TPT but did not start it compared with those who initiated TPT.

The findings show that preventive treatment for contacts exposed to DR-TB, including exposure to strains resistant to rifampicin and fluoroquinolones, can be delivered safely and effectively. Using moxifloxacin and bedaquiline as part of targeted TPT programs proved feasible in a real-world city program, with careful monitoring by monthly lab tests and ECGs to watch for adverse drug reactions. This approach represents a novel paradigm for TB prevention in high-burden DR-TB settings: selecting regimens based on the index patient’s drug-susceptibility testing and offering drugs active against resistant strains. The study supports incorporating moxifloxacin and bedaquiline into comprehensive search-treat-prevent approaches to protect contacts, reduce transmission, and potentially lower the incidence of DR-TB. For programs working in similar settings, these results suggest that tailored preventive regimens can be an important tool in the fight against drug-resistant tuberculosis.