Implementing a Program of Comprehensive Tuberculosis Preventive Treatment: Safety, Effectiveness, and Acceptability of Moxifloxacin or Bedaquiline Use for Contacts Exposed to Drug-Resistant Strains.

BACKGROUND

Rates of drug-resistant tuberculosis (DR-TB) are increasing worldwide. Tuberculosis preventive treatment (TPT) for contacts of people with active TB is essential to halt infection progression and transmission. While newer TPT regimens for exposure to drug-susceptible and rifampin (R)-resistant strains (MDR-TB/RR-TB) are expanding, optimal treatment for contacts exposed to fluoroquinolone-resistant strains of TB (pre-XDR- or XDR-TB) remains unclear. In 2019-2020, Vladimir City, Russia, introduced moxifloxacin (Mfx)- and bedaquiline (Bdq)-based TPT regimens to prevent disease development in contacts exposed to MDR/RR-TB and pre-XDR-TB.

METHODS

We conducted a retrospective cohort study of adult TB contacts, people experiencing homelessness, and people with HIV who received TPT in Vladimir between 2019 and 2020. Those without TB disease but with indications for TPT were offered 1 of 6 regimens, based on drug-susceptibility testing results of the index patient: rifapentine/isoniazid (3HP), isoniazid (6H), rifabutin/isoniazid (3HRb), 4R, 4Mfx, or 3Bdq. Adverse drug reactions (ADRs) were monitored with monthly lab tests and electrocardiogram (ECGs). Outcome measures included ADRs, TPT completion, and TB disease incidence during the 12-month follow-up period.

RESULTS

Over 24 months, 403 people started TPT. No life-threatening ADRs or deaths occurred. The lowest ADR rate and highest completion were seen with 3Bdq (95.2%) compared to 3HP (75.9%, Mid-P exact = .03). Tuberculosis incidence per 1000 person-years was 4 times higher among eligible individuals who declined TPT versus those initiating it.

CONCLUSIONS

Preventive therapy for drug-resistant TB, including fluoroquinolone-resistant strains, is acceptable, safe, and effective. Implementation of comprehensive TPT programs in high-burden DR-TB settings can protect contacts and reduce transmission.