Estimating the Early Transmission Inhibition of new treatment regimens for drug-resistant tuberculosis.

Introduction: Most drug-resistant tuberculosis (DR-TB) occurs due to transmission of unsuspected or ineffectively treated DR-TB. The duration of treatment to stop person-to-person spread of DR-TB is uncertain. We evaluated the impact of novel regimens, including BPaL, on DR-TB transmission using the human-to-guinea pig (H-GP) transmission model.

Methods: In Experiment 1, patients initiated an optimized DR-TB regimen including bedaquiline (BDQ) and linezolid (LZD). In Experiment 2, patients initiated the BPaL regimen (BDQ, 1200mg LZD and pretomanid). We measured baseline infectivity for each cohort by exhausting ward air to one of two GP exposure rooms (Control), each containing 90 GPs, for 8 patient-days. Then, after 72 hours of treatment, ward air was exhausted to the second GP exposure room for 8 patient-days (Intervention). The infectiousness of each cohort was compared by performing tuberculin skin tests (TST) in GPs at baseline (pre-treatment) and 6 weeks after the exposure period.

Results: In Experiment 1, pre-treatment, five DR-TB patients infected 24/90 (26.7%) GPs (Control). Post-treatment (72 hours after drug initiation), the same patients infected 25/90 (27.8%) GPs (Intervention) (p = 1.00). In Experiment 2, pre-treatment, nine DR-TB patients infected 40/90 (44.4%) GPs (Control). Post-treatment (beginning 72 hours after drug initiation), the same patients infected 0/90 (0%) GPs (Intervention) (p < 0.0001).

Conclusions: In this study, DR-TB drug regimens including BDQ and standard-dose LZD for 72 hours did not decrease DR-TB transmission. In contrast, transmission was rapidly and completely inhibited in patients treated with BPaL for 72 hours, suggesting an early and profound impact on transmission.