Estimating the Early Transmission Inhibition of New Treatment Regimens for Drug-Resistant Tuberculosis

Background. Most drug-resistant tuberculosis occurs due to transmission of unsuspected or ineffectively treated drug-resistant tuberculosis. The duration of treatment to stop person-to-person spread of drug-resistant tuberculosis is uncertain. We evaluated the impact of novel regimens, including BPaL (bedaquiline, 1200-mg linezolid, and pretomanid), on drug-resistant tuberculosis transmission, using the human-guinea pig (H-GP) transmission model. Methods. In experiment 1, patients initiated an optimized drug-resistant tuberculosis regimen including bedaquiline and linezolid. In experiment 2, patients initiated the BPaL regimen. We measured baseline infectivity for each cohort by exhausting ward air to one of two guinea pig exposure rooms (control group), each containing 90 guinea pigs, for 8 patient-days. Then, after 72 hours of treatment, ward air was exhausted to the second guinea pig exposure room for 8 patient-days (intervention group). The infectiousness of each cohort was compared by performing tuberculin skin tests in guinea pigs at baseline (before treatment) and 6 weeks after the exposure period. Results. In experiment 1, before treatment, 5 patients with drug-resistant tuberculosis infected 24 of 90 guinea pigs (26.7%) (control group). After treatment (72 hours after drug initiation), the same patients infected 25 of 90 guinea pigs (27.8%) (intervention group) (P > .99). In experiment 2, before treatment, 9 patients with drug-resistant tuberculosis infected 40 of 90 guinea pigs (44.4%) (control group). After treatment (beginning 72 hours after drug initiation), the same patients infected 0 of 90 guinea pigs (0%) (intervention group) (P < .0001). Conclusions. In this study, drug-resistant tuberculosis drug regimens, including bedaquiline and standard-dose linezolid for 72 hours, did not decrease drug-resistant tuberculosis 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.