Impact of Dose, Duration, and Immune Status on Efficacy of Ultrashort Telacebec Regimens in Mouse Models of Buruli Ulcer

Abstract

Telacebec (Q203) is a new antituberculosis drug in clinical development that has extremely potent activity against Mycobacterium ulcerans , the causative agent of Buruli ulcer (BU). The potency of Q203 has prompted investigation of its potential role in ultrashort, even single-dose, treatment regimens for BU in mouse models. However, the relationships of Q203 dose, dose schedule, duration, and host immune status to treatment outcomes remain unclear, as does the risk of emergence of drug resistance with Q203 monotherapy. Here, we used mouse footpad infection models in immunocompetent BALB/c and immunocompromised SCID-beige mice to compare different Q203 doses, different dosing schedules, and treatment durations ranging from 1 day to 2 weeks, on long-term outcomes.