Deep whole-genome sequencing reveals no evidence for heteroresistance influencing treatment outcomes among drug-susceptible tuberculosis patients.

The purpose of this study was to investigate the minimum level of heteroresistance that predicts poor tuberculosis treatment outcomes. This retrospective study enrolled 45 new tuberculosis patients with varied treatment outcomes and 16 drug-susceptible retreatment cases. Pretreatment isolates from these 61 patients were whole genome sequenced to detect heteroresistance. Heteroresistance was not found in isolates from any of the new patients, but was detected in isolates from retreatment patients who were nevertheless cured. The results of our small series of patients suggest that heteroresistance <1%, the threshold used to define resistance with the phenotypic proportion method, is not associated with poor treatment outcomes.