Acquisition of clofazimine resistance following bedaquiline treatment for multidrug-resistant tuberculosis

ObjectivesWe described the prevalence of clofazimine (CFZ) resistance in a multidrug-resistant tuberculosis (MDR-TB) cohort China. We also aimed to identify dynamic changes CFZ susceptibility and its molecular mechanism after exposure bedaquiline (BDQ) and/or CFZ.MethodsThe experimental settings were conducted based on our MDR-TB receiving BDQ-containing regimens. Sequential isolates obtained from patients. BDQ determined using minimum inhibitory concentration (MIC) method. The fragments Rv0678 pepQ sequenced.ResultsA total 277 patients infected with included study. was noted 23 (23/277, 8.3%) isolates. rate acquired (12/189, 6.3%) significantly greater than that primary (11/88, 12.5%, P = 0.028). Out CFZ-resistant isolates, five (5/23) BDQ-resistant, other 18 (18/23) susceptible BDQ. Of note, nine 9/23) out had mutations within either target genes. Kaplan-Meier analysis demonstrated baseline no influence time culture conversion (P 0.828). Acquired emerged eight (8/94, 8.5%) during treatment for MDR-TB, including three regimens without CFZ.ConclusionsOur results demonstrate high among Patients treated achieve comparative regardless susceptibility. presence CFZ-resistance following known mutation indicates mechanisms conferring cross these two compounds may exist.