Primary Clofazimine and Bedaquiline Resistance among Isolates from Patients with Multidrug-Resistant Tuberculosis.
Clofazimine has been repurposed for the treatment of tuberculosis, especially for multidrug-resistant tuberculosis (MDR-TB). To test the susceptibility to clofazimine ofMycobacterium tuberculosisclinical isolates, MICs of clofazimine were determined using the microplate alamarBlue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. For five clofazimine-resistant strains isolated from previously treated pre-extensively drug-resistant TB (pre-XDR-TB) and XDR-TB patients without prior exposure to clofazimine or bedaquiline, clofazimine MICs were ≥1.2 μg/ml. Four isolates with cross-resistance to bedaquiline hadRv0678mutations. The other isolate with no resistance to bedaquiline had anRv1979cmutation. This study adds to a recent study showing that 6.3% of MDR-TB patients without prior clofazimine or bedaquiline exposure harbored isolates withRv0678mutations, which raises concern that preexisting resistance to these drugs may be associated with prior TB treatment. Furthermore, we propose a tentative breakpoint of 1.2 μg/ml for clofazimine resistance using the MABA method. More-widespread surveillance and individualized testing for clofazimine and bedaquiline resistance, together with assessment of their clinical usage, especially among previously treated and MDR-TB patients, are warranted.
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China.
Jian
J
Xu
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China.
Bin
B
Wang
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China.
Minghao
M
Hu
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China.
Fengmin
F
Huo
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China.
Shaochen
S
Guo
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China.
Wei
W
Jing
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Eric
E
Nuermberger
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China luyu4876@hotmail.com.
Yu
Y
Lu
D000995:Antitubercular Agents / Q000494:pharmacology*; D002991:Clofazimine / Q000494:pharmacology*; D064687:Diarylquinolines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000472:pathogenicity; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics / Q000382:microbiology
D000995:Antitubercular Agents; D064687:Diarylquinolines; C493870:bedaquiline; D002991:Clofazimine
Mycobacterium tuberculosis; Rv0678; bedaquiline; clofazimine; resistance