Bedaquiline drug resistance emergence assessment in MDR-TB (DREAM): A 5-Year prospective in-vitro surveillance study of bedaquiline and other second-line drug-susceptibility testing in MDR-TB isolates
Document Type
Article
Department
Pathology and Laboratory Medicine
Abstract
Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant-tuberculosis (MDR-TB) (DREAM) was a 5-year (2015-2019) phenotypic drug-resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5036 MDR-TB isolates of bedaquiline-treatment-naïve patients to bedaquiline and other anti-tuberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) minimal inhibitory concentration (MIC) methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015-0.12 μg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cut-off values of 0.12 μg/ml by BMD and 0.25 μg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or Intermediate category was set at 0.25 μg/ml and 0.5 μg/ml for BMD and AD, respectively. When applied to the 5036 MDR-TB isolates, bedaquiline-susceptible, intermediate and bedaquiline-resistant rates were 97.9%, 1.5% and 0.6%, respectively, for BMD, and 98.8%, 0.8% and 0.4% for AD. Resistance rates were: ofloxacin 35.1%, levofloxacin 34.2%, moxifloxacin 33.3%, 1.5% linezolid and 2% clofazimine. Phenotypic cross resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Co-resistance to bedaquiline and linezolid, and clofazimine and linezolid, were 0.1% and 0.3%, respectively, in MDR-TB, and 0.2% and 0.4% in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naïve population. No treatment-limiting patterns for cross-resistance and co-resistance have been identified with key TB drugs to date.
Publication (Name of Journal)
Journal of Clinical Microbiology
Recommended Citation
Kaniga, K.,
Hasan, R.,
Jou, R.,
Vasiliauskienė, E.,
Chuchottaworn, C.,
Ismai, N.,
Metchock, B.,
Miliauskas, S.,
Nhung, N. V.,
Rodrigues, C.
(2021). Bedaquiline drug resistance emergence assessment in MDR-TB (DREAM): A 5-Year prospective in-vitro surveillance study of bedaquiline and other second-line drug-susceptibility testing in MDR-TB isolates. Journal of Clinical Microbiology.
Available at:
https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/1363
Comments
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