AI Article Synopsis
- Bedaquiline (BDQ) is a new drug approved for treating multi-drug resistant tuberculosis (MDR-TB), and this study aimed to establish threshold values for BDQ effectiveness, assess its resistance patterns, and evaluate its relationship with another drug, clofazimine (CFZ).
- The research involved analyzing 391 tuberculosis samples to determine susceptibility levels, with specific minimum inhibitory concentrations (MICs) indicating resistant, intermediate, and susceptible categories for BDQ and CFZ.
- Findings showed that patients with specific genetic mutations (Rv0678) and non-susceptible BDQ levels faced higher treatment failures, highlighting the need for improved testing methods to detect BDQ resistance, while emphasizing that cross-resistance with
Article Abstract
Background: Bedaquiline (BDQ) is a novel agent approved for use in combination treatment of multi-drug resistant tuberculosis (MDR-TB). We sought to determine BDQ epidemiological cut-off values (ECVs), define and assess interpretive criteria against putative resistance associated variants (RAVs), microbiological outcomes and cross resistance with clofazimine (CFZ).
Methods: A retrospective cohort study was conducted. Minimal inhibitory concentrations (MIC) to BDQ were determined using 7H9 broth microdilution (BMD) and MGIT960. RAVs were genetically characterised using whole genome sequencing. BDQ ECVs were determined using ECOFFinder and compared with 6-month culture conversion status and CFZ MICs.
Findings: A total of 391 isolates were analysed. Susceptible and intermediate categories were determined to have MICs of ≤0.125μg/ml and 0.25μg/ml using BMD and ≤1μg/ml and 2μg/ml using MGIT960 respectively. Microbiological failures occurred among BDQ exposed patients with a non-susceptible BDQ MIC, an Rv0678 mutation and ≤2 active drug classes. The Rv0678 RAVs were not the dominant mechanism of CFZ resistance and cross resistance was limited to isolates with an Rv0678 mutation.
Interpretation: Criteria for BDQ susceptibility are defined and will facilitate improved early detection of resistance. Cross- resistance between BDQ and CFZ is an emerging concern but in this study was primarily among those with an Rv0678 mutation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835552 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2018.01.005 | DOI Listing |
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