Evaluation of breakpoints for bedaquiline resistance determination: a multi-method, multi-country study.

Evaluation of breakpoints for bedaquiline resistance determination: a multi-method, multi-country study. Antimicrob Agents Chemother. 2020 Jul 13;: Authors: Ismail NA, Aono A, Borroni E, Cirillo DM, Desmaretz C, Hasan R, Mitarai S, Shakoor S, Torrea G, Kaniga K, Omar SV Abstract Criteria defining bedaquiline resistance for tuberculosis have been proposed addressing an emerging concern. We evaluated bedaquiline phenotypic drug susceptibility testing (pDST) criteria using drug-resistant tuberculosis clinical isolates tested at five reference laboratories. Isolates were tested at the proposed bedaquiline MGIT960 and 7H11 Agar Proportion (AP) critical concentrations, and dilutions higher. The epidemiological cut-off value for the broth microdilution (BMD) plates (frozen and dry) was investigated. Any isolate testing resistant had Sanger sequencing performed (atpE and Rv0678 genes). The composite reference standard (CRS) defined susceptibility or resistance as is, if all pDST methods agreed. If pDST was discordant sequencing results was used for final classification. Geographically-diverse and bedaquiline unexposed isolates were tested (N=495). The epidemiological cutoff value for BMD was confirmed to be 0.12 μg/mL. The majority of isolates were susceptible by all methods (467/495; 94.3%) and 28 were resistant by at least one method; of which 4 were resistant by all methods. 12/28 harboured Rv0678 mutations exclusively. Isolates with ins...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research