The performance of the WHO mutation catalog of <i>Mycobacterium tuberculosis</i> in the diagnosis of drug resistance to rifampicin-resistant strains in Wenzhou, China

WHO released the first and second editions of Mycobacterium tuberculosis complex (MTBC) mutations catalog associated with drug resistance in 2021 and 2023, respectively. The aim of this study was to evaluate the resistance prediction by mutation catalog for nine anti-tuberculosis drugs in rifampicin (RIF)-resistant tuberculosis (RR-TB) in Wenzhou, China. Over the period from 2020 to 2022, 301 RR-TB cases were continuously prospectively collected in Wenzhou Central Hospital. A total of 214 MTBC isolates were collected with drug susceptibility testing using the MGIT960 system and MYCOTB plates. Whole-genome sequencing (WGS) was performed for resistance prediction using mutation catalog by the WHO and freely available tools (TB-Profiler). Among 214 RR-TB isolates, drug resistance prediction using the WHO second edition mutation catalog demonstrated high sensitivity when stratified by the two predominant lineages. In Beijing lineage (L2, n = 171) isolates, sensitivity was 98.73% for RIF, 95.77% for isoniazid (INH), 89.29% for ethambutol (EMB), and 98.04% for moxifloxacin (MFX). Corresponding values in Euro-American lineage (L4, n = 43) isolates were 100.00% for RIF, 92.11% for INH, 94.44% for EMB, and 75.00% for MFX. Specificity exceeded 80% for all drugs except RIF in both lineages. Additionally, three potential resistance-associated mutations were determined ( ahpC _-52C>T for INH, embA _-11C>A for EMB, eis _-10G>A for Kanamycin). Resistance prediction based on mutation catalog offers better patient-tailored treatment of tuberculosis. Integrating more new drug mutations from different geographic areas would improve the accuracy of resistance prediction.IMPORTANCEBased on the catalog of mutations in Mycobacterium tuberculosis complex (MTBC) and their association with drug resistance published by the WHO in 2021 and 2023, this study evaluated the predictive performance of the catalogs for resistance to nine anti-tuberculosis drugs among 214 MTBC isolates from Wenzhou Central Hospital. The results demonstrated high accuracy of resistance prediction using the second edition. Three potential resistance-associated mutations were also identified. These findings not only confirm the reliability of the current catalog but may also provide valuable insights for future updates.