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 <i>Mycobacterium tuberculosis</i> 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, <i>n</i> = 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, <i>n</i> = 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 (<i>ahpC</i>_-52C>T for INH, <i>embA</i>_-11C>A for EMB, <i>eis</i>_-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 <i>Mycobacterium tuberculosis</i> 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.