Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance, 3rd ed.

Overview

Rapid and accurate detection of drug resistance is essential to ensure that people with tuberculosis (TB) receive appropriate and effective treatment. The WHO Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance provides a standardized reference for interpreting genetic mutations associated with phenotypic drug resistance and supports sequencing-based drug susceptibility testing, diagnostic development, surveillance and research.

This third edition substantially expands the evidence available for genomic drug-resistance interpretation, drawing on paired whole-genome sequencing and phenotypic drug susceptibility testing data from more than 71 000 clinical isolates from over 75 countries. It includes expanded evidence for newer and repurposed anti-TB medicines, including bedaquiline, linezolid, delamanid, pretomanid and cycloserine, as well as updated bioinformatic and statistical methods, an enhanced interpretation framework and strengthened practical guidance. Because interpretation of some mutations depends on genomic context, the Graded Mutation List must be applied together with the catalogue's additional grading rules and other interpretation criteria, ideally through validated bioinformatics workflows that integrate these components to support sample-level resistance interpretation.