WHO operational handbook on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection: web annex C: technical manual for culture-based drug susceptibility testing of anti-tuberculosis drugs used in the treatment of tuberculosis

This web annex to the WHO operational handbook on tuberculosis, Module 3: Diagnosis, provides technical guidance for culture-based drug susceptibility testing (DST) of anti-tuberculosis drugs used in the treatment of tuberculosis. The manual describes standardized phenotypic DST methods using solid and liquid culture media, including Löwenstein–Jensen, Middlebrook 7H10 and 7H11 agar, and the BACTEC MGIT system. It presents critical concentrations and clinical breakpoints for first-line, second-line, newer and repurposed anti-tuberculosis agents, and outlines WHO recommendations for diagnostic approaches and interpretation of susceptibility results.

The document addresses the continuing role of phenotypic DST in the context of expanding molecular diagnostic technologies, particularly for drugs lacking validated rapid molecular resistance tests and for resolving discordant results. It includes guidance on biosafety requirements, preparation of media and drug solutions, inoculum preparation, quality control procedures and reporting of results. The annex also summarizes the evidence basis used to establish critical concentrations and highlights methodological considerations affecting the reliability and reproducibility of testing for specific drugs. The manual is intended to support laboratories in implementing quality-assured DST procedures for the management of drug-susceptible and drug-resistant tuberculosis.