WHO operational handbook on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection: web annex B: critical concentrations for pretomanid and cycloserine: WHO policy statement

This WHO policy statement presents the evidence review and recommendations supporting the establishment of critical concentrations for pretomanid and cycloserine drug susceptibility testing in tuberculosis (TB). The document addresses a major gap in the laboratory diagnosis and management of drug-resistant TB, given the increasing use of pretomanid-containing regimens and the absence of WHO-endorsed phenotypic testing criteria for these medicines. It summarizes systematic reviews, individual-level data analyses, pharmacokinetic and pharmacodynamic assessments, and evaluations of minimum inhibitory concentration distributions across Mycobacterium tuberculosis lineages.

Based on review by the WHO Technical Advisory Group on TB Diagnostics and Laboratory Strengthening, the publication recommends the use of two pretomanid test concentrations (0.5 mg/L and 2.0 mg/L) and establishes a critical concentration of 16 mg/L for cycloserine using the MGIT method. The document also discusses lineage-specific variability, interpretive uncertainties, implementation considerations for laboratories and TB programmes, and research priorities related to resistance mechanisms, breakpoint determination and treatment monitoring.