Classifying new anti-tuberculosis drugs: rationale and future perspectives

- The World Health Organization (WHO) 2016 guidelines for multidrug-resistant tuberculosis (MDR-TB) propose a regrouping of anti-TB drugs for the treatment of MDR-TB.
- The classification of anti-TB drugs guides the clinician in designing an appropriate multidrug-/extensively drug-resistant TB regimen.
- Discussion on possible future changes to the anti-TB drug groupings has started.
- Based on recent evidence on some compounds, certain drugs are likely to increase or decrease in importance in the future.
- If the efficacy and safety profile of linezolid, bedaquiline, and delamanid is confirmed, they might move up the anti-TB drug hierarchy.

SummaryThe classification of anti-tuberculosis (TB) drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO) has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2-5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification) and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed.