Pyrazinamide (PZA), is regarded as an important agent in the management of multi-drug resistant tuberculosis (MDR-TB) (defined as resistance to at least rifampicin and isoniazid) and has been shown to reduce treatment duration for drug-sensitive TB (1). Since the inclusion of PZA in a MDR-TB regimen adds significantly to both the pill burden and the side effects, (mainly arthralgia and hepatitis), it is logical to limit usage to patients where PZA has a proven effect. The current World Health Organisation (WHO) recommendation is to include PZA in MDR-TB regimens unless there is demonstrated evidence of resistance (2). However, large-scale data supporting this recommendation are lacking. No evidence was shown of an association between a successful outcome and PZA susceptibility for MDR-TB patients treated with a full intensive phase PZA standard WHO regimen in a high MDR-TB burden setting. Furthermore, there was no evidence of a dose-response association between a successful outcome and different PZA treatment regimens in the intensive phase. The major limitations was the low power for the main analysis and the retrospective and observational nature of the study contributing to an increased risk of bias. A possible explanation for the results might be that PZA treatment mainly has its effect in shortening a regimen (7) instead of improving outcomes or that patients had sufficient likely effective drugs in their regimen. The generalisability would be limited to settings with low HIV prevalence and where there is a high background prevalence of SLD resistance. This study provides provocative but insufficient evidence to warrant changing PZA treatment protocols, although the evidence relating to PZA for the WHO 2016 guideline is weak. Until further evidence emerges supporting these findings, it seems prudent to continue including PZA in standard MDR-TB regimens unless resistance is certain. We recommend research into alternative add-on agents in settings with high PZA resistance
