Global status of phenotypic pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates: an updated systematic review and meta-analysis

Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of updated meta-analysis was to estimate the PZA weighted pooled resistance (WPR) rate in M. tuberculosis isolates based on publication date and WHO regions. We systematically searched the related reports in PubMed, Scopus, and Embase (from January 2015 to July 2022). Statistical analyses were performed using STATA software. The 115 final reports in the analysis investigated phenotypic PZA resistance data. The WPR of PZA was 57% (95% CI 48-65%) in MDR-TB cases. According to the WHO regions, the higher WPRs of PZA were reported in the Western Pacific (32%; 95% CI 18-46%), South East Asian region (37%; 95% CI 31-43%), and the Eastern Mediterranean (78%; 95% CI 54-95%) among any-TB patients, high risk of MDR-TB patients, and MDR-TB patients, respectively. A negligible increase in the rate of PZA resistance were showed in MDR-TB cases (55% to 58%). The rate of PZA resistance has been rising in recent years among MDR-TB cases, underlines the essential for both standard and novel drug regimens development.