Global mapping of bedaquiline-resistant Mycobacterium tuberculosis: a systematic review

BACKGROUND: Tuberculosis (TB) is one of the deadliest bacterial infectious diseases worldwide, with rising cases of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Bedaquiline (BDQ)-containing regimens have become important for the treatment of MDR/XDR-TB, and resistance to BDQ is increasing. Understanding genetic mutations is crucial for early detection of BDQ-resistant strains and thus maintaining the effectiveness of these drugs. This study aimed to review mutations associated with BDQ-resistant TB globally. METHODS: This study systematically searched the keywords TB, XDR, MDR, BDQ, and genes in the PubMed, Scopus, Web of Science, and Embase databases for studies reporting BDQ-resistant TB and their associated genes globally from 2014 to 2025. RESULTS: This systematic review included 40 studies and 25,234 patient samples with MDR and XDR-TB from around the world. Results showed significant variation in BDQ resistance across the World Health Organization (WHO) regions, with the highest in the Eastern Mediterranean and the lowest in the Western Pacific. Furthermore, the data collected showed that, among the continents studied, resistance was highest in Africa and lowest in the Americas. The country distribution showed that resistance rates were higher in Iran (n = 24), Moldova (n = 26), and Armenia (n = 35), and lower in Italy (n = 1001) and the Philippines (n = 724) than in other countries in the analysis. Genetically, the most resistance-associated mutations were observed in the Rv0678, atpE, and pepQ genes, respectively. CONCLUSION: Given the increasing BDQ resistance and regional variability, it is essential to develop early detection systems, genomic surveillance, robust drug policy enforcement, and rapid diagnostics to maintain treatment effectiveness and curb the spread of resistance. Future research should focus on elucidating resistance mechanisms and developing novel therapeutic strategies.