Emerging bedaquiline resistance: A threat to the global fight against drug-resistant tuberculosis

Abstract

Bedaquiline resistance is increasingly observed in the treatment of rifampicin-resistant tuberculosis (TB), yet standardized regimens for managing bedaquiline-resistant TB are lacking. Studies indicate a high proportion of bedaquiline-resistant cases have previously been treated for TB, and often involve strains resistant to quinolones. Regular monitoring of the culture status in patients receiving bedaquiline resistance treatment is advised. Methods such as experimental evolution, protein modeling, genome sequencing, and phenotypic analysis have been instrumental in identifying the mechanisms of bedaquiline resistance. Specifically, variants in the Rv0678 transcriptional repressor of the MmpS5-MmpL5 efflux system are linked to this type of resistance. Bayesian probability estimates show promise in determining the genotypic–phenotypic association for bedaquiline resistance, suggesting potential utility in clinical practice. Future research should explore the practical application of Bayesian probabilities in managing bedaquiline resistance. Sequencing-based technologies are anticipated to play a vital role in the early detection and management of drug-resistant TB strains.