Synergism in drug combination of new tuberculosis antibiotics for drug-resistant Mycobacterium tuberculosis in vitro.

The treatment of drug-resistant tuberculosis (DR-TB) faces significant challenges. Novel antituberculosis drugs such as bedaquiline (BDQ), pretomanid (Pa824), and delamanid (DLM) offer a promising treatment for DR-TB. However, the synergistic effects of these drugs have been insufficiently explored. In this research, we evaluated the synergistic effects of two dual-drug combinations (BDQ-Pa824 and BDQ-DLM) and four triple-drug combinations (BDQ-DLM-clofazimine [CFZ], BDQ-DLM-linezolid [LZD], BDQ-Pa824-CFZ, and BDQ-Pa824-LZD) against 30 Mycobacterium tuberculosis (MTB) strains isolated from TB patients. The results indicated that the synergistic antimycobacterial effects of BDQ-DLM-LZD and BDQ-Pa824-LZD show no statistically significant difference, suggesting that BDQ-DLM-LZD could be considered a potential therapeutic alternative for DR-TB. This provides evidence for the development of more flexible treatment options for DR-TB.IMPORTANCEThe rapid emergence of antimicrobial resistance in Mycobacterium tuberculosis (MTB) presents a critical challenge for global public health. Given that the synergistic effects of antituberculosis drugs against drug-resistant tuberculosis have not been systematically analyzed. In this research, we evaluated the synergistic antimycobacterial efficacy of the new optimized antituberculosis regimen (BDQ-DLM-LZD or BDQ-DLM-CFZ) and the standard regimen (BDQ-Pa824-LZD or BDQ-Pa824-CFZ) for TB strains. This highlights the therapeutic substitutability of BDQ-DLM or BDQ-Pa824-based triple-drug regimens for TB strains.