Bedaquiline, Delamanid, Linezolid, Clofazimine, and Capreomycin MIC Distributions for Drug Resistance Mycobacterium tuberculosis in Shanghai, China

Background: New antituberculosis drugs have recently been approved for the treatment of multidrug-resistant tuberculosis TB (MDR-TB). We aimed to describe the distributions of bedaquiline, delamanid, linezolid, clofazimine, and capreomycin MIC values forMethods: M. tuberculosis clinical isolates were originally isolated from 2020 to 2021 from 1452 different pulmonary tuberculosis patients of the Shanghai Pulmonary Hospital in China. The drug susceptibility testing was performed using the Sensititre custom plates (bedaquiline, delamanid, clofazimine, capreomycin) antimicrobial agents. MICs were determined for linezolid using a microdilution method.Results: Based on the latest definitions, 156 (10.74%) were MDR-TB, 93 (6.40%) were pre-XDR-TB, and 27 (1.86%) were XDR-TB. The rate of BDQ resistance in cases of MDR-TB was 7.69%, while it was observed to be 10.75% in cases of pre-XDR-TB, and significantly higher at 37.04% in cases of XDR-TB. The lowest rate of drug resistance against M. tuberculosis was DLM (0.14%). For LZD, 11 (0.76%) clinical isolates were resistant, based on the CLSI breakpoint of 1 mu g/mL. The five strains with a MIC value of >32 for LZD resistance were XDR-TB isolates. Among all MDR, pre-XDR, and XDR isolates tested, LZD' MIC50 increased from 0.25 and 0.5 to 1 mu g/mL. The MIC90 value of LZD against XDR-TB isolates was 32 mu g/mL. For CFZ, six isolates with elevated MICs of >= 2 mu g/mL. CFZ's MIC50 and MIC90 values in all isolates were 0.12 mu g/mL and 0.25 mu g/mL, respectively.Conclusion: The study findings indicate that BDQ, DLM, CFZ, and LZD may exhibited excellent in vitro activity against MDR-TB isolates. Detection of resistance to BDQ and LZD was alarming for XDR-TB isolates. It is necessary to perform universal drug sensitivity testing for M. tuberculosis, especially MDR-TB and XDR-TB patients.

Automated summary

This study found that bedaquiline, delamanid, clofazimine, and linezolid may exhibit excellent in vitro activity against multidrug-resistant tuberculosis (MDR-TB) isolates. The detection of resistance to bedaquiline and linezolid in extremely drug-resistant tuberculosis (XDR-TB) isolates is concerning. Universal drug susceptibility testing for Mycobacterium tuberculosis, especially in MDR-TB and XDR-TB patients, is necessary.