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

Abstract

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 for M. tuberculosis.

Methods

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 (SHTBMY) (TREK Diagnostic Systems, Thermo Fisher Scientific In., USA) consisting of a 96-well microtitre plate containing 4 (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 1μg/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 1μg/mL. The MIC₉₀ value of LZD against XDR-TB isolates was 32μg/mL. For CFZ, six isolates with elevated MICs of ≥2μg/mL. CFZ’s MIC₅₀ and MIC₉₀ values in all isolates were 0.12μg/mL and 0.25μg/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.

Keywords:

• Mycobacterium tuberculosis
• MIC distributions
• bedaquiline
• delamanid
• linezolid

Ethics Statement

The research plan received approval from the Ethics Committees of Shanghai Pulmonary Hospital, a subsidiary of Tongji University in Shanghai, China. The study adhered to the ethical principles set forth in the 1964 Declaration of Helsinki and its subsequent revisions. During the study, patients were granted written informed consent for the inclusion of their data. A parent or legal guardian of patients under 18 years of age provided informed consent.

Acknowledgments

We express our utmost gratitude to the Clinical Laboratory of Shanghai Pulmonary Hospital for their valuable support in the execution of this project. This project was supported by grants from the Shanghai Clinical Research Center for infectious diseases (tuberculosis) (19MC1910800 to W.S.) and Outstanding Medical Academic Leader (2019LJ13).

Disclosure

No potential conflict of interest was reported by the authors.