In vitro Susceptibility of Nontuberculous Mycobacteria to Tedizolid

Abstract

Objective

Nontuberculous mycobacteria (NTM) can cause pulmonary and extrapulmonary diseases. Tedizolid (TZD) is a new oxazolidinone with in vitro activity against NTM such as Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus complex. The aim of this study was to evaluate the TZD susceptibility profiles of clinical isolates of NTM.

Methods

The microdilution method was used to identify the minimum inhibitory concentration (MIC) of TZD and linezolid (LZD) for 133 clinical NTM isolates. Broth microdilution chequerboard assays were used to investigate the synergistic effects of TZD and three antibiotics on two reference isolates and eleven clinical isolates of NTM.

Results

The TZD MIC₅₀ and MIC₉₀ for M. abscessus complex were 2 and 4 μg/mL, 16 and >32 μg/mL for MAC, respectively. TZD exhibited lower MICs than that of LZD for most NTM, which were positively correlated. Due to the high MIC values of TZD against MAC, it is necessary to conduct drug sensitivity tests before TZD administration. TZD-clarithromycin combination had synergistic response on M. abscessus complex in 3 of the 8 isolates, which lasted only 3–5 days. TZD-cefoxitin had synergistic effect against all five M. fortuitum isolates.

Conclusion

Our study demonstrates that TZD had greater in vitro potency than LZD, and synergy studies suggested that TZD may be an important component of multi-drug treatment regimen.

Keywords:

• tedizolid
• susceptibility testing
• nontuberculous mycobacteria
• linezolid
• oxazolidinone

Ethics Approval and Informed Consent

The research for the current study has been approved by the Institutional Review Board (IRB) of Huashan Hospital, Fudan University (Number: 2022-291). Our study is a retrospective study without direct contact with the patient, and did not involve personal privacy or commercial interests, so the informed consent was waived. This study is in accordance with the Helsinki Declaration and the information of all patients included in the study remained confidential.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

We thank for the support from the National Natural Science Foundation of China (32170176).