Huiyun Zhang1, Wenya Hua1, Siran Lin1, Yu Zhang1, Xinchang Chen1, Shiyong Wang1, Jiazhen Chen1, Wenhong Zhang1,2,3. 1. Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. 2. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China. 3. Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
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.
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.
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