In vitro Susceptibility of Nontuberculous Mycobacteria to Tedizolid

Abstract

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 MIC 50 and MIC 90 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.

Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine

“…Tedizolid is the second approved oxazolidinones derivate. Compared to Linezolid, they showed a lower in vitro MIC for the most common species of isolated NTM except for Mabs, but it is still promising considering the synergism with other common drugs used in clinical practice [ 143 , 144 ]. Linezolid has multiple severe adverse drug reaction, such as cytopenia, peripheral neuropathy and optic neuritis, and considering the treatment length, ADRs must be investigated routinely: for example, in a study during NTM treatment, the 45% of patients had adverse event attributed to linezolid after 19.9 weeks and the 87% stopped treatment [ 145 , 146 ].…”