In Vitro Susceptibility Testing of Tedizolid against Nontuberculous Mycobacteria

Abstract

Tedizolid is a new oxazolidinone with improved in vitro and intracellular potency against Mycobacterium tuberculosis , including multidrug-resistant strains, and some species of nontuberculous mycobacteria (NTM) compared with that of linezolid. Using the current Clinical and Laboratory Standards Institute (CLSI)-recommended method of broth microdilution, susceptibility testing of 170 isolates of rapidly growing mycobacteria showed equivalent or lower (1- to 8-fold) MIC ₅₀ and/or MIC ₉₀ values for tedizolid compared with that for linezolid. The tedizolid MIC ₉₀ values for 81 isolates of M. abscessus subsp. abscessus and 12 isolates of M. abscessus subsp. massiliense were 8 μg/ml and 4 μg/ml, respectively, compared with linezolid MIC ₉₀ values of 32 μg/ml for both. The MIC ₉₀ values for 20 isolates of M. fortuitum were 2 μg/ml for tedizolid and 4 μg/ml for linezolid. Twenty-two isolates of M. chelonae had tedizolid and linezolid MIC ₉₀ s of 2 μg/ml and 16 μg/ml, respectively. One hundred forty-two slowly growing NTM, including 7/7 M. marinum , 7/7 M. kansasii , and 7/11 of other less commonly isolated species, had tedizolid MICs of ≤1 μg/ml and linezolid MICs of ≤4 μg/ml. One hundred isolates of Mycobacterium avium complex and eight M. simiae isolates had tedizolid MIC ₅₀ s of 8 μg/ml and linezolid MIC ₅₀ s 32 and 64 μg/ml, respectively. Nine M. arupense isolates had MIC ₅₀ s of 4 μg/ml and 16 μg/ml for tedizolid and linezolid, respectively. These findings demonstrate a greater in vitro potency of tedizolid than linezolid against NTM and suggest that an evaluation of tedizolid as a potential treatment agent for infections caused by selected NTM is warranted.