Comparative study of in vitro activity of tedizolid and linezolid against Mycobacterium avium complex.

OBJECTIVES:The aim of this study is to compare the in vitro activity and minimal inhibitory concentration (MIC) distributions of tedizolid and linezolid against Mycobacterium avium complex (MAC) strains using a reference broth microdilution assay and a macrodilution assay with the Bactec-MGIT-960. METHODS:A total of 37 clinical isolates of MAC were included in the study. Reference broth microdilution was performed according to CLSI guidelines in a range of concentrations from 64 to 0.064 mg/L. Macrodilution was performed with the Bactec-MGIT-960 system. The cut-off points defined by CLSI for linezolid (resistant: > 16 mg/L, intermediate: 16 mg/L, susceptible: <16 mg/L) were used to define clinical categories of this drug. Essential agreement for both linezolid and tedizolid and categorical agreement for linezolid were defined following FDA criteria. RESULTS:The MIC50 (16mg/L) and MIC90 (32mg/L) values for linezolid were identical with both methods. However, the MIC50 and MIC90 of tedizolid by microdilution (4 mg/L and 8 mg/L, respectively) were one twofold dilution higher than by macrodilution (2 mg/L and 4 mg/L, respectively). Ninety-four percent and 2.7% of the strains had MICs of tedizolid ≤4 mg/L and ≤ 0.5 mg/L, respectively, by the reference method. The linezolid macrodilution assay showed a categorical agreement of 40.5%, a minor error rate of 56.7% and a major error rate of 2.7% with respect to the reference method. CONCLUSIONS:Tedizolid showed higher in vitro activity than linezolid against the tested MAC isolates. Macrodilution using the BD Bactec-MGIT-960 system is a practical approach to determine the susceptibility of MAC strains to tedizolid.