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

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.

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.

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.

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.