Abstract:

Objective: To evaluate the in vitro inhibitory activity of lefamulin against mycobacteria. Methods: A total of 47 standard mycobacterial strains (including 27 rapidly growing mycobacteria (RGM) and 20 slowly growing mycobacteria (SGM)) and 49 non-tuberculous mycobacteria (NTM) clinical isolates (including 22 Mycobacterium avium clinical isolates and 27 Mycobacterium intracellulare clinical isolates) preserved in the strain library of Beijing Chest Hospital, Capital Medical University, were selected as study strains. Broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the novel antibiotic lefamulin against these strains, and the distribution of MIC values was analyzed; Cytotoxicity assays (CCK8) were performed to calculate cell viability. Results: For 27 RGM standard strains, the strains with MIC ≤16 μg/ml, ≤8 μg/ml, ≤2 μg/ml, and ≤0.5 μg/ml were 12 (44.4%), 10 (37.0%), 4 (14.8%), and 1 (3.7%), respectively. For 20 SGM standard strains, the strains with MIC ≤16 μg/ml, ≤4 μg/ml, ≤2 μg/ml, and ≤0.5 μg/ml were 16 (80.0%), 14 (70.0%), 9 (45.0%), and 6 (30.0%), respectively. For 22 Mycobacterium avium clinical isolates, the MIC₅₀ and MIC₉₀ were 0.125 and 1 μg/ml, respectively. For 27 Mycobacterium intracellulare clinical isolates, the MIC₅₀ and MIC₉₀ were 2 and 4 μg/ml, respectively. Cytotoxicity assays in THP-1 adherent cells showed concentration-dependent and time-dependent decreases in viability following 12, 24, and 48 hours of incubation with lefamulin (0, 5, 10, 20 μg/ml): 12 h:98.80%、95.22%、89.94%、85.78%;24 h:97.99%、91.89%、89.55%、85.61%;48 h:97.33%、91.16%、88.56%、85.02%. Conclusion: Compared to the RGM standard strain, lefamulin exhibits strong inhibitory activity against SGM, with particularly good effects on the Mycobacterium avium complex and its clinical isolates.

Key words: Mycobacterium, Mycobacterium avium-intracellulare infection, Microbial sensitivity tests, Lefamulin