Spectrum of activity of levofloxacin against nontuberculous mycobacteria and its activity against the Mycobacterium avium complex in combination with ethambutol, rifampin, roxithromycin, amikacin, and clofazimine

Abstract

The spectrum of activity of levofloxacin was initially determined against 29 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs. Levofloxacin MICs were 1 to 2 dilutions lower compared with those obtained for ofloxacin and 8 to 64 dilutions lower compared with those obtained for its D-isomer. Levofloxacin MICs were below its peak level in serum (5.5 μg/ml following administration of a single oral dose of 350 mg) for 25 of 29 isolates tested. It possessed MICs below its peak level in serum for M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, M. chelonei, M. abcessus, M. fortuitum, and M. peregrinum. Regarding the M. avium complex, the MICs of levofloxacin for 11 clinical isolates (7 from human immunodeficiency virus-positive patients and 4 from human immunodeficiency virus-negative patients) were 1 to 2 dilutions lower than those of ofloxacin. Among 20 isolates belonging to 12 pathogenic mycobacterial species, the MBC/MIC ratios varied from 1 to 4 for levofloxacin and 2 to 4 for ofloxacin. When drug combinations were screened by using the radiometric x/y quotient methodology against five M. avium complex isolates, levofloxacin activity against all five isolates was enhanced by ethambutol and activity against three isolates was enhanced by clofazimine. Screening of three-drug combinations showed that the combination levofloxacin-ethambutol with a third potential anti-M. avium drug (rifampin, roxithromycin, amikacin, or clofazimine) resulted in enhanced activity for all 20 drug combinations screened.