Activities of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with amikacin, against acinetobacters as determined by checkerboard and time-kill studies

Abstract

A total of 101 Acinetobacter genospecies (77 Acinetobacter baumannii strains and 24 non-A. baumannii strains) were tested for their susceptibilities to levofloxacin, ofloxacin, and ciprofloxacin and for synergy between the quinolones and amikacin by checkerboard titration and time-kill analyses. The MICs at which 50% of the isolates are inhibited (MIC50)/MIC90s for the 101 strains were as follows (in micrograms per milliliter): levofloxacin, 0.25/16.0; ofloxacin, 0.5/32.0; ciprofloxacin, 0.25/> 64.0; and amikacin, 1.0/> 32.0. At empiric breakpoints of < or = 2.0 microg/ml, 61% of the strains were susceptible to all three quinolones. At a breakpoint of < or = 16.0 microg/ml, 84% of the strains were susceptible to amikacin. Checkerboard titrations yielded synergistic fractional inhibitory concentration (FIC) indices (< or = 0.5) for one strain with levofloxacin and amikacin and for two strains with ofloxacin and amikacin. Indices of > 0.5 to 1.0 were seen for 57, 54, and 55 strains with levofloxacin plus amikacin, ofloxacin plus amikacin, and ciprofloxacin plus amikacin, respectively, and indices of > 1.0 in 43, 45, and 46 strains, respectively, were found with the above three combinations. No strains yielded antagonistic FIC indices (> 4.0). Most FIC results of > 1.0 occurred in strains for which the quinolone MICs were > 2.0 microg/ml and for which the amikacin MICs were > or = 32.0 microg/ml. By contrast, synergy (defined as > or = 2 log10 decrease compared to the more active compound alone by time-kill analysis) was found in all seven strains tested for which the quinolone MICs were < or = 2.0 microg/ml. For eight other strains for which the quinolone MICs were > 2.0 microg/ml as determined by time-kill analysis, quinolone and amikacin concentrations in combination were usually too high to permit clinical use. Time-kill analysis was found to be more sensitive in detecting synergy than was the checkerboard method.