In vitro and in vivo activities of newer fluoroquinolones against Vibrio vulnificus

Abstract

The MICs of six fluoroquinolones as well as minocycline and cefotaxime for 46 clinical isolates of Vibrio vulnificus were determined by the agar dilution method. All the drugs tested had good activities against all isolates, with the MICs at which 90% of the isolates tested were inhibited (MIC(90)s) by five of the fluoroquinolones ranging between 0.03 and 0.06 micro g/ml. The MIC(90) of lomefloxacin, on the other hand, was 0.12 micro g/ml. Time-kill studies were conducted with these agents and a clinical strain of V. vulnificus, VV5823. When approximately 5 x 10(5) CFU of V. vulnificus/ml was incubated with any one of the above-mentioned six fluoroquinolones at concentrations of two times the MIC, there was an inhibitory effect on V. vulnificus that persisted for more than 48 h with no noted regrowth. The efficacies of the fluoroquinolones were further evaluated in vivo in the mouse model of experimental V. vulnificus infection and compared to the efficacy of a combination therapy using cefotaxime plus minocycline. With an inoculum of 1.5 x 10(7) CFU, 28 (87.5%) of 32 mice in the cefotaxime-minocycline-treated group survived and 29 (91%) of the 32 mice in the moxifloxacin-treated group survived while none of the 32 mice in the control group did. With an inoculum of 3.5 x 10(7) CFU, the difference in survival rates among groups of 15 mice treated with levofloxacin (13 of 15), moxifloxacin (10 of 15), gatifloxacin (10 of 15), sparfloxacin (11 of 15), ciprofloxacin (12 of 15), or lomefloxacin (10 of 15) was not statistically significant while none of the 15 mice treated with saline survived. We concluded that the newer fluoroquinolones as single agents are as effective as the cefotaxime-minocycline combination in inhibiting V. vulnificus both in vitro and in vivo.

FIG. 1.

(a) Inhibition of growth curves of V. vulnificus VV5823 (inoculum size, 5 × 10⁵ CFU/ml) after incubation with different fluoroquinolones at MICs. The lower limit of detection was set at 10 colonies (100 CFU/ml). (b) Inhibition of growth curves of V. vulnificus VV5823 (inoculum, 5 × 10⁵ CFU/ml) after incubation with minocycline, cefotaxime alone, a combination of cefotaxime and minocycline, or different concentrations of moxifloxacin. MICs of cefotaxime, minocycline, and moxifloxacin were 0.06 μg/ml.

FIG. 2.

(a) Survival rates of mice (n = 15) subcutaneously injected with 1.5 × 10⁷ CFU of V. vulnificus following treatment with a cefotaxime-minocycline combination, moxifloxacin, or saline. The differences between moxifloxacin- and saline-treated groups and between cefotaxime-minocycline-treated and saline-treated groups were significant (P < 0.001) by log rank test, while that between cefotaxime-minocycline-treated and moxifloxacin-treated groups was not significant. (b) With an inoculum of 3.5 × 10 ⁷ CFU and antibiotic treatment for 36 rather than 42 h, survival rates among mice (n = 15) treated with the fluoroquinolones were significantly higher than that of the saline-treated control group (P < 0.01, log rank test) but not significantly different from one another.