IN-VITRO SYNERGISM BETWEEN CEFOTAXIME AND MINOCYCLINE AGAINST VIBRIO-VULNIFICUS

We conducted time-kill studies to evaluate the inhibitory activities o f either cefotaxime or minocycline alone and the two drugs in combinat ion against a clinical strain of Vibrio vulnificus. The MICs of cefota xime and minocycline were 0.03 and 0.06 mu g/ml, respectively. When ap proximately 5 x 10(5) CFU of V. vulnificus per mi was incubated with c efotaxime at 0.03 or 0.05 mu g/ml, the bacterial growth was inhibited during the initial 2 and 8 h, respectively. Thereafter, V. vulnificus regrew and the level of growth reached that of the control. Within the dose range of less than five times the MIC, the duration of the inhib itory effect of cefotaxime was proportional to its concentration. When minocycline at 0.015, 0.03, 0.045, and 0.06 mu g/ml was used to evalu ate the inhibitory effect, a similar trend was observed. Either antibi otic at a concentration of five times the MIC or greater prevented the regrowth of V. vulnificus for at least 48 h. When cefotaxime at 0.05 mu g/ml and minocycline at 0.0-15 mu g/ml were combined in the same cu lture, the inhibitory effect against V. vulnificus persisted for more than 48 h, with no regrowth noted. The use of a combination of these t wo antibiotics resulted in the reduction of growth by 6 orders of magn itude compared to the use of either of the two antibiotics alone, and the number of surviving organisms in the presence of the antibiotics c ombined was approximately 3 orders of magnitude less than that in the starting inoculum. We conclude that cefotaxime and minocycline acted s ynergistically in inhibiting V. vulnificus in vitro.