SYNERGISTIC EFFECT OF AMOXICILLIN AND CEFOTAXIME AGAINST ENTEROCOCCUS-FAECALIS

The antibacterial efficacy of the combination of amoxicillin and cefot axime was assessed against 50 clinical strains of Enterococcus faecali s. For 48 of 50 strains, the MIC of amoxicillin that inhibited 50% of isolates tested decreased from 0.5 mu g/ml (range, 0.25 to 1 mu g/ml) to 0.06 mu g/ml (range, 0.01 to 0.25 mu g/ml) in the presence of only 4 mu g of cefotaxime per mi, Alternatively, the MIC of cefotaxime that inhibited 50% of isolates tested decreased from 256 mu/ml (range, 8 t o 512 mu g/ml) to 1 mu g/ml (range, 0.5 to 16 mu g/ml) in the presence of only 0.06 mu g of amoxicillin per ml. For JH2-2, a reference strai n of E. faecalis, the MICs of amoxicillin, cefotaxime, and amoxicillin in the presence of cefotaxime (4 mu g/ml) were 0.5, 512, and 0.06 mu g/ml, respectively, By using a penicillin-binding protein (PBP) compet ition assay, it was shown that with cefotaxime, 50% saturation of PBPs 2 and 3 was obtained at very low concentrations (<1 mu g/ml), while 5 0% saturation of PBPs 1, 4, and 5 was obtained with greater than or eq ual to 128 mu g/ml. With amoxicillin, 50% saturation of PBPs 4 and 5 w as obtained at 0.12 and 0.5 mu g/ml, respectively, Therefore, the part ial saturation of PBPs 4 and 5 by amoxicillin combined with the total saturation of PBPs 2 and 3 by cefotaxime could be responsible for the observed synergy between these two compounds.