[In vitro synergy between cefotaxime and its main metabolite, desacetylcefotaxime]

In vitro synergistic interaction between cefotaxime (CTX) and its main metabolite, desacetyl-cefotaxime (DCTX), against 7 species of clinical isolates (23-27 strains per species) was examined. Complete or partial synergy was noted with a 1:1 combination of CTX and DCTX against 22-78% of the Bacteroides fragilis, Staphylococcus aureus, Citrobacter freundii, Pseudomonas cepacia and Enterobacter cloacae isolates examined. Antagonistic effects of the drugs appeared against 11% of Proteus vulgaris and 4% of Serratia marcescens. When combined at various ratios by the checkerboard method and tested against B. fragilis, CTX and DCTX were found to act synergistically, and no antagonism occurred. The combined use of CTX and DCTX exhibited strong bactericidal activity against B. fragilis and inhibited bacterial regrowth. An experiment with concentrations of CTX and DCTX simulating human serum levels after intravenous administration also showed that the coexistence of DCTX augmented bactericidal activity of CTX against B. fragilis and brought inhibitory effects on bacterial regrowth. It is presumed from the present results that clinically applied CTX would have more potent effects than expected from in vitro sensitivity test data.