Interaction of cefotaxime and desacetylcefotaxime against pathogenic bacteria. Assessment with the serum bactericidal test.
Cefotaxime (CTX), a third-generation cephalosporin with high potency against virtually all Enterobacteriaceae as well as many other clinically important facultative and anaerobic bacteria, is metabolized in vivo to desacetylcefotaxime (des-CTX), which also has intrinsic antibacterial activity, albeit less than the parent compound. To assess the possible additive or synergistic interaction of CTX and its main metabolite, we used a micromethod to measure serum bactericidal activity in samples containing CTX with and without des-CTX. Forty subject samples with 0.8-55.8 micrograms/ml of CTX and 1.1-11.6 micrograms/ml of des-CTX and matched simulated serum samples with 0.8-57.2 micrograms/ml were tested against clinical strains of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis. Both sets of sera were reproducibly bactericidal with titers of less than 2-32 against S. aureus, 16-greater than or equal to 2048 against E. coli, and less than 2-64 against B. fragilis. Serum bactericidal titers against B. fragilis were higher in 10 of 23 (43%) subject samples in which concentrations of the desacetyl metabolite exceeded 50% of those of CTX when compared with matched simulated samples containing CTX alone in equivalent concentrations. This effect was not observed with samples tested against S. aureus or E. coli. The ultimate clinical importance of any in vitro interaction between CTX and its desacetyl metabolite, however, can likely only be determined by controlled clinical trials.
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