In Vitro Activity of Desacetylcefotaxime and the Interaction with its Parent Compound, Cefotaxime

Summary

Antibacterial activities of cefotaxime and its major metabolite, desacetylcefotaxime, against 178 strains (of 10 species) were assessed in terms of minimum inhibitory concentrations (MIC₅₀ and MIC₈₀), and were compared with those of cefoperazone and ceftazidime.

The activity of desacetylcefotaxime was several times less than that of cefotaxime against almost all of the species tested. Against Staphylococcus aureus, Morganella morganii, Enterobacter cloacae and Pseudomonas aeruginosa, the M1C8O values of desacetylcefotaxime were higher than those of cefoperazone and ceftazidime. The antibacterial potency of desacetylcefotaxime against Klebsiella pneumoniae and Pseudomonas cepacia was superior to that of cefoperazone and ceftazidime, and comparable with the activities of the latter compounds against the other 4 Gramnegative species.

Partial synergy was demonstrated in the activity of cefotaxime and desacetylcefotaxime against most of the strains examined. Antagonism was observed in activity against 2 of 18 strains of M. morganii. In general, desacetylcefotaxime enhances the potency of its parent compound, cefotaxime, when they coexist.

Intravenous infusion of cefotaxime Ig over a period of 1 hour resulted in mean peak serum concentrations of 48.5 mg/L of cefotaxime and 6.5 mg/L of desacetylcefotaxime at the end of the infusion. The mean elimination half life in β-phase of cefotaxime was 0.8 hour and that of desacetylcefotaxime was 2 hours.