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  • Title: Comparative pharmacokinetics of cefotaxime and ceftizoxime and the role of desacetylcefotaxime in the antibacterial activity of cefotaxime.
    Author: Quintiliani R, Nightingale CH, Tilton R.
    Journal: Diagn Microbiol Infect Dis; 1984 Jun; 2(3 Suppl):63S-70S. PubMed ID: 6086220.
    Abstract:
    A single 15 mg/kg i.v. dose of cefotaxime (CTX) and ceftizoxime (CTZ) were given to six adult volunteers on two separate occasions in a cross-over experiment to determine the pharmacokinetics of each drug and the desacetyl metabolite of cefotaxime, desacetylcefotaxime (des-CTX). From these data, mock serum samples were prepared in human serum to simulate the concentrations of CTX, CTZ, and des-CTX at the following times postdose: 5, 10, 30, and 45 min; 1, 1.5, 2, 3, 4, 5, 6, 8, and 10 hr. At each of these time periods, serum bacteriostatic and bactericidal assays were performed against selected pathogens (Escherichia coli, Serratia marcescens, Enterobacter species) with similar susceptibilities to CTX and CTZ, but with varying sensitivity to des-CTX, and against one organism (Bacteroides fragilis) toward which CTX and des-CTX exhibited synergistic activity. From these studies, it was found that des-CTX can appreciably lengthen the microbiologic action of CTX when it has a high degree of inherent activity (MIC less than or equal to mcg/ml) against the organism, or when it behaves synergistically with CTX toward the bacterium, or both. It is possible that the major advance of CTX and CTZ pertains to their ability to kill many organisms at extremely low concentrations, allowing for monotherapy with low and infrequent dosing, which is very cost-effective in comparison with high and more frequent dosing required by older agents or with antibiotic combinations.
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