Pharmacodynamics of cefepime.
The microbiological activity of cefepime was assessed in vitro against 232 clinical isolates coupled with a pharmacokinetic evaluation at steady state in six patients receiving 1 g every 12 h. MIC90s were less than or equal to 0.25 mg/l for Enterobacteriaceae and streptococci. 1 mg/l for Staphylococcus aureus and 8 mg/l for Pseudomonas aeruginosa. Mean serum concentrations in patients were 62.5 +/- 2.7 mg/l (end infusion) and 1.1 +/- 0.8 mg/l (at 12 h) with an elimination half-life 2.72 +/- 0.59 h. These data together with those published for currently marketed cephalosporins were integrated to generate an Intensity Index incorporating both the magnitude and duration that drug concentrations exceed the MIC during steady-state dosing. Cefepime demonstrated comparable or superior indices to cefazolin against Gram-positive microorganisms and to cefuroxime and ceftazidime against Gram-negatives. Serum bacteriostatic and bactericidal activity from the kinetic samples corresponded with the duration that serum cefepime concentrations exceeded the MIC and MBC, respectively, for selected strains. This pharmacodynamic evaluation suggests that cefepime 1 g every 12 h potentially provides inhibitory serum concentrations for the majority of common Enterobacteriaceae, streptococci and S. aureus over the dosing interval but that higher doses or more frequent administration may be necessary for some pseudomonal infections.
Kovarik
J
J
Department of Clinical Microbiology, University Hospital Utrecht, The Netherlands.
Rozenberg-Arska
M
M
Visser
M
M
Verhoef
J
J
D001419:Bacteria / Q000187:drug effects*; D000077723:Cefepime; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D015610:Serum Bactericidal Test
D002511:Cephalosporins; D000077723:Cefepime