Comparison of the antibacterial effects of cefepime and ceftazidime against Escherichia coli in vitro and in vivo.
The efficacies of cefepime and ceftazidime in an experimental Escherichia coli infection in granulocytopenic mice were related to their in vitro activities and their pharmacokinetic profiles. Cefepime had a higher intrinsic activity in vitro than ceftazidime, and it had a different pharmacokinetic profile, resulting in higher peak concentrations in plasma and a longer elimination half-life. To predict the antibacterial efficacy in vivo on the basis of in vitro activity and pharmacokinetics, we applied a mathematical model in which the in vitro effect is expressed as the difference in growth rate between control cultures and cultures grown in the presence of the antibiotic (ER), whereas the in vivo effect is given by the difference in the number of CFU between controls and antibiotic-treated animals (EN). The integral of ER over time, called ERt, was calculated by using in vivo concentrations. A significant linear relationship was found between EN and ERt for different doses at various times up to 4 h after administration, although the slope of this relationship was slightly but significantly less for cefepime (0.44) than for ceftazidime (0.59).
Mattie
H
H
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Sekh
B A
BA
van Ogtrop
M L
ML
van Strijen
E
E
D000818:Animals; D000077723:Cefepime; D002442:Ceftazidime / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests
D002511:Cephalosporins; D000077723:Cefepime; D002442:Ceftazidime