title: Antibacterial activity of four cephalosporins in an experimental infection in relation to in vitro effect and pharmacokinetics.
abstract: The in vitro activity of four cephalosporins was compared with their effects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of the plasma concentrations in vivo and those of the Hill equation the corresponding time course of ER was calculated and by integration with respect to time (0tERdt), an estimate was obtained of the effect on bacteria. For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h.
authors: Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
authors: H
authors: H
authors: Mattie
authors: A M
authors: AM
authors: van Dokkum
authors: L
authors: L
authors: Brus-Weijer
authors: A M
authors: AM
authors: Krul
authors: E
authors: E
authors: van Strijen
mesh_terms: D000380:Agranulocytosis / Q000150:complications; D000818:Animals; D002435:Cefamandole / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002442:Ceftazidime / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002443:Ceftriaxone / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002444:Cefuroxime / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy*; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D051379:Mice; D011485:Protein Binding; D013047:Specific Pathogen-Free Organisms
chemical_list: D002511:Cephalosporins; D002435:Cefamandole; D002443:Ceftriaxone; D002442:Ceftazidime; D002444:Cefuroxime