title: Peritoneal pharmacokinetics of cefepime in laparotomy patients with inflammatory bowel disease, and dosage considerations for surgical intra-abdominal infections based on pharmacodynamic assessment.
abstract: This study aimed to examine the peritoneal pharmacokinetics of cefepime and to assess its pharmacodynamic exposure in peritoneal fluid (PF). Cefepime (1 g) was administered to eight patients with inflammatory bowel disease before abdominal surgery. Venous blood and PF samples were obtained at the end of the 0.5-h infusion and at 1, 2, 3, 4, 5, and 6 h thereafter. Drug concentrations in plasma and PF were determined, analyzed pharmacokinetically, and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. Cefepime penetrated well into PF, with a maximum drug concentration in a PF/plasma ratio of 0.59 +/- 0.15 (mean +/- SD, n = 8), and an area under the concentration-time curve ratio of 0.90 +/- 0.10. The probabilities of attaining the bacteriostatic and bactericidal targets (40% and 70% of the time above the MIC, respectively) in PF were > or =85% against Escherichia coli, Klebsiella species, and Enterobacter cloacae with 0.5 g every 12 h, 1 g every 12 h, 1 g every 8 h, and 2 g every 12 h. However, 1 g every 8 h or 2 g every 12 h was required for bacteriostatic and bactericidal probabilities > or =85% against Pseudomonas aeruginosa. These conventional regimens did not achieve a high probability against Bacteroides species. These results should help to give us a better understanding of the peritoneal pharmacokinetics of cefepime while also helping to choose the appropriate dosage to prevent surgical intra-abdominal infections on the basis of the pharmacodynamic assessment.
authors.affiliation: Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan. higuchi@med.kagawa-u.ac.jp
authors.forename: Kazuko
authors.initials: K
authors.lastname: Higuchi
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohge
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Houchi
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001202:Ascitic Fluid / Q000378:metabolism*; D001420:Bacteria, Aerobic / Q000187:drug effects; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000601:surgery*; D008297:Male; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime