Penetration and Exposure of Cefotiam into the Peritoneal Fluid of Abdominal Surgery Patients after Intravenous Administration

Abstract

The present study aimed to examine the peritoneal pharmacokinetics and pharmacodynamic exposure of intravenous cefotiam. One gram of cefotiam was administered to eight patients before abdominal surgery. Venous blood and peritoneal fluid (PF) samples were obtained at the end of infusion (0.5 h) and 1, 2, 3, 4, 5, and 6 h afterwards. The drug concentrations in the plasma and PF were determined, analyzed pharmacokinetically, and used for a stochastic simulation with minimum inhibitory concentration (MIC) data. Cefotiam penetrated well into the PF with the area under the drug concentration-time curve ratio of 0.88 +/- 0.18 (mean +/- SD, n = 8). Regarding the pharmacodynamic exposures against Escherichia coli and Klebsiella species, the probabilities of attaining the bacteriostatic target (40% of the time above MIC) in the PF using 0.5 g every 12 h, 1 g every 12 h, and 2 g every 12 h were 88.3-93.6%. However, 1 g every 8 h was needed for 89.7 and 91.6% probabilities of attaining the bactericidal target (70% of the time above MIC). These results should help us to understand better the peritoneal pharmacokinetics of cefotiam while also helping us to choose the appropriate dosage for intra-abdominal infections.

Pharmacokinetics of Beta-Lactam Antibiotics in Patients with Intra-Abdominal Disease: A Structured Review

“…Further, no samples were obtained from peritoneal fluid, which would have been indicative of antibiotic effects at the site of infection. Other studies [14,[31][32][33] have been performed in patients after abdominal surgery. In these studies, the AUC ratio of peritoneal exudates:plasma was *90% for cefepime, cefozopran, and cefotiam (cefozopran and cefotiam are available only in certain countries; e.g., China and Japan).…”

Improving antimicrobial use in critically ill patients

“…Further, no samples were obtained from peritoneal fluid, which would have been indicative of antibiotic effects at the site of infection. Other studies [71,100,101,107] have been performed in patients after abdominal surgery. In these studies, the AUC ratio of peritoneal exudate: plasma was ~90% for each of cefepime, cefozopran and cefotiam respectively (cefozopran and cefotiam are only available at certain countries, e.g.…”