The objective of this study was to characterize the relationship between
gentamicin concentrations during surgery and the development of
wound infection following colorectal operations. Despite decades of research in surgical prophylaxis, the relationship between intraoperative
antibiotic concentrations and postoperative
infection and the concentrations required for effective prophylaxis have not been established. A pharmacodynamic analysis was conducted using data from a previous prospective, randomized, double-blind clinical study which compared two dosage regimens of
gentamicin plus
metronidazole for prophylaxis in connection with elective colorectal surgery. Univariate and multivariate analyses of risk factors for
postoperative wound infection were conducted, and the relationship between intraoperative
gentamicin concentrations and surgical outcome was characterized. The
gentamicin concentration at the time of surgical closure was one of the strongest independent risk factors for
infection (P = 0.02), along with the presence of
diabetes mellitus (P = 0.02), stoma (P = 0.04), and advanced age (P = 0.05).
Gentamicin concentrations at closure of less than 0.5 mg/liter were associated with an
infection rate of 80% (representing 8 of 10 patients with concentrations below that level) (P = 0.003). Receiver operating characteristic curve analysis identified a critical closure concentration of 1.6 mg/liter for effective surgical prophylaxis (P = 0.002; sensitivity, 70.8%; specificity, 65.9%). This study provides new and important information on
antibiotic pharmacodynamics in surgical prophylaxis. It demonstrates the critical effect of the
antibiotic concentration at closure on
wound infection and suggests a significant association between the concentration and other well-established risk factors, like the timing of preoperative
antibiotic administration and surgery duration.