Role of antimicrobial pharmacokinetics and pharmacodynamics in surgical prophylaxis

The pharmacokinetic and pharmacodynamic properties of antimicrobial agents used for surgical prophylaxis are reviewed. Since levels in tissue homogenates depend on the amount of drug present intracellularly, they do not accurately describe the relation between concentrations in serum and those in interstitial fluid. Levels of free drug in serum are good predictors of the time course of concentrations of unbound drug in interstitial fluid. An increase in protein binding does not reduce the area under the curve (AUC) of free drug for beta-lactam agents eliminated predominantly by glomerular filtration. Pharmacodynamic studies of persistent growth suppression and bactericidal activity predict that the period for which the free-drug concentration exceeds the minimal inhibitory concentration (MIC) is an important parameter in the efficacy of beta-lactam antibiotics. In contrast, the AUC is the major parameter in the efficacy of aminoglycosides and quinolones. Although studies with animals support the above concepts, data for humans are limited. Until additional clinical trials dictate other conclusions, the goal of prophylaxis with beta-lactam agents should be to provide serum levels of free drug above the MIC for common contaminating bacteria for the entire surgical period.