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 in...

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Bibliographic Details
Published in:Reviews of infectious diseases 1991-09, Vol.13, p.S790-S799
Main Authors: Jay Redington, Steven C. Ebert, Craig, William A.
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - pharmacology
Antibacterials
Antibiotics
Antimicrobials
Bacteria - drug effects
Biological and medical sciences
Body Fluids - metabolism
Cephalosporins
Dosage
Extracellular Space - metabolism
General aspects
Humans
Infections
Infectious diseases
Interstitial fluids
Medical sciences
Muscle tissues
Pharmacokinetics
Premedication
Protein Binding
Secretion
Session I: Theoretical and Preclinical Experimental Bases of Prophylaxis
Surgical Wound Infection - prevention & control
Tissue Distribution
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Summary: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 β-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 β-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 β-lactam agents should be to provide serum levels of free drug above the MIC for common contaminating bacteria for the entire surgical period.
ISSN:0162-0886