Introduction

In critically ill patients, the pharmacokinetic behavior of many antibiotics is unpredictable and clinical trials are difficult to perform and interpret. Antibiotic dose has to be modified repeatedly according to the observed renal or hepatic function. Pharmacodynamic factors are important, i.e. the rapidity of bactericidal effect, the postantibiotic effect (the length of suppression of bacterial growth after antibiotic concentrations have fallen below inhibitory levels), and the serum half-life and tissue penetration of the antibiotic. The intravenous route is used because intramuscular administration is affected by changes in tissue perfusion.

The penicillins, glycopeptides, and cephalosporins act against the cell wall of the organism and bacterial killing depends more on the time during which the minimum inhibitory concentration (MIC) is exceeded than the absolute tissue concentration, provided that the lowest concentration is at least four times the MIC. The aminoglycosides and quinolones require high peaks because bacterial killing depends on concentration rather than duration of exposure. The area under the curve of serum concentration (AUC) versus time and over the MIC (area under the inhibitory curve AUIC) can be used to predict efficacy:

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