Predicting the clinical efficacy of antibiotics: toward definitive criteria.

BACKGROUND: Both the in vitro microbiologic activity of an antibiotic drug and its pharmacokinetic characteristics are important criteria to be considered when predicting clinical efficacy. At present, however, it is not clear which pharmacokinetic parameters are the most useful in determining optimal therapeutic approaches.
OBJECTIVES: To review the various pharmacokinetic properties of antibiotics, with special reference to the cephalosporins, and to consider the contributions that these make to the definitive prediction of clinical efficacy. DISCUSSION: It is important, when attempting to use the pharmacokinetic parameters in conjunction with the minimum inhibitory concentrations for possible pathogens to predict clinical efficacy, to measure the concentration of an antibacterial drug at the site of bacterial proliferation. In most cases bacteria proliferate in the interstitial fluid; therefore it is important to choose an antibiotic that achieves high concentrations in this compartment; the intracellular concentration is less critical. The interstitial fluid concentration is in equilibrium with the free (i.e. non-protein-bound) serum concentration and either of these antibiotic levels is more predictive of clinical efficacy than are intracellular levels.