Methods for evaluating the penetration of beta-lactam antibiotics into tissues.

Methods for the study of tissue penetration by beta-lactam antibiotics have been critiqued and compared. Mathematical models may be useful in assessments of the influence of lipid solubility and protein binding on tissue penetration. In vitro models may be used for evaluation of the probable pharmacokinetic properties of beta-lactams but are of greater use in studies of the interaction between antimicrobial concentrations and the kinetics of bacterial killing. Numerous animal models have been used. Fibrin clots, intraperitoneal cages, and soft tissue models all tend to yield limited information on tissue penetration as they often have no pathophysiologic counterpart in humans. Three types of studies in humans--tissue homogenates, body fluids, and experimental fluids--all entail certain advantages and problems. Tissue homogenates are often contaminated with body fluids, such as urine and bile. The usefulness of drug assays in ascitic or pleural fluid is limited by the depot effect. Studies of experimental fluids (e.g., fluid from blisters induced chemically or by suction) may have some clinical relevance and yield consistent results.