Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives

The treatment of intracellular infections requires the use of antibiotics presenting appropriate cellular pharmacokinetic and pharmacodynamic properties. These properties, however, cannot be predicted on the simple basis of cellular drug accumulation and minimum inhibitory concentration in broth. In most cases, intracellular activity is actually lower than extracellular activity, despite the fact that all antibiotics reach intracellular concentrations that are at least equal to, and more often higher than the extracellular concentrations. This discrepancy may result from impairment of the expression of antibiotic activity or a change in bacterial responsiveness inside the cells. It therefore appears important to evaluate the intracellular activity of antibiotics in appropriate models.