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Macrolides and ketolides are characterized by a very wide tissular distribution, which is related to their capacity to accumulate in the acidic compartments of the cells. This property is considered an advantage, because it concentrates the drug at the site of infection. Yet, the low serum levels consecutive to this tissular distribution may favor the selection of resistance. Macrolides are essentially bacteriostatic and ketolides are slowly bactericidal. The pharmacodynamic indice that best predicts effi cacy is the free 24 h-AUC/MIC ratio for both subclasses. Despite their high concentration inside the cells, macrolides and ketolides remain bacteriostatic against intracellular bacteria, with a potency similar to that observed extracellularly. New formulations have been developed to optimize patient’s adherence (extended release tablets) or to further increase antibiotic concentration at the site of infection (powders for inhalation)

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics