PHARMACODYNAMICS OF MACROLIDES, AZALIDES, AND STREPTOGRAMINS - EFFECTON EXTRACELLULAR PATHOGENS

The efficacy of macrolides against extracellular pathogens depends on extracellular levels of free drug and the organisms' patterns of susce ptibility to the macrolides. The effect of macrolides against most bac teria is considered time-dependent. The size of inoculum affects eryth romycin's activity against streptococci and, moreover, against staphyl ococci. The optimal effect is observed at a pH of 8. A significant pos tantibiotic effect (PAE), lasting similar to 9 hours, has been shown w ith erythromycin and roxithromycin against gram-positive cocci. Azalid es share the same properties. For the streptogramin synercid, a dose-d ependent bactericidal activity within a range of low concentrations ha s been demonstrated. The serum area under the curve appeared to be the best predictor of in vivo effect on the mouse thigh model. Synercid a lso exhibited a prolonged PAE (similar to 10 hours) against the main p athogens of its spectrum. A better knowledge of the pharmacodynamic pr operties of macrolides and streptogramins is essential for definition of proper dosing regimens.