Macrolides and Ketolides

Abstract

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).

Pharmacokinetics / pharmacodynamics consideration in treating critically septic patients and correlates of bacterial killing: a review article

“…Other agents have a similar efficacy index like Fluoroquinolones, Daptomycin, GLycopeptides, Amphotericin B, and Echinocandins [23]. The third type of PK/PD bacterial killing is the mixed pattern, and that is dependent on both attaining a sufficient concentration for a sufficient time above the antimicrobial MIC, examples are Fluoroquinolones, Daptomycin, GLycopeptides, Ketolides, Macrolides, Clindamycin, Streptogramins, Oxazolidonoes, Tetracyclines, Glycycyclines, Aminoglycosides, Triazoles, and Echinocandins ( Figure 2C) [24].…”

Population-based meta-analysis of roxithromycin pharmacokinetics: dosing implications of saturable absorption and protein binding

“…Using these simulations, pharmacodynamic target attainment on day 7 of therapy was predicted as the proportion of individuals achieving a pharmacodynamic target of an fAUC/MIC ratio .20, associated with optimal antibacterial activity. 20 Proportions were evaluated with decreasing pathogen susceptibility (increasing MIC), and against MIC distributions for pathogens commonly treated with roxithromycin obtained from EUCAST. 21…”

In vitro synergistic interaction between Melaleuca armillaris essential oil and erythromycin against Staphylococcus aureus isolated from dairy cows

“…They can reach high intracellular concentrations ( 10 ) and decreases it antimicrobial activity at pH 5.0 ( 11 , 13 ). Intracellular activity of most macrolides is low ( 14 ), it seems to be associated with inactivation due to acidic pH of the phagolysosome (pH near 5) where they are located ( 15 ). These antibiotics lose approximately 90% of their activity for each pH unit that decreases ( 16 ).…”

“…These antibiotics lose approximately 90% of their activity for each pH unit that decreases ( 16 ). However, new macrolides such as azithromycin present intracellular activity in vivo against S. aureus ( 13 , 14 ).…”