Post-antibiotic effect of azithromycin on respiratory tract pathogens

Azithromycin is a new azalide antibiotic with structural modifications that confer to the molecule acid stability, extension of antibacterial spectrum that includes important Gram-negative pathogens, long elimination half-life, and tendency to concentrate into various tissues where it persists for extended periods of time. The existence and length of a post-antibiotic effect (PAE), an important parameter for the characterization of new antibiotic molecules, has not yet been evaluated for this agent. In this study the PAE of azithromycin was assessed against representative respiratory pathogens included in the in vitro antimicrobial activity of the drug. The results obtained indicate that azithromycin produce a significant PAE on all Gram-positive and Gram-negative bacteria tested, resulting in an average value of 3.5 h for both S. pyogenes and S. pneumoniae, 3 h for B. catarrhalis and H. influenzae, and 2 h for Klebsiella spp. These findings support previous reports underlining the remarkable in vitro activity of azithromycin against H. influenzae, a pathogen poorly susceptible to the classical macrolides. Furthermore, the present demonstration of the existence of a long PAE of azithromycin against other Gram-positive and Gram-negative bacteria extends the pharmacokinetic advantages of the drug and strongly supports the application of this azalide in the therapy of respiratory infections.