BACKGROUND

Azithromycin (Zithromax tablet, Pfizer), classified as an azalide, a subclass of macrolides, and clarithromycin (Biaxin canadian, Abbott), a semisynthetic macrolide, have been available in the U.S. for about a decade. Even though they are chemically related to erythromycin and share a common mechanism of action, their pharmacokinetic properties are better than those of erythromycin. Azithromycin and are resistant to degradation by acid catalysis, thereby allowing dosing once or twice per day.

These two drugs are commonly prescribed for the treatment of upper and lower respiratory tract infections because of their enhanced activity, convenient dosing, and improved tolera-bility. In 1993, 17.7 million macrolide prescriptions were filled; by the year 1999, the number of prescriptions increased by 20%. During that time period, resistance to macrolides for pneumococcal infections also increased by 9.8%.

Researchers have speculated that a major route of macrolide resistance is via an efflux mechanism expressed on mefgenes. In this process, the antibiotic is actively pumped out of the microbe. An alter native mechanism of resistance is via methy-lation of the ribosomal binding site. Because of the documented increase in resistance, these antibiotics should be prescribed appropriately in an attempt to decrease resistance.

Nine clinical trials comparing the efficacy and safety of azithromycin canadian and clarithromycin have been published. Two of the nine were performed in children with acute otitis media

(middle-ear infection) or pharyngitis. One trial was published in Japanese, and these results were not incorporated.

On the basis of six out of nine studies, we observed no significant differences in the efficacy and safety of azithromycin and clarithromycin, but patients who received azithromycin experienced more adverse drug events (ADEs) than those taking clarithromycin generic. Therefore, the goal of this retrospective study was to determine whether there was a difference in effectiveness, defined as therapeutic failure, between the two drugs for the outpatient treatment of community-acquired infections.

For our study, we defined therapeutic failure as the need for a subsequent antibiotic prescription within 21 days after the initiation of azithromycin or clarithromycin treatment for a given subject. Our primary objective was to compare the failure rates of versus clarithromycin in subjects new to antibiotic therapy (i.e., patients who had received no antibiotic prescriptions within 21 days before taking the study drug).

Our secondary objectives included (1) an assessment of failure rates with the two antibacterials in subjects who did not respond to any antibiotics 21 days before receiving either study drug and (2) a cost-minimization analysis of the two drugs.