AZITHROMYCIN - THE FIRST OF THE TISSUE-SELECTIVE AZALIDES

The azalide azithromycin, which is derived from erythromycin, contains a methyl-substituted nitrogen in the lactone ring. This 15-membered e xpanded lactone ring results in improved acid stability and oral bioav ailability compared with erythromycin. Azithromycin possesses a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including enhanced activity compared with the macrolides against Haem ophilus influenzae and Moraxella catarrhalis. In vitro activity of azi thromycin against intracellular and clinically atypical pathogens is a lso good. Azithromycin has a distinct pharmacokinetic profile compared with other antimicrobial agents, the most prominent feature is its hi gh tissue selectivity. Concentrations of azithromycin in respiratory t ract, gynaecological tissue and prostate remain above minimum inhibito ry concentrations of pathogens for several days, thus making it possib le to use a short-course, once-daily dosing regimen. Another feature o f azithromycin is that it rapidly penetrates phagocytic cells, with th e release of the antibiotics at local sites of infection. Comparative clinical trials have shown that azithromycin given once daily for 3 or 5 days is comparable to comparator drugs given for 7 or 10 days in th e treatment of otitis media, sinusitis, pharyngitis, acute bronchitis, acute infectious exacerbations of chronic bronchitis, community-acqui red pneumonia and skin and soft tissue infections in adults. Azithromy cin given once daily for 3 days has also been shown to be effective in the treatment of respiratory tract and skin and soft tissue infection s in children. In addition, some sexually-transmitted diseases are eff ectively treated by a single 1-g dose of azithromycin; clinical and mi crobiological responses were comparable to those recorded using doxycy cline given twice daily for 7 days. The short-duration, once-daily dos ing regimen is well tolerated in adults and children, and there is no evidence of interaction between azithromycin and theophylline, terfena dine, or cimetidine.