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The newer macrolides azithromycin, clarithromycin, dirithromycin and roxithromycin have longer elimination half-lives and greater tissue penetration than erythromycin, and thus can be administered once or twice daily. Generally, they appear to have similar antibacterial activity to erythromycin, with some exceptions. For example, clarithromycin is effective in the treatment of Mycobacterium avium-intracellulare complex (MAC) infections in patients with AIDS. However, these agents all show a high degree of cross-resistance with erythromycin.They are as effective as erythromycin for respiratory tract infections, and azithromycin, clarithromycin and roxithromycin have shown efficacy in the treatment of respiratory tract infections caused by Haemophilus influenzae.Azithromycin, clarithromycin and roxithromycin appear to cause fewer gastrointestinal adverse effects than erythromycin. All of the newer agents appear to have a lower drug interaction potential than erythromycin.The newer agents have higher acquisition costs than erythromycin, which still remains a useful antibacterial agent. Additions of other macrolide antibacterial agents to a formulary list are likely to depend on the ability of these agents to fill a niche unoccupied by erythromycin.