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Update on the use of the macrolides for community-acquired respiratory tract infections

Joseph M Blondeau

The use of macrolides dates back more than 50 years, when erythromycin was the first of this class to be introduced into clinical practice. In the early 1990s, the so-called ‘newer’ or extended-spectrum macrolides were approved for clinical use in patients with a variety of infectious diseases. While clinically efficacious, the pharmacokinetic (frequent daily dosing) and adverse-events profile (specifically gastrointestinal) of erythromycin initially limited its use as an alternative agent for patients with allergy to β-lactam agents. Erythromycin could be characterized as being active against Gram-positive and atypical pathogens but has limited in vitro activity against Gram-negative organisms (particularly Haemophilus influenzae). The newer macrolide compounds, azithromycin and clarithromycin, were characterized has having in vitro antibacterial activity that was similar to that of erythromycin but with enhanced in vitro activity against Gram-negative respiratory tract pathogens, most notably, H. influenzae. These ‘newer’ macrolides also offered better pharmacokinetic/pharacodynamic properties with less frequent daily dosing and reduced gastrointestinal side effects. The role of atypical and/or new pathogens combined with the global escalation of acquired antimicrobial resistance continues to redefine and impact on the selection of empiric versus organism-directed therapy for respiratory infectious diseases. Macrolide compounds continue to be a valuable class of antimicrobial compounds, as evidenced by their continued prominent place in various guidelines. The key to the long-term viability of the macrolide class appears to be centered around understanding the factors that lead to the selection of macrolide resistance and the role that different macrolide compounds may have in this process.