Management of Community-Acquired Pneumonia: Defining the Role of Azithromycin
Nishan S. Gunasekara
Julia A. Barman Balfour
Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality and is associated with the consumption of considerable health resources worldwide. Initial treatment of patients with CAP is often empirical. Growing concern about the increasing prevalence of atypical organisms is reflected in North American guidelines, which place considerable emphasis on the use of the macrolides. Azithromycin, the prototype azalide, is a macrolide derivative with a broad antimicrobial spectrum including enhanced activity against Haemophilus influenzae relative to erythromycin. Its distinctive pharmacokinetic profile is characterised by extensive and prolonged tissue distribution accompanied by low serum drug concentrations. An estimated tissue half-life of between 2 and 3 days enables the drug to be administered as a once daily, abbreviated regimen for the treatment of patients with CAP. This provides the drug with an advantage over other macrolides including erythromycin and clarithromycin, which require a longer treatment duration. However, the potential for prolonged subinhibitory tissue concentrations of azithromycin to promote the development of resistant microorganisms requires further evaluation. Clinical trials have demonstrated the efficacy of 3- to 5-day regimens of oral azithromycin (total dose 1.5g) in patients with CAP. These regimens were generally as effective as longer treatment durations with other commonly used antimicrobials including other macrolides and amoxicillin/clavulanic acid. Importantly, azithromycin is well tolerated and is associated with a lower incidence of gastrointestinal adverse events than erythromycin. Azithromycin is also associated with fewer pharmacokinetic drug interactions than erythromycin or clarithromycin. According to US prescribing information, orally administered azithromycin is not recommended for use (presumably as monotherapy) in patients with moderate to severe pneumonia, bacteraemia or significant underlying health problems, or in elderly or debilitated patients. A recently developed intravenous formulation of azithromycin may be of value in some of these patients but this requires confirmation. Conclusion: Oral azithromycin is an attractive antimicrobial option in patients with mild CAP and has a role in both empirical therapy and pathogen-directed treatment against atypical organisms. However, its usefulness, as for other macrolides, may be limited in regions with a high prevalence of macrolide-resistant pneumococci. Particular benefits over erythromycin and some other macrolides include enhanced activity against Gram-negative pathogens, an improved tolerability profile, a once daily abbreviated treatment regimen (which may result in improved patient compliance) and few pharmacokinetic drug interactions. The development of an intravenous preparation may expand the use of azithromycin in patients with CAP requiring hospitalisation.
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