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Am Fam Physician. 2004;69(2):420

Most guidelines on the management of community-acquired pneumonia advocate adding a macrolide antibiotic to a second- or third-generation cephalosporin for empiric therapy. Macrolides offer better coverage of atypical pneumonia pathogens and have anti-inflammatory effects that may be beneficial in patients with pneumonia. Sánchez and co-investigators compared the relative clinical efficacy of azithromycin or clarithromycin as the added macrolide for the treatment of community-acquired pneumonia.

The study initially screened all patients who presented with community-acquired pneumonia to the emergency department of a large university teaching hospital over a three-year period. Exclusion criteria included outpatient antibiotic treatment for three or more days before admission, the need for mechanical ventilation, and death or discharge before at least one completed day of antibiotic therapy.

All patients received intravenous ceftriaxone in a dosage of 1,000 mg daily as initial empiric therapy. Addition of a macrolide and selection of azithromycin or clarithromycin were done at the discretion of the treating physician. Patients were not randomized, and medication use was not blinded to the outcome evaluators (i.e., an “open-label” study). Of the 896 patients admitted for pneumonia, 603 (67 percent) were included in the study.

Azithromycin in a dosage of 500 mg once daily was given orally for three days. Clarithromycin in a dosage of 500 mg twice daily was given intravenously initially; patients were switched to oral administration after three days if clinical improvement had occurred, for a total course of at least 10 days. More patients received azithromycin (64 percent) than clarithromycin (37 percent). Risk scoring for pneumonia severity at study entry was similar in the two macrolide treatment groups. Patients taking azithromycin were older (71.5 years) on average than those who received clarithromycin (65.8 years).

The average length of hospital stay was shorter in the group receiving azithromycin (7.3 days) than in those treated with clarithromycin (9.4 days). The range in length of stay for both groups, however, was fairly large and overlapping (standard deviation: five to seven days, respectively). Overall mortality rates were significantly lower in patients treated with azithromycin (3.7 percent) than in those treated with clarithromycin (7.3 percent). The incidence of bacteremia, which was associated with a higher risk of mortality, was similar in the two macrolide treatment groups. No significant survival benefit of azithromycin therapy was noted in the subgroup of 82 patients with the highest scores of pneumonia severity.

The authors conclude that adding azithromycin to ceftriaxone in the treatment of community-acquired pneumonia is associated with a shorter hospital stay and a lower rate of mortality, compared with adding clarithromycin.

editor's note: Studies such as this are easily reduced to catchy news headlines or pharmaceutical company soundbites (e.g., “Azithromycin is better than clarithromycin”), but careful scientific interpretation of the results reveals important caveats. Lack of randomization, no blinding of the evaluators to the treatment assignment, and a large portion of initially enrolled subjects who were excluded from the final data analysis are factors that should temper any enthusiasm about simply accepting the authors' suggestion that azithromycin is the “first-choice macrolide for community-acquired pneumonia.”—B.Z.

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