Level 2: Mid-level evidence

A systematic review of 15 randomized trials evaluated short course (≤7 days) vs. extended course (>7 days) antibiotic monotherapy in 2,796 patients older than 12 years with radiographically confirmed mild-to-moderate community-acquired pneumonia (CAP) (Am J Med. 2007;120:783-790). Ten trials with 1,093 patients evaluated short-course azithromycin [Zithromax] (three days in six trials, five days in four trials); eight of the 10 trials compared azithromycin with extended courses of other macrolides. Two trials with 848 patients evaluated short-course fluoroquinolones (compared with the same fluoroquinolone in one trial and with amoxicillin-clavulanate [Augmentin] in one trial); two trials with 296 patients evaluated short-course beta-lactams (compared with extended-course for same beta-lactams); one trial with 559 patients evaluated short-course ketolide (telithromycin [Ketek]) compared with extended-course clarithromycin (Biaxin). The time to outcome assessment ranged from 10 to 42 days.

In a meta-analysis of 15 trials with 2,796 patients, 26.1% of short-course-treated patients vs. 25.6% of extended-course-treated patients failed to improve clinically. The differences were not statistically significant, but the confidence intervals were wide and it is unclear if a meta-analysis combining azithromycin with trials of other antibiotics is appropriate. There were no significant differences in subgroup analyses by class of short-course antibiotic. Three trials suggested improvement with short-course antibiotics (all using azithromycin for three days); 12 trials suggested no differences. There were no differences in a subgroup analysis of eight higher-quality trials.

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No significant differences were observed in overall mortality, which was 1.7% (range 0.9%-6.7%) in eight trials with deaths; seven trials had no deaths.