Single vs Multiple Antibiotics in Community-Acquired Pneumonia

By Richard G. Wunderink, MD, FCCP; and Grant W. Waterer, MBBS, FCCP

Explanations for the findings of this study have generally suggested that coverage of atypical microorganisms, mainly Legionella, is important to improve outcome in CAP.^1,8 In support of this possibility, Houck et al¹⁶ demonstrated a similar benefit for combination therapy in some years but not others, suggesting that the advantage of cephalosporin-based combination therapy was dependent on seasonal variations. This variable antibiotic response probably reflects variation in the frequency of atypical microorganisms on a year-to-year basis.

The difficulties with using retrospective data for definitive answers is illustrated by other findings of the study by Gleason et al.¹⁵ Figure 2 demonstrates the actual adjusted odds ratio for death for each of the common therapies. Patients who receive a combination of a b-lactam/b-lactamase and a macrolide have a significantly higher mortality rate than patients who receive either drug as monotherapy. The reason for this worse associated mortality is not entirely clear. The macrolide should cover atypical microorganisms and the b-lactam (ampicillin, carbenicillin, or piperacillin), if sensitive, should cover S pneumoniae just as well as a cephalosporin. An antagonist effect of the b-lactam and the macrolide is unlikely. A more likely explanation is a selective use of this combination in a high-risk subgroup of CAP. One of the more likely reasons to use a b-lactam/b-lactamase instead of a cephalosporin for CAP is suspicion of aspiration. Clinical suspicion of aspiration has been shown to be a risk factor for CAP mortality.¹⁷

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