Single vs Multiple Antibiotics in Community-Acquired Pneumonia

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

Single vs Multiple Antibiotics for CAP in General

Probably the best-documented indication for monotherapy is the outpatient treatment of CAP. The microbiologic etiology is shifted in favor of the atypical microorganisms, making monotherapy with macrolides or quinolones very appropriate.

Given the greater frequency of both antibiotic resistance and unusual pathogens, the greatest debate on monotherapy vs combination treatment involves the hospitalized CAP patient. Several randomized trials have demonstrated that newer-generation quinolones are at least equivalent to cephalosporin-based combination therapy.^5,6,8 Vergis et al⁹ also demonstrated that monotherapy with azithromycin was equivalent to a cephalosporin plus erythromycin, with fewer side effects. This latter finding was incorporated into the American Thoracic Society's recommendations for empiric treatment of hospitalized CAP patients without underlying disease, but not the recommendations of the Infectious Diseases Society of America. The majority of published trials have been from pharmaceutical industry-sponsored trials designed to show equivalency for FDA registration purposes,^7,10 and are subject to the limitations discussed above.

A better assessment of the overall adequacy of monotherapy compared with combination therapy may come from retrospective analysis of large databases. Comparison of death rates also allows direct comparison of an objective, meaningful endpoint. Analysis of nearly 13,000 elderly patients (> 65 years) with CAP by Gleason et al¹⁵ is probably the best-known comparison of monotherapy and combination therapy. As seen in Figure 1, a survival advantage was found for patients treated with either quinolone monotherapy or combination therapy with a second- or third-generation cephalosporin and a macrolide. Conversely, any aminoglycoside-containing regimen and the combination of a b-lactam/b-lactamase inhibitor and a macrolide were associated with significantly higher mortality rates. Therefore, it appears that cephalosporin combination therapy is superior to cephalosporin monotherapy, and quinolone monotherapy was equivalent to a cephalosporin combination.

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