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N Engl J Med. 2015 Apr 2;372(14):1312-23. doi: 10.1056/NEJMoa1406330.

Antibiotic treatment strategies for community-acquired pneumonia in adults.

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From the Julius Center for Health Sciences and Primary Care (D.F.P., C.H.W., M.J.M.B.) and the Departments of Internal Medicine and Infectious Diseases (D.F.P., A.I.M.H., J.J.O.) and Medical Microbiology (M.J.M.B.), University Medical Center Utrecht, and the Departments of Internal Medicine (D.F.P.), Pulmonology (L.J.R.E.), and Medical Microbiology (S.F.T.T.), Diakonessenhuis Utrecht, Utrecht, the Department of Medical Microbiology, Amphia Ziekenhuis Breda, Breda (J.A.J.W.K.), the Department of Pulmonology, Medisch Centrum Alkmaar, Alkmaar (W.G.B.), the Department of Internal Medicine, Kennemer Gasthuis Haarlem, Haarlem (C.J.C.), the Department of Pulmonology, Spaarne Ziekenhuis, Hoofddorp (E.W.), and the Department of Internal Medicine, Academic Medical Center Amsterdam, Amsterdam (J.M.P.) - all in the Netherlands.



The choice of empirical antibiotic treatment for patients with clinically suspected community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. We compared strategies of empirical treatment (allowing deviations for medical reasons) with beta-lactam monotherapy, beta-lactam-macrolide combination therapy, or fluoroquinolone monotherapy.


In a cluster-randomized, crossover trial with strategies rotated in 4-month periods, we tested the noninferiority of the beta-lactam strategy to the beta-lactam-macrolide and fluoroquinolone strategies with respect to 90-day mortality, in an intention-to-treat analysis, using a noninferiority margin of 3 percentage points and a two-sided 90% confidence interval.


A total of 656 patients were included during the beta-lactam strategy periods, 739 during the beta-lactam-macrolide strategy periods, and 888 during the fluoroquinolone strategy periods, with rates of adherence to the strategy of 93.0%, 88.0%, and 92.7%, respectively. The median age of the patients was 70 years. The crude 90-day mortality was 9.0% (59 patients), 11.1% (82 patients), and 8.8% (78 patients), respectively, during these strategy periods. In the intention-to-treat analysis, the risk of death was higher by 1.9 percentage points (90% confidence interval [CI], -0.6 to 4.4) with the beta-lactam-macrolide strategy than with the beta-lactam strategy and lower by 0.6 percentage points (90% CI, -2.8 to 1.9) with the fluoroquinolone strategy than with the beta-lactam strategy. These results indicated noninferiority of the beta-lactam strategy. The median length of hospital stay was 6 days for all strategies, and the median time to starting oral treatment was 3 days (interquartile range, 0 to 4) with the fluoroquinolone strategy and 4 days (interquartile range, 3 to 5) with the other strategies.


Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality. (Funded by the Netherlands Organization for Health Research and Development; CAP-START number, NCT01660204.).

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