Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults

Douwe F. Postma, Cornelis H. Van Werkhoven*, Leontine J R Van Elden, Steven F T Thijsen, Andy I M Hoepelman, Jan A J W Kluytmans, Wim G. Boersma, Clara J. Compaijen, Eva Van Der Wall, Jan M. Prins, Jan J. Oosterheert, Marc J M Bonten

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Original languageEnglish
Pages (from-to)1312-1323
Number of pages12
JournalNew England Journal of Medicine
Volume372
Issue number14
DOIs
Publication statusPublished - 2 Apr 2015

Keywords

  • BETA-LACTAM MONOTHERAPY
  • CONSORT 2010 STATEMENT
  • ATYPICAL PATHOGENS
  • RANDOMIZED-TRIALS
  • ECONOMIC BURDEN
  • CLINICAL-TRIALS
  • THERAPY
  • DESIGN
  • GUIDELINES
  • NONINFERIORITY

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