β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.

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Serval ID
serval:BIB_6377CAD0EAE6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.
Journal
Jama Internal Medicine
Author(s)
Garin N., Genné D., Carballo S., Chuard C., Eich G., Hugli O., Lamy O., Nendaz M., Petignat P.A., Perneger T., Rutschmann O., Seravalli L., Harbarth S., Perrier A.
ISSN
2168-6114 (Electronic)
ISSN-L
2168-6106
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
174
Number
12
Pages
1894-1901
Language
english
Notes
Publication types: Journal Article
Abstract
IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial.
OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia.
DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation.
INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm.
MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7.
RESULTS: After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms.
CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818610.
Pubmed
Web of science
Open Access
Yes
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02/01/2015 9:33
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20/08/2019 14:20
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