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, CAP-START Study Group, D F Postma, C H van Werkhoven, F Teding van Berkhout, A I M Hoepelman, J J Oosterheert, M J M Bonten, D F Postma, S F T Thijsen, S U C Sankatsing, L J R van Elden, J A J W Kluytmans, J G J V Aerts, W G Boersma, C J Compaijen, R Soetekouw, R H veenhoven, E van der Wall, I van der Lee, J M Prins, R E Jonkers, 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, CAP-START Study Group, D F Postma, C H van Werkhoven, F Teding van Berkhout, A I M Hoepelman, J J Oosterheert, M J M Bonten, D F Postma, S F T Thijsen, S U C Sankatsing, L J R van Elden, J A J W Kluytmans, J G J V Aerts, W G Boersma, C J Compaijen, R Soetekouw, R H veenhoven, E van der Wall, I van der Lee, J M Prins, R E Jonkers
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. (Funded by the Netherlands Organization for Health Research and Development; CAP-START ClinicalTrials.gov number, NCT01660204.).
Source: PubMed