Narrow-spectrum antibiotics for community-acquired pneumonia in Dutch adults (CAP-PACT): a cross-sectional, stepped-wedge, cluster-randomised, non-inferiority, antimicrobial stewardship intervention trial.

Autor:	Schweitzer VA; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, Netherlands. Electronic address: v.a.schweitzer-2@umcutrecht.nl., van Heijl I; Julius Centre for Health Sciences and Primary Care, Utrecht, Netherlands; Department of Clinical Pharmacy, Tergooi Hospital, Hilversum, Netherlands., Boersma WG; Department of Pulmonary Diseases, Northwest Hospital Group, Alkmaar, Netherlands., Rozemeijer W; Department of Medical Microbiology, Northwest Hospital Group, Alkmaar, Netherlands., Verduin K; Department of Microbiology and Infection Prevention, Amphia Hospital, Breda, Netherlands., Grootenboers MJ; Department of Pulmonary Diseases, Amphia Hospital, Breda, Netherlands., Sankatsing SUC; Department of Internal Medicine, Diakonessenhuis Utrecht, Utrecht, Netherlands., van der Bij AK; Department of Medical Microbiology, Diakonessenhuis Utrecht, Utrecht, Netherlands., de Bruijn W; Department of Clinical Pharmacy, Diakonessenhuis Utrecht, Utrecht, Netherlands., Ammerlaan HSM; Department of Internal Medicine, Catharina Hospital, Eindhoven, Netherlands., Overdevest I; Department of Medical Microbiology, Catharina Hospital, Eindhoven, Netherlands., Roorda-van der Vegt JMM; Department of Pulmonary Diseases, Ziekenhuisgroep Twente, Almelo, Netherlands., Engel-Dettmers EM; Department of Clinical Pharmacy, Ziekenhuisgroep Twente, Almelo, Netherlands., Ayuketah-Ekokobe FE; Department of Internal Medicine, LangeLand Hospital, Zoetermeer, Netherlands., Haeseker MB; Department of Medical Microbiology, LangeLand Hospital, Zoetermeer, Netherlands., Dorigo-Zetsma JW; Department of Medical Microbiology, Tergooi Hospital, Hilversum, Netherlands., van der Linden PD; Department of Clinical Pharmacy, Tergooi Hospital, Hilversum, Netherlands., Boel CHE; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, Netherlands., Oosterheert JJ; Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, Netherlands., van Werkhoven CH; Julius Centre for Health Sciences and Primary Care, Utrecht, Netherlands., Bonten MJM; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, Netherlands; Julius Centre for Health Sciences and Primary Care, Utrecht, Netherlands.
Jazyk:	angličtina
Zdroj:	The Lancet. Infectious diseases [Lancet Infect Dis] 2022 Feb; Vol. 22 (2), pp. 274-283. Date of Electronic Publication: 2021 Oct 07.
DOI:	10.1016/S1473-3099(21)00255-3
Abstrakt:	Background: Adults hospitalised to a non-intensive care unit (ICU) ward with moderately severe community-acquired pneumonia are frequently treated with broad-spectrum antibiotics, despite Dutch guidelines recommending narrow-spectrum antibiotics. Therefore, we investigated whether an antibiotic stewardship intervention would reduce the use of broad-spectrum antibiotics in patients with moderately severe community-acquired pneumonia without compromising their safety. Methods: In this cross-sectional, stepped-wedge, cluster-randomised, non-inferiority trial (CAP-PACT) done in 12 hospitals in the Netherlands, we enrolled immunocompetent adults (≥18 years) who were admitted to a non-ICU ward and had a working diagnosis of moderately severe community-acquired pneumonia. All participating hospitals started in a control period and every 3 months a block of two hospitals transitioned from the control to the intervention period, with all hospitals eventually ending in the intervention period. The unit of randomisation was the hospital (cluster), and electronic randomisation (by an independent data manager) decided the sequence (the time of intervention) by which hospitals would cross over from the control period to the intervention period. Blinding was not possible. The antimicrobial stewardship intervention was a bundle targeting health-care providers and comprised education, engaging opinion leaders, and prospective audit and feedback of antibiotic use. The co-primary outcomes were broad-spectrum days of therapy per patient, tested by superiority, and 90-day all-cause mortality, tested by non-inferiority with a non-inferiority margin of 3%, and were analysed in the intention-to-treat population, comprising all patients who were enrolled in the control and intervention periods. This trial was prospectively registered at ClinicalTrials.gov, NCT02604628. Findings: Between Nov 1, 2015, and Nov 1, 2017, 5683 patients were assessed for eligibility, of whom 4084 (2235 in the control period and 1849 in the intervention period) were included in the intention-to-treat analysis. The adjusted mean broad-spectrum days of therapy per patient were reduced from 6·5 days in the control period to 4·8 days in the intervention period, yielding an absolute reduction of -1·7 days (95% CI -2·4 to -1·1) and a relative reduction of 26·6% (95% CI 18·0-35·3). Crude 90-day mortality was 10·9% (242 of 2228 died) in the control period and 10·8% (199 of 1841) in the intervention period, yielding an adjusted absolute risk difference of 0·4% (90% CI -2·7 to 2·4), indicating non-inferiority. Interpretation: In patients hospitalised with moderately severe community-acquired pneumonia, a multifaceted antibiotic stewardship intervention might safely reduce broad-spectrum antibiotic use. Funding: None. Competing Interests: Declaration of interests CHvW reports grants from Pfizer; personal fees from Pfizer and MSD/Merck; non-financial support from BioMérieux and DA Volterra, outside the submitted work; and a patent issued for the prediction of clinical manifestations of gut microbiota. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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