Biomarker guided antibiotic stewardship in community acquired pneumonia: A randomized controlled trial

PLoS One. 2024 Aug 20;19(8):e0307193. doi: 10.1371/journal.pone.0307193. eCollection 2024.

Affiliations

¹ Department of Pulmonary Medicine, Northwest Hospital, Alkmaar, the Netherlands.
² Department of Pulmonary Medicine, Zaans Medical Centre, Zaandam, the Netherlands.
³ Department of Pulmonary Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands.
⁴ Department of Pulmonary Medicine, ISALA, Zwolle, the Netherlands.
⁵ Department of Clinical Chemistry, Haematology & Immunology, Northwest Hospital, Alkmaar, the Netherlands.
⁶ Julius Centre for Health Sciences and Primary Care Health, University Medical Centre Utrecht, Utrecht, the Netherlands.

Abstract

Background: In community-acquired pneumonia (CAP), the role of biomarkers to shorten duration of antibiotic treatment has not been firmly established. We assessed the effectiveness of active feedback of treatment algorithms based on procalcitonin (PCT) and C-reactive protein (CRP), compared to standard care, on the duration of antibiotic treatment in patients hospitalized with community-acquired pneumonia (CAP) in non-ICU wards.

Methods and findings: We performed a randomised, open label, parallel group, multi-centre trial in 3 Dutch teaching hospitals. Treatment was guided by a PCT algorithm, CRP algorithm or standard care. Participants were recruited by a member of the study team and randomised at day 2-3 of admission in a 1:1:1 ratio. Treatment was discontinued upon predefined thresholds of biomarkers that were assessed on admission, day 4 and days 5-7 if indicated. The primary outcome was total days on antibiotic treatment until day 30. In total 468 participants were included in this study. The median days on antibiotics (IQR) was 7 (IQR 7-10) in the control group, 4 (IQR 3-7) in the CRP group (rate ratio (RR) of 0.70, 95% CI 0.61-0.82 compared to standard care; p <0.001), and 5.5 (IQR 3-9) in the PCT group (RR of 0.78, 95% CI 0.68-0.89 compared to standard care; p <0.001). New antibiotics within the first 30 days were prescribed to 24, 23 and 35 patients in standard care, CRP and PCT groups, respectively. The hazard ratio for a new prescription in patients in the PCT group compared to standard care 1.63 (CI 0.97-2.75; p = 0.06). No difference in time to clinical stability or length of stay was found.

Conclusions: A strategy of feedback of CRP-guided and PCT-guided treatment algorithms reduced the number of days on antibiotic in the first 30 days after hospital admission in non-ICU wards for CAP. The study was not powered to determine safety of shortening duration of antibiotic treatment. (NCT01964495).

Copyright: © 2024 Duijkers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Aged
Aged, 80 and over
Algorithms
Anti-Bacterial Agents* / administration & dosage
Anti-Bacterial Agents* / therapeutic use
Antimicrobial Stewardship* / methods
Biomarkers* / blood
C-Reactive Protein* / analysis
Community-Acquired Infections* / drug therapy
Female
Humans
Male
Middle Aged
Pneumonia* / drug therapy
Procalcitonin* / blood

Substances

Anti-Bacterial Agents
C-Reactive Protein
Biomarkers
Procalcitonin

Associated data

ClinicalTrials.gov/NCT01964495

Grants and funding

The research was funded by an unrestricted grant from Pulmoscience and the Foreest Medical School. Pulmoscience is owned and funded by the pulmonologists of the Northwest hospital and Foreest Medical School is a non-profit institution connected to the Northwest hospital. The funders had no role in the design and conduct of the study, in the collection, management, analysis and interpretation of the data, in the preparation, review or approval of the manuscript, or in the decision to submit the manuscript for publication.