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Randomized Controlled Trial
. 2024 Mar 4;7(3):e240830.
doi: 10.1001/jamanetworkopen.2024.0830.

Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing: A Randomized Clinical Trial

Dagfinn L Markussen  1   2 , Sondre Serigstad  1   2   3 , Christian Ritz  1   4 , Siri T Knoop  1   5 , Marit H Ebbesen  5 , Daniel Faurholt-Jepsen  4 , Lars Heggelund  1   6 , Cornelis H van Werkhoven  7 , Tristan W Clark  8 , Rune O Bjørneklett  2   3 , Øyvind Kommedal  5 , Elling Ulvestad  1   5 , Harleen M S Grewal  1   5
Affiliations
Randomized Controlled Trial

Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing: A Randomized Clinical Trial

Dagfinn L Markussen et al. JAMA Netw Open. .

Erratum in

  • Error in Figure 1.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Apr 1;8(4):e258665. doi: 10.1001/jamanetworkopen.2025.8665. JAMA Netw Open. 2025. PMID: 40168029 Free PMC article. No abstract available.

Abstract

Importance: Lower respiratory tract (LRT) infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. Molecular tests have the potential to optimize treatment decisions and management of CAP, but limited evidence exists to support their routine use.

Objective: To determine whether the judicious use of a syndromic polymerase chain reaction (PCR)-based panel for rapid testing of CAP in the emergency department (ED) leads to faster, more accurate microbiological test result-based treatment.

Design, setting, and participants: This parallel-arm, single-blinded, single-center, randomized clinical superiority trial was conducted between September 25, 2020, and June 21, 2022, in the ED of Haukeland University Hospital, a large tertiary care hospital in Bergen, Norway. Adult patients who presented to the ED with suspected CAP were recruited. Participants were randomized 1:1 to either the intervention arm or standard-of-care arm. The primary outcomes were analyzed according to the intention-to-treat principle.

Intervention: Patients randomized to the intervention arm received rapid syndromic PCR testing (BioFire FilmArray Pneumonia plus Panel; bioMérieux) of LRT samples and standard of care. Patients randomized to the standard-of-care arm received standard microbiological diagnostics alone.

Main outcomes and measures: The 2 primary outcomes were the provision of pathogen-directed treatment based on a microbiological test result and the time to provision of pathogen-directed treatment (within 48 hours after randomization).

Results: There were 374 patients (221 males [59.1%]; median (IQR) age, 72 [60-79] years) included in the trial, with 187 in each treatment arm. Analysis of primary outcomes showed that 66 patients (35.3%) in the intervention arm and 25 (13.4%) in the standard-of-care arm received pathogen-directed treatment, corresponding to a reduction in absolute risk of 21.9 (95% CI, 13.5-30.3) percentage points and an odds ratio for the intervention arm of 3.53 (95% CI, 2.13-6.02; P < .001). The median (IQR) time to provision of pathogen-directed treatment within 48 hours was 34.5 (31.6-37.3) hours in the intervention arm and 43.8 (42.0-45.6) hours in the standard-of-care arm (mean difference, -9.4 hours; 95% CI, -12.7 to -6.0 hours; P < .001). The corresponding hazard ratio for intervention compared with standard of care was 3.08 (95% CI, 1.95-4.89). Findings remained significant after adjustment for season.

Conclusions and relevance: Results of this randomized clinical trial indicated that routine deployment of PCR testing for LRT pathogens led to faster and more targeted microbial treatment for patients with suspected CAP. Rapid molecular testing could complement or replace selected standard, time-consuming, laboratory-based diagnostics.

Trial registration: ClinicalTrials.gov Identifier: NCT04660084.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Serigstad reported receiving grants from Trond Mohn Foundation, grants from Research Council of Norway, and nonfinancial support from Haukeland University Hospital during the conduct of the study. Dr van Werkhoven reported receiving grants paid to the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht from Research Council of Norway during the conduct of the study and grants paid to the the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht from LimmaTech and DaVolterra, nonfinancial support from bioMérieux, and personal fees paid to the the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht from MSD/Merck and Sanofi-Pasteur outside the submitted work. Prof Clark reported receiving grants and personal fees from bioMérieux/Biofire during the conduct of the study and outside the submitted work as well as grants and personal fees from bioMérieux/Biofire; grants and personal fees from Qiagen; personal fees from Janssen, Roche, Cepheid, Shionogi, Seqirus, Sanofi, Medscape, and Synairgen; and grants from Sherlock Biosciences, National Institute for Health Research UK, and Inflammatix outside the submitted work. Professor Ulvestad reported receiving grants from Research Council of Norway and Trond Mohn Foundation during the conduct of the study. Professor Grewal reported receiving grants from Research Council of Norway and Trond Mohn Foundation during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Study Participants
CAP indicates community-acquired pneumonia; COPD, chronic obstructive pulmonary disease; FAP plus, BioFire FilmArray Pneumonia plus Panel; LRT, lower respiratory tract; RTI, respiratory tract infection. aThere was 1 withdrawal. One died within 48 hours after randomization.
Figure 2.
Figure 2.. Kaplan-Meier Curve of the Proportion of Patients Receiving Pathogen-Directed Treatment
The dotted line at 48 hours indicates the censoring threshold for the primary outcome of time to pathogen-directed treatment.
See this image and copyright information in PMC

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