Evaluating the Impact of Diagnostic Stewardship in Community-Acquired Pneumonia with Syndromic Molecular Testing: A Randomized Clinical Trial

Abstract Importance Lower respiratory tract infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. An aetiological diagnosis of CAP is delayed due to long turnaround times with laboratory testing. Rapid microbiologic diagnosis is imperative for the management of CAP and may limit antibiotic overuse. 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 use of a syndromic PCR-based panel for rapid testing of CAP in the emergency department (ED) leads to faster, more accurate microbiology-result-based treatment. Design, Setting, and Participants A pragmatic, parallel-arm, single-blinded, single-centre, randomised controlled superiority trial conducted in the emergency department of a large tertiary care Norwegian hospital, where adult patients with suspected CAP were recruited. Intervention Patients were randomly assigned 1:1 to rapid syndromic molecular panel testing (FAP-plus) of lower respiratory tract (LRT) samples and standard-of-care or standard-of-care alone. Main Outcomes and Measures 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 48h from randomisation). Results Between Sep 25, 2020, and Jun 21, 2022, 374 patients were enrolled, with 187 in each arm. Analysis of primary outcomes showed that 66 (35%) of 187 patients in the FAP-plus arm and 24 (13%) of 187 patients 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%) and an OR for the FAP-plus arm of 3.53 (95% CI 2.13–6.02; p<0.0001). The mean time to provision of pathogen-directed treatment within 48h was 34.5h in the FAP-plus arm and 43.8h in the standard-of-care arm (mean difference -9.4h, 95% CI -12.7– -6.0h; p<0.0001). The corresponding hazard ratio for FAP-plus compared to standard of care was 3.08 (95% CI 1.95–4.89). Findings remained unaltered after adjustment for season. Conclusions and Relevance The routine deployment of PCR testing for LRT-pathogens enables 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 Key Points Question Does the judicious use of a syndromic PCR-based panel for rapid testing of patients hospitalised with suspected community-acquired pneumonia (CAP) lead to faster, more accurate microbiology-result-based treatment? Findings In this randomised controlled diagnostic stewardship trial, molecular testing significantly in-creased the proportion of suspected CAP patients that received pathogen-directed treatment and reduced the mean time to pathogen-directed treatment by 9.4h compared to standard-of-care. A syndromic PCR-based result was delivered within 4 hours for all CAP patients. Meaning The routine deployment of PCR testing for LRT-pathogens enables faster and targeted microbial treatment for patients with suspected CAP. Rapid molecular testing could complement or replace selected standard time-consuming laboratory-based diagnostics.