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

Abstract

ImportanceLower 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.ObjectiveTo 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 ParticipantsA 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.InterventionPatients 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 MeasuresPrimary 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).ResultsBetween 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 RelevanceThe 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 registrationClinicalTrials.govIdentifier:NCT04660084Key PointsQuestionDoes 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?FindingsIn 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.MeaningThe 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.

Multiplex real-time PCR in non-invasive respiratory samples to reduce antibiotic use in community-acquired pneumonia: a randomised trial

“…Two recent randomised trials have explored the efficacy of multiplex real-time PCR in non-invasive respiratory samples to reduce antibiotic use in CAP, yielding divergent results. 12,13 Our main finding aligns with a trial conducted across three Danish medical emergency departments, wherein the integration of point-of-care PCR into the diagnostic regimen did not increase the number of CAP patients with a more targeted and appropriate use of antibiotics. 12 Conversely, a single-centre randomised trial in Norway revealed that implementing a PCR-based panel for rapid testing in the emergency department facilitated swifter and more tailored antibiotic therapy for individuals with suspected CAP.…”

“…Furthermore, this difference was not correlated with significant variations in lenght of hospital stay, mortality rates, and hospital readmissions. 13 In our trial, although the multiplex real-time PCR plus conventional microbiological testing group achieved an aetiological diagnosis more frequently and more rapidly than the control group, this did not correlate with a significant reduction in antibiotic consumption. Among the factors that may have contributed to this finding is physician behaviour.…”

“…12 Conversely, a single-centre randomised trial in Norway revealed that implementing a PCR-based panel for rapid testing in the emergency department facilitated swifter and more tailored antibiotic therapy for individuals with suspected CAP. 13 However, the difference in the time taken to administer pathogen-directed treatment between patients undergoing PCR and those undergoing standard microbiological diagnostic tests alone was modest. Furthermore, this difference was not correlated with significant variations in lenght of hospital stay, mortality rates, and hospital readmissions.…”

“…10,11 Two recent studies investigating the efficacy of multiplex real-time PCR in non-invasive respiratory samples for antimicrobial stewardship in CAP have yielded conflicting findings. 12,13 Current guidelines for CAP do not incorporate multiplex PCR pneumonia panels into their recommendations for initial microbiological diagnostic testing. 2,14,15 Furthermore, the guidance regarding conventional microbiological testing methods like sputum culture, blood cultures, and urinary antigen tests lacks consistency and is predominantly grounded in low or very low-quality evidence.…”