Patients hospitalized with suspected community-acquired pneumonia (CAP) received pathogen-targeted treatment sooner with polymerase chain reaction (PCR) testing in the emergency medicine department (EMD) than with standard-of-care microbiologic detection, in a randomized trial of this approach to enhance diagnostic stewardship.1
The investigators point out that the standard, culture-based methods to diagnose CAP are labor intensive, detect a pathogen in only 20 to 40% of patients, and are insufficient to inform early treatment decisions. This trial, they indicate, is the first to examine the relative clinical utility of “judicious,” syndromic rapid PCR pneumonia panel testing of patients presenting with suspected CAP.
“Most previous studies did not use a comprehensive syndromic PCR panel or included patients shortly after admission, potentially limiting the advantages or rapid molecular testing,” commented Harleen Grewal, MD, PhD, Department of Clinical Science, Bergen Integrated Diagnostic Stewardship Cluster, University of Bergen, Bergen, Norway, and colleagues.
“Another aspect of its novelty is the emphasis on pragmatism whereby decisions to continue, switch, or discontinue antimicrobial treatment were at the discretion of the treating physician alone,” the investigators noted.
The pragmatic, parallel-arm, single–blinded trial was conducted at a large tertiary care hospital in Bergen, Norway in 2 separate periods between September 2020 and June 2022. For the study, 374 participants were identified from patients with suspected CAP presenting to the EMD with at least 2 of the following: new or worsening cough, expectoration or dyspnea; pleuritic chest pain; radiological evidence of pneumonia; abnormalities on chest auscultation and/or percussion; or fever.
They had 187 participants randomized to the syndromic PCR testing and 187 to the standard-of-care microbiological diagnostics.The participants and the EMD clinicians were blinded to the treatment group allocation. The PCR panel applied in the ER tested orophayngeal and/or nasopharyngeal swabs for 27 bacterial and viral respiratory pathogens with 7 antimicrobial resistance genes.The standard-of-care microbiological diagnostics included blood cultures, pneumococcal urine test, and an in-house PCR test for respiratory viruses and atypical bacteria.
Grewal and colleagues found that pathogen-directed treatment was provided to 66 patients (35.3%) in the intervention group compared to 25 (13.4%) in the standard-of-care group; corresponding to a reduction in absolute risk of 21.9% (95% CI, 13.5-30.3).The median time to provision of treatment within 48 hours was 34.5 (31.6-37.3) hours in the intervention group and 43.8 (42.0-45.6) hours with standard-of-care.
The investigators note that the findings remained significant after adjustment for season.They stopped the trial earlier than planned because an ad hoc interim analysis showed substantial differences between the intervention and standard-of-care groups for both primary outcomes.
Although no significant differences in the secondary clinical outcomes were found between groups, the investigators indicate that the trial was designed principally to compare methods for facilitating timely diagnosis and targeted treatment.The intervention was associated with median 9.4 hours reduction in time without provision of pathogen-directed treatment within the first 48 hours after randomization. Outside the 48 hour period, the PCR testing in the EMD reduced the time from admission to a relevant test result by as much as 53.8 hours.
“A faster microbiological diagnosis allows for directed therapy, which has been shown in previous studies to improve outcomes, limit antibiotic overuse, and prevent antimicrobial resistance,” Grewal and colleagues observed.
Reference
Markussen DL, Serigstad S, Ritz C, et al. Diagnostic stewardship in community-acquired pneumonia with syndromic molecular testing. A randomized clinical trial. JAMA Netw Open. 2024; 7(3)e240830. doi:10.1001/jamanetworkopen.2024.0830. Accessed March 9, 2024.
