For people with suspected community-acquired pneumonia (CAP) in the emergency department (ED), routine polymerase chain reaction (PCR) testing on lower respiratory tract samples led to faster and more targeted treatment, according to a randomized, single-center trial.
People who got rapid PCR tests were more likely to receive pathogen-directed treatment in the first 48 hours post-randomization compared with those receiving standard of care (35.3% vs 13.4%; OR 3.53, 95% CI 2.13-6.02). And in those receiving a pathogen-directed agent in that timeframe, the intervention group received treatment significantly sooner (median 34.5 vs 43.8 hours, P<0.001), reported Harleen Grewal, MD, PhD, of the University of Bergen in Norway, and coauthors.
Among patients with confirmed CAP, rapid PCR was associated with both greater pathogen-directed treatment (47.4% vs 15.5%, P<0.001) and faster time to such treatment (median 29.9 vs 42.3 hours, P<0.001) within 48 hours, the superiority trial published in found.
"Routinely deployed rapid syndromic testing could complement or replace targeted components of the standard laboratory-based diagnostic repertoire for patients who are admitted to the hospital with an acute respiratory illness," the authors concluded from their 374-person study, which had been stopped early for efficacy.
Current culture-based methods are labor intensive and in most cases fail to detect a pathogen for targeted treatment, Grewal's group explained.
Despite the limited evidence so far, a PCR panel for CAP is believed by some to improve pathogen detection, reduce unnecessary antibiotic use, shorten hospital length of stay, and potentially facilitate pathogen-directed treatment.
Yet Susan Butler-Wu, PhD, D(ABMM), of the Keck School of Medicine at the University of Southern California in Los Angeles, warned that "despite assertions to the contrary, this is not a replacement for culture. Culture is essential to assess the quality of the specimen, and critically, for performing antimicrobial susceptibility testing."
She expressed concerns about the present study's generalizability, noting that participating labs called ordering providers to inform them that a PCR result was available -- "a practice that isn't operationally feasible for many clinical labs."
"To get the most benefit from tests such as the one studied in this paper, it has to be combined with rapidly directing results to individuals who will rapidly take action. Otherwise, it won't necessarily get acted upon in an ultra-rapid fashion when the result solely just goes into the medical chart alone," she told Ƶ via email.
The study was conducted within the ED of Haukeland University Hospital in Bergen, Norway, with recruitment spanning 2020 to 2022.
In order to be included in the trial, patients needed to experience two or more symptoms: new or worsening cough, expectoration, or dyspnoea; hemoptysis; pleuritic chest pain; radiological evidence of pneumonia; abnormalities on chest auscultation and/or percussion; or a fever of 38 °C (100.4 °F) or higher.
Patients were excluded from the trial if they were diagnosed with cystic fibrosis, were experiencing severe bronchiectasis, were hospitalized within the past 14 days before admission, were under a palliative approach, or were not willing to provide a lower respiratory tract sample for analysis.
Ultimately, there were 374 patients randomized 1:1 to have lower respiratory tract samples undergo either the BioFire FilmArray Pneumonia plus panel or standard of care (blood cultures, a pneumococcal urine test, and an in-house PCR test for oropharyngeal and/or nasopharyngeal swabs targeting respiratory viruses and atypical bacteria). Both the trial participants and the ED clinicians were blinded to patient randomization.
The cohort averaged 72 years old and 59% were men. Just under 20% of patients in both treatment groups were current smokers. Over half of the patients had received their annual influenza vaccine, while just under 40% had received a pneumococcal vaccine within the previous 5 years.
As for the trial's secondary endpoints, patient turnaround time was nearly 54 hours shorter in the intervention group than in the standard of care group (P<0.001).
Use of pathogen-directed treatment within the first 48 hours led to more broad-spectrum antimicrobial treatment in 14.4% of intervention patients and 3.9% of standard care patients (P=0.009). Empirical antibiotic treatment was de-escalated to a more narrow-spectrum treatment in 10.3% and 4.9%, respectively (P=0.14). Empirical treatment was maintained in 16.5% and 6.8%, respectively (P=0.03).
Length of stay, readmittance, and death rates did not significantly differ between the two groups, and no serious adverse events were observed.
Researchers cited the single-center design and early termination as major limitations of the trial.
"Future studies should examine the effect of comprehensive rapid syndromic testing on clinical outcomes, the cost-effectiveness of this diagnostic tool, and the development of implementation strategies that facilitate the integration of rapid syndromic testing into routine clinical practice," Grewal's group urged.
Disclosures
This trial was supported by the Research Council of Norway, the Trond Mohn Foundation, the University of Bergen, and Haukeland University Hospital.
Markussen reported no disclosures. Coauthors reported various relationships with industry, government, and non-governmental organizations.
Butler-Wu has served as a consultant to BioFire.
Primary Source
JAMA Network Open
Markussen DL, et al "Diagnostic stewardship in community-acquired pneumonia with syndromic molecular testing: a randomized clinical trial" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.0830.