A randomized controlled trial (RCT) in Norway found that the use of rapid molecular testing in the emergency department (ED) resulted in more targeted antibiotic treatment for pneumonia, researchers reported today JAMA Network Open.
The trial found that patients with suspected community-acquired pneumonia (CAP) who received rapid syndromic polymerase chain reaction (PCR) testing were more than three times more likely to get pathogen-directed antibiotic treatment than those who received standard microbiologic testing. They also received pathogen-directed treatment faster.
The trial was stopped early after interim analysis found substantial differences between the two arms for the two primary outcomes.
The investigators say the findings, published today in JAMA Network Open, suggest rapid syndromic PCR tests could complement or replace culture-based diagnostic procedures for patients with lower respiratory infections. While culture-based methods are considered the standard for diagnosing bacterial pneumonia, they note that those methods detect a pathogen only 20% to 40% of the time, and it takes longer to get definitive results, which prevents clinicians from providing early, targeted antibiotic treatment.
"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," they wrote.
Faster pathogen-directed treatment
The trial, conducted and led by researchers at Haukeland University Hospital in Bergen, Norway, included adults who presented to the ED with symptoms of CAP from September 25, 2020, to June 1, 2021. Patients were randomized 1:1 to receive either rapid syndromic PCR testing using the BioFire FilmArray Pneumonia plus panel (FAP plus), which detects 27 bacterial and viral respiratory pathogens, or standard-of-care microbiologic methods (blood culture, pneumococcal urine test, and an in-house PCR test).
The two primary outcomes were provision of pathogen-directed treatment based on test results and the time to provision of pathogen-directed treatment (within 48 hours of randomization). Pathogen-directed treatment was defined as a change in antibiotic treatment, continuation of correctly initiated antibiotic treatment, or discontinuation of antibiotic treatment.
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.
A total of 374 patients (59.1% male; median age, 72 years) were included in the trial, with 187 assigned to each arm.
Forty-eight hours after randomization, 66 (35.3%) of 187 patients in the intervention arm received pathogen-directed treatment, compared with 25 (13.4%) of 187 patients in the standard-of-care arm, for an absolute reduction of risk of 21.9 (95% confidence interval [CI], 13.5 to 30.3) percentage points. The odds ratio (OR) for the intervention arm compared with the standard-of-care arm was 3.53 (95% CI, 2.13 to 6.02).
The median time to provision of pathogen-directed treatment was 34.5 hours in the intervention arm and 43.8 hours in the standard-of-care arm (mean difference, –9.4 hours; 95% CI, –12.7 to –6.0 hours), for a corresponding hazard ratio (HR) of 3.08 (95% CI, 1.94 to 4.89).
For the 200 patients with a CAP diagnosis, the results were even better for patients in the intervention arm, with 47.4% receiving pathogen-directed treatment compared with 15.5% in the standard-of-care arm (OR, 4.90; 95% CI, 19.7 to 44.0). The corresponding HR for time to provision of pathogen-directed treatment was 3.45 (95% CI, 1.98 to 6.02) in favor of the intervention arm.
Quicker turnaround time
Analysis of secondary end points showed that the median turnaround time for testing—from admission to receiving a test result—was reduced by nearly 54 hours for the intervention arm. More patients in the intervention arm were escalated to broader-spectrum antibiotics (14.4% vs 3.9%), de-escalated to narrower-spectrum antibiotics (10.3% vs 4.9%), and continued appropriate antibiotic treatment (16.5% vs 6.8%) within 48 hours than in the standard-of-care arm.
"The higher rate of continuation of appropriate empirical treatment for patients with CAP in the intervention arm suggests that this diagnostic tool assists in confirming the appropriateness of the initial empirical therapy and prevents unnecessary changes in treatment," the study authors wrote.
In addition, 4.3% of patients in the intervention arm received only a single dose of antibiotics, compared with none in the standard-of-care arm.
No significant difference in clinical outcome was observed between the two arms.
Although the trial was small and conducted in a single setting, the authors say the findings should be generalizable to similar hospital settings.
"We sought to reduce the time to provision of pathogen-directed treatment, potentially decreasing unnecessary or broad-spectrum antibiotic use and fostering antimicrobial stewardship," they wrote. "Future research should continue to explore innovative approaches to improving the diagnosis and management of respiratory infections, such as incorporating clinical decision support tools and antimicrobial stewardship programs into routine practice."
