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

The aetiology of community-acquired pneumonia (CAP) is often not identified and patients are overtreated with antibiotics. We assessed whether multiplex real-time PCR plus conventional microbiological testing is safe and more effective than conventional microbiological testing alone for reducing antibiotic use in community-acquired pneumonia (CAP). In this randomised trial, we recruited adult patients hospitalised with CAP at four Spanish hospitals. Patients were randomly assigned (1:1) to undergo either multiplex real-time PCR in non-invasive respiratory samples plus conventional microbiological testing or conventional microbiological testing alone. The primary endpoint was antibiotic use measured by days of antibiotic therapy (DOT). Between February 20, 2020, and April 24, 2023, 341 patients were assessed for inclusion, of whom 242 were finally enrolled. Of these, 119 were randomly assigned to multiplex real-time PCR plus conventional microbiological testing and 123 to conventional microbiological testing alone. The median DOT was 10.04 (IQR 7.98-12.94) in the multiplex PCR plus conventional microbiological testing group and 11.33 (IQR 8.15-16.16) in the conventional microbiological testing alone group (difference -1.04; 95% CI, -2.42-0.17; p=0.093). No differences between groups were observed in relevant secondary outcomes, including adverse events and 30-day all-cause mortality. Our findings do not support the routine implementation of multiplex real-time PCR in the initial microbiological testing in hospitalised patients with CAP. Further randomised controlled trials are needed to assess the safety and effectiveness of multiplex real-time PCR testing in improving antibiotic use and clinical outcomes in CAP. Clinicaltrials.gov registration: NCT04158492.