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

Abstract

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 adults 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, 242 patients were enrolled; 119 were randomly assigned to multiplex real-time PCR plus conventional microbiological testing and 123 to conventional microbiological testing alone. All but one of the patients allocated to multiplex real-time PCR plus conventional microbiological testing underwent PCR, which was performed in sputum samples in 77 patients (65.2%) and in nasopharyngeal swabs in 41 (34.7%). 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 to 0.17; p = 0.093). No differences were observed in adverse events and 30-day mortality. Our findings do not support the routine implementation of multiplex real-time PCR in the initial microbiological testing in hospitalised patients with CAP. Clinicaltrials.gov registration: NCT04158492.

Fig. 1. Study flowchart.

CONSORT diagram indicating participant numbers and dispositions troughout the course of the trial.

Fig. 2. Primary endpoint: antibiotic use measured by days of antibiotic therapy (DOT).

The figure presents a box-plot analysis of the primary endpoint, days of antibiotic therapy (DOT), in both study groups; multiplex real-time PCR plus conventional microbiological testing (left, red box-plot) and conventional microbiological testing alone (right, teal box-plot). The median DOT in the multiplex real-time PCR plus conventional microbiological testing is 10.04, with an interquartile range spanning from 7.98 to 12.94. The median DOT in the conventional microbiological testing alone is 11.33, with an interquartile range spanning from 8.15 to 16.16. Outliers were distributed similarly between bout groups with extended DOT up to 60 days.