PCR-based syndromic tests for antibiotic stewardship in non-ventilated patients with hospital-acquired pneumonia: a multicentre randomized controlled trial

Objectives To evaluate whether syndromic multiplex PCR (mPCR) with expert guidance improves antibiotic stewardship in patients with hospital-acquired pneumonia (HAP). Methods We conducted a multicentre, open-label randomized controlled trial across seven French tertiary hospitals. Adults with non-ventilator-associated HAP in intensive care unit (ICU) or non-ICU wards were randomized (1:1) to conventional microbiology or mPCR testing. Empirical therapy was clinician-guided. In the intervention group, treatment was subsequently adapted according to mPCR results with expert advice. The primary endpoint was duration of broad-spectrum antibiotics (days of therapy/100 patient-days) in patients alive at end of follow-up. Secondary outcomes included appropriateness of antibiotic therapy, adverse outcomes, length of stay and costs. Results From February 2020 to August 2023, 116 patients were randomized and 109 included in follow-up (mPCR n = 55; control n = 54). Recruitment was disrupted by the COVID-19 pandemic, leading to early trial termination at half of the planned sample size. Median age was 66 years (IQR: 55–76), 66% patients were in ICU. Mean duration of broad-spectrum antibiotics was 37.6 days of therapy/100 patient-days (standard deviation, SD 44.1) in the mPCR group versus 48.7 (SD 54.5) in controls (P = 0.41). mPCR significantly increased appropriate antibiotic therapy at day 0 (47% versus 24%, P = 0.01). No differences were evidenced in adverse outcomes, length of stay or costs. Conclusions In this prematurely discontinued trial, mPCR with expert guidance did not reduce broad-spectrum antibiotic exposure, but improved early appropriateness of antibiotic therapy in HAP. These findings highlight the potential role of rapid diagnostics in optimizing initial antibiotic decisions, while underscoring challenges of demonstrating reductions in antibiotic consumption.