INHALE WP3, a multicentre, open-label, pragmatic randomised controlled trial assessing the impact of rapid, ICU-based, syndromic PCR, versus standard-of-care on antibiotic stewardship and clinical outcomes in hospital-acquired and ventilator-associated pneumonia.

Summary

In a pragmatic, multicenter RCT (n=554), rapid ICU-based syndromic PCR with optional guidance increased appropriate and proportionate antibiotic use at 24 hours by 21% versus standard care, but did not demonstrate non-inferiority for 14-day clinical cure. Secondary outcomes (mortality, ΔSOFA) modestly favored standard care without statistical significance.

Key Findings

• Appropriate and proportionate antibiotic use at 24 h improved to 76.5% with rapid PCR versus 55.9% with standard care (difference 21%; 95% CI 13–28%).
• Non-inferiority for 14-day clinical cure was not demonstrated (56.7% vs 64.5%; difference −6%, 95% CI −15 to 2%).
• Secondary outcomes (mortality, ΔSOFA) trended in favor of standard care but without clear statistical significance.

Clinical Implications

Rapid PCR can be incorporated to improve early antibiotic appropriateness in HAP/VAP, but clinicians should monitor patient trajectories closely and avoid overreliance on diagnostics for de-escalation until clinical effectiveness on cure is clarified.

Limitations

• Open-label design with potential performance bias
• Optional adherence to prescribing guidance and heterogeneous implementation across sites

Future Directions

Cluster-randomized or stepped-wedge effectiveness trials assessing standardized PCR-guided algorithms on patient-centered outcomes (cure, mortality) and antimicrobial resistance trajectories.