A framework for outcome determination of nosocomial pneumonia treatment in ventilated critically ill patients

Abstract Background Treatment failure of hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) is a common endpoint in clinical research, yet the absence of a reproducible definition hampers comparability across studies. We propose an operational framework for assessing treatment outcomes in critically ill patients with nosocomial pneumonia. Methods We included patients with ventilated nosocomial pneumonia from two ICU cohorts in the Netherlands and France. An expert panel defined clinical, radiological and microbiological criteria to assess daily treatment response (day 1–10). This framework was subsequently validated in terms of concurrent and predictive validity through association with patient-centered outcomes. Results We analyzed 1,941 pneumonia episodes (44% HAP; 56% VAP). Clinical resolution comprised successful extubation, or improved oxygenation (PaO₂/FiO₂ >300 mm Hg or > 100 mm Hg increase) together with ≥ 2 of: fever resolution (< 38.3 °C), leukocyte normalization (4–12 × 10⁹/L), or CRP decline (> 20%). Radiological and microbiological resolution entailed improvement of baseline consolidations and eradication of causative pathogens, respectively. All criteria needed to be maintained ≥ 5 days. Death or transfer before treatment success were considered indeterminate outcomes, occurring in 19% of Dutch and 9% of French episodes. By day 10, treatment success was observed in 78% of classifiable Dutch and 57% of classifiable French episodes, based on either clinical resolution or concurrent radiological and microbiological resolution, while treatment failure occurred in 22% and 43%. Failure was significantly associated with continued antibiotic use and increased duration of mechanical ventilation, ICU stay and 90-day mortality. Conclusion This study proposes a standardized, reproducible framework to evaluate HAP/VAP treatment outcomes in the ICU, aligned with patient-centered outcomes.