Risk Factors for Ventilator-Associated Pneumonia in Patients Ventilated for Non-Pulmonary Conditions: A Prospective Multicenter Cohort Study (PULMIVAP)

Background: Ventilator-associated pneumonia (VAP) is a frequent complication of invasive mechanical ventilation (IMV), yet its determinants in patients ventilated for non-pulmonary indications remain poorly characterized. Methods: Data were derived from the PULMIVAP multicenter prospective cohort (ClinicalTrial: NCT04849039), conducted in 8 Northern Italian intensive care units (January 2021-April 2024). All adults receiving IMV for non-pulmonary indications were enrolled if expected to require IMV >48 hours and antibiotic-free for ≥3 days preceding intubation. Clinical and therapeutic data were collected for up to 15 days of IMV; microbiological sampling was performed according to clinical indication. The primary outcome was time to first VAP within 15 days of IMV (VAP15). Associations between baseline characteristics, time-varying exposures, and VAP15 were evaluated. Thirty-day mortality from IMV initiation was a secondary outcome. Results: Among 406 patients, 148 (36%) developed VAP15, at a median of 6 days (IQR 4.0-7.5) with an incidence rate of 43.2 per 1000 ventilator-days at risk (95% confidence intervals [95% CI], 36.4-49.9). Non-neurologic diagnosis (adjusted hazard ratio [aHR] 0.51; 95% CI, 0.31-0.86), female sex (aHR, 0.52; 95% CI, 0.36-0.75), and early antibiotic initiation (days 1-2 of IMV, aHR, 0.65; 95% CI, 0.45-0.93) were independently associated with lower risk of VAP15. Predominant pathogens were Staphylococcus aureus, Klebsiella spp., and Haemophilus influenzae; multidrug-resistant organisms were uncommon. VAP15 showed no competing relationship or significant association with mortality (overall, 20.4%). Conclusions: In patients receiving IMV for non-pulmonary indications, non-neurologic diagnosis, female sex, and early antibiotic exposure were associated with lower observed VAP incidence, though causality cannot be inferred. Risk-stratified prevention strategies warrant further investigation into this population.