Independent Determinants of Ventilator-Associated Pneumonia in Critically Ill Mechanically Ventilated Patients: A Prospective Multicenter Cohort Study

Abstract

Introduction: Procalcitonin (PCT) is increasingly used to support antibiotic stewardship in sepsis, particularly for guiding antimicrobial discontinuation. Although randomized trials suggest that PCT-guided strategies reduce antibiotic exposure without harm, their effectiveness in heterogeneous intensive care unit (ICU) populations remains unclear.

Methods: We conducted a prospective multicenter cohort study of adult ICU patients with sepsis managed using either a PCT-guided discontinuation protocol or standard care protocol. The protocol recommended antibiotic discontinuation when PCT decreased by at least 80% from peak values or reached 0.5 ng/mL or lower, provided that stability was achieved. The primary outcome was the duration of antibiotics for the index sepsis episode. Secondary outcomes included 28-day mortality, ICU length of stay, antibiotic consumption measured by days of therapy and defined daily doses, and direct costs of treatment. Mixed-effects regression and propensity score weighting were used to adjust for confounding and center-level variabilities.

Results: Among 1,284 patients, 642 received PCT-guided antibiotic stewardship and 642 received standard care. PCT-guided stewardship was associated with shorter antibiotic duration (6.1 vs. 7.5 days; adjusted difference, −1.2 days; 95% CI, −1.6 to −0.8; p<0.001). There was no increase in 28-day mortality (18.9% vs. 20.4%; adjusted OR, 0.92; 95% CI, 0.71–1.18). Antibiotic consumption was lower (612 vs. 742 DOT per 1,000 ICU-days), with reduced direct costs despite PCT testing.

Conclusion: PCT-guided antibiotic stewardship reduced antibiotic exposure and costs without compromising survival, supporting its integration as a pragmatic adjunct to clinical judgment in ICU sepsis management.