Timing of Tracheostomy and Risk of Ventilator-Associated Pneumonia in Patients Requiring Prolonged Mechanical Ventilation: A Case–Cohort Study with Time-to-Event Analysis

Background/Objectives: Intubation and tracheostomy were previously considered dis-tinct approaches to airway management during mechanical ventilation. Ventila-tor-associated pneumonia (VAP) remains a leading cause of morbidity and mortality in patients requiring prolonged mechanical ventilation. The role of tracheostomy in modify-ing VAP risk is controversial, especially when taking into account how exposure changes over time and the conditions typically found in real intensive care unit (ICU) settings. This study was conducted to evaluate whether tracheostomy timing influences the VAP risk and hospital length of stay in patients undergoing prolonged mechanical ventilation. Methods: We conducted a hybrid case–cohort study in a tertiary-care ICU in Mexico City, enrolling patients receiving invasive mechanical ventilation for ≥ 48 h (January–December 2023). Patients undergoing a tracheostomy were compared with an age- and sex-matched subcohort of intubated patients. VAP incidence was evaluated using cumulative incidence and incidence density. Multivariable generalized linear models, Kaplan–Meier survival analysis, and Cox regression were used to identify risk factors and assess time-to-event outcomes. Results: A total of 218 patients were included (55 tracheostomies vs. 163 intu-bations). The incidence density of VAP was similar between groups (31.5 vs. 30.3 per 1000 ventilator-days; RR 1.04, 95% CI 0.7–1.7). However, cumulative incidence was higher in tracheostomized patients (61.8% vs. 22.7%; RR 2.7, 95% CI 1.9–3.9), reflecting prolonged exposure. Independent risk factors included broad-spectrum antibiotics, mechanical ven-tilation ≥ 5 days, chronic pulmonary disease, and ICU stay. In contrast, tracheostomy was associated with a lower time-dependent hazard of VAP (HR 0.43, 95% CI 0.25–0.75). Gram-negative microorganisms predominated, with higher antimicrobial resistance in tracheostomized patients. A class-based analysis showed that MDR was primarily driven by E. coli, with consistent resistance to cephalosporins and fluoroquinolones. The MAR index was higher in tracheostomized patients (0.50 vs. 0.25), indicating a greater burden of antimicrobial resistance. Conclusions: Tracheostomy increases cumulative VAP inci-dence due to longer exposure but is associated with a reduced time-dependent risk. These findings highlight the importance of accounting for exposure time and support targeted strategies integrating airway management and antimicrobial stewardship to reduce VAP burden in real-world ICU settings.