Timing of nebulized colistimethate sodium following bronchodilator airway conditioning in hospital-acquired pneumonia: a target trial emulation study.

Background: Evidence for nebulized colistimethate sodium (CMS) in hospital-acquired pneumonia (HAP) remains inconsistent, potentially due to heterogeneity in airway conditions and delivery timing. We evaluated whether timely initiation of nebulized CMS following bronchodilator airway pre-treatment was associated with microbiological outcomes in critically ill patients. Methods: We conducted a multicenter retrospective cohort study using target trial emulation among adult ICU patients with HAP who received nebulized CMS following bronchodilator nebulization. Two per-protocol strategies were compared: initiation within 90 min of bronchodilator nebulization (LE90) versus later initiation (GT90). Cloning, censoring, and inverse probability of censoring weighting were applied to address time-dependent confounding. The primary outcome was 14-day cumulative incidence of microbiological clearance, treating death as a competing event. Results: Among 218 eligible patients, timely initiation was associated with a higher weighted cumulative incidence of microbiological clearance at day 14 (71.9% vs. 52.6%; absolute difference 19.3%, 95% CI 4.8-32.5; Conclusion: Timely initiation of nebulized CMS within a defined post-bronchodilator window was associated with higher microbiological clearance and reduced persistent infection, without increased airway adverse events. These findings are hypothesis-generating and require prospective validation, particularly with respect to patient-centered outcomes.