Supplementary file 1_Timing of nebulized colistimethate sodium following bronchodilator airway conditioning in hospital-acquired pneumonia: a target trial emulation study.docx

We evaluated whether timely initiation of nebulized CMS following bronchodilator airway pre-treatment was associated with microbiological outcomes in critically ill patients.</p>Methods<p>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.</p>Results<p>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; P = 0.012) and a shorter restricted mean time alive and not microbiologically cleared (6.85 vs. 10.08 days; difference −3.23 days, 95% CI −4.30 to −2.08; P < 0.001).