Abstract
<jats:p>Background/Objectives: Ventilator-associated pneumonia (VAP) is the leading indication for antibiotic therapy in intensive care units (ICUs), and patients with traumatic brain injury (TBI) are at particularly high risk of early-onset VAP (eVAP). Antibiotic prophylaxis reduces eVAP but may exert selective pressure favouring multidrug-resistant (MDR) organisms. We assessed whether prophylactic exposure extending beyond 24 h was associated with eVAP and with MDR aetiology of the subsequent pneumonia episode. Methods: Retrospective single-centre cohort of adults with moderate-to-severe TBI (Glasgow Coma Scale ≤12) receiving invasive mechanical ventilation in a Brazilian reference trauma ICU (January–August 2016). Patients were grouped by prophylactic exposure during the first 24 h of ICU admission: no antibiotic or a single dose (Group &lt;24 h) versus ≥24 consecutive hours (Group ≥24 h). The primary outcome was eVAP (48–96 h of ventilation); secondary outcomes included MDR or extensively drug-resistant (XDR) aetiology of the first episode, length of stay (LOS), tracheostomy, mortality and neurological outcome. Multivariable logistic regression with backward selection was complemented by a pre-specified forced-entry sensitivity model. Results: Of 907 admissions, 231 patients were included (123 Group &lt;24 h; 108 Group ≥24 h). Group ≥24 h had less eVAP (19.4% versus 36.6%; adjusted odds ratio [OR] 0.47, 95% confidence interval [CI] 0.25–0.87) and shorter hospital LOS (median 45 versus 61 days), but a higher proportion of MDR/XDR organisms in the first VAP episode (48.6% versus 27.4%; adjusted OR 3.23, 95%CI 1.27–8.33) and more purulent tracheal secretions from day 5 of ventilation onwards. Mortality and neurological outcome did not differ. Conclusions: Prophylaxis beyond 24 h was associated with less eVAP but with greater antimicrobial resistance pressure, supporting a stewardship-guided 24 h exposure ceiling. These hypothesis-generating findings require prospective confirmation.</jats:p>