Duration of Antibiotic Prophylaxis, Early-Onset Ventilator-Associated Pneumonia and Selection of Multidrug-Resistant Organisms in Mechanically Ventilated Patients with Traumatic Brain Injury: A Retrospective Cohort Study

Background/Objectives: Ventilator-associated pneumonia (VAP) is a major 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). Prophylaxis reduces eVAP but may select multidrug-resistant (MDR) organisms. We assessed whether prophylactic exposure beyond 24 h was associated with eVAP and with MDR aetiology of the subsequent episode. Methods: This study involved a retrospective single-centre cohort of adults with moderate-to-severe TBI (Glasgow Coma Scale ≤ 12) on 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 recorded prophylaxis or a single recorded administration (short-course group) versus prophylaxis documented for ≥24 consecutive hours (prolonged group); because administration times were documented in whole days, these categories reflect recorded rather than directly measured exposure. The primary outcome was eVAP (48–96 h of ventilation); secondary outcomes included MDR or extensively drug-resistant (XDR) aetiology of the first episode, tracheostomy, mortality and neurological outcome. Multivariable logistic regression with backward selection was complemented by a pre-specified forced-entry model. Results: Of 907 admissions, 231 were included (123 short-course; 108 prolonged). The prolonged group had less eVAP (19.4% versus 36.6%; adjusted odds ratio [OR] 0.47, 95% CI 0.25–0.87; forced-entry model OR 0.51, 95% CI 0.26–0.99). Among the 97 patients with quantitative culture confirmation of the first VAP episode, MDR/XDR organisms were more frequent in the prolonged group than in the short-course group (48.6% versus 27.4%; adjusted OR 3.23, 95% CI 1.27–8.33); this estimate rests on 34 resistant episodes and is exploratory. Mortality and neurological outcome did not differ. Conclusions: Prolonged prophylactic exposure was associated with less eVAP but with a higher proportion of resistant organisms among culture-confirmed episodes. These observational findings are hypothesis-generating; they do not establish causality or identify an optimal duration, and support prospective evaluation of short-course strategies.