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To investigate the role of antibiotic prophylaxis (AP) in the incidence of ventilator-associated pneumonia (VAP) in patients suffering from traumatic brain injury (TBI).This post hoc analysis was conducted based on data from 2 multicentre double-blind studies that aimed to prevent VAP using hydrocortisone or povidone iodine. Data from TBI patients were extracted and pooled. Patients were classified into 2 groups: those who received an AP (AP group) and those who did not (control group).295 patients were included (AP group, n=146; control group, n=149). The incidence of VAP was 145 (49%). VAP incidence was lower in the AP group (39% vs 59%, Relative Risk=0.33, 95%CI, 0.19–0.56, p=0.001). Time to VAP occurrence was delayed (Hazard Ratio=0.50, 95%CI 0.36–0.69, p<0.001). The incidence of early VAP (>2 and≤5days) was lower in the AP group (10% vs 32%; p<0.001), whereas that of late VAP (>5days) did not differ (AP group 29% vs control group 28%; p=0.811). Length of stay and mortality did not differ between the 2 groups.Early use of AP delayed and may prevent the occurrence of VAP in severe TBI patients but did not change length of stay or mortality.Antibiotic prophylaxis may decrease the occurrence of ventilator-associated pneumonia.Only the incidence of early ventilator-associated pneumonia decreased.Length of stay and mortality was not reduced by antibiotic prophylaxis.