Optimal guidelines for empiric antibiotic (EAB) therapy in cases of suspected post-traumatic ventilator-associated pneumonia (VAP) are not well defined. EAB administration is thought to increase the incidence of opportunistic organisms; however, culture-directed (as opposed to empiric) treatment may delay antibiotic administration with possible adverse consequences. Our goal was to examine the impact of EAB administration on the incidence of subsequent VAP and opportunistic organisms in a series of critically injured patients with sepsis syndrome. This is a retrospective review of all patients admitted to a Level I trauma center who underwent multiple fiberoptic bronchoscopies (FOBs) for diagnosis of suspected VAP as the cause of postinjury sepsis syndrome. The relationships between EAB administration, positive cultures (>10(5) colony-forming units) at repeat FOB, and prevalence of opportunistic organisms (methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Stenotrophomonas species, Acinetobacter species, and/or yeast) were evaluated. Over a 13-month period ending on January 1, 1999, 36 intubated trauma patients underwent more than one FOB during their intensive care unit stay. Twenty-nine patients received EAB immediately after the initial FOB. There was no difference in the rate of EAB administration in patients who developed subsequent VAP after initial FOB (19 of 24, 79%) versus those who did not develop VAP (10 of 12, 83%; P = 0.65). There were 30 VAPs diagnosed in 58 subsequent FOBs (i.e., after the initial FOB) of which 23 were due to an opportunistic organism compared with two VAPs due to an opportunistic organism diagnosed at initial FOB (P < 0.001). Twenty-one of the 23 opportunistic VAPs at subsequent FOBs had received EAB before the first FOB compared with four of seven nonopportunistic organisms (P = 0.06). Administration of EAB does not impact the incidence of subsequent VAP. However, EAB may be related to the development of subsequent opportunistic pulmonary infections.