Background:Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Guidelines recommend dual coverage of P. aeruginosa, but the beneficial effect of combination therapy is controversial. We described antibiotic prescriptions and evaluated the clinical impact of initial combination antibiotic therapy and de-escalation strategy in patients with VAP caused by P. aeruginosa.Methods: Between 1994 and 2014, all 100 patients with VAP caused by P. aeruginosa in our intensive care unit (ICU) were included in a retrospective cohort study to evaluate the prognostic impact of initial combination antibiotic therapy.Results: Eighty-five patients received initial combination antibiotic therapy and 15 monotherapy. Nine patients received inadequate initial antibiotic therapy. De-escalation was performed in 42 patients. Thirty-nine patients died in the ICU. Factors independently associated with death were SAPS II score [SAPS II >= 40 versus < 40: hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.08-5.70, p = 0.03] and septic shock (HR = 4.80, 95% CI = 1.90-12.16, p < 0.01) at onset of VAP. Initial combination antibiotic therapy (HR = 1.97, 95% CI = 0.56-6.93, p = 0.29) and early de-escalation (HR = 0.59, 95% CI = 0.27-1.31, p = 0.19) had no impact on mortality. In multivariate analysis, the risk for inappropriate initial antibiotic therapy was higher in cases with multi-drug resistant P. aeruginosa [odd ratio (OR) = 7.11, 95% CI = 1.42-35.51, p = 0.02], but lower in cases with initial combination antibiotic therapy (OR = 0.12, 95% CI = 0.02-0.63, p = 0.01).Conclusion: In our cohort, combination therapy increased the likelihood of appropriate therapy but did not seem to impact on mortality.