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Background: Stress ulcer prophylaxis (SUP) using ranitidine, a histamine H2 receptor antagonist, has been associated with an increased risk of ventilator-associated pneumonia. The proton pump inhibitor (PPI) pantoprazole is also commonly used for SUP. PPI use has been linked to an increased risk of community-acquired pneumonia. The objective of this study was to determine whether SUP with pantoprazole increases pneumonia risk compared with ranitidine in critically ill patients.Methods: The cardiothoracic surgery database at our institution was used to identify retrospectively all patients who had received SUP with pantoprazole or ranitidine, without crossover between agents. From January 1, 2004, to March 31, 2007, 887 patients were identified, with 53 patients excluded (pantoprazole, 30 patients; ranitidine, 23 patients). Our analysis compared the incidence of nosocomial pneumonia in 377 patients who received pantoprazole with 457 patients who received ranitidine.Results: Nosocomial pneumonia developed in 35 of the 377 patients (9.3%) who received pantoprazole, compared with 7 of the 457 patients (1.5%) who received ranitidine (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.9 to 14.9). Twenty-three covariates were used to estimate the probability of receiving pantoprazole as measured by propensity score (C-index, 0.77). Using this score, pantoprazole and ranitidine patients were stratified according to their probability of receiving pantoprazole. After propensity adjusted, multivariable logistic regression, pantoprazole treatment was found to be an independent risk factor for nosocomial pneumonia (OR, 2.7; 95% CI, 1.1 to 6.7; p = 0.034).Conclusion: The use of pantoprazole for SUP was associated with a higher risk of nosocomial pneumonia compared with ranitidine. This relationship warrants further study in a randomized controlled trial. [ABSTRACT FROM AUTHOR]