Empiric, Broad-Spectrum Antibiotic Therapy with an Aggressive De-Escalation Strategy Does Not Induce Gram-Negative Pathogen Resistance in Ventilator-Associated Pneumonia Michael L. Hibbard, 1 Tammy R. Kopelman, 1 Patrick J. O’Neill, 1 Tyler J. Maly, 1 Marc R. Matthews, 1 Jordy C. Cox, 1 Sydney J. Vail, 1 Asia N. Quan, 2 and David A. Drachman 3 Abstract Background: Early, empiric, broad-spectrum antibiotics followed by de-escalation to pathogen-specific therapy is the standard of care for ventilator-associated pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used until quantitative bronchoalveolar lavage results are finalized, at which time de-escalation occurs to pathogen-specific agents. With this practice, however, alterations in antimicrobial resistance remain a concern. Our hypothesis was that this strict regimen does not alter antimicrobial susceptibility of common gram-negative VAP pathogens in our SICU. Methods: After Institutional Review Board approval, a retrospective review of SICU-specific antibiograms was performed for the sensitivities of common gram-negative VAP pathogens. Time periods were defined as early ( January–June 2005) and late ( July–December 2006). Chart review of empiric and de-escalation antibiotic usage was obtained. Data were collated, and statistical significance was assessed with the chi-square test using the on- line Simple Interactive Statistical Analysis tool. Results: Imipenem-cilastatin was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times, respectively. Collectively, the susceptibility of gram-negative organisms to I-C did not change (early 91.4%; late 97%; p ¼ 0.33). Individually, non-significant trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa (early 85.7%; late 90.9%; p ¼ 0.73) and Acinetobacter baumannii (early 80%; late 100%; p ¼ 0.13). Further, both TOB (early 77.1%; late 70.0%; p ¼ 0.49) and LEV (early 74.3%; late 70.0%; p ¼ 0.67) were found to maintain their susceptibility profiles. The frequency of resistant gram-positive VAPs was unchanged during the study period. Our de-escalation compliance (by 96 h) was 78% for I-C, 77.2% for TOB, and 59% for LEV. When infections requiring I-C were removed from the analysis, de-escalation compliance was improved to 92%. Conclusions: In our SICU, early, empiric broad-spectrum VAP therapy followed by de-escalation to pathogen- specific agents did not alter antimicrobial resistance and is a valid practice. Further, our compliance with de- escalation practices was higher than published rates. V entilator-associated pneumonia (VAP) is a common nosocomial infection that arises 48–72 h after endotra- cheal intubation and is the leading cause of morbidity and death in the surgical intensive care unit (SICU) [1,2]. The incidence (10–30% of intubated patients) differs greatly depending on patient risk factors, and the attributable mor- tality rate (approximately 30–50%) increases when more virulent or resistant organisms are involved [3-5]. The mor- tality rate is increased further if inadequate empiric antimi- crobial therapy is initiated or proper treatment is delayed 1 Division of Burns, Trauma Surgery, and Surgical Critical Care, Department of Surgery, 2 Department of Pharmacy, and 3 Department of Research, Maricopa Medical Center, Phoenix, Arizona. Presented at the Society of Critical Care Medicine 37 th Critical Care Congress, Honolulu, Hawaii, February 2–6, 2008. SURGICAL INFECTIONS Volume 11, Number 5, 2010 ª Mary Ann Liebert, Inc. DOI: 10.1089/sur.2009.046 427