Empiric, broad-spectrum antibiotic therapy with an aggressive de-escalation strategy does not induce gram-negative pathogen resistance in ventilator-associated pneumonia

Surg Infect (Larchmt). 2010 Oct;11(5):427-32. doi: 10.1089/sur.2009.046.


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 = 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 = 0.73) and Acinetobacter baumannii (early 80%; late 100%; p = 0.13). Further, both TOB (early 77.1%; late 70.0%; p = 0.49) and LEV (early 74.3%; late 70.0%; p = 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.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Infections / drug therapy*
  • Cilastatin / therapeutic use
  • Cilastatin, Imipenem Drug Combination
  • Drug Combinations
  • Drug Resistance, Bacterial*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / isolation & purification
  • Humans
  • Imipenem / therapeutic use
  • Levofloxacin
  • Microbial Sensitivity Tests
  • Ofloxacin / therapeutic use
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Retrospective Studies
  • Tobramycin / therapeutic use


  • Anti-Bacterial Agents
  • Drug Combinations
  • Cilastatin
  • Levofloxacin
  • Imipenem
  • Cilastatin, Imipenem Drug Combination
  • Ofloxacin
  • Tobramycin