title: Empiric, broad-spectrum antibiotic therapy with an aggressive de-escalation strategy does not induce gram-negative pathogen resistance in ventilator-associated pneumonia.
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 = 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.
authors.affiliation: Department of Surgery, Maricopa Medical Center , Phoenix, AZ, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hibbard
authors.forename: Tammy R
authors.initials: TR
authors.lastname: Kopelman
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: O'Neill
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Maly
authors.forename: Marc R
authors.initials: MR
authors.lastname: Matthews
authors.forename: Jordy C
authors.initials: JC
authors.lastname: Cox
authors.forename: Sydney J
authors.initials: SJ
authors.lastname: Vail
authors.forename: Asia N
authors.initials: AN
authors.lastname: Quan
authors.forename: David A
authors.initials: DA
authors.lastname: Drachman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D015377:Cilastatin / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000627:therapeutic use; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D012189:Retrospective Studies; D014031:Tobramycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D064704:Levofloxacin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D015242:Ofloxacin; D014031:Tobramycin