title: Early use of imipenem/cilastatin and vancomycin followed by de-escalation versus conventional antimicrobials without de-escalation for patients with hospital-acquired pneumonia in a medical ICU: a randomized clinical trial.
abstract: BACKGROUND
  Although early use of broad-spectrum antimicrobials in critically ill patients may increase antimicrobial adequacy, uncontrolled use of these agents may select for more-resistant organisms. This study investigated the effects of early use of broad-spectrum antimicrobials in critically ill patients with hospital-acquired pneumonia.
  
  
  METHODS
  We compared the early use of broad-spectrum antimicrobials plus subsequent de-escalation (DE) with conventional antimicrobial treatment (non-de-escalation, NDE) in critically ill patients with hospital-acquired pneumonia (HAP). This open-label, randomized clinical trial was performed in patients in a tertiary-care center medical intensive care unit (MICU) in Korea. Patients (n=54) randomized to the DE group received initial imipenem/cilastatin plus vancomycin with subsequent de-escalation according to culture results, whereas patients randomized to the NDE group (n=55) received noncarbapenem, nonvancomycin empiric antimicrobials.
  
  
  RESULTS
  Between November 2004 and October 2006, 109 MICU patients with HAP were enrolled. Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms (100% versus 14.3%; P<0.001), but not for Gram-negative organisms (64.3% versus 85.7%; P=0.190). Mean intensive care unit (ICU) stay, and 14-day, 28-day, and overall mortality rates did not differ in the two groups. Among culture-positive patients, mortality from methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was higher in the DE group, even after early administration of vancomycin. Multidrug-resistant organisms, especially MRSA, were more likely to emerge in the DE group (adjusted hazard ratio for emergence of MRSA, 3.84; 95% confidence interval, 1.06 to 13.91).
  
  
  CONCLUSIONS
  The therapeutic advantage of early administration of broad-spectrum antimicrobials, especially with vancomycin, was not evident in this study.
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Joowon
authors.initials: J
authors.lastname: Chung
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Hang Jea
authors.initials: HJ
authors.lastname: Jang
authors.forename: Sang-Bum
authors.initials: SB
authors.lastname: Hong
authors.forename: Chae-Man
authors.initials: CM
authors.lastname: Lim
authors.forename: Younsuck
authors.initials: Y
authors.lastname: Koh
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D015377:Cilastatin / Q000008:administration & dosage*; D000077728:Cilastatin, Imipenem Drug Combination; D003428:Cross Infection / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D004338:Drug Combinations; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage*; D007362:Intensive Care Units / Q000592:standards* / Q000639:trends; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage*
chemical_list: D000890:Anti-Infective Agents; D004338:Drug Combinations; D015377:Cilastatin; D014640:Vancomycin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination