title: A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia.
abstract: BACKGROUND
  The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria.
  
  
  METHODS
  This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011).
  
  
  RESULTS
  The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0).
  
  
  CONCLUSIONS
  Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00589693.
authors.forename: Marin H
authors.initials: MH
authors.lastname: Kollef
authors.forename: Jean
authors.initials: J
authors.lastname: Chastre
authors.forename: Marc
authors.initials: M
authors.lastname: Clavel
authors.forename: Marcos I
authors.initials: MI
authors.lastname: Restrepo
authors.forename: Bart
authors.initials: B
authors.lastname: Michiels
authors.forename: Koné
authors.initials: K
authors.lastname: Kaniga
authors.forename: Iolanda
authors.initials: I
authors.lastname: Cirillo
authors.forename: Holly
authors.initials: H
authors.lastname: Kimko
authors.forename: Rebecca
authors.initials: R
authors.lastname: Redman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015780:Carbapenems / Q000008:administration & dosage / Q000627:therapeutic use*; D015377:Cilastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D000077726:Doripenem; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D015377:Cilastatin; D015378:Imipenem; D000077726:Doripenem