title: Antimicrobial treatment and clinical outcomes of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia.
abstract: OBJECTIVE
  Carbapenem-resistant (CR) Acinetobacter baumannii is an important pathogen in ventilator-associated pneumonia (VAP), but therapeutic options are limited. We describe the clinical outcomes of the largest case series of CR-Acinetobacter VAP reported to date.
  
  
  METHODS
  A retrospective analysis of 55 participants with CR-Acinetobacter VAP from July 2004 to December 2007 was undertaken. The primary endpoint was clinical response or microbiological eradication. Secondary endpoint was treatment-associated nephrotoxicity defined as ≥ 50% increase in serum creatinine or an increase of ≥ 0.5 mg/dL during therapy.
  
  
  RESULTS
  Forty-two (76.4%) participants achieved clinical response at the completion of therapy. Clinical responses were achieved in 60.0% of sulbactam-based, 66.7% of polymyxin-based, 77.8% of aminoglycoside-based, 80.6% of minocycline-based, and 90.0% of tigecycline-based regimens. Follow-up sputum cultures were available in 6 of 10 tigecycline-treated participants with 4 of 6 isolates developing intermediate resistance to tigecycline while on therapy. Ten (18.2%) participants without preexisting renal disease developed treatment-associated nephrotoxicity. Baseline serum creatinine was 0.9 ± 0.1 mg/dL (range: 0.6-1.0 mg/dL) at the start of therapy and peaked at 1.9 ± 0.5 mg/dL (range: 1.6-3.0 mg/dL) during therapy. After excluding other potential concomitant renal toxic agents, nephrotoxicity developed in 6 of 30 (20.0%) and 4 of 7 (57.1%) participants treated with an aminoglycoside-or polymyxin-based regimen, respectively.
  
  
  CONCLUSIONS
  Our results demonstrated that CR-Acinetobacter VAP can be effectively treated with second-line agents. However, colistin-related nephrotoxicity was much higher than recently reported and decreased susceptibility to tigecycline emerged on therapy demonstrating the limitations of alternative regimens.
authors.affiliation: Department of Pharmacy, Harborview Medical Center, Seattle, WA 98104, USA. jdchan@u.washington.edu
authors.forename: Jeannie D
authors.initials: JD
authors.lastname: Chan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Graves
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Dellit
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems