title: Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report.
abstract: OBJECTIVE
  Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed.
  
  
  METHODS
  The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-beta-naphthylamide (PAbetaN), an efflux pump inhibitor.
  
  
  RESULTS
  Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbetaN, the MICs reduced to 1 and 4 mg/L, respectively.
  
  
  CONCLUSIONS
  To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Peleg
authors.forename: Brian A
authors.initials: BA
authors.lastname: Potoski
authors.forename: Rhonda
authors.initials: R
authors.lastname: Rea
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adams
authors.forename: Jigme
authors.initials: J
authors.lastname: Sethi
authors.forename: Blair
authors.initials: B
authors.lastname: Capitano
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Kwak
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Bhat
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000188:drug therapy*; D004151:Dipeptides / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; C419365:phenylalanine arginine beta-naphthylamide; D000078304:Tigecycline; D008911:Minocycline