title: Colistin-resistant Acinetobacter baumannii: beyond carbapenem resistance.
abstract: BACKGROUND
  With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging.
  
  
  METHODS
  Patients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry.
  
  
  RESULTS
  Twenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates.
  
  
  CONCLUSIONS
  Colistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Zubair A
authors: ZA
authors: Qureshi
authors: Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore.
authors: Lauren E
authors: LE
authors: Hittle
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Jessica A
authors: JA
authors: O'Hara
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Jesabel I
authors: JI
authors: Rivera
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Alveena
authors: A
authors: Syed
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Ryan K
authors: RK
authors: Shields
authors: Clinical Microbiology Laboratory, University of Pittsburgh Medical Center, Pennsylvania.
authors: Anthony W
authors: AW
authors: Pasculle
authors: Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore.
authors: Robert K
authors: RK
authors: Ernst
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Yohei
authors: Y
authors: Doi
mesh_terms: D000151:Acinetobacter Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000627:therapeutic use; D015780:Carbapenems / Q000494:pharmacology* / Q000627:therapeutic use; D003091:Colistin / Q000494:pharmacology* / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D057286:Electronic Health Records; D016521:Electrophoresis, Gel, Pulsed-Field; D004983:Ethanolamines / Q000737:chemistry; D005260:Female; D006801:Humans; D008050:Lipid A / Q000737:chemistry; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000382:microbiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013407:Sulbactam / Q000627:therapeutic use
chemical_list: D015780:Carbapenems; D004983:Ethanolamines; D008050:Lipid A; C035444:sultamicillin; C005448:phosphorylethanolamine; D000667:Ampicillin; D013407:Sulbactam; D003091:Colistin
keywords: Acinetobacter baumannii; carbapenem resistance; colistin resistance; lipid A; molecular typing
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