title: Diabetic murine models for Acinetobacter baumannii infection.
abstract: OBJECTIVE
  Extremely drug-resistant (XDR; i.e. resistant to all antibiotics except colistin or tigecycline) Acinetobacter baumannii has emerged as one of the most common and highly antibiotic-resistant causes of infection. Diabetes is a risk factor for acquisition of and worse outcomes from A. baumannii infection. We sought to develop diabetic mouse models of A. baumannii bacteraemia and pneumonia and validate these models by comparing the efficacy of antibiotic treatment in these models with the established neutropenic mouse models.
  
  
  METHODS
  Diabetic or neutropenic mice were infected via intravenous inoculation or inhalation in an aerosol chamber with an XDR A. baumannii. Treatment with colistin started 24 h after infection and continued daily for 7 days. Survival served as the primary endpoint while tissue bacterial burden and histopathological examination served as secondary endpoints.
  
  
  RESULTS
  Lethal infection was achieved for the neutropenic and diabetic mice when infected intravenously or via inhalation. Neutropenic mice were more susceptible to infection than diabetic mice in the pneumonia model and equally susceptible in the bacteraemia model. Both models of bacteraemia were sensitive enough to detect virulence differences among different clinical strains of A. baumannii. In the pneumonia model, colistin treatment was effective in improving survival, reducing lung bacterial burden and histologically resolving the infection compared with placebo only in diabetic mice.
  
  
  CONCLUSIONS
  We developed novel models of A. baumannii bacteraemia and pneumonia in diabetic mice. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies and evaluate drug efficacies against highly lethal A. baumannii infections.
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Guanpingsheng
authors.initials: G
authors.lastname: Luo
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Teclegiorgis
authors.initials: T
authors.lastname: Gebremariam
authors.forename: Michael
authors.initials: M
authors.lastname: Bolaris
authors.forename: Hongkyu
authors.initials: H
authors.lastname: Lee
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D040981:Acinetobacter baumannii / Q000472:pathogenicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D058491:Bacterial Load; D003091:Colistin / Q000008:administration & dosage; D048909:Diabetes Complications; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D006651:Histocytochemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin