title: Intratracheal colistin sulfate for BALB/c mice with early pneumonia caused by carbapenem-resistant Acinetobacter baumannii.
abstract: OBJECTIVE
  : To study the efficacy of intratracheal colistin sulfate therapy in a murine model of acute pneumonia caused by a clinical CRAB strain, Ab396. Colistin therapy has currently achieved a favorable outcome in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but parenteral colistin may have limited therapeutic efficacy for CRAB pneumonia.
  
  
  METHODS
  : A controlled, in vivo experimental study.
  
  
  METHODS
  : Research laboratory of a medical center.
  
  
  METHODS
  : Female BALB/c mice.
  
  
  METHODS
  : The minimal inhibitory concentrations of antibiotics were measured. Acute pneumonia was established by intratracheal inoculation with an inoculum size of 2.5 x 10 colony-forming units Ab396 plus 10% porcine mucin into the lungs of mice, verified by histopathological examinations, and then treated with or without antibiotics. Mice received intratracheal saline treatment as a control group, intraperitoneal administration (IP) imipenem/cilastatin plus sulbactam (IP IS group, 80/80 mg/kg and 40 mg/kg every 8 hrs, n = 30), IP colistin sulfate (IP CS group, 150,000 U/kg every 8 hrs, n = 30), and intratracheal colistin sulfate (intratracheal CS group, 75,000 U/kg every 8 hrs, n = 30) at 2 hrs after intratracheal inoculation of Ab396.
  
  
  RESULTS
  : The minimal inhibitory concentrations of colistin sulfate, imipenem/cilastatin, or sulbactam for Ab396 were 2 microg/mL, 128 microg/mL, or 32 microg/mL, respectively. Compared with the mice in the control, IP IS, and IP CS groups, those in intratracheal CS group had a significantly favorable outcome at 72 hrs after infection (survival rate = 0%, 10%, 0% and 100%, respectively; all p < .001, log-rank test). Furthermore, intratracheal therapy decreased significantly the bacterial loads in the lungs and normalized the wet lung/body weight ratios in mice with acute pneumonia.
  
  
  CONCLUSIONS
  : The intratracheal colistin sulfate therapy led to more favorable outcomes than therapies by IP colistin sulfate or imipenem/cilastatin plus sulbactam in mice with early CRAB pneumonia.
authors.affiliation: Departments of Internal Medicine (S-RC, Y-CC, H-JT), Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Shyh-Ren
authors.initials: SR
authors.lastname: Chiang
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Tang
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chen
authors.forename: Chung-Hua
authors.initials: CH
authors.lastname: Chen
authors.forename: Nan-Yao
authors.initials: NY
authors.lastname: Lee
authors.forename: Chen-His
authors.initials: CH
authors.lastname: Chou
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ko
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015780:Carbapenems / Q000494:pharmacology*; D003091:Colistin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology*; D013997:Time Factors; D014132:Trachea
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D003091:Colistin