title: Comparative evaluation of intratracheal colistimethate sodium, imipenem, and meropenem in BALB/c mice with carbapenem-resistant Acinetobacter baumannii pneumonia.
abstract: OBJECTIVE
  The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB).
  
  
  METHODS
  A murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 × 10⁷ colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4h the infected BALB/c mice were treated intratracheally with 25μl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20mg/kg, meropenem group), every 8h. The therapeutic efficacy of these agents was examined.
  
  
  RESULTS
  A. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p<0.001 vs. the control and CMS groups, p=0.006 vs. the imipenem group, by log-rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs.
  
  
  CONCLUSIONS
  Administration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia.
authors.affiliation: Department of Internal Medicine, Chi Mei Medical Center, 901, Chung-Hwa Road, Yung-Kang City, Tainan, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Tang
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ko
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chen
authors.forename: Jiunn-Min
authors.initials: JM
authors.lastname: Shieh
authors.forename: Chung-Hua
authors.initials: CH
authors.lastname: Chen
authors.forename: Nan-Yao
authors.initials: NY
authors.lastname: Lee
authors.forename: Shyh-Ren
authors.initials: SR
authors.lastname: Chiang
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D015780:Carbapenems / Q000627:therapeutic use; D015377:Cilastatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077728:Cilastatin, Imipenem Drug Combination; D003091:Colistin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D005260:Female; D015378:Imipenem / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077731:Meropenem; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D013234:Stem Cells / Q000187:drug effects; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D016207:Cytokines; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; C004691:colistinmethanesulfonic acid; D000077731:Meropenem; D003091:Colistin