title: Efficacy of doripenem against Escherichia coli and Klebsiella pneumoniae in experimental meningitis.
abstract: OBJECTIVE
  In this study the efficacy of doripenem, a new broad-spectrum carbapenem, was tested against an Escherichia coli strain and a Klebsiella pneumoniae strain in an experimental animal model. The comparator was cefepime monotherapy.
  
  
  METHODS
  The rabbit meningitis model was used in this study and the penetration of doripenem through uninflamed and inflamed meninges was determined.
  
  
  RESULTS
  Doripenem, injected three times (75 mg/kg), led to serum peak levels around 100 mg/L and trough levels around 5 mg/L, resulting in a penetration rate of 14% through inflamed meninges and 7% through uninflamed meninges. Against K. pneumoniae, doripenem was slightly but not significantly more efficacious than cefepime over 8 h (5.40 ± 1.37 log(10) cfu/mL versus 3.59 ± 0.89 log(10) cfu/mL for cefepime). Also against the E. coli strain doripenem was slightly superior to the comparator (5.55 ± 0.87 log(10) cfu/mL versus 3.80 ± 1.10 log(10) cfu/mL for cefepime), although the difference was not significant.
  
  
  CONCLUSIONS
  Doripenem is a potential monotherapy for the treatment of meningitis due to Gram-negative microorganisms.
authors.affiliation: Clinic for Pneumology and Rehabilitation, Heiligenschwendi,  Switzerland.
authors.forename: Armin
authors.initials: A
authors.lastname: Stucki
authors.forename: Marianne
authors.initials: M
authors.lastname: Cottagnoud
authors.forename: Fernando
authors.initials: F
authors.lastname: Acosta
authors.forename: Ueli
authors.initials: U
authors.lastname: Egerman
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Laeuffer
authors.forename: Philippe
authors.initials: P
authors.lastname: Cottagnoud
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D015780:Carbapenems / Q000008:administration & dosage*; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage; D004195:Disease Models, Animal; D000077726:Doripenem; D004926:Escherichia coli / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy*; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000302:isolation & purification; D016920:Meningitis, Bacterial / Q000188:drug therapy*; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D000077723:Cefepime; D000077726:Doripenem