Efficacy of doripenem against Escherichia coli and Klebsiella pneumoniae in experimental meningitis

Objectives: 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 (5.401.37 log(10) cfu/mL versus 3.590.89 log(10) cfu/mL for cefepime). Also against the E. coli strain doripenem was slightly superior to the comparator (5.550.87 log(10) cfu/mL versus 3.801.10 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.