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 (5.40 ± 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.