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Ceftobiprole is superior to cefepime against a Klebsiella pneumoniae strain in experimental meningitis

Abstract number: P1933

Cottagnoud M., Acosta F., Stucki A., Gerber P., Cottagnoud P.H.

Objectives: In the present study we tested ceftobiprole (CFT) and cefepime (CPM) as monotherapy against a Klebsiella pneumoniae strain in the rabbit meningitis model and determined the penetration of CFT into inflamed meninges.

Methods: We used the rabbit meningitis model as described by Dacey and Sande. The Klebsiella pneumoniae strain has been kindly provided by Dr. S. Droz, Inst. Inf. Dis., Bern. The MICs (mg/L) were the following: CPM: 0.25 mg/L, CFT: 0.25 mg/L. Meningitis was induced by intracisternal inoculation of 106 CFU. 8 hours later treatment was started for 8 hours. CFT (40 mg/kg) was injected once at h 0 in order to mimic kinetics in humans. CPM (100 mg/kg) was injected at hour 0 and 4, as a standard dose previously used in this model and corresponding to high doses in humans. CSF samples were repeatedly collected during therapy in order to determine killing rates. Results of the bactericidal activity are expressed in delta log10 CFU/ml·h and delta log10 CFU/ml over 8 h. Penetration of CFT into inflamed meninges was measured by comparison of CSF AUC/serum AUC (Area Under the Curve).

Results: Killing rates of the different regimens are presented in the table.

Penetration of ceftobiprole into inflamed meninges: mean: 16.37±5.4%. Min.: 9.9%; Max.: 23%

Conclusions:

1Ceftobiprole is superior to cefepime in the treatment of meningitis due to Klebsiella pneumoniae determined by killing per hour or by killing rate over 8 hours.

2The penetration of ceftobiprole into inflamed meninges ranged around 16%.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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