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Ceftaroline is superior to cefepime against a Klebsiella pneumoniae strain an experimental rabbit meningitis model

Abstract number: P1569

Cottagnoud P., Stucki A., Accosta F., Eggerman U., Biek D., Cottagnoud M.

Objectives: In the present study we tested ceftaroline versus cefepime as monotherapy against a Klebsiella pneumoniae strain in the rabbit meningitis model and determined the penetration of ceftaroline into inflamed meninges and uniflamed meninges. Ceftaroline is a novel, parenteral, broad-spectrum cephalosporin exhibiting bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), as well as common Gram-negative pathogens.

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: cefepime: 0.25 mg/L, ceftaroline: 1 mg/L. Meningitis was induced by intracisternal inoculation of 106 CFU. Treatments were administered 8 h after inoculation and evaluations were performed over a period of 8 h. Ceftaroline (40 mg/kg) was injected at h 0 and 4 in order to mimic kinetics in humans. Cefepime (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 ceftaroline into inflamed meninges was measured by comparison of CSF AUC/serum AUC (Area Under the Curve). Killing rates of the different regimens are presented in the following table.

Results: Penetration of ceftaroline into inflamed meninges: 15.1%±9.7, and into uninflamed: 3.17%±1.3.

Conclusions: 1. Ceftaroline was superior to cefepime against Klebsiella pneumoniae in this experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was 15% and 3% into uninflamed meninges.

Groups (N)Inoculum (log10 CFU/ml)Killing rates/h (delta log10 CFU/ml·h)Killing rates/8 h (delta log10 CFU/ml·8 h)
Controls (10)6.13±0.24+0.12±0.02+1.0.8±0.22
Cefepime (10)5.82±0.88-0.48±0.09-3.54±0.94
Ceftaroline (10)6.18±0.70-0.70±0.17*-5.61±1.08**
*P < 0.01, ceftaroline versus cefepime; **P < 0.01, ceftaroline versus cefepime.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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