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Standarisation of a rabbit model of methicillin-susceptible, methicillin-resistant and glycopeptide intermediate Staphylococcus aureus meningitis

Abstract number: 1733_1280

Taberner F., Ribes S., Force E., Cabellos C., Dominguez M.A., Ariza J., Gudiol F.

Staphylococcus aureus meningitis is a rare but severe disease with high mortality rates. It is usually nosocomial-acquired and associated with neurosurgical procedures.

Objective: To study the ability of three strains of S. aureus with different susceptibility to b-lactams and glycopeptides to induce meningitis and inflammatory activity in CSF and to standardise the rabbit meningitis model to study the efficacy of different antibiotics against them.

Methods: Three different staphylococcal strains were used: Strain A, methicillin-susceptible S. aureus (MSSA) with MICs (in mg/L) to cloxacillin (CLOXA) 0.25 and to vancomycin (VAN) 1; strain B, methicillin-resistant S. aureus (MRSA): CLOXA 512, VAN 2; and strain C, glycopeptide-intermediate S. aureus (GISA): CLOXA 1024, VAN 4. Meningitis was induced in New Zealand white rabbits (n ≥ 6 per group) by intracisternal inoculation of an inoculum of 107 CFU/mL for MSSA strain and of 108 for MRSA and GISA strains. Bacterial growth curve was assessed in CSF of rabbits after 10 h and 20 h of inoculation. Additionally, CSF samples were used to quantify CSF leukocyte counts, lactate and protein concentrations. Statistical analysis was performed using T-student for bacterial counts and for inflammatory activity.

Results: All tested animals developed meningitis after 10 hours of inoculation. Bacterial titers (median ± SD) with all tested strains at different time points are shown in the table. Some inflammatory activity is shown in the table. All blood cultures were negative. Without treatment, all animals survived at least 24 h after the inoculation point.

 10 h after inoculation20 h after inoculation
0 h2 h6 h24 h0 h2 h6 h24 h 
Log cfu/mL
Strain A4.1±0.84±0.83±0.813±1.94.7±1.44.2±1.63.8±2.94.8±2.0
Strain B5.2±0.4*4.8±0.7*4.2±0.4*3.7±1.1*3.8±0.53.5±0.82.8±0.72.2±1
Strain C4.8±0.4*4.7±0.4*4.5±0.6*2.9±0.7*2.6±1.32.2±1.72±1.61.4±1.5
[Lactate] mmol/L
Strain A10.1±3*10.7±3*10.3±2.5*5.6±2.76±0.34.2±0.26±3.23.5
Strain B12.5±1.4*11.1±1.7*9.3±1.1*7.2±2.7*6.2±2.45.1±1.54.7±1.64.4±1.3
Strain C11.6±1.6*9.7±1.5*7.5±1*5.9±1.2*5.7±0.94.9±1.64.1±1.63.5±1.1
*Statistical difference 10 h vs 20 h.

Conclusion: All three Staphylococcus aureus strains were able to induce meningitis and inflammatory activity without statistically significant differences at 10 h. Log CFU/mL and inflammatory parameters were higher (with statistical significance) and more homogeneous at 10 h time point than at 20 h. This time point has been choosed to begin therapeutic schedules.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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