Impact of Bacteremia on the Pathogenesis of Experimental Pneumococcal Meningitis
1National Center for Antimicrobials and Infection Control, and 2The Pneumococcus Laboratory, Statens Serum Institut, 3Copenhagen HIV Programme, Faculty of Health Sciences, University of Copenhagen, 4Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, and 5Clinical Microbiological Department, University Hospital Herlev, Copenhagen, Denmark
Background.
Bacteremia plays a major role in the outcome of pneumococcal meningitis. This experimental study investigated how bacteremia influences the pathophysiologic profile of the brain.
Methods.Rats with Streptococcus pneumoniae meningitis were randomized to 1 of 3 groups of infected study rats: (1) rats with attenuated bacteremia resulting from intravenous injection of serotype‐specific pneumococcal antibody, (2) rats with early‐onset bacteremia resulting from concomitant intravenous infection, or (3) a meningitis control group. The blood‐brain barrier (BBB) breakdown, ventricle size, brain water distribution, and brain pathologic findings were analyzed using magnetic resonance morphological and functional imaging. Laboratory data and clinical disease scores were obtained.
Results.Attenuation of the bacteremic component of pneumococcal meningitis improved clinical disease symptoms and significantly reduced ventricle expansion and BBB breakdown (
). Early‐onset bacteremia did not further increase ventricle size or BBB leakage. Significantly increased brain edema developed among rats with both attenuated and early‐onset bacteremia (
). Focal brain pathologic findings were unaffected by bacteremia and were found to be associated with cerebrospinal fluid inflammation.
Conclusion.Although brain lesions appear to result from local meningeal infection, systemic infection significantly contributes to clinical disease presentation and the pathophysiology of BBB breakdown and ventricle expansion. The different end points affected by the systemic and local infectious processes should be addressed in future studies.
Received 20 May 2007; accepted 7 August 2007; electronically published 3 January 2008.
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Online publication date: 15-Aug-2008.
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Potential conflicts of interest: none reported.
Financial support: Lundbeck Foundation; Augustinus Foundation; Copenhagen HIV Programme; Statens Serum Institut; Direktør Jacob Madsen og Hustru Olga Madsens Fond; Dagmar Marshalls Fond; Scandanavian Society for Antimicrobial Chemotherapy Fondet.