Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone

Böttcher, T; Ren, H; Goiny, M; Gerber, J; Lykkesfeldt, J; Kuhnt, U; Lotz, M; Bunkowski, S; Werner, C; Schau, I; Spreer, A; Christen, S; Nau, R (2004). Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone. Journal of neurochemistry, 91(6), pp. 1450-60. Oxford: Wiley-Blackwell 10.1111/j.1471-4159.2004.02837.x

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In animal models of Streptococcus pneumoniae meningitis, rifampin is neuroprotective in comparison to ceftriaxone. So far it is not clear whether this can be generalized for other protein synthesis-inhibiting antimicrobial agents. We examined the effects of the bactericidal protein synthesis-inhibiting clindamycin (n = 12) on the release of proinflammatory bacterial components, the formation of neurotoxic compounds and neuronal injury compared with the standard therapy with ceftriaxone (n = 12) in a rabbit model of pneumococcal meningitis. Analysis of the CSF and histological evaluation were combined with microdialysis from the hippocampal formation and the neocortex. Compared with ceftriaxone, clindamycin reduced the release of lipoteichoic acids from the bacteria (p = 0.004) into the CSF and the CSF leucocyte count (p = 0.011). This led to lower extracellular concentrations of hydroxyl radicals (p = 0.034) and glutamate (p = 0.016) in the hippocampal formation and a subsequent reduction of extracellular glycerol levels (p = 0.018) and neuronal apoptosis in the dentate gyrus (p = 0.008). The present data document beneficial effects of clindamycin compared with ceftriaxone on various parameters linked with the pathophysiology of pneumococcal meningitis and development of neuronal injury. This study suggests neuroprotection to be a group effect of bactericidal protein synthesis-inhibiting antimicrobial agents compared with the standard therapy with beta-lactam antibiotics in meningitis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Christen, Stephan

ISSN:

0022-3042

ISBN:

15584921

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:55

Last Modified:

04 May 2014 23:16

Publisher DOI:

10.1111/j.1471-4159.2004.02837.x

PubMed ID:

15584921

Web of Science ID:

000226115900020

URI:

https://boris.unibe.ch/id/eprint/23680 (FactScience: 43464)

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