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Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone

Tobias Böttcher1, Hao Ren, Michel Goiny

  • 1Department of Neurology, University of Rostock, Rostock, Germany.

Journal of Neurochemistry
|December 9, 2004
PubMed

Insights

Clindamycin, a protein synthesis-inhibiting antibiotic, demonstrated neuroprotective effects in a rabbit model of Streptococcus pneumoniae meningitis, outperforming ceftriaxone. This suggests neuroprotection may be a class effect for such agents against bacterial meningitis.

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Pharmacology

Background:

  • Rifampin shows neuroprotection in Streptococcus pneumoniae meningitis models, but it's unclear if this applies to other protein synthesis inhibitors.
  • Ceftriaxone is a standard therapy, but its neuroprotective effects compared to other classes are less understood.

Purpose of the Study:

  • To investigate the neuroprotective potential of clindamycin, a bactericidal protein synthesis inhibitor, against pneumococcal meningitis in rabbits.
  • To compare the effects of clindamycin versus ceftriaxone on inflammatory markers, neurotoxic compound formation, and neuronal injury.

Main Methods:

  • A rabbit model of Streptococcus pneumoniae meningitis was used, with 12 animals in the clindamycin group and 12 in the ceftriaxone group.
  • Cerebrospinal fluid (CSF) analysis, histological evaluation, and microdialysis of the hippocampal formation and neocortex were performed.
  • Measurements included lipoteichoic acid release, leukocyte count, hydroxyl radical and glutamate concentrations, glycerol levels, and neuronal apoptosis.

Main Results:

  • Clindamycin significantly reduced lipoteichoic acid release and CSF leukocyte counts compared to ceftriaxone.
  • Lower extracellular concentrations of hydroxyl radicals and glutamate were observed in the hippocampus with clindamycin treatment.
  • Clindamycin led to reduced extracellular glycerol levels and decreased neuronal apoptosis in the dentate gyrus.

Conclusions:

  • Clindamycin exhibits beneficial effects on parameters associated with pneumococcal meningitis pathophysiology and neuronal injury compared to ceftriaxone.
  • Neuroprotection may be a characteristic of bactericidal protein synthesis-inhibiting antimicrobial agents when compared to beta-lactam antibiotics in meningitis treatment.

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