Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone

• Published in: Journal of neurochemistry Vol. 91; no. 6; pp. 1450 - 1460
• Main Authors: Böttcher, Tobias, Ren, Hao, Goiny, Michel, Gerber, Joachim, Lykkesfeldt, Jens, Kuhnt, Ulrich, Lotz, Miriam, Bunkowski, Stephanie, Werner, Carola, Schau, Ingmar, Spreer, Annette, Christen, Stephan, Nau, Roland
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-12-2004; Blackwell
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Biological and medical sciences; Body Temperature - drug effects; Brain - metabolism; ceftriaxone; Ceftriaxone - pharmacology; Cell Line, Tumor; Cerebrospinal Fluid - microbiology; Cerebrospinal Fluid Proteins - metabolism; clindamycin; Clindamycin - pharmacology; Colony Count, Microbial; Glutamic Acid - metabolism; Glycerol - metabolism; Humans; Lactic Acid - cerebrospinal fluid; Lactic Acid - metabolism; Leukocyte Count; Lipid Peroxidation; Lipopolysaccharides - cerebrospinal fluid; Male; Medical sciences; Medicin och hälsovetenskap; Meningitis, Pneumococcal - cerebrospinal fluid; Meningitis, Pneumococcal - metabolism; Meningitis, Pneumococcal - microbiology; Meningitis, Pneumococcal - physiopathology; Microdialysis; Neuropharmacology; neuroprotection; Neuroprotective agent; Neuroprotective Agents - pharmacology; Pharmacology. Drug treatments; Rabbits; Streptococcus pneumoniae meningitis; Teichoic Acids - cerebrospinal fluid; Tyrosine - biosynthesis; Neuroprotection; Nervous system diseases; Experimental disease; Microdialysis; Clindamycin; Central nervous system disease; Meningitis; Neuroprotective agent; Ceftriaxone; Streptococcus pneumoniae meningitis
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2004.02837.x

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 β‐lactam antibiotics in meningitis.