title: Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone.
abstract: 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.
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Böttcher
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.forename: Michel
authors.initials: M
authors.lastname: Goiny
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerber
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kuhnt
authors.forename: Miriam
authors.initials: M
authors.lastname: Lotz
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bunkowski
authors.forename: Carola
authors.initials: C
authors.lastname: Werner
authors.forename: Ingmar
authors.initials: I
authors.lastname: Schau
authors.forename: Annette
authors.initials: A
authors.lastname: Spreer
authors.forename: Stephan
authors.initials: S
authors.lastname: Christen
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002443:Ceftriaxone / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002555:Cerebrospinal Fluid / Q000382:microbiology; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism; D002981:Clindamycin / Q000494:pharmacology*; D015169:Colony Count, Microbial; D018698:Glutamic Acid / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D007958:Leukocyte Count; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000134:cerebrospinal fluid; D008297:Male; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011817:Rabbits; D013682:Teichoic Acids / Q000134:cerebrospinal fluid; D014443:Tyrosine / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D002556:Cerebrospinal Fluid Proteins; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D013682:Teichoic Acids; D019344:Lactic Acid; D018698:Glutamic Acid; D002981:Clindamycin; D014443:Tyrosine; C009900:lipoteichoic acid; D002443:Ceftriaxone; C015566:3-tyrosine; D005990:Glycerol