Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone.
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.
Böttcher
Tobias
T
Department of Neurology, University of Rostock, Rostock, Germany.
Ren
Hao
H
Goiny
Michel
M
Gerber
Joachim
J
Lykkesfeldt
Jens
J
Kuhnt
Ulrich
U
Lotz
Miriam
M
Bunkowski
Stephanie
S
Werner
Carola
C
Schau
Ingmar
I
Spreer
Annette
A
Christen
Stephan
S
Nau
Roland
R
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
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