title: Rifampin reduces production of reactive oxygen species of cerebrospinal fluid phagocytes and hippocampal neuronal apoptosis in experimental Streptococcus pneumoniae meningitis.
abstract: Bacterial compounds induce the production of reactive oxygen species (ROS) in meningitis. Rifampin releases smaller quantities of proinflammatory compounds from Streptococcus pneumoniae than do beta-lactam antibiotics. Therefore, rabbits infected intracisternally with S. pneumoniae were treated intravenously either with rifampin 5 mg/kg/h or ceftriaxone 10 mg/kg/h (n=9 each). Before initiation of antibiotic treatment, a strong positive correlation between ROS production of cerebrospinal fluid (CSF) phagocyte populations and bacterial CSF titers was observed (granulocytes: rs=.90, P<.0001; monocytes: rs=.81, P<.0001). CSF leukocytes from rifampin-treated rabbits produced less ROS (monocytes at 2 h after initiation of treatment: P=.045; at 5 h: P=.014; granulocytes at 5 h: P=.036) than did leukocytes from animals receiving ceftriaxone. The CSF malondialdehyde concentrations and the density of apoptotic neurons in the dentate gyrus were lower in rifampin- than in ceftriaxone-treated animals (P=.002 and.005). The use of rifampin to reduce the release of ROS and to decrease secondary brain injury appears promising.
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Böttcher
authors.forename: J
authors.initials: J
authors.lastname: Gerber
authors.forename: A
authors.initials: A
authors.lastname: Wellmer
authors.forename: A V
authors.initials: AV
authors.lastname: Smirnov
authors.forename: F
authors.initials: F
authors.lastname: Fakhrjanali
authors.forename: E
authors.initials: E
authors.lastname: Mix
authors.forename: J
authors.initials: J
authors.lastname: Pilz
authors.forename: U K
authors.initials: UK
authors.lastname: Zettl
authors.forename: R
authors.initials: R
authors.lastname: Nau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002443:Ceftriaxone / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000166:cytology*; D006624:Hippocampus / Q000187:drug effects*; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012293:Rifampin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002443:Ceftriaxone; D012293:Rifampin