Abstract | OBJECTIVE: In bacterial meningitis, severe systemic and local inflammation causes long-term impairment and death of affected patients. The current antibiotic therapy relies on cell wall-active beta-lactam antibiotics, which rapidly sterilize the cerebrospinal fluid (CSF). However, beta-lactams inhibit cell wall synthesis, induce bacteriolysis, and thereby evoke a sudden release of high amounts of toxic and proinflammatory bacterial products. Because tissue damage in bacterial meningitis is the result of bacterial toxins and the inflammatory host response, any reduction of free bacterial compounds promises to prevent neuronal damage. DESIGN: In vitro experiments and randomized prospective animal study. SETTING: University research laboratories. SUBJECTS: Streptococcus pneumoniae broth cultures and New Zealand White rabbits. INTERVENTIONS: MEASUREMENTS AND MAIN RESULTS: In pneumococcal cultures, quantitative immunoblotting and real-time polymerase chain reaction revealed a reduced release of pneumolysin and bacterial DNA by rifampicin pretreatment for 30 minutes in comparison with ceftriaxone treatment alone. In vivo, a 1-hour rifampicin pretreatment reduced the release of bacterial products and attenuated the inflammatory host response, as demonstrated by decreased CSF levels of prostaglandin E2 and total protein and increased glucose CSF/plasma ratios. Rifampicin pretreatment reduced infection-associated neuronal apoptotic cell loss compared with ceftriaxone-treated controls. CONCLUSIONS:
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Authors | Annette Spreer, Raimond Lugert, Valentin Stoltefaut, Anna Hoecht, Helmut Eiffert, Roland Nau |
Journal | Critical care medicine
(Crit Care Med)
Vol. 37
Issue 7
Pg. 2253-8
(Jul 2009)
ISSN: 1530-0293 [Electronic] United States |
PMID | 19487938
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Ceftriaxone
- Rifampin
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Topics |
- Animals
- Anti-Bacterial Agents
(administration & dosage, pharmacology)
- Apoptosis
(drug effects)
- Ceftriaxone
(administration & dosage)
- Cell Culture Techniques
- Disease Models, Animal
- Drug Administration Schedule
- Drug Therapy, Combination
- Meningitis, Pneumococcal
(drug therapy, etiology, pathology)
- Neurons
(drug effects)
- Rabbits
- Rifampin
(administration & dosage, pharmacology)
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