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Reduced activation of microglial cells by Streptococcus pneumoniae after treatment with nonbacteriolytic antibiotics in comparison to ceftriaxone

Abstract number: p1175

Spreer  A., Hernekamp  I.M., Lotz  M., Ebert  S., Eiffert  H., Nau   R.

Objective: 

Neuronal injury in pneumococcal meningitis is a consequence of the direct toxicity and proinflammatory activity of bacterial components. Antibiotic standard therapy consists of highly effective bacteriolytic beta-lactam antibiotics. However, beta-lactam antibiotics act by bacterial lyses resulting in an increased release of bacterial products.

Methods: 

Primary cultures of mouse microglial cells and primary mouse cortex neurons were exposed to culture supernatants of Streptococcus pneumoniae, grown in tryptic soy broth without addition of antibiotics or after treatment with non-bacteriolytic antibiotics (clindamycin, rifampin) or ceftriaxone.

Results: 

Primary mouse microglial cells were activated by culture supernatants of Streptococcus pneumoniae, while no direct toxic effect of pneumococcal culture supernatants on primary neurons was detected. Treatment of pneumococcal cultures with clindamycin or rifampin in comparison to ceftriaxone significantly reduced the proinflammatory action of culture supernatant on microglial cells. This effect was also present after sequential therapy with nonbacteriolytic and bacteriolytic antibiotics.

Conclusion: 

During bacterial meningitis, the occurring neuronal damage is in parts ascribed to microglia-mediated toxicity. In vitro, the extent of microglial activation by pneumococcal culture supernatants is reduced by the usage of non-bacteriolytic antibiotics in comparison to beta-lactams. Therefore antibiotic regimens relying on bactericidal protein synthesis inhibitors should be evaluated for meningitis therapy.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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