Pathophysiologie des neuronalen Schadens bei bakterieller Meningitis und experimentelle adjuvante Therapieansätze

Zusammenfassung

Trotz moderner Intensivtherapie und effektiver Antibiotika ist die Mortalität der bakteriellen Meningitis unverändert hoch. Tod und neurologische Langzeitschäden werden nicht monokausal verursacht. Die derzeit übliche initiale antibiotische Therapie der bakteriellen Meningitis mit Beta-Laktamen führt zu einer schnellen Lyse der Bakterien. Die dabei freigesetzten proinflammatorischen Bakterienzellwandbestandteile haben ein massives Aufflammen der meningealen Entzündung zur Folge. Die bislang einzig zugelassene adjuvante Therapie ist die Gabe von Kortikosteroiden. In Tiermodellen der experimentellen Pneumokokken-Meningitis konnten durch den Einsatz nicht bakteriolytischer, Proteinsynthese-hemmender Antibiotika und der damit einhergehenden Attenuierung des Entzündungsprozesses vielversprechende neuroprotektive Effekte erreicht werden.

Abstract

In bacterial meningitis, death and long-term neurological sequelae are caused jointly by several factors. Despite highly qualified intensive care and effective antibacterial therapy mortality rates remain high. Beta-lactam antibiotics, currently used for initial therapy of bacterial meningitis, lead to a rapid lysis of bacteria with a consecutive profound release of proinflammatory bacterial cell wall components, causing a substantial burst of meningeal inflammation. The only approved adjunctive therapy so far is corticosteroids. The use of nonbacteriolytic, protein-synthesis inhibiting antibiotics in experimental models of pneumococcal meningitis appeared to be a promising therapeutic approach towards neuroprotection by diminishing the inflammatory process.

Schlüsselwörter

bakterielle Meningitis - neuronaler Schaden - adjuvante Therapie - nicht bakteriolytische Antibiotika

Key words

bacterial meningitis - neuronal injury - adjunctive therapy - non-bacteriolytic antibiotics

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