Jan P Bewersdorf1, Denis Grandgirard2, Uwe Koedel1, Stephen L Leib2. 1. Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians-Universität München, Munich, Germany. 2. Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Abstract
PURPOSE OF REVIEW: Pneumococcal meningitis is the most frequent form of bacterial meningitis in Europe and the United States. Although early antimicrobial and adjuvant therapy with dexamethasone have helped to improve disease outcome in adults, mortality and morbidity rates remain unsatisfactorily high, emphasizing the need for additional treatment options. Promising targets for adjuvant therapy have been identified recently and will be the focus of this review. RECENT FINDINGS: Brain disease in pneumococcal meningitis is caused by direct bacterial toxicity and excessive meningeal inflammation. Accordingly, promising targets for adjuvant therapy comprise limiting the release of toxic bacterial products and suppressing inflammation in a way that maximally protects against tissue injury without hampering pathogen eradication by antibiotics. Among the agents tested so far in experimental models, complement inhibitors, matrix-metalloproteinase inhibitors, and nonbacteriolytic antibiotics or a combination of the above have the potential to more efficiently protect the brain either alone (e.g., in children and outside the high-income settings) or in addition to adjuvant dexamethasone. Additionally, new protein-based pneumococcal vaccines are being developed that promise to improve disease prevention, namely by addressing the increasing problem of serotype replacement seen with pneumococcal conjugate vaccines. SUMMARY: Pneumococcal meningitis remains a life-threatening disease requiring early antibiotic and targeted anti-inflammatory therapy. New adjuvant therapies showed promising results in animal models but need systematic clinical testing.
PURPOSE OF REVIEW: Pneumococcal meningitis is the most frequent form of bacterial meningitis in Europe and the United States. Although early antimicrobial and adjuvant therapy with dexamethasone have helped to improve disease outcome in adults, mortality and morbidity rates remain unsatisfactorily high, emphasizing the need for additional treatment options. Promising targets for adjuvant therapy have been identified recently and will be the focus of this review. RECENT FINDINGS:Brain disease in pneumococcal meningitis is caused by direct bacterial toxicity and excessive meningeal inflammation. Accordingly, promising targets for adjuvant therapy comprise limiting the release of toxic bacterial products and suppressing inflammation in a way that maximally protects against tissue injury without hampering pathogen eradication by antibiotics. Among the agents tested so far in experimental models, complement inhibitors, matrix-metalloproteinase inhibitors, and nonbacteriolytic antibiotics or a combination of the above have the potential to more efficiently protect the brain either alone (e.g., in children and outside the high-income settings) or in addition to adjuvant dexamethasone. Additionally, new protein-based pneumococcal vaccines are being developed that promise to improve disease prevention, namely by addressing the increasing problem of serotype replacement seen with pneumococcal conjugate vaccines. SUMMARY:Pneumococcal meningitis remains a life-threatening disease requiring early antibiotic and targeted anti-inflammatory therapy. New adjuvant therapies showed promising results in animal models but need systematic clinical testing.