Background: We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. Methods: In this prospective, investigator-blinded, randomized trial, 96 mice were infected intracisternally with 10 7 CFU/ml Streptococcus pneumoniae serotype 3, treated with intraperitoneal ceftriaxone at 20h, and randomly assigned to intraperitoneal adjunctive treatment with placebo (saline), dexamethasone, anti-C5 antibodies, or dexamethasone plus anti-C5 antibodies. The primary outcome was survival during a 72-h observational period that was analyzed with the log-rank test. Secondary outcome was clinical severity, scored on a validated scale using a linear mixed model. Results: Mortality rates were 16 of 16 mice (100%) in the placebo group, 12 of 15 mice (80%) in the dexamethasone group, 25 of 31 mice (80%) in the anti-C5 antibody group, and 18 of 30 mice (60%) in the dexamethasone plus anti-C5 antibody group (Fisher's exact test for overall difference, P =.012). Mortality of mice treated with dexamethasone plus anti-C5 antibodies was lower compared to the anti-C5 antibody-treated mice (log-rank P =.039) and dexamethasone-treated mice (log-rank P =.040). Clinical severity scores for the dexamethasone plus anti-C5 antibody-treated mice increased more slowly (0.199 points/h) as compared to the anti-C5 antibody-treated mice (0.243 points/h, P =.009) and dexamethasone-treated mice (0.249 points/h, P =.012). Modeling of severity data suggested an additive effect of dexamethasone and anti-C5 antibodies. Conclusion: Adjunctive treatment with dexamethasone plus anti-C5 antibodies improves survival in severe experimental meningitis caused by S. pneumoniae serotype 3, posing an important new treatment strategy for patients with pneumococcal meningitis.
CITATION STYLE
Kasanmoentalib, E. S., Valls Seron, M., Morgan, B. P., Brouwer, M. C., & van de Beek, D. (2015). Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: A randomized controlled trial. Journal of Neuroinflammation, 12(1). https://doi.org/10.1186/s12974-015-0372-y
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