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Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial

Kasanmoentalib, E. Soemirien, Valls Seron, Mercedes, Morgan, B. Paul, Brouwer, Matthijs C. and van de Beek, Diederik 2015. Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial. Journal of Neuroinflammation 12 (1) , 149. 10.1186/s12974-015-0372-y

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Abstract

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 107 CFU/ml Streptococcus pneumoniae serotype 3, treated with intraperitoneal ceftriaxone at 20 h, 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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: BioMed Central
ISSN: 1742-2094
Date of First Compliant Deposit: 21 October 2020
Date of Acceptance: 6 August 2015
Last Modified: 22 Oct 2020 13:15
URI: http://orca.cardiff.ac.uk/id/eprint/135840

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