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

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 107cfu/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. © 2015 kasanmoentalib et al.