Abstract
We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. 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 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. 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. 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
Original language | English |
---|---|
Pages (from-to) | 149 |
Journal | Journal of neuroinflammation |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2015 |
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Kasanmoentalib, E. S., Valls Seron, M., Morgan, B. P., Brouwer, M. C. (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. https://doi.org/10.1186/s12974-015-0372-y
Kasanmoentalib, E. Soemirien ; Valls Seron, Mercedes ; Morgan, B. Paul et al. / Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial. In: Journal of neuroinflammation. 2015 ; Vol. 12, No. 1. pp. 149.
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title = "Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial",
abstract = "We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. 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 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. 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. 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",
author = "Kasanmoentalib, {E. Soemirien} and {Valls Seron}, Mercedes and Morgan, {B. Paul} and Brouwer, {Matthijs C.} and {van de Beek}, Diederik",
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Kasanmoentalib, ES, Valls Seron, M, Morgan, BP, Brouwer, MC 2015, 'Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial', Journal of neuroinflammation, vol. 12, no. 1, pp. 149. https://doi.org/10.1186/s12974-015-0372-y
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 et al.
In: Journal of neuroinflammation, Vol. 12, No. 1, 2015, p. 149.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial
AU - Kasanmoentalib, E. Soemirien
AU - Valls Seron, Mercedes
AU - Morgan, B. Paul
AU - Brouwer, Matthijs C.
AU - van de Beek, Diederik
PY - 2015
Y1 - 2015
N2 - We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. 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 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. 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. 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
AB - We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. 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 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. 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. 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
U2 - https://doi.org/10.1186/s12974-015-0372-y
DO - https://doi.org/10.1186/s12974-015-0372-y
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SN - 1742-2094
VL - 12
SP - 149
JO - Journal of neuroinflammation
JF - Journal of neuroinflammation
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ER -
Kasanmoentalib ES, Valls Seron M, Morgan BP, Brouwer MC, van de Beek D. Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial. Journal of neuroinflammation. 2015;12(1):149. doi: https://doi.org/10.1186/s12974-015-0372-y