title: Raxibacumab augments hemodynamic support and improves outcomes during shock with B. anthracis edema toxin alone or together with lethal toxin in canines.
abstract: BACKGROUND
  Lethal and edema toxin contribute to shock and lethality with Bacillus anthracis. We showed previously in a 96-h sedated canine model that raxibacumab, a monoclonal antibody against protective antigen, augmented hemodynamic support (HS) and improved survival with lethal toxin challenge. Here we study raxibacumab further. Using this model, we have now studied raxibacumab with 24 h edema toxin challenges (Study 1), and lethal and edema toxin challenges together (Study 2).
  
  
  METHODS
  Using our canine model, we have now studied raxibacumab with 24h edema toxin challenges (Study-1), and lethal and edema toxin challenges together (Study-2).
  
  
  RESULTS
  In Study 1, compared to no treatment, HS (titrated fluid and norepinephrine) increased mean arterial blood pressure (MAP, p ≤ 0.05) but not survival [0 of 10 (0/10) animals survived in each group] or median survival time [43.8 h (range 16.8 to 80.3) vs. 45.2 h (21.0 to 57.1)]. Compared to HS, HS with raxibacumab treatment at or 6 h after the beginning of edema toxin increased MAP and survival rate (6/7 and 7/8, respectively) and time [96.0 h (39.5 to 96.0) and 96.0 h (89.5 to 96.0), respectively]; (p ≤ 0.05). HS with raxibacumab at 12 h increased MAP (p ≤ 0.05) but not survival [1/5; 55.3 h (12.6 to 96.0)]. In Study-2, survival rate and time increased with HS and raxibacumab at 0 h (4/4) or 6 h after (3/3) beginning lethal and edema toxin compared to HS [0/5; 71.5 h (65 to 93)] (p = 0.01 averaged over raxibacumab groups).
  
  
  CONCLUSIONS
  Raxibacumab augments HS and improves survival during shock with lethal and edema toxin.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. kenneth.remy@mail.nih.gov.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Remy
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. CXizhong@cc.nih.gov.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. yli3@cc.nih.gov.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. junfeng.sun@nih.gov.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. SSolomon@cc.nih.gov.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Solomon
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. YFitz@cc.nih.gov.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Fitz
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. barochiaav@nhlbi.nih.gov.
authors.forename: Amisha V
authors.initials: AV
authors.lastname: Barochia
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. mariam.alhamad@gmail.com.
authors.forename: Mariam
authors.initials: M
authors.lastname: Al-Hamad
authors.affiliation: National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. mmoayeri@niaid.nih.gov.
authors.forename: Mahtab
authors.initials: M
authors.lastname: Moayeri
authors.affiliation: National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. sleppla@niaid.nih.go.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. PEichacker@cc.nih.gov.
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
keywords: B. anthracis; Edema toxin; Lethal toxin; Monoclonal antibody; Protective antigen; Raxibacumab