Raxibacumab augments hemodynamic support and improves outcomes during shock with B. anthracis edema toxin alone or together with lethal toxin in canines

Kenneth E Remy; Xizhong Cui; Yan Li; Junfeng Sun; Steven B Solomon; Yvonne Fitz; Amisha V Barochia; Mariam Al-Hamad; Mahtab Moayeri; Stephen H Leppla; Peter Q Eichacker

doi:10.1186/s40635-015-0043-4

Raxibacumab augments hemodynamic support and improves outcomes during shock with B. anthracis edema toxin alone or together with lethal toxin in canines

Intensive Care Med Exp. 2015 Dec;3(1):9. doi: 10.1186/s40635-015-0043-4. Epub 2015 Feb 28.

Authors

Affiliations

¹ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. kenneth.remy@mail.nih.gov.
² Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. CXizhong@cc.nih.gov.
³ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. yli3@cc.nih.gov.
⁴ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. junfeng.sun@nih.gov.
⁵ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. SSolomon@cc.nih.gov.
⁶ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. YFitz@cc.nih.gov.
⁷ National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. barochiaav@nhlbi.nih.gov.
⁸ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. mariam.alhamad@gmail.com.
⁹ National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. mmoayeri@niaid.nih.gov.
¹⁰ National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. sleppla@niaid.nih.go.
¹¹ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA. PEichacker@cc.nih.gov.

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.

Keywords: B. anthracis; Edema toxin; Lethal toxin; Monoclonal antibody; Protective antigen; Raxibacumab.

Grants and funding

Z99 CL999999/Intramural NIH HHS/United States