Anthrax immune globulin improves hemodynamics and survival during B. anthracis toxin-induced shock in canines receiving titrated fluid and vasopressor support

  title={Anthrax immune globulin improves hemodynamics and survival during B. anthracis toxin-induced shock in canines receiving titrated fluid and vasopressor support},
  author={Dante A. Suffredini and Xizhong Cui and Dharmvir S. Jaswal and Kenneth E. Remy and Yan Li and Junfeng Sun and Steven B. Solomon and Yvonne Fitz and Mahtab Moayeri and Stephen H Leppla and Peter Q. Eichacker},
  journal={Intensive Care Medicine Experimental},
BackgroundAlthough anthrax immune globulin (AIG) improved survival in antibiotic-treated Bacillus anthracis-challenged animal models, whether it adds to the benefit of conventional hemodynamic support for B. anthracis toxin-associated shock is unknown.MethodsWe therefore tested AIG in sedated, mechanically ventilated canines challenged with 24-h B. anthracis lethal and edema toxin infusions and supported for 96 h with a previously demonstrated protective regimen of titrated normal saline and… 
A Review of the Efficacy of FDA-Approved B. anthracis Anti-Toxin Agents When Combined with Antibiotic or Hemodynamic Support in Infection- or Toxin-Challenged Preclinical Models
A review of the controlled preclinical experience of anthrax anti-toxin antibody preparations in antibiotic-treated B. anthracis models or in titrated hemodynamic-supported toxin-challenged canines examines the strength and weaknesses of these preclinical experiences.


Protective antigen antibody augments hemodynamic support in anthrax lethal toxin shock in canines.
PA-mAb may augment conventional hemodynamic support during anthrax LT-associated shock and produce higher survival, central venous pressures, and left ventricular ejection fractions, and lower heart rates, norepinephrine requirements and fluid retention.
Raxibacumab augments hemodynamic support and improves outcomes during shock with B. anthracis edema toxin alone or together with lethal toxin in canines
Raxibacumab augments HS and improves survival during shock with lethal and edema toxin, and this model shows previously in a 96-h sedated canine model.
Anthrax lethal and edema toxins produce different patterns of cardiovascular and renal dysfunction and synergistically decrease survival in canines.
Shock with ETx or LeTx may require differing supportive therapies, whereas toxin antagonists should likely target both toxins.
Bacillus anthracis edema and lethal toxin have different hemodynamic effects but function together to worsen shock and outcome in a rat model.
ETx was approximately 10 times less lethal than LeTx but produced greater hypotension and added to the latter's harmful effects, suggesting that it may be appropriate for antitoxin therapies for B. anthracis to target both ETx and LeTx.
Anthrax Toxins Induce Shock in Rats by Depressed Cardiac Ventricular Function
Results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload, which should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections.
Combination Therapy with Antibiotics and Anthrax Immune Globulin Intravenous (AIGIV) Is Potentially More Effective than Antibiotics Alone in Rabbit Model of Inhalational Anthrax
The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure.
Added Benefit of Raxibacumab to Antibiotic Treatment of Inhalational Anthrax
Overall, raxibacumab provided a meaningful benefit over antibiotic alone when administered late in the disease course, and microscopic findings considered consistent with anthrax were present in animals that died or became moribund on study in both treatment groups, and there were no anthrax-related findings in Animals that survived.
Evaluation of Intravenous Anthrax Immune Globulin for Treatment of Inhalation Anthrax
In a time-based treatment study, AIGIV protected 89 to 100% of animals when administered 12 h postexposure; however, a lower survival rate was observed when animals were treated 24 h post exposure, underscoring the need for early intervention.
Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax
Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery.
A canine model of septic shock: balancing animal welfare and scientific relevance.
In this model, the pain control regimen did not mask changes in metabolic function and lung injury or the need for more hemodynamic and pulmonary support related to increasing severity of sepsis and the integration into this model of both specific and supportive titrated therapies routinely used in septic patients may provide a more realistic setting to evaluate therapies for sepsi.