Anthrax research: Estimating the post-exposure period for effective treatment of human inhalational anthrax.
August 2nd, 2017Rubinson L, Corey A, Hanfling D. Estimation of Time Period for Effective Human Inhalational Anthrax Treatment Including Antitoxin Therapy. PLOS Currents Outbreaks. 2017 Jul 28 . Edition 1.
doi: 10.1371/currents.outbreaks.7896c43f69838f17ce1c2c372e79d55d.
“…..Results: For antibiotic sensitive infections, treatment with antibiotics alone ≤4 days after spore exposure prevents toxemia. Administration of raxibacumab together with antibiotics protects ≥ 80% of subjects for 3 additional days (7 days post exposure). In the setting of antibiotic resistance, raxibacumab would be protective for at least 6 days post exposure.
Conclusions: Although the animal model of disease does not reflect the potential impact of supportive care (e.g. fluid resuscitation received by critically ill patients) on PA kinetics and raxibacumab PK, the simulations suggest that administration of antitoxin in combination with antibiotics should provide a longer postexposure window for effective treatment than for antibiotics alone. In addition, raxibacumab administration soon after exposure to an antibiotic resistant strain should provide effective treatment…..”
- Raxibacumab, an IgG monoclonal antibody against protective antigen (PA);
- For inhalational anthrax, protective antigen (PA) drives much of the mortality
- Raxibacumab is an anti-PA monoclonal antibody
- The anthrax toxin is a tripartite toxin: lethal factor (LF) and edema factor (EF) have enzymatic activities, while PA binds to cell receptors. PA binds and translocates LF and EF into the cell. Inhibition of PA binding to cell receptors blocks binding and internalization of LF and EF.