Citation

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Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Post-Exposure Prophylaxis in Animal Models of Inhalational Anthrax

Yamamoto, BJ;Shadiack, AM;Carpenter, S;Sanford, D;Henning, LN;Gonzales, N;O'Connor, E;Casey, LS;Serbina, NV;

Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. Impact of toxin neutralization with oblitoxaximab during pre- and post-exposure prophylaxis was explored and efficacy results that supported the prophylaxis indication are presented here. NZW rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous 4-16 mg/kg dose at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 hours post-challenge singly or combined with a 5-day levofloxacin regimen protected 89%-100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1-3 days pre-exposure and 83%-100% survival when given 18-24 hours post-exposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25%-50%) survival rates reflective of treatment setting. 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.