Combination Therapy with Antibiotics and Anthrax Immune Globulin Intravenous (AIGIV) Is Potentially More Effective than Antibiotics Alone in Rabbit Model of Inhalational Anthrax

Background We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax. Methods Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain) and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV) or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30–96 hours) after anthrax exposure. Results The majority of treated animals (>88%) survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points. Conclusions 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. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.

[1]  M. Fiscella,et al.  Bacillus anthracis Protective Antigen Kinetics in Inhalation Spore-Challenged Untreated or Levofloxacin/Raxibacumab-Treated New Zealand White Rabbits , 2013, Toxins.

[2]  J. Mott,et al.  Characterization of a Therapeutic Model of Inhalational Anthrax Using an Increase in Body Temperature in New Zealand White Rabbits as a Trigger for Treatment , 2012, Clinical and Vaccine Immunology.

[3]  H. Levy,et al.  Antibiotics Cure Anthrax in Animal Models , 2011, Antimicrobial Agents and Chemotherapy.

[4]  S. Ullrich,et al.  Raxibacumab for the treatment of inhalational anthrax. , 2009, The New England journal of medicine.

[5]  N. Vietri,et al.  A short course of antibiotic treatment is effective in preventing death from experimental inhalational anthrax after discontinuing antibiotics. , 2009, The Journal of infectious diseases.

[6]  K. Bush,et al.  Pharmacokinetic Considerations and Efficacy of Levofloxacin in an Inhalational Anthrax (Postexposure) Rhesus Monkey Model , 2006, Antimicrobial Agents and Chemotherapy.

[7]  J. Peterson,et al.  Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax , 2006, Infection and Immunity.

[8]  N. Vietri,et al.  Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[9]  E. Scolnick,et al.  Anthrax lethal factor inhibition , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Shiloach,et al.  Treatment of anthrax infection with combination of ciprofloxacin and antibodies to protective antigen of Bacillus anthracis. , 2004, FEMS immunology and medical microbiology.

[11]  D. Kobiler,et al.  Postexposure Prophylaxis against Anthrax: Evaluation of Various Treatment Regimens in Intranasally Infected Guinea Pigs , 2002, Infection and Immunity.

[12]  Elizabeth R. Zell,et al.  Antimicrobial Postexposure Prophylaxis for Anthrax: Adverse Events and Adherence , 2002, Emerging infectious diseases.

[13]  M. Whitby,et al.  Biological agents as weapons 2: anthrax and plague , 2002, The Medical journal of Australia.

[14]  Jerome Hauer,et al.  Anthrax as a biological weapon, 2002: updated recommendations for management. , 2002, JAMA.

[15]  Tanja Popovic,et al.  Fatal inhalational anthrax in a 94-year-old Connecticut woman. , 2002, JAMA.

[16]  C. P. Quinn,et al.  Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. , 2001, Emerging infectious diseases.

[17]  Philip K. Russell,et al.  Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. , 1999, JAMA.

[18]  B. Ivins,et al.  The pathology of experimental anthrax in rabbits exposed by inhalation and subcutaneous inoculation. , 1998, Archives of pathology & laboratory medicine.

[19]  J. Ezzell,et al.  Postexposure prophylaxis against experimental inhalation anthrax. , 1993, The Journal of infectious diseases.

[20]  A. Rowan Guide for the Care and Use of Laboratory Animals , 1979 .

[21]  W. S. Gochenour,et al.  Observations on penicillin prophylaxis of experimental inhalation anthrax in the monkey , 1962, Journal of Hygiene.

[22]  D. W. Henderson,et al.  Observations on the prophylaxis of experimental pulmonary anthrax in the monkey , 1956, Journal of Hygiene.