Aerosolized Bacillus anthracis Infection in New Zealand White Rabbits: Natural History and Intravenous Levofloxacin Treatment

作者: Steven B Yee , Steven A Orr , Joshua M Hatkin , David N Dyer , M Louise M Pitt

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摘要: The natural history for inhalational Bacillus anthracis (Ames strain) exposure in New Zealand white rabbits was investigated to better identify potential, early biomarkers of anthrax. Twelve SPF Bordetella-free were exposed 150 LD(50) aerosolized B. spores, and clinical signs, body temperature, complete blood count, bacteremia, presence protective antigen the (that is, antigenemia) examined. development antigenemia bacteremia coincided preceded both pyrexia inversion heterophil:lymphocyte ratio, an indicator infection. Antigenemia determined within 1 h by electrochemiluminescence immunoassay, compared with 24-h traditional culture needed determination. Rabbits appeared clinically normal until shortly before succumbing anthrax approximately 47 after challenge or 22 antigenemia, which suggests a relatively narrow therapeutic window opportunity. To evaluate rabbit model, anthracis-exposed treated (after determination later confirmed be bacteremic) intravenously fluoroquinolone antibiotic levofloxacin 5 d at total daily dose 25 12.5 mg/kg, resulting nearly 90% 70% survival, respectively, study end (28 challenge). peak level mg/kg equivalent that observed 500-mg humans. These results suggest intravenous is effective against Taken together, our findings indicate viable biomarker infection can used as treatment trigger allow timely intervention this highly pathogenic disease.

参考文章(41)
Lori E Weaver, Jason M Hardcastle, Elbert B Whorton, William S Lawrence, Johnny W Peterson, Douglas L Brining, Cindy Ponce, The physiologic responses of Dutch belted rabbits infected with inhalational anthrax. Comparative Medicine. ,vol. 59, pp. 257- 265 ,(2009)
B E Ivins, A M Friedlander, G M Zaucha, J Estep, L M Pitt, The pathology of experimental anthrax in rabbits exposed by inhalation and subcutaneous inoculation. Archives of Pathology & Laboratory Medicine. ,vol. 122, pp. 982- 992 ,(1998)
T.J. Leighton, Roy H. Doi, The Stability of Messenger Ribonucleic Acid during Sporulation in Bacillus subtilis Journal of Biological Chemistry. ,vol. 246, pp. 3189- 3195 ,(1971) , 10.1016/S0021-9258(18)62213-6
N. Arora, S.H. Leppla, Residues 1-254 of anthrax toxin lethal factor are sufficient to cause cellular uptake of fused polypeptides Journal of Biological Chemistry. ,vol. 268, pp. 3334- 3341 ,(1993) , 10.1016/S0021-9258(18)53698-X
C D Hewitt, D J Innes, J Savory, M R Wills, Normal biochemical and hematological values in New Zealand white rabbits. Clinical Chemistry. ,vol. 35, pp. 1777- 1779 ,(1989) , 10.1093/CLINCHEM/35.8.1777
Karla D Passalacqua, Nicholas H Bergman, Bacillus anthracis: interactions with the host and establishment of inhalational anthrax. Future Microbiology. ,vol. 1, pp. 397- 415 ,(2006) , 10.2217/17460913.1.4.397
L.W.J. Baillie, Past, imminent and future human medical countermeasures for anthrax Journal of Applied Microbiology. ,vol. 101, pp. 594- 606 ,(2006) , 10.1111/J.1365-2672.2006.03112.X
Irma A.J.M. Bakker-Woudenberg, Experimental models of pulmonary infection. Journal of Microbiological Methods. ,vol. 54, pp. 295- 313 ,(2003) , 10.1016/S0167-7012(03)00118-0
Pierre L. Goossens, Animal models of human anthrax: The Quest for the Holy Grail Molecular Aspects of Medicine. ,vol. 30, pp. 467- 480 ,(2009) , 10.1016/J.MAM.2009.07.005