This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Altboum, Z. Articles by Kobiler, D. Search for Related Content PubMed PubMed Citation Articles by Altboum, Z. Articles by Kobiler, D.

Postexposure Prophylaxis against Anthrax: Evaluation of Various Treatment Regimens in Intranasally Infected Guinea Pigs

Departments of Infectious Diseases,¹ Biotechnology, Israel Institute for Biological Research, Ness-Ziona 74100, Israel²

Received 3 April 2002/ Returned for modification 13 June 2002/ Accepted 14 August 2002

The efficiency of postexposure prophylaxis against Bacillus anthracis infection was tested in guinea pigs infected intranasally with either Vollum or strain ATCC 6605 spores (75 times the 50% lethal dose [LD₅₀] and 87 times LD_50, respectively). Starting 24 h postinfection, animals were treated three times per day for 14 days with ciprofloxacin, tetracycline, erythromycin, cefazolin, and trimethoprim-sulfamethoxazole (TMP-SMX). Administration of cefazolin and TMP-SMX failed to protect the animals, while ciprofloxacin, tetracycline, and erythromycin prevented death. Upon cessation of treatment all erythromycin-treated animals died; of the tetracycline-treated animals, two of eight infected with Vollum and one of nine infected with ATCC 6605 survived; and of the ciprofloxacin group injected with either 10 or 20 mg/kg of body weight, five of nine and five of five animals, respectively, survived. To test the added value of extending the treatment period, Vollum-infected (46 times the LD₅₀) animals were treated for 30 days with ciprofloxacin or tetracycline, resulting in protection of eight of nine and nine of nine animals, respectively. Once treatment was discontinued, only four of eight and five of nine animals, respectively, survived. Following rechallenge (intramuscularly) of the survivors with 30 times the LD₅₀ of Vollum spores, all ciprofloxacin-treated animals were protected while none of the tetracycline-treated animals survived. In an attempt to confer protective immunity lasting beyond the termination of antibiotic administration, Vollum-infected animals were immunized with a protective antigen (PA)-based vaccine concurrently with treatment with either ciprofloxacin or tetracycline. The combined treatment protected eight of eight and nine of nine animals. Following cessation of antibiotic administration seven of eight and eight of eight animals survived, of which six of seven and eight of eight resisted rechallenge. These results indicate that a combined treatment of antibiotics together with a PA-based vaccine could provide long-term protection to prevent reoccurrence of anthrax disease.

Editor: D. L. Burns

This article has been cited by other articles:

• Chitlaru, T., Gat, O., Grosfeld, H., Inbar, I., Gozlan, Y., Shafferman, A. (2007). Identification of In Vivo-Expressed Immunogenic Proteins by Serological Proteome Analysis of the Bacillus anthracis Secretome. Infect. Immun. 75: 2841-2852 [Abstract] [Full Text]  
• Kedar, G. C., Brown-Driver, V., Reyes, D. R., Hilgers, M. T., Stidham, M. A., Shaw, K. J., Finn, J., Haselbeck, R. J. (2007). Evaluation of the metS and murB Loci for Antibiotic Discovery Using Targeted Antisense RNA Expression Analysis in Bacillus anthracis. Antimicrob. Agents Chemother. 51: 1708-1718 [Abstract] [Full Text]  
• Schmitt, B., Dobrez, D., Parada, J. P., Kyriacou, D. N., Golub, R. M., Sharma, R., Bennett, C. (2007). Responding to a Small-scale Bioterrorist Anthrax Attack: Cost-effectiveness Analysis Comparing Preattack Vaccination With Postattack Antibiotic Treatment and Vaccination. Arch Intern Med 167: 655-662 [Abstract] [Full Text]  
• Heine, H. S., Bassett, J., Miller, L., Hartings, J. M., Ivins, B. E., Pitt, M. L., Fritz, D., Norris, S. L., Byrne, W. R. (2007). Determination of Antibiotic Efficacy against Bacillus anthracis in a Mouse Aerosol Challenge Model. Antimicrob. Agents Chemother. 51: 1373-1379 [Abstract] [Full Text]  
• Kobiler, D., Weiss, S., Levy, H., Fisher, M., Mechaly, A., Pass, A., Altboum, Z. (2006). Protective antigen as a correlative marker for anthrax in animal models.. Infect. Immun. 74: 5871-5876 [Abstract] [Full Text]  
• Gat, O., Grosfeld, H., Ariel, N., Inbar, I., Zaide, G., Broder, Y., Zvi, A., Chitlaru, T., Altboum, Z., Stein, D., Cohen, S., Shafferman, A. (2006). Search for Bacillus anthracis Potential Vaccine Candidates by a Functional Genomic-Serologic Screen. Infect. Immun. 74: 3987-4001 [Abstract] [Full Text]  
• Mabry, R., Brasky, K., Geiger, R., Carrion, R. Jr., Hubbard, G. B., Leppla, S., Patterson, J. L., Georgiou, G., Iverson, B. L. (2006). Detection of Anthrax Toxin in the Serum of Animals Infected with Bacillus anthracis by Using Engineered Immunoassays. CVI 13: 671-677 [Abstract] [Full Text]  
• Peterson, J. W., Comer, J. E., Noffsinger, D. M., Wenglikowski, A., Walberg, K. G., Chatuev, B. M., Chopra, A. K., Stanberry, L. R., Kang, A. S., Scholz, W. W., Sircar, J. (2006). Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax. Infect. Immun. 74: 1016-1024 [Abstract] [Full Text]  
• Weiss, S., Kobiler, D., Levy, H., Marcus, H., Pass, A., Rothschild, N., Altboum, Z. (2006). Immunological Correlates for Protection against Intranasal Challenge of Bacillus anthracis Spores Conferred by a Protective Antigen-Based Vaccine in Rabbits. Infect. Immun. 74: 394-398 [Abstract] [Full Text]  
• Mabry, R., Rani, M., Geiger, R., Hubbard, G. B., Carrion, R. Jr, Brasky, K., Patterson, J. L., Georgiou, G., Iverson, B. L. (2005). Passive Protection against Anthrax by Using a High-Affinity Antitoxin Antibody Fragment Lacking an Fc Region. Infect. Immun. 73: 8362-8368 [Abstract] [Full Text]  
• Barth, H., Aktories, K., Popoff, M. R., Stiles, B. G. (2004). Binary Bacterial Toxins: Biochemistry, Biology, and Applications of Common Clostridium and Bacillus Proteins. Microbiol. Mol. Biol. Rev. 68: 373-402 [Abstract] [Full Text]  
• Steward, J., Lever, M. S., Simpson, A. J. H., Sefton, A. M., Brooks, T. J. G. (2004). Post-exposure prophylaxis of systemic anthrax in mice and treatment with fluoroquinolones. J Antimicrob Chemother 54: 95-99 [Abstract] [Full Text]  
• Brookmeyer, R., Johnson, E., Bollinger, R. (2003). Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak. Proc. Natl. Acad. Sci. USA 100: 10129-10132 [Abstract] [Full Text]