Nicholas J Vietri1, Steven A Tobery1, Donald J Chabot1, Susham Ingavale1, Brandon C Somerville1, Jeremy A Miller1, Chris W Schellhase2, Nancy A Twenhafel2, David P Fetterer3, Christopher K Cote1, Christopher P Klimko1, Anne E Boyer4, Adrian R Woolfitt4, John R Barr4, Mary E Wright5, Arthur M Friedlander6,7. 1. Division of Bacteriology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA. 2. Division of Pathology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA. 3. Division of Biostatistics, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA. 4. National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 5. Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. 6. Headquarters, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA. 7. Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Abstract
BACKGROUND: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking. METHODS: Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic. Circulating anthrax lethal factor and protective antigen were quantitated pretreatment and 1.5 and 12 hours after beginning antibiotics. RESULTS: In the clindamycin group, 8 of 11 (73%) survived demonstrating its efficacy for the first time in inhalational anthrax, compared to 9 of 9 (100%) with ciprofloxacin, and 8 of 11 (73%) with ciprofloxacin + clindamycin. These differences were not statistically significant. There were no significant differences between groups in lethal factor or protective antigen levels from pretreatment to 12 hours after starting antibiotics. Animals that died after clindamycin had a greater incidence of meningitis compared to those given ciprofloxacin or ciprofloxacin + clindamycin, but numbers of animals were very low and no definitive conclusion could be reached. CONCLUSION: Treatment of inhalational anthrax with clindamycin was as effective as ciprofloxacin in the nonhuman primate. Addition of clindamycin to ciprofloxacin did not enhance reduction of circulating toxin levels.
BACKGROUND: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking. METHODS:Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic. Circulating anthrax lethal factor and protective antigen were quantitated pretreatment and 1.5 and 12 hours after beginning antibiotics. RESULTS: In the clindamycin group, 8 of 11 (73%) survived demonstrating its efficacy for the first time in inhalational anthrax, compared to 9 of 9 (100%) with ciprofloxacin, and 8 of 11 (73%) with ciprofloxacin + clindamycin. These differences were not statistically significant. There were no significant differences between groups in lethal factor or protective antigen levels from pretreatment to 12 hours after starting antibiotics. Animals that died after clindamycin had a greater incidence of meningitis compared to those given ciprofloxacin or ciprofloxacin + clindamycin, but numbers of animals were very low and no definitive conclusion could be reached. CONCLUSION: Treatment of inhalational anthrax with clindamycin was as effective as ciprofloxacin in the nonhuman primate. Addition of clindamycin to ciprofloxacin did not enhance reduction of circulating toxin levels.
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