title: Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits.
abstract: Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Altboum
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Glinert
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Josef
authors.initials: J
authors.lastname: Schlomovitz
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Assa
authors.initials: A
authors.lastname: Sittner
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Bar-David
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Kobiler
authors.affiliation: Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel haiml@iibr.gov.il.
authors.forename: Haim
authors.initials: H
authors.lastname: Levy
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D002939:Ciprofloxacin / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D000069349:Linezolid / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D012293:Rifampin / Q000494:pharmacology; D013171:Spores, Bacterial / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D016019:Survival Analysis; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D002939:Ciprofloxacin; D014640:Vancomycin; D015378:Imipenem; D019980:Amoxicillin-Potassium Clavulanate Combination; D017291:Clarithromycin; D000069349:Linezolid; D004318:Doxycycline; D012293:Rifampin