Antibiotics cure anthrax in animal models.
Respiratory anthrax, in the absence of early antibiotic treatment, is a fatal disease. This study aimed to test the efficiency of antibiotic therapy in curing infected animals and those sick with anthrax. Postexposure prophylaxis (24 h postinfection [p.i.]) of guinea pigs infected intranasally with Bacillus anthracis Vollum spores with doxycycline, ofloxacin, imipenem, and gentamicin conferred protection. However, upon termination of treatment, the animals died from respiratory anthrax. Combined treatment with antibiotics and active vaccination with a protective antigen-based vaccine leads to full protection even after cessation of treatment. Delaying the initiation of antibiotic administration to over 24 h p.i. resulted in treatment of animals with anthrax exhibiting various degrees of bacteremia and toxemia. Treatment with doxycycline or ciprofloxacin cured sick guinea pigs and rabbits exhibiting bacteremia levels up to 10(5) CFU/ml. Addition of anti-protective antigen (PA) antibodies augmented the efficiency of protection, allowing the cure of guinea pigs and rabbits with 10- to 20-fold-higher bacteremia levels, up to 7 × 10(5) CFU/ml and 2 × 10(6) CFU/ml, respectively. Treatment with ciprofloxacin and a monoclonal anti-PA antibody rescued rabbits with bacteremia levels up to 4 × 10(6) CFU/ml. During antibiotic administration, all surviving animals developed a protective immune response against development of a fatal disease and subcutaneous challenge with Vollum spores. In conclusion, these results demonstrate that antibiotic treatment can prevent the development of fatal disease in respiratory-anthrax-infected animals and can cure animals after disease establishment. A therapeutic time window of 40 h to 48 h from infection to initiation of efficient antibiotic-mediated cure was observed.
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
Shay
S
Weiss
David
D
Kobiler
Haim
H
Levy
Avi
A
Pass
Yakir
Y
Ophir
Nili
N
Rothschild
Arnon
A
Tal
Josef
J
Schlomovitz
Zeev
Z
Altboum
D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D022122:Anthrax Vaccines / Q000276:immunology; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology; D001408:Bacillus anthracis / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity*; D016470:Bacteremia / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D004318:Doxycycline / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005839:Gentamicins / Q000627:therapeutic use; D006168:Guinea Pigs; D015378:Imipenem / Q000627:therapeutic use; D015242:Ofloxacin / Q000627:therapeutic use; D011817:Rabbits
D022122:Anthrax Vaccines; D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D005839:Gentamicins; D015378:Imipenem; D015242:Ofloxacin; D004318:Doxycycline
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