Alternative pre-approved and novel therapies for the treatment of anthrax.
BACKGROUND
Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies.


METHODS
A literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009.


RESULTS
The alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered.


CONCLUSIONS
Several novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium.
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada. umheadb@outlook.com.
Breanne M
BM
Head
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.
Ethan
E
Rubinstein
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.|National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Canada.|Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
Adrienne F A
AF
Meyers
D000510:Alpha-Globulins / Q000627:therapeutic use; D000881:Anthrax / Q000188:drug therapy*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D000992:Antitoxins / Q000627:therapeutic use*; D001408:Bacillus anthracis; D001427:Bacterial Toxins; D004265:DNA Helicases / Q000037:antagonists & inhibitors; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D055808:Drug Discovery; D024841:Fluoroquinolones; D006801:Humans; D007369:Interferon Inducers / Q000627:therapeutic use; D064704:Levofloxacin; D000069349:Linezolid; D000077266:Moxifloxacin; D015242:Ofloxacin; D061065:Polyketides / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D013994:Tilorone / Q000627:therapeutic use; D014774:Virulence
D000510:Alpha-Globulins; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D024841:Fluoroquinolones; D007369:Interferon Inducers; D061065:Polyketides; D015842:Serine Proteinase Inhibitors; C583934:anthracimycin; C030325:anthrax toxin; C000611266:obiltoxaximab; C011877:inter-alpha-inhibitor; C015018:baumycins; D064704:Levofloxacin; C542124:raxibacumab; D004317:Doxorubicin; D015242:Ofloxacin; D004265:DNA Helicases; D000069349:Linezolid; D013994:Tilorone; D000077266:Moxifloxacin; D003630:Daunorubicin
Anthrax; Anti-toxins; Antibiotics; Bacillus anthracis; Spore; Therapeutics; Toxin