An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis.
BACKGROUND
Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to improve clinical outcomes. Since lethal toxin and edema toxin (LT and ET) make central contributions to the pathogenesis of B. anthracis, these have been major targets in this effort.


METHODS
Here, the authors review different investigative biopharmaceuticals that have been recently identified for their therapeutic potential as inhibitors of LT or ET. Among these inhibitors are two antibody preparations that have been included in the Strategic National Stockpile (SNS) and several more that have reached Phase I testing. Presently, however, many of these candidate agents have only been studied in vitro and very few tested in bacteria-challenged models.


CONCLUSIONS
Although a large number of drugs have been identified as potential therapeutic inhibitors of LT and ET, in most cases their testing has been limited. The use of the two SNS antibody therapies during a large-scale exposure to B. anthracis will be difficult. Further testing and development of agents with oral bioavailability and relatively long shelf lives should be a focus for future research.
National Institutes of Health, Clinical Center, Critical Care Medicine Department , Building 10, Room 2C145, Bethesda, MD 20892 , USA +1 301 402 2914 ; +1 301 402 1213 ; peichacker@mail.cc.nih.gov.
Lernik
L
Ohanjanian
Kenneth E
KE
Remy
Yan
Y
Li
Xizhong
X
Cui
Peter Q
PQ
Eichacker
D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000378:metabolism; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin
Bacillus anthracis; anthrax; lethal and edema toxins; toxin-directed agents; treatment