An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• anthrax
• Bacillus anthracis
• lethal and edema toxins
• toxin-directed agents
• treatment

Declaration of interest

The authors are employees of the National Institutes of Health and are supported by the Intramural Program of the NIH, via the Clinical Center, Critical Care Medicine Department. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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