Concern about use of
anthrax as a bioweapon prompted development of novel
anthrax antitoxins for treatment. Clinical guidelines for the treatment of
anthrax recommend
antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass
anthrax incident may exceed
antitoxin availability and create a need for judicious
antitoxin use. We conducted a systematic review of
antitoxin treatment of
inhalation anthrax in humans and experimental animals to inform
antitoxin recommendations during a large-scale or mass
anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified.
Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-
antitoxin therapy in nonhuman primates and rabbits. With
delayed treatment,
antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of
antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive
antitoxin therapy may improve survival.
Delayed treatment studies suggest improved survival with combined
antitoxin-antimicrobial
therapy, although a survival difference compared with antimicrobial
therapy alone was not demonstrated statistically. In a mass
anthrax incident with limited
antitoxin supplies,
antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide
antitoxin use during a large-scale
anthrax incident.