title: Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.
abstract: 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.
authors.forename: Eileen
authors.initials: E
authors.lastname: Huang
authors.forename: Satish K
authors.initials: SK
authors.lastname: Pillai
authors.forename: William A
authors.initials: WA
authors.lastname: Bower
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hendricks
authors.forename: Julie T
authors.initials: JT
authors.lastname: Guarnizo
authors.forename: Jamechia D
authors.initials: JD
authors.lastname: Hoyle
authors.forename: Susan E
authors.initials: SE
authors.lastname: Gorman
authors.forename: Anne E
authors.initials: AE
authors.lastname: Boyer
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Quinn
authors.forename: Dana
authors.initials: D
authors.lastname: Meaney-Delman
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000881:Anthrax / Q000188:drug therapy*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial / Q000276:immunology; D000992:Antitoxins / Q000627:therapeutic use*; D023482:Bioterrorism; D004359:Drug Therapy, Combination; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D054527:Mass Casualty Incidents; D011817:Rabbits; D012141:Respiratory Tract Infections / Q000188:drug therapy*
chemical_list: C000609458:Anthrax Immune Globulin Intravenous; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D000992:Antitoxins; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; C542124:raxibacumab