Human botulism immune globulin for the treatment of infant botulism.
BACKGROUND
We created the orphan drug Human Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and efficacy in treating infant botulism, the intestinal-toxemia form of human botulism.


METHODS
We performed a five-year, randomized, double-blind, placebo-controlled trial statewide, in California, of BIG-IV in 122 infants with suspected (and subsequently laboratory-confirmed) infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin); treatment was given within three days after hospital admission. We subsequently performed a 6-year nationwide, open-label study of 382 laboratory-confirmed cases of infant botulism treated within 18 days after hospital admission.


RESULTS
As compared with the control group in the randomized trial, infants treated with BIG-IV had a reduction in the mean length of the hospital stay, the primary efficacy outcome measure, from 5.7 weeks to 2.6 weeks (P<0.001). BIG-IV treatment also reduced the mean duration of intensive care by 3.2 weeks (P<0.001), the mean duration of mechanical ventilation by 2.6 weeks (P=0.01), the mean duration of tube or intravenous feeding by 6.4 weeks (P<0.001), and the mean hospital charges per patient by 88,600 dollars (in 2004 U.S. dollars; P<0.001). There were no serious adverse events attributable to BIG-IV. In the open-label study, infants treated with BIG-IV within seven days of admission had a mean length of hospital stay of 2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay significantly more than did later treatment.


CONCLUSIONS
Prompt treatment of infant botulism type A or type B with BIG-IV was safe and effective in shortening the length and cost of the hospital stay and the severity of illness.
Arnon
Stephen S
SS
Infant Botulism Treatment and Prevention Program, California Department of Health Services, Richmond, CA 94804, USA. sarnon@dhs.ca.gov
Schechter
Robert
R
Maslanka
Susan E
SE
Jewell
Nicholas P
NP
Hatheway
Charles L
CL
D001905:Botulinum Toxins / Q000276:immunology; D019274:Botulinum Toxins, Type A / Q000276:immunology; D001906:Botulism / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007136:Immunoglobulins / Q000009:adverse effects / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007902:Length of Stay; D008297:Male; D016896:Treatment Outcome
D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; C068584:botulism immune globulin; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A