A new therapeutic method using human antibodies to neutralize toxins was found to prevent Clostridium difficile-induced de ath in hamsters say researchers from New Jersey and Massachusetts. They report their findings in the November 2006 issue of the journal Infection and Immunity.
C. difficile is the leading cause of nosocomial antibiotic-associated diarrhea, often resulting from the administration of antibiotics such as clindamycin, ampicillin, or cephalosporins. C. difficile associated diarrhea (CDAD) effects approximately 300,000 patients per year in the U.S. alone. Treatment available to date includes discontinuation of the antibiotic causing the illness as well as administration of medication such as metronidazole or vancomycin. Although both methods offer initial relief, there is currently a 10 to 20% relapse rate among patients. Due to the recent emergence of more virulent C. difficile strains, in addition to increasing vancomycin resistance, researchers are focusing on new treatments and relapse prevention therapy.
In the study mice were used to isolate human monoclonal antibodies (HuMAbs) capable of neutralizing C. difficile toxins A and B. Researchers then tested anti-toxin A HuMAb CDA1 alone and in conjunction with anti-toxin B HUMAb MDX-1388 for the ability to protect hamsters from C.difficle-induced de ath and relapse prevention. Results showed that combination therapy reduced mortality from 100% to 45% in the primary disease model and from 78% to 32% in the relapse model.
“These human and animal studies, taken together, demonstrate the relevance of toxin-reactive antibodies in disease outcomes,” say the researchers. “Here we describe the characterization of a panel of neutralizing, fully human monoclonal antibodies (HuMAbs) directed against either toxin A or toxin B. HuMAb CDA1 (against toxin A) alone could protect hamsters from mortality, but significantly enhanced protection was observed when the antibodies were administered as a combination therapy.”
(G.J. Babcock, T.J. Broering, H.J. Hernandez, R.B. Mandell, K. Donahue, N. Boatright, A.M. Stack, I. Lowy, R. Graziano, D. Molrine, D.M. Ambrosino, W.D. Thomas, Jr. 2006. Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters. Infection and Immunity, 74. 11: 6339-6347.)