Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI)
Massachusetts Biologic Laboratories; Department of Pediatrics
Aged; Antibodies, Bacterial; Antibodies, Monoclonal; Antitoxins; Bacterial Proteins; Bacterial Toxins; Biological Markers; Double-Blind Method; Enterocolitis, Pseudomembranous; Enterotoxins; Female; Humans; Male; Placebos; Prospective Studies; Recurrence
Life Sciences | Medicine and Health Sciences
BACKGROUND: Previous studies have demonstrated a correlation between Clostridium difficile anti-toxin A serum antibodies and protection against symptomatic disease and recurrence.
METHODS: A neutralizing monoclonal antibody to C. difficile toxin A (CDA1) developed by MBL and Medarex, Inc. was studied in a phase II, randomized, double-blind, placebo-controlled trial in patients receiving standard of care treatment for C. difficile infection (CDI). Twenty-nine subjects received a single intravenous infusion of 10mg/kg CDA1 and 17 subjects received placebo and were evaluated for recurrence of CDI during the 56-day study period. Serum antibodies against C. difficile toxin A and B were measured by ELISA and cytotoxicity assay at various time points before and after infusion.
FINDINGS: CDI recurrence occurred in 5 of 29 (17%) in the CDA1 group and 3 of 17 (18%) (p=NS) in the placebo group with a trend toward delay in time to recurrence in the group treated with CDA1. The geometric mean concentration of antibody to an epitope of the receptor-binding domain of toxin B (0.300 and 1.20microg/ml, respectively; p=0.02) and geometric mean titer of neutralizing B antibody (8.00 and 100, respectively; p=0.02) at study day 28 were lower for those subjects with recurrence compared to those who did not recur. In addition, a significantly greater proportion of subjects who recurred were infected with the epidemic BI/NAP1/027 strain compared with those that did not recur (88% vs. 22%; p=0.002). Finally, in a multiple logistic regression analysis neutralizing anti-toxin B at day 14 (p<0.001), anti-toxin A at day 28 (p<0.001) and infection with the BI/NAP1/027 strain at enrollment (p=0.002) were all predictive of CDI recurrence.
INTERPRETATION: In this prospective study, lower concentrations of neutralizing anti-toxin B and anti-toxin A antibody and infection with the BI/NAP1/027 strain of C. difficile were significantly associated with recurrence of CDI.
DOI of Published Version
Vaccine. 2010 Jan 22;28(4):965-9. Epub 2009 Nov 24. Link to article on publisher's site
Leav, Brett A.; Blair, Barbara M.; Leney, Mark; Knauber, Michael; Reilly, Courtney; Lowy, Israel; Gerding, Dale N.; Kelly, Ciaran P.; Katchar, Kia; Baxter, Roger; Ambrosino, Donna M.; and Molrine, Deborah C., "Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI)" (2010). University of Massachusetts Medical School. Senior Scholars Program. Paper 138.