Treatment with monoclonal antibodies against Clostridium difficile toxins.
BACKGROUND
New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection.


METHODS
We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo.


RESULTS
Among the 200 patients who were enrolled (101 in the antibody group and 99 in the placebo group), the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies (7% vs. 25%; 95% confidence interval, 7 to 29; P<0.001). The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8% for the antibody group and 32% for the placebo group (P=0.06); among patients with more than one previous episode of C. difficile infection, recurrence rates were 7% and 38%, respectively (P=0.006). The mean duration of the initial hospitalization for inpatients did not differ significantly between the antibody and placebo groups (9.5 and 9.4 days, respectively). At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group (P=0.09).


CONCLUSIONS
The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection. (ClinicalTrials.gov number, NCT00350298.)
Lowy
Israel
I
Medarex, Princeton, NJ, USA.
Molrine
Deborah C
DC
Leav
Brett A
BA
Blair
Barbra M
BM
Baxter
Roger
R
Gerding
Dale N
DN
Nichol
Geoffrey
G
Thomas
William D
WD
Leney
Mark
M
Sloan
Susan
S
Hay
Catherine A
CA
Ambrosino
Donna M
DM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000992:Antitoxins / Q000009:adverse effects / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000276:immunology*; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000188:drug therapy*; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D055502:Secondary Prevention; D014640:Vancomycin / Q000627:therapeutic use; D055815:Young Adult
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D008795:Metronidazole; D014640:Vancomycin