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Host Response and Inflammation

Antibodies to Recombinant Clostridium difficile Toxins A and B Are an Effective Treatment and Prevent Relapse of C. difficile-Associated Disease in a Hamster Model of Infection

John A. Kink, Jim A. Williams
John A. Kink
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Jim A. Williams
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DOI: 
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  • Fig. 1.
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    Fig. 1.

    C. difficile toxin A gene and locations of expression clones. The amino acid interval expressed in each clone is as follows: for Int. A-1, aa 30 to 100; for Int. A-2, aa 300 to 660; for Int. A-3, aa 660 to 1100; for Int. A-4, aa 1100 to 1610; for Int. A-5, aa 1450 to 1870; and for Int. A-6, aa 1870 to 2680. The shaded region at the 3′ end represents the repetitive domain of the toxin A gene.

  • Fig. 2.
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    Fig. 2.

    C. difficile toxin B gene and locations of expression clones. Int. B-4 and Int. B-(1+2) each comprise a pool of two or three smaller fragments. The amino acid interval expressed in each clone is as follows: for Int. B-4, aa 10 to 330 and aa 260 to 520; for Int. B-(1+2), aa 510 to 1110, aa 820 to 1110, and aa 1110 to 1530; for Int. B-5, aa 1530 to 1750; and for Int. B-3, aa 1750 to 2360. The shaded region at the 3′ end represents the repetitive domain of the toxin B gene.

  • Fig. 3.
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    Fig. 3.

    Cumulative mortalities caused by clindamycin-induced CDAD in hamsters treated t.i.d. with placebo (preimmune IgY) (⧫), anti-rTox A (▪), or a mixture of anti-rTox A and anti-rTox B (▴).

  • Fig. 4.
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    Fig. 4.

    Effect of CDAD antitoxin dose on death in hamsters afterC. difficile challenge. Seven hamsters were tested at each CDAD antitoxin dose. Hamsters were treated q.d. for 3 days. The equation of the line that approximates the best fit of the data points is shown.

  • Fig. 5.
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    Fig. 5.

    Cumulative mortalities caused by clindamycin-induced CDAD in hamsters that were either untreated (⧫), treated q.d. with 0.2 (□), 1.0 (▵), or 5.0 (○) of oral vancomycin/kg, or treated with CDAD antitoxin at a 40-mg dose t.i.d. (×). Nineteen animals were used in the CDAD antitoxin treatment group, and six animals were used in each of the untreated and vancomycin-treated groups.

  • Fig. 6.
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    Fig. 6.

    Effect of CDAD antitoxin on mortality after C. difficile rechallenge in the hamster model. Hamsters were induced with clindamycin, challenged with C. difficile ATCC 43596 (first challenge [1st]), then treated q.d. for 3 days with 80 mg of CDAD antitoxin (□) (see Materials and Methods). These treated hamsters were then rechallenged at the time points indicated with clindamycin and C. difficile ATCC 43596 (2nd), VPI 7698 (3rd), and ATCC 43255 (4th). Hamsters treated with placebo (preimmune IgY, given at 80 mg q.d. for 3 days) at the first C. difficile challenge (○) and untreated hamsters at the second (▴), third (×), and fourth (•) C. difficile challenges served as controls. Six to nine hamsters were used in each challenge experiment.

Tables

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  • Table 1.

    Anti-rTox A and anti-rTox B antibodies reduce CDAD morbidity

    Treatment groupa% Diarrhea% Weight lossb
    Placebo100NA
    Anti-rTox A90c 16d
    Anti-rTox A and anti-rTox B0d 1c
    • ↵a There were 10 hamsters in each treatment group.

    • ↵b Compared to starting weight. NA, not applicable.

    • ↵c Not significant.

    • ↵d P < 0.001.

  • Table 2.

    Results of prophylactic and therapeutic treatment studies with anti-rTox A

    Time of 1st dose (h)aDose (mg) and frequency (no. of days)bNo. of hamstersReduction of mortality (%)
    −2440, t.i.d. (12)7100
    −2440, t.i.d. (7)7100
    −2440, t.i.d. (7)7100
    −2440, t.i.d. (7)7100
    −2440, t.i.d. (7)7100
    −2480, q.d. (4)1060
    +340, t.i.d. (4)1250
    +480, q.d. (3)956
    +16–2480, t.i.d. (2)2045
    • ↵a −, before challenge; +, after challenge.

    • ↵b A regimen of 40 mg t.i.d. for 7 days was used in four independent experiments.

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Antibodies to Recombinant Clostridium difficile Toxins A and B Are an Effective Treatment and Prevent Relapse of C. difficile-Associated Disease in a Hamster Model of Infection
John A. Kink, Jim A. Williams
Infection and Immunity May 1998, 66 (5) 2018-2025; DOI:

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Antibodies to Recombinant Clostridium difficile Toxins A and B Are an Effective Treatment and Prevent Relapse of C. difficile-Associated Disease in a Hamster Model of Infection
John A. Kink, Jim A. Williams
Infection and Immunity May 1998, 66 (5) 2018-2025; DOI:
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