Transcript C. difficile_4122010

Leav, B. A., et al.(2010) “Serum Anti-toxin B Antibody
Correlates with Protection from Recurrent Clostridium
Difficile Infection (CDI)”. Vaccine 28: 965-69.
Clostridium difficile
• Anaerobic, gram-positive, spore forming bacteria
• Produces two toxins, A and B
• The most common cause of nosocomial infectious diarrhea in the US.
Therefore, patients can get Clostridium difficile infection (CDI) when
exposed to spores in hospitals.
• Known to cause human gastrointestinal microbiota disorder through the
use of broad spectrum antibiotics. Too much use of antibiotics kills both
bad and good bacteria, causing C. difficile to produce too much pathogenic
toxins A and B.
Experimental Procedure:

14 hospitals in CA and 1 hospital in MA for 56 days

47 subjects were over 18 years of age with diarrhea and positive for C.
difficile infection.

29 subjects received human monoclonal antibody against toxin A of C.
difficile (CDA1) and 17 received placebo. All subjects were also treated
with antibiotics (both metronidazole and vancomycin).
• ELISA & cytotoxicity assay were used to measure the concentration of
serum anti-toxin A antibody and anti-toxin B antibody.
Results:
• 8 subjects with recurrent CDI had low concentrations of anti-toxin B
antibodies when qualitatively compared with the subjects who did not
recur. (Lowest concentration on day 14 & 28). These 8 subjects also had
the unusual C. difficile strain (B1/NAP1/027).
•
Subjects’ concentration levels of serum anti-toxin A antibodies were stable
throughout the study.
•
17.2% of the subjects who received CDA1 vaccination had a recurrence of
CDI, and 17.7% of the placebo subjects had the recurrence of CDI.
Figure A-D: The antibody concentrations of 8 subjects with recurrent CDI are indicated by
red unbroken lines. Red arrows indicate the day on which the eight subjects recurred.
Figure A shows that Anti-toxin A antibody concentration is higher that anti-toxin B
concentration because of the CDA1 vaccine.
Critique:
• The graph was hard to analyze
• Number of subjects were very small compared to a lot of CDI patients
• Should have applied CDB1 vaccination in the study
• Did not explain why 14 hospitals in CA and 1 in MA patients were chosen
• Did not explain why the subjects were required to be 18 years old and over
• ELISA and cytotoxicity assay technique were good to detect the toxins and
to analyze the concentrations of both toxins A and B
Discussion:
• Toxins A and B are needed in order for the C. difficile infection to occurs.
• The study used only human monoclonal antibody against toxin A of C.
difficile (CDA1) because the amount of anti-toxin antibody response,
particularly against Toxin A, turns up to associate with resistance to
symptomatic infection and protection against CDI recurrence.
• The researchers found that patients with CDI need both human monoclonal
antibodies against Toxins A and B. Also, CDA1 and antibiotics will not
prevent recurrence of CDI if the patient’s serum concentration level of
anti-toxin B antibody is very low.