Treatment of Clostridium difficile -associated Disease

1. Dr Anjum Hashmi
MBBS,CCS(USA),MPH
Infection Control Director
Maternity & Children’s Hospital
Najran KSA

2.  Clostridium difficile (C. difficile), Gram-positive,
spore-forming bacteria, is the most important and
common nosocomial pathogen of healthcare-
associated diarrhoea in hospitalised patients.
 It is the cause of at least 25% of all cases of antibiotic
associated diarrhoea and accounts for nearly all cases
of pseudomembranous colitis.
 C. difficile-associated disease (CDAD) covers a broad
spectrum of patient conditions, ranging from mild
diarrhoea to life-threatening complications, such as
ileal perforation, fulminant colitis, toxic megacolon,
or brain empyema.
 C. difficile produce enterotoxin (toxin A), cytotoxin
(toxin B), and binary toxin.

3.  C. defficile causes millions of human infections worldwide
annually.
 In the United States and developed countries, the number
of hospital discharges with CDAD more than doubled from
2001 to 2005.
 C. defficile infection has reached at door steps of Middle
East.
 C. difficile isolated in 113 patients and the environment of
intensive care units (ICUs) of four teaching hospitals in
Kuwait.
 A recent study conducted among hospitalized Jordanian
patients also found C. defficile.

4. • CDAD patients were associated with more severe and
complex conditions leading to longer hospital stay
(nearly three times higher than average), and higher
mortality rate (about 4.5 times higher than average).
• During the past several years, CDAD has become more
frequent and severe, more refractory to standard
therapy, and more likely to relapse.

5. • Mature colonic bacterial microbiota in a healthy adult
is generally resistant to C. difficile colonization.
•
• Any factors associated with the alteration of normal
intestinal microbiota increases the risk of C. difficile
colonisation after exposure to the bacteria.
• The most common risk factor is the use of broad-
spectrum antibiotics, or concomitant use of multiple
and prolonged antimicrobials.

6. • Standard treatment of CDAD includes:
• Discontinuation of the offending/inducing antibiotics.
• C. difficile targeted antibiotic therapy with oral
metronidazole, or vancomycin (the only US FDA approved
drug for CDAD).
• Although it is generally effective in the majority of patients
in achieving clinical improvement, the use of antibiotics
(e.g. vancomycin) does not restore intestinal microbiota,
nor does it reduce the exposure to C. difficile in the
environment, co-morbidities or other host risk factors.

7.  Despite the fact that more than 90% of patients
respond to the treatment initially, 20% to 60% of
patients will experience at least one recurrence within
a few weeks of completion of the vancomycin
treatment.
 The major problem in treating CDAD is the high
recurrence rate and the emergence of the new strain of
C. difficile (BI/NAP1/027) which complicates matters.

8.  Administration of probiotics and intravenous
immunoglobulin, toxin binding, faecal
transplantation, have been used with varying degrees
of success.
 Faecal transplantation (FT), also known as faecal
bacteriotherapy, faecal microbiota transplantation
done into upper gastrointestinal tract through a
nasogastric / nasoduodenal catheter / gastroscopy,
or into the colon through colonoscopy or rectal
catheter

9.  The use of human faecal microbiota to treat
gastrointestinal disorders is not a novel concept.
 FT has been used sporadically in one form or another
since the mid-1950s, primarily for antibiotic-associated
diarrhoea and severe C. difficile-related diarrhoea.
 One recent literature review observed a trend of
increased interest in this procedure as demonstrated
by the increased volume of clinical studies published
since 2005 and reported promising results from 22
publications in a total of 239 patients with for the
treatment of CDAD or ulcerative colitis.

12.  Individuals who had not received antimicrobial therapy for
the past 6 months were considered to be suitable for
potential stool donation.
 Preferred stool donors (in order of preference) were (1)
individuals who had had intimate physical contact with the
patients (spouse or significant partner), (2) family household
members, or (3) any other healthy donors.
 During the 30 days before transplantation— usually the last
7 days—stool donor were screened for evidence of previous
exposure to contagious infectious agents. Screening of blood
included serologic testing for hepatitis A, B, and C viruses;
HIV-1 and HIV-2; and syphilis.
 All donor stool samples were cultured for enteric bacterial
pathogens, and each stool sample was screened by light
microscopy for presence of ova and parasites.

13. Laboratory screening protocol for donor blood and stool samples
obtained before stool transplantation.
© 2003 by the Infectious Diseases Society of America
Aas J et al. Clin Infect Dis. 2003;36:580-585

14.  Before the procedure, stool transplant recipient was
pretreated with a 4-day course of oral vancomycin (250
mg tid) to reduce the C. difficile load.
 This treatment was discontinued on the evening before
transplantation.
 On the morning of the transplantation, patient orally
receive 20 mg of omeprazole.
 On the morning of the procedure, a nasogastric tube
was placed in the patient’s stomach, and the tip
placement position was confirmed by abdominal
radiography.

15.  Take 30 gm of sample and 50-70 ml of 0.9% N. saline
and blind in home blander for 3-4 minutes and filter it
by paper coffee filter.
 25 ml of the transplant stool suspension was drawn up
in a syringe and instilled into the stomach via the
nasogastric tube.
 The nasogastric tube was then flushed with 25 ml of
sterile 0.9 N saline and removed.
 Patient allowed to resume a normal diet and physical
activities immediately.
 During the weeks after the transplantation, stool
specimens were examined for the presence of
C. difficile toxin A in patient.

16. Preparation of donor stool sample before stool transplantation.
© 2003 by the Infectious Diseases Society of America Aas J et al. Clin Infect Dis. 2003;36:580-585

17. Preparation of stool transplant recipient and description of the
transplantation procedure.
© 2003 by the Infectious Diseases Society of America
Aas J et al. Clin Infect Dis. 2003;36:580-585

18. 1.The mean patient age was 73+/_9 years (range
is 51–88 years)
2.Thirteen (72%) of the 18 patients were
women.
3. The mean period between diagnosis of C.
difficile colitis and the stool transplantation
was 102+/_24 days (range is 25–497 days).
4. During this period, the 18 patients had a
combined total of 58 test results positive for
C. difficile and had received a combined total
of 64 courses of antimicrobials.

19. 5. One patient developed diarrhea 17 days after
undergoing stool transplantation, and the
results of an additional C. difficile stool toxin
test was positive. He was treated with a 10-day
course of orally administered vancomycin, and
the diarrhea resolved within 4 days. The
patient did not experience any further episodes
of diarrhea, and the stool C. difficile toxin test
yielded a negative result 6 months later.

20. 6. Seven patients had not experienced any
recurrence of diarrhea after the stool
transplantation. Patients remained free of
diarrhea during the 90-day follow-up
period.
7. One patient experienced treatment failure.
8. Two patients died after feacal implant
autopsy revealed end stage renal disease and
complicating COPD with atherosclerosis
were the causes of death.

21. Demographic and clinical information for 18 patients treated for
Clostridium difficile colitis with stool transplantation (ST).
© 2003 by the Infectious Diseases Society of America Aas J et al. Clin Infect Dis. 2003;36:580-585

22.  This technique is an effective and safe treatment for
recurrent CDAD. Faecal transplantation via a
nasogastric tube could be considered in patients with
refractory relapsing CDAD.
 The use of donor stool has yet to be subjected to a
randomized, controlled trial, this therapy has the
potential of providing patients and clinicians with an
effective, low-risk, and inexpensive alternative to
conventional antimicrobial treatment regimens.
 Additional studies will be needed to better define the
role of faecal transplantation in the management of
recurrent CDAD, for broader clinical use.

24.  Macconnachie AA, Fox R, Kennedy DR, Seaton RA. Faecal transplant for
recurrent Clostridium difficile-associated diarrhoea: a UK case series. QJM 2009;
102: 781–4
 Landy J, Al-Hassi HO, McLaughlin SD, et al. Review article: faecal transplantation
therapy for gastrointestinal disease. Aliment Pharmacol Ther 2011; 34: 409–15
 Guo B, Nguyen T, Ohinmaa A, Harstall C. Fecal transplantation for the treatment
of Clostridium difficule associated disease or ulcerative colitis. Edmonton AB:
Institute of Health Economics, 2011.
 Garborg K, Waagsbo B, Stallemo A, Matre J, Sundoy A. Results of faecal donor
instillation therapy for recurrent Clostridium difficile-associated diarrhoea.
Scand J Infect Dis 2010; 42: 857–61
 Mellow MH, Kanatzar A. Colonoscopic fecal bacteriotherapy in the treatment of
recurrent Clostridium difficile infection– results and follow-up. J Okla State Med
Assoc 2011; 104: 89–91
 Rohlke F, Surawicz CM, Stollman N. Fecal flora reconstitution for recurrent
Clostridium difficile infection: results and methodology. J Clin Gastroenterol 2010;
44: 567–70

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