Dr Anjum HashmiMBBS,CCS(USA),MPH

Infection Control DirectorMaternity & Children’s Hospital

Najran KSA

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.

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.

• 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.

• 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.

• 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.

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.

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

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.

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.

Laboratory screening protocol for donor blood and stool samples obtained before stool transplantation.

Aas J et al. Clin Infect Dis. 2003;36:580-585© 2003 by the Infectious Diseases Society of America

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.

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.

Preparation of donor stool sample before stool transplantation.

Aas J et al. Clin Infect Dis. 2003;36:580-585© 2003 by the Infectious Diseases Society of America

Preparation of stool transplant recipient and description of the transplantation procedure.

Aas J et al. Clin Infect Dis. 2003;36:580-585© 2003 by the Infectious Diseases Society of America

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.

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.

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.

Demographic and clinical information for 18 patients treated for Clostridium difficile colitis with stool transplantation (ST).

Aas J et al. Clin Infect Dis. 2003;36:580-585© 2003 by the Infectious Diseases Society of America

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.

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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