Fecal Transplant vs Vancomycin for Recurrent Clostridium Diffile

Objective: To compare fecal transplant and vancomycin in the treatment of recurrent clostridium difficile to determine which has the higher cure rate. Design: Systematic literature review. Methods: Pubmed, Google Scholar, and TRIP database using the search terms “recurrent clostridium difficile. ” Filters were implemented in the Pubmed database including: randomized control trials, English, and published in the past 5 years. Records were screened for RCT with fecal transplant and full-text. Results: van Nood et al. revealed an initial cure rate of 81% for the infusion group, and a re-treated cure rate of 94%, compared to the vancomycin alone group of 31% cure rate and the vancomycin plus bowel lavage group of 23% cure rate. Cammarota et al. determined an initial cure rate of 65% for the infusion group, and a re-treated cure rate of 90%, compared to the vancomycin only group of 26% cure rate. Conclusion: An initial abbreviated dose of vancomycin at the start of fecal transplant has a significantly higher cure rate in treating recurrent clostridium difficile infections when compared to standard vancomycin therapy. Introduction Clostridium difficile (C. difficile), a gram-positive, anaerobic bacillus bacterium, is spread via the fecal-oral route, and is known for it’s colonization of the gastrointestinal tract, commonly after a regimen of antibiotic therapy has been used, altering the normal gut flora of the patient. In the United States, C. difficile infection is the most common healthcare associated infection, and is increasing in both frequency and severity of infection. High-risk populations include 65 years or older, less than 1 year old with underlying condition, male gender, increased hospitalization time, and recent antimicrobial therapy. Known antibiotics associated with the development of C. difficile include fluoroquinolones, clindamycin, penicillins, and cephalosporins. According to Barbut et al, C. difficile infections may cost up to $3.2 billion per year, along with causing an estimated 15,000 – 20,000 deaths annually in the United States alone. There are seven stages of C. diff infection, including: Carrier stage, C. difficileassociated diarrhea, C. difficile-associated Colitis, Pseudomembranous Colitis, Fulminant Colitis, Recurrent Clostridium difficile infection (CDI), and Extracolonic Infections. The studies included in this systematic literature review are looking at recurrent Clostridium difficile primarily, which involves the complete resolution of symptoms associated with the initial occurrence of C. difficile after therapy, followed by a relapse of symptoms and C. difficile infection. In approximately 10 – 25% of patients who have completed C. difficile therapy, recurrence will occur. Symptoms associated with recurrent C. difficile include the cardinal symptom of watery diarrhea with at least 3 stools within 24 hours, abdominal pain, low-grade fever, nausea, and anorexia. Diagnosis of CDI infection is primarily clinical, with a history including recent antimicrobial use and diarrhea. Laboratory tests are performed on unformed stool samples.The best sample for diagnosis consists of watery or loose stool, as fresh as possible. Culture may be performed, but is not routinely done due to the cost and clinician experience needed. If culture is performed, it is recommended to do so with the assistance of infectious disease specialist and/or gastroenterology specialists. There is a variety of toxin assays that may be used for the detection of Clostridium difficile, including cell culture neutralization assay, which is highly sensitive and specific, but time-consuming and labor-intensive. Immunoassay detects both toxins A and B, utilizing methods such as enzyme immunoassay and immunochromatography. Nucleic Acid Amplication, with sensitivity of 90-100% and specificity of 94-100%, are the most recent methods, able to identify genes of Clostridium difficile. Latex agglutination assay detects glutamate dehydrogenase, but is not used routinely. If there are normal stool laboratory test results with high suspicion, then sigmoidoscopy and colonoscopy may be used for diagnosis. Initial treatment for a patient with C. difficile begins with the cessation of any current antibiotics that the patient may be taking, if possible. After stopping the offending medication, current treatment options for recurrent Clostridium difficile include primarily a course of vancomycin or fixoxamycin; however, fecal transplant is now becoming a viable option. Standard vancomycin for the treatment of Clostridium difficile is 500 mg PO QID. According to Goudarzi et al., approximately 25% of patients with C. difficile who have been treated with either metronidazole or vancomycin experience recurrent symptoms, within 4 weeks of completing therapy. The basis of fecal microbiota transplant involves the restoration and recolonization of healthy, normal gut flora in the affected gastrointestinal tract due to C. difficile invasion or irritable bowel disease, along with other various causes of altered gut flora. Fecal transplant implements a donor that undergoes extensive screening and testing. The donors are screened via a questionnaire on such things as medical history, lifestyle habits, antibiotic use in the past 6 months, intestinal diseases and/or symptoms. The donor stool is screened for C. difficile enteric bacteria, protozoa, helminthes, as well as drug resistant bacteria. The donors blood is also tested for hepatitis A, B and C, HIV1 and HIV-2 antibodies, Epstein-Barr virus, Treponema pallidm, Strongyloides stercoralis and Entamoeba histolytica. First the feces is collected from the donors on the day of infusion and then diluted with 500 mL of sterile saline (0.9%) and blended. Finally the supernatant was strained and stored in a sterile container until infusion. The feces can be given to the patient via nasogastric tube, colonoscopy, enema, and via capsulated pill. Of these routes, for patients with recurrent C. difficile, colonoscopic fecal microbial transplant is superior to nasogastric fecal transplant in regards to the cure rate of this infection. Diarrhea, constipation, abdominal cramping, gurgling, and gas are the adverse effects that have been present after a fecal microbial transplant, although considered brief and minor occurances. Infection control is an important aspect throughout the treatment of a CDI infection. One of the most important aspects of CDI prevention is hand washing with both soap and water, which is more effective compared to an alcohol based solution. Appropriate contact precaution including wearing gloves and gowns when working with these patients is important to reduce the spread as well. Clinical Question: In patients over 18 years old who have developed recurrent Clostridium difficile, is fecal transplantation compared to vancomycin more efficacious in the treatment of recurrent Clostridium difficile infection? Methods In October of 2015 the PubMed database was searched using the terms recurrent clostridum difficile, which yielded 669 results initially. Searches of Google Scholar and TRIP databases produced no additional articles. These results were then limited to English only and randomized control trials within the past 5 years. This reduced the number of results to 10. Next these trials were reviewed and only those that involved fecal microbiota transplant were chosen. There were a total of three trials that met these criteria. Of the three trials only two looked at fecal microbiota transplant v.s. vancomycin. The third trial was a pilot RCT assessing administration routes for fecal microbiota transplant and was eliminated. The two articles meeting these criteria were Duodenal Infusion of Donor Feces for Recurrent Closridium difficile. Van Nood et al and Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Cammarota et al. Figure 1 provides a visual PRISMA flow diagram of this process. Results Study #1 Duodenal Infusion of Donor Feces for Recurrent Closridium difficile. Els van Nood et al.