Aliment Pharmacol Ther. 2015 Aug;42(4):470-6. doi: 10.1111/apt.13290.

Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate.

 

Fischer M1, Sipe BW2, Rogers NA1, Cook GK1, Robb BW3, Vuppalanchi R1, Rex DK1.
  • 1Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • 2Community Hospital, Anderson, IN, USA.
  • 3Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

 

Abstract

BACKGROUND: Severe and severe/complicated Clostridium difficile infection (CDI) can result in ICU admission, sepsis, toxic megacolon and death. In this setting, colectomy is the standard of care but it is associated with a 50% mortality.

AIM: To evaluate safety and efficacy of a sequential faecal microbiota transplantation (FMT) and antibiotic protocol in severe and severe/complicated CDI patients who are at high risk for colectomy.

METHODS: All patients with severe and severe/complicated CDI refractory to oral vancomycin ± rectal vancomycin and intravenous metronidazole therapy were offered FMT. Treatment consisted of sequential FMTs via colonoscopy with the need for repeat FMT and continued vancomycin guided by clinical response and pseudomembranes at colonoscopy.

RESULTS: A total of 29 patients underwent FMT between July 2013 and August 2014. The overall treatment response of endoscopic sequential FMT was 93% (27/29), with 100% (10/10) for severe CDI and 89% (17/19) for severe/complicated CDI. A single FMT was performed in 62%, two FMTs were performed in 31% and three FMTs in 7% of patients. The use of non-CDI antibiotics predicted repeat FMT (odds ratio = 17.5). The 30-day all-cause mortality after FMT was 7%, and the cumulative 3-month survival was 76%. Of the two patients who died within 30 days, one underwent colectomy and succumbed to sepsis; the other died from septic shock related to CDI.

CONCLUSION: The success of a treatment protocol for severe and severe/complicated involving faecal microbiota transplantation and continued vancomycin in selected patients was high, and it warrants further evaluation.

PMID: 26096320

 

Supplement

Clostridium difficile infection (CDI) is an infection of the colon previously believed to affect mostly hospitalized and institutionalized patients. Over the past few years, this infection has become more common in the general population and is increasingly resistant to the traditional antibiotic therapies that worked well in the past. In 2011, almost 500,000 patients contracted this infection, with approximately 29,000 of those patients eventually dying of the illness1. Approximately 10% of patient with CDI will progress to a severe form of the disease, some of them requiring surgical removal of the colon (colectomy), which carries significant morbidity and mortality2.

Picture 1.

Fecal microbiota transplant (FMT) is a new technique that has shown great promise in the treatment of CDI. FMT involves instilling liquefied stool from a healthy donor into the colon of an infected patient during a colonoscopy. Antibiotics are typically stopped after FMT. While the initial results using this technique at our institution showed great efficacy, we noted that several patients with severe CDI still went on to succumb to the disease, particularly patients who were found to have pseudomembranes (Picture 1.), dense layers of mucus and exudate lining the colon. We hypothesized that patients with pseudomembranes at the time of the initial FMT would have better clinical outcomes if antibiotics were continued and FMT was repeated sequentially until clinical improvement was observed.

 

Based on our hypothesis, we devised a protocol where patient with severe CDI who were found to have pseudomembranes at the time of their initial FMT were continued on standard antibiotics, then had repeat FMT done every 6-7 days if no clinical improvement was noted.   Antibiotics were continued until pseudomembranes were no longer visible on colonoscopy. Initially, we used patient directed stool donors and fresh stool from unrelated healthy individuals. The logistics of this approach was quite challenging and often limiting given the severity of the disease and the urgent need for therapy. Upon availability of frozen stool specimen from the national stool bank, Openbiome, we exclusively switched to their product. The availability of the screened, prepared stool in the freezer streamlined the process and allowed for prompt FMT therapy. (Picture 2.)

 

Picture 2

Our study retrospectively studied a total of 29 patients with severe CDI at our institution who underwent this protocol. We looked at a variety of clinical variables, including mortality, length of hospital stay and risk factors for need for repeat FMT. Using our protocol, 27 of the 29 patients (93%) had complete recovery from their CDI without colectomy.   Of the two treatment failures, one patient died of sepsis after colectomy, the other died of CDI-related septic shock within 24 hours of the first FMT. Pseudomembranes were found in 72% of patients during the first FMT. Only one FMT was performed in the majority of cases (62%), while 31% of patients required a second FMT, and 7% of patients required a third. Exposure to antibiotics not directed against CDI was significantly associated with need for repeat FMT.

Our findings lend support to the hypothesis that severe CDI patients with pseudomembranes on colonoscopy may have better outcomes if antibiotics are continued and FMT is repeated if there is no clinical improvement within a few days. This hypothesis is based on the thought that patients with severe CDI and pseudomembranes likely have a larger burden of bacteria. FMT in these patient is likely insufficient to clear the bacteria, but may decrease the bacterial load to the point that the patient will be more responsive to antibiotics. Our study also suggests that this protocol may help reduce the need for colectomy, a procedure many of our patients decline due to the substantial risks. At this point, the next step is to study our protocol in a prospective trial.

 

References:

  1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile Infection in the United States. N Engl J Med 2015; 372:825-34.
  2. Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg 2011; 254:423-7.

 

 

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