The Long-term Effects of Faecal Microbiota Transplantation for Gastrointestinal Symptoms and General Health in Patients With Recurrent Clostridium Difficile Infection

J. Jalanka; A. Hillamaa; R. Satokari; E. Mattila; V.-J. Anttila; P. Arkkila

Disclosures

Aliment Pharmacol Ther. 2018;47(3):371-379. 

In This Article

Methods

Study Population

This study was a retrospective comparative observational follow-up study on patients who were successfully treated for recurrent C. difficile infection in the Hospital District of Helsinki and Uusimaa (HUS) area in 2007–2014. The study had the ethical approval of HUS (Dnro 48/2013) and all patients provided an informed consent. The treatment group received FMT for recurrent C. difficile infection and the control group patients were treated with antibiotics. FMT-group patients contained some subjects whom had previously had a serious, life threatening infection and to prevent further recurrent C. difficile infection episodes they were given the FMT treatment. The patients were not selected to a certain treatment group based on the previous GI-tract complications. The controls were selected from the infectious diseases register of Helsinki and Uusimaa hospital district to match patients in the FMT group in age, sex and number of infection episodes.

In both groups, the patients had had at least two episodes of C. difficile infection, one initial and one recurrent infection in during a 6-month period. Our routine is to use FMT after three relapses of C. difficile infection, but we have done FMT for a few patients after the second relapse due to the very severe previous C. difficile infection episodes. In both groups, the primary infection was treated either with metronidazole or vancomycin or with both medicines depending on diseases severity. In the antibiotic group, the recurrent infections were treated with either metronidazole or vancomycin until either resolution of symptoms or a negative C. difficile toxin laboratory test. FMT treatment was available throughout the follow-up period independent of availability of family donors.

Questionnaire

All together 130 patients (55 patients in the FMT group and 75 patients in the antibiotic, AB-group) were sent a 45-item questionnaire collecting information about the patient demographics, their physical and mental health, allergies, infections, gastroenterological conditions such as IBD and IBS, diabetes, autoimmune diseases, neurological disorders, mental wellbeing and malignancies (for the English translated questionnaire see Data S1). The selected questions were taken from validated Rome III questionnaire. The use of medication, antibiotics as well as the patients' willingness to FMT treatment in the future was recorded. The filled questionnaire was returned by 84 patients (64.6%) of which 45 were successfully treated with FMT and 39 with antibiotics. The information for the questionnaires was completed by reviewing patients' medical records and interviewing patients when necessary.

Faecal Microbiota Transplantation Protocol

The patients in the FMT group were all referred to HUS Infectious Diseases Clinic for C. difficile infection that was refractive to standard therapy. Exclusion criteria for FMT included any contraindication for colonoscopy and inadequate mental status or dementia. The screening of the donor and the faecal transplantation process has been previously described.[1,26] Stool was donated by either the patient's relatives, individuals in intimate physical contact with the patient such as their spouse or universal donors. In line with a recent consensus report,[27] the donors were suitable if they had not had antimicrobial treatment in 6 months, did not have any intestinal symptoms, obesity, high risk of sexual behaviour or history of cancer or other severe disease. Donor blood samples tests also included total blood count, C-reactive protein, creatinine and liver enzymes. In case of universal donors, the stool was frozen according the protocol described by Satokari and colleagues.[26]

The patients were treated with vancomycin or metronidazole until a reduction in symptoms occurred. This treatment was discontinued on average 36 hours before the transplantation and the patients performed a bowel cleansing prior the FMT. The procedure was determined as successful if a resolution of symptoms occurred or C. difficile culture and toxin measurements were negative. Two patients received FMT for the second time, 6 or 9 months after their first FMT. One patient mistakenly continued to using antibiotics after the FMT, and another patient received antibiotics for an unrelated infection. In both cases the C. difficile infection recurred after the use of antibiotics, and was resolved by the second FMT, after which the follow-up data were collected.

Statistical Analysis

The collected questionnaire data were analysed by using r (version 3.2.3). The statistical significance of categorical data were determined with Fisher's exact test and the significance of parametric data was determined using analysis of variance (ANOVA) with Tukey-HSD post-hoc test. All P-values below 0.05 were considered to be significant.

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