Screening stool tests: Clostridium difficile toxin B PCR, MC&S, ova, cysts and parasites, Giardia, Cryptosporidium, H pylori antigen. PPI: Not described. Antimotility: Not described. Prokinetics: Not described. Time before CDI treatment was stopped before FMT: 2 days.
Vancomycin 67 (84%), fidaxomicin 23 (29%), rifaximin 13 (16%), metronidazole 55 (69%). sedation for colonoscopic FMT).
orally three times a day for 14 days, then vancomycin 125mg four times a day for 14 days, then fidaxomicin 200mg twice a day for 10 days; for severe disease (defined as AKI, paralytic ileus, or peritoneal fluid), used vancomycin and metronidazole for primary infection, then fidaxomicin if relapse/ failure. Time before CDI treatment was stopped before FMT: Not specified.
Pre-FMT antibiotics: Not defined for non-IBD; for IBD, 15 vancomycin alone, 5 vancomycin and oral metronidazole. Time before CDI treatment was stopped before FMT: No specific deails.
Allegretti et al, Gastroenterology (abstract), 2016 Intervention: Low dose FMT capsules (30 pills once). Number of patients: 10. Female: male: Not stated. Age (mean/median): Not stated. Comparator: High dose FMT. capsules (30 pills daily on two consecutive days). Number of patients: 9. Female: male: Not stated. Age (mean/median): Not stated. Comorbidities: Not stated. CDI features:Not stated. CDI diagnosis confirmation: Not stated. Pre-FMT antibiotics: Not stated. Total follow up period: 8 weeks. Cochrane Collaboration risk of bias assessment: uncertain risk of bias. Donors were unrelated donors from universal stool bank (OpenBiome). Donors working in healthcare: No. Donor demographics: mean age 26, mean BMI 22.2. Donor screening: Questionnaire - as per OpenBiome protocol. Travel and antibiotic exclusion period: As per OpenBiome protocol. Screening bloods: As per OpenBiome protocol. Screening stools: As per OpenBiome protocol. Amount of stool per transplant / administered to patients: 30 pills a day for one day. Diluent used to prepare: Not stated. Diluent used to store if frozen: Stored at -80oC prior to use. Preparation methods: Capsules physically stable for 30 days at 25oC using an emulsion-based production protocol. Time from preparation to transplant (fresh): Not stated. Time period for storage (frozen): Not stated. Route administered: All capsule – as described above. Number of infusions: 30 tablets (over one day). Bowel purgative: Not stated. PPI: Not stated. Antimotility: Not stated. Prokinetics: Not stated. Time before CDI treatment was stopped before FMT: Not stated. Treatment arm: Low dose FMT capsules (30 pills once). Overall cure rate: 70% (n=7/10). Treatment arm: High dose FMT capsules (30 pills daily on two consecutive days). Overall cure rate: 77.8% (n=7/9). Minor GI adverse events: None. Minor non-GI adverse events: None. Serious adverse events: None. Deaths: None.
Cochrane Collaboration risk of bias assessment: uncertain risk of bias. O157, ova and parasites (including general microscopy, acid-fast staining, and/or antigen testing for Giardia, Cryptosporidium, Isospora, and Microsporidia), C difficile, and Helicobacter pylori antigen. loperamide prior to procedure. Prokinetics: Nil. Time before CDI treatment was stopped before FMT: Patients were required to discontinue all antibiotics at least 48 hours prior to the procedure.
Concomitant medications: Stable dose thiopurines, mesalamine, corticosteroids, and anti-TNF allowed as long as stable dose for at least 12 weeks (4 weeks for steroids). Total follow-up period: Up to 12 months. Cochrane Collaboration risk of bias assessment: low risk of bias. and required colectomy. Deaths: None.
E It would be useful to have a standard UK pre and post questionnaire for patients to standardise recording (8.1.2.3) We agree that the introduction of standardised questionnaires would have clear potential advantages for clinical care and/ or research. We now discuss this further in Section 10, ‘further research’. F It may useful to consider measuring the micriobiol strains of donors to monitor the impact of combinations of specific microbial strains to understand the undefined nature of faecal preparations We agree of the importance of this, and this is now discussed in more detail in Section 10, ‘further research’. G The lack of universal definitions of cures (8.1.2.4) is likely to hamper future studies We agree with this comment. Section 10, ‘further research’ has been amended accordingly. Furthermore, we expect that the attention generated by this guideline will highlight this inadequacy. H With the introduction of the clinical term SNOMECT across primary care in 2018 and secondary care in 2020 it is important to record faecal microbiota transplant so that long term sequaelae can be measured and patients can be potentially contacted in the future. We agree that there should be specific procedure codes for FMT (according to route of administration), so that this can be accurately recorded in the patient’s medical record. This would also lay the foundation for a future HRG code and tariff for the procedure which is not currently funded by CCGs. Members of the working group are in discussion with NHS England about this. Closing date: Please forward this electronically by 5pm on January 2018 at the very latest to Healthcare Infection Society Consultation – The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.
We agree. 8.1.2.3. Management of the FMT recipient: Immediate management after endoscopic administration of FMT should be as per endoscopy unit protocol (strong). Patients should be warned about short term adverse events, in particular the possibility of self-limiting GI symptoms. They should be advised that serious adverse events are rare (strong). After enteral tube administration, patients may have the tube removed and oral water given from 30 minutes (strong). We agree. Thank you for this comment. 8.1.2.4. Definition of cure post-FMT for CDI: A decision regarding cure/remission from CDI should be recorded during follow-up. However, this has no uniformly-agreed definition, and should be decided on a case-by-case basis (strong). We agree. Thank you for this comment. 8.1.2.5. Definition of treatment failure for CDI: Treatment failure/recurrence should be defined on a case-by-case basis. Routine testing for C. difficile toxin after FMT is not recommended, but is appropriate to consider in the case of persistent CDI symptoms/suspected relapse (strong). When testing is to be performed, we would recommend clinicians follow the 2016 European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for CDI testing, which state that no single commercial test can be used as a stand-alone test for diagnosing CDI, and recommend a 2-step approach (highly sensitive with reflex to highly specific test). These guidelines recommend performing an initial test with a high negative predicative value; therefore, if negative, no further testing needs to be done. We agree on the use of ESCMID guidelines in CDI testing, and refer to these clearly in Section 8.1.1.1. However, Section 8.1.2.5 specifically refers to diagnosing failure for CDI rather than initial diagnosis of CDI, and no good uniform definition exists for this. We think that the guidance given, to define treatment failure on a basis, is the most fair summary of the current literature on this topic.
The 5D framework: a clinical primer for fecal microbiota transplantation to treat <em>Clostridium difficile</em> infection. Gastrointest Endosc [Internet]. 2017 Jul 26; Available from: http://dx.doi.org/10.1016/j.gie.2017.05.036 8.2.2. Immunosuppression and FMT: FMT should be offered with caution to immunosuppressed patients, in whom FMT appears efficacious without significant additional adverse effects (strong). We agree. Thank you for this comment. 8.2.3. Other and FMT: Recommendation: FMT should be offered to those with recurrent CDI and inflammatory bowel disease (strong). FMT should be considered for appropriate patients with recurrent CDI regardless of other comorbidities (conditional). We agree. Thank you for this comment. 8.3.1. General approach to donor selection: Related or unrelated donors should both be considered acceptable. However, where possible, FMT is best sourced from a centralised stool bank, from a healthy unrelated donor (conditional). We agree. Thank you for this comment. 8.3.2. Age and BMI restrictions for potential donors: People should only be considered as potential FMT donors if they are ≥18 and ≤60 years old, and have a BMI of <30 kg/m2 (conditional). We agree. Thank you for this comment. 8.3.3. General approach to the donor screening assessment: A donor-screening history/ questionnaire is mandatory (Table 2) (strong). Receipt of antimicrobials within the past three months.