Journal of Crohn's and Colitis, 2015, 367 doi:10.1093/ecco-jcc/jjv034 Advanced Access publication February 16, 2015 Letter to the Editor

Letter to the Editor Fecal Microbiota Transplantation for Recurrent C. difficile Infection in a Patient with Chronic Refractory Ulcerative Colitis Annalisa Aratari,aGiovanni Cammarota,b Claudio Papia Gastroenterology and Hepatology Unit, San Filippo Neri Hospital, Rome, Italy bDepartment of Internal Medicine, Gastroenterology Division, Catholic University, Rome, Italy

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Corresponding author: Claudio Papi, UOC Gastroenterologia & Epatologia, Osp. S Filippo Neri, via Martinotti 20, 00135, Rome, Italy. Tel.: +39 0633063169; Fax: +39 0633062641; E-mail: [email protected]

Fecal microbiota transplantation [FMT] is a strategy that restores the diversity of the gut microflora, which may confer protection against toxigenic Clostridium difficile infection. FMT holds considerable promise as a therapy for recurrent C.  difficile infection [CDI] although randomized controlled trials are lacking.1,2 Conversely, limited efficacy of FMT has been reported in inflammatory bowel disease [IBD].3 Increasing incidence and severity of CDI in IBD patients has been recently reported and immunomodulator use has been suggested as a major risk factor.4 We report the case of a patient with steroid-dependent ulcerative colitis [UC] receiving infliximab [IFX], who developed recurrent CDI which was successfully treated with FMT. A 28-year-old man with 2-year history of left-sided UC received IFX 5 mg/kg induction and maintenance because of steroid dependency and intolerance to thiopurines [fever and arthralgia]. After initial remission, secondary loss of response occurred early after the three-dose induction. IFX dose escalation was attempted but, a few days after the first maintenance infusion at the dose of 10 mg/kg, a severe clinical deterioration occurred: more than 10 bowel movements/day, rectal bleeding, and abdominal pain. Endoscopy showed diffuse erythema, marked friability, and erosions. Enzyme-linked immunosorbent assay [ELISA] testing for C. difficile toxins A and B was positive: a 14-day oral vancomycin course [250 mg qid] was started, with rapid symptom resolution and negative toxin test at the end of treatment. One month later, a few days before the planned second IFX maintenance infusion, symptomatic CDI recurred. The hypervirulent C. difficile strain 027 ribotype was excluded by real-time polymerase chain reaction [PCR] for tcdC nt 117 deletion. IFX was discontinued and fidaxomicin 200 mg bid for 10 days was started. Despite symptomatic improvement, C. difficile toxin was still detected in the stool and a second 10-day course of fidaxomicin was attempted without eradication of CDI.

FMT was then performed. The fecal donor was an healthy unrelated young male with negative screening investigations for hepatitis A, B and C virus, Epstein-Barr virus, cytomegalovirus, and HIV, and negative stool tests for C.  difficile toxin, bacterial pathogens, ova, and parasites. Stools were freshly prepared and a single infusion via colonoscopy was performed using 150 g stool in 500 ml saline solution. Clinical improvement rapidly occurred: C. difficile toxin assay was negative as well as real-time PCR for toxin gene detection. After 20 days from FMT, IFX re-induction was performed [5 mg/kg] and complete clinical remission rapidly occurred. At the fifth IFX infusion, the patient is still in remission, C-reactive protein is normal and C. difficile toxin assay is negative. To our knowledge, this is the first case of FMT performed in Italy for recurrent CDI in a patient with UC. FMT allowed definitive eradication of CDI so that scheduled IFX maintenance could be successfully restored for the underlying chronic steroid-refractory UC.

Conflict of interest None.

References 1 Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013;108:500–8. 2 Cammarota G, Ianiro G, Gasbarrini A. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol 2014;48:693–702. 3 Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: A  systematic review and meta-analysis. J Crohns Colitis 2014;8:156981. 4 Issa M, Vijayapal A, Graham MB, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5:345–51.

Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]

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Fecal microbiota transplantation for recurrent C. difficile infection in a patient with chronic refractory ulcerative colitis.

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