Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients

A multicenter experience

Yao Wen Cheng, Emmalee Phelps, Vincent Ganapini, Noor Khan, Fangqian Ouyang, Huiping Xu, Sahil Khanna, Raseen Tariq, Rachel J. Friedman-Moraco, Michael H. Woodworth, Tanvi Dhere, Colleen S. Kraft, Dina Kao, Justin Smith, Lien Le, Najwa El-Nachef, Nirmal Kaur, Sree Kowsika, Adam Ehrlich, Michael Smith & 8 others Nasia Safdar, Elizabeth Ann Misch, Jessica R. Allegretti, Ann Flynn, Zain Kassam, Asif Sharfuddin, Raj Vuppalanchi, Monika Fischer

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.

Original languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

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Clostridium Infections
Clostridium difficile
Microbiota
Transplants
Organ Transplantation
Therapeutics
Anti-Bacterial Agents
Fecal Microbiota Transplantation
Transplant Recipients
Diarrhea
Pseudomembranous Enterocolitis
Safety
Bacteremia
Cytomegalovirus
Inflammatory Bowel Diseases

Keywords

  • clinical research/practice
  • complication: infectious
  • immunosuppression/immune modulation
  • infection and infectious agents - bacterial: Clostridium difficile
  • infectious disease
  • intestinal disease: infectious
  • organ transplantation in general
  • patient safety

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients : A multicenter experience. / Cheng, Yao Wen; Phelps, Emmalee; Ganapini, Vincent; Khan, Noor; Ouyang, Fangqian; Xu, Huiping; Khanna, Sahil; Tariq, Raseen; Friedman-Moraco, Rachel J.; Woodworth, Michael H.; Dhere, Tanvi; Kraft, Colleen S.; Kao, Dina; Smith, Justin; Le, Lien; El-Nachef, Najwa; Kaur, Nirmal; Kowsika, Sree; Ehrlich, Adam; Smith, Michael; Safdar, Nasia; Ann Misch, Elizabeth; Allegretti, Jessica R.; Flynn, Ann; Kassam, Zain; Sharfuddin, Asif; Vuppalanchi, Raj; Fischer, Monika.

In: American Journal of Transplantation, 01.01.2018.

Research output: Contribution to journalArticle

Cheng, YW, Phelps, E, Ganapini, V, Khan, N, Ouyang, F, Xu, H, Khanna, S, Tariq, R, Friedman-Moraco, RJ, Woodworth, MH, Dhere, T, Kraft, CS, Kao, D, Smith, J, Le, L, El-Nachef, N, Kaur, N, Kowsika, S, Ehrlich, A, Smith, M, Safdar, N, Ann Misch, E, Allegretti, JR, Flynn, A, Kassam, Z, Sharfuddin, A, Vuppalanchi, R & Fischer, M 2018, 'Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience', American Journal of Transplantation. https://doi.org/10.1111/ajt.15058
Cheng, Yao Wen ; Phelps, Emmalee ; Ganapini, Vincent ; Khan, Noor ; Ouyang, Fangqian ; Xu, Huiping ; Khanna, Sahil ; Tariq, Raseen ; Friedman-Moraco, Rachel J. ; Woodworth, Michael H. ; Dhere, Tanvi ; Kraft, Colleen S. ; Kao, Dina ; Smith, Justin ; Le, Lien ; El-Nachef, Najwa ; Kaur, Nirmal ; Kowsika, Sree ; Ehrlich, Adam ; Smith, Michael ; Safdar, Nasia ; Ann Misch, Elizabeth ; Allegretti, Jessica R. ; Flynn, Ann ; Kassam, Zain ; Sharfuddin, Asif ; Vuppalanchi, Raj ; Fischer, Monika. / Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients : A multicenter experience. In: American Journal of Transplantation. 2018.
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AU - Ganapini, Vincent

AU - Khan, Noor

AU - Ouyang, Fangqian

AU - Xu, Huiping

AU - Khanna, Sahil

AU - Tariq, Raseen

AU - Friedman-Moraco, Rachel J.

AU - Woodworth, Michael H.

AU - Dhere, Tanvi

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AU - Ehrlich, Adam

AU - Smith, Michael

AU - Safdar, Nasia

AU - Ann Misch, Elizabeth

AU - Allegretti, Jessica R.

AU - Flynn, Ann

AU - Kassam, Zain

AU - Sharfuddin, Asif

AU - Vuppalanchi, Raj

AU - Fischer, Monika

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N2 - Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.

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