2016Open Forum Infectious DiseasesOpen access

Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infections Using Recipient-Directed Donors Sero-Matched for Latent Viruses: The University of Pittsburgh Medical Center (UPMC) Experience

Scott Curry, Tatiana Bogdanovich, Diana L. Pakstis, Marc Schwartz, David G. Binion

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Abstract

Background. Fecal microbiota transplantation (FMT) is effective for recurrent C. difficile infections (rCDI), but donor-derived infections remain a concern. We report the success rates and seroprevalence of herpes viruses/JC virus among FMT donors and recipients at UPMC, which matches FMT recipients who are seronegative for HSV, CMV, EBV, and JC virus to seronegative donors. Methods. All patients undergoing FMT for rCDI at UPMC were included. Donors were selected by recipients and pre-screened including serostatus for HSV1/2, CMV, EBV, and JC virus within 90 days before FMT; seropositive donors were excluded for seronegative recipients. Unrelated donors were allowed. Route of FMT delivery (colonoscopic versus nasoduodenal (ND) tube) was recipient-selected. FMT doses were prepared in a dedicated laboratory and used within 8 hours of defecation. The primary outcome was any occurrence of diarrhea and C. difficile+ stool testing ≤12 weeks from FMT. Results. Nineteen FMTs were done using 14 donors with 11/12 (92%) successes by ND tube, 6/7 (86%) by colonoscopy (86%) and 17/19 (89%) overall. FMTs were performed at 17–275 days (median 110, mean 106) from recipient evaluation. Recipients had a median age of 68 (range 25–85), 58% female, 2–11 pre-FMT episodes of CDI, and included 4 (21%) solid organ transplant patients. Recipients were seronegative for CMV, EBV, HSV1, HSV2, and JC virus in 10 (53%), 1 (5%), 12 (63%), 17 (89%), and 6 (32%) cases, respectively. Donors had a median age of 35 (range 25–71), 10/14 (71%) had BMI >25 kg/m2, and 1 (7%), 13 (93%), 2 (14%), 0 (0%), and 7 (50%) were seropositive for CMV, EBV, HSV1, HSV2, and JC virus, respectively. Spouses, 1st-degree relatives, 2nd-degree relatives, friends, and unrelated donors were used in 5/19 (26%), 6/19 (32%), 2/19 (11%), 1/19 (5%), and 5/19 (26%) of FMTs, respectively. Diarrhea on the day of FMT occurred in 9/19 (47%) recipients. Only 2 serious adverse events occurred: Candida esophagitis and colectomy, both unrelated to FMT. Conclusion. FMT using HSV1/2, EBV, CMV, and JC virus seromatched donors for seronegative recipients with rCDI is achievable. Success in our experience is comparable to prior studies of FMT for rCDI. Use of frozen stool doses from pre-screened volunteer donors may reduce the time to FMT for patients with rCDI. Disclosures. D. Binion, Merck: Grant Investigator, Grant recipient and Research support. Janssen Biotech: Grant Investigator and Speaker's Bureau, Grant recipient, Research grant and Speaker honorarium. UCB Pharma: Grant Investigator and Speaker's Bureau, Grant recipient, Research grant and Speaker honorarium

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Background. Fecal microbiota transplantation (FMT) is effective for recurrent C. difficile infections (rCDI), but donor-derived infections remain a concern. We report the success rates and seroprevalence of herpes viruses/JC virus among FMT donors and recipients at UPMC, which matches FMT recipients who are seronegative for HSV, CMV, EBV, and JC virus to seronegative donors. Methods. All patients undergoing FMT for rCDI at UPMC were included. Donors were selected by recipients and pre-screened including serostatus for HSV1/2, CMV, EBV, and JC virus within 90 days before FMT; seropositive donors were excluded for seronegative recipients. Unrelated donors were allowed. Route of FMT delivery (colonoscopic versus nasoduodenal (ND) tube) was recipient-selected. FMT doses were prepared in a dedicated laboratory and used within 8 hours of defecation. The primary outcome was any occurrence of diarrhea and C. difficile+ stool testing ≤12 weeks from FMT. Results. Nineteen FMTs were done using 14 donors with 11/12 (92%) successes by ND tube, 6/7 (86%) by colonoscopy (86%) and 17/19 (89%) overall. FMTs were performed at 17–275 days (median 110, mean 106) from recipient evaluation. Recipients had a median age of 68 (range 25–85), 58% female, 2–11 pre-FMT episodes of CDI, and included 4 (21%) solid organ transplant patients. Recipients were seronegative for CMV, EBV, HSV1, HSV2, and JC virus in 10 (53%), 1 (5%), 12 (63%), 17 (89%), and 6 (32%) cases, respectively. Donors had a median age of 35 (range 25–71), 10/14 (71%) had BMI >25 kg/m2, and 1 (7%), 13 (93%), 2 (14%), 0 (0%), and 7 (50%) were seropositive for CMV, EBV, HSV1, HSV2, and JC virus, respectively. Spouses, 1st-degree relatives, 2nd-degree relatives, friends, and unrelated donors were used in 5/19 (26%), 6/19 (32%), 2/19 (11%), 1/19 (5%), and 5/19 (26%) of FMTs, respectively. Diarrhea on the day of FMT occurred in 9/19 (47%) recipients. Only 2 serious adverse events occurred: Candida esophagitis and colectomy, both unrelated to FMT. Conclusion. FMT using HSV1/2, EBV, CMV, and JC virus seromatched donors for seronegative recipients with rCDI is achievable. Success in our experience is comparable to prior studies of FMT for rCDI. Use of frozen stool doses from pre-screened volunteer donors may reduce the time to FMT for patients with rCDI. Disclosures. D. Binion, Merck: Grant Investigator, Grant recipient and Research support. Janssen Biotech: Grant Investigator and Speaker's Bureau, Grant recipient, Research grant and Speaker honorarium. UCB Pharma: Grant Investigator and Speaker's Bureau, Grant recipient, Research grant and Speaker honorarium

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Available abstract

Background. Fecal microbiota transplantation (FMT) is effective for recurrent C. difficile infections (rCDI), but donor-derived infections remain a concern. We report the success rates and seroprevalence of herpes viruses/JC virus among FMT donors and recipients at UPMC, which matches FMT recipients who are seronegative for HSV, CMV, EBV, and JC virus to seronegative donors. Methods. All patients undergoing FMT for rCDI at UPMC were included. Donors were selected by recipients and pre-screened including serostatus for HSV1/2, CMV, EBV, and JC virus within 90 days before FMT; seropositive donors were excluded for seronegative recipients. Unrelated donors were allowed. Route of FMT delivery (colonoscopic versus nasoduodenal (ND) tube) was recipient-selected. FMT doses were prepared in a dedicated laboratory and used within 8 hours of defecation. The primary outcome was any occurrence of diarrhea and C. difficile+ stool testing ≤12 weeks from FMT. Results. Nineteen FMTs were done using 14 donors with 11/12 (92%) successes by ND tube, 6/7 (86%) by colonoscopy (86%) and 17/19 (89%) overall. FMTs were performed at 17–275 days (median 110, mean 106) from recipient evaluation. Recipients had a median age of 68 (range 25–85), 58% female, 2–11 pre-FMT episodes of CDI, and included 4 (21%) solid organ transplant patients. Recipients were seronegative for CMV, EBV, HSV1, HSV2, and JC virus in 10 (53%), 1 (5%), 12 (63%), 17 (89%), and 6 (32%) cases, respectively. Donors had a median age of 35 (range 25–71), 10/14 (71%) had BMI >25 kg/m2, and 1 (7%), 13 (93%), 2 (14%), 0 (0%), and 7 (50%) were seropositive for CMV, EBV, HSV1, HSV2, and JC virus, respectively. Spouses, 1st-degree relatives, 2nd-degree relatives, friends, and unrelated donors were used in 5/19 (26%), 6/19 (32%), 2/19 (11%), 1/19 (5%), and 5/19 (26%) of FMTs, respectively. Diarrhea on the day of FMT occurred in 9/19 (47%) recipients. Only 2 serious adverse events occurred: Candida esophagitis and colectomy, both unrelated to FMT. Conclusion. FMT using HSV1/2, EBV, CMV, and JC virus seromatched donors for seronegative recipients with rCDI is achievable. Success in our experience is comparable to prior studies of FMT for rCDI. Use of frozen stool doses from pre-screened volunteer donors may reduce the time to FMT for patients with rCDI. Disclosures. D. Binion, Merck: Grant Investigator, Grant recipient and Research support. Janssen Biotech: Grant Investigator and Speaker's Bureau, Grant recipient, Research grant and Speaker honorarium. UCB Pharma: Grant Investigator and Speaker's Bureau, Grant recipient, Research grant and Speaker honorarium

Key concepts: Clostridium difficile, Fecal bacteriotherapy, Medicine, C difficile, Feces, Transplantation, Gut flora, Virology

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Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infections Using Recipient-Directed Donors Sero-Matched for Latent Viruses: The University of Pittsburgh Medical Center (UPMC) Experience — Research Paper | ScholarLens