Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2018; 24(47): 5403-5414
Published online Dec 21, 2018. doi: 10.3748/wjg.v24.i47.5403
Five years of fecal microbiota transplantation - an update of the Israeli experience
Sharon A Greenberg, Ilan Youngster, Nathaniel A Cohen, Dan M Livovsky, Jacob Strahilevitz, Eran Israeli, Ehud Melzer, Kalman Paz, Naomi Fliss-Isakov, Nitsan Maharshak
Sharon A Greenberg, Nathaniel A Cohen, Naomi Fliss-Isakov, Nitsan Maharshak, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
Ilan Youngster, Assaf Harofe Medical Center, Zerifin 70300, Israel
Dan M Livovsky, Kalman Paz, Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel
Jacob Strahilevitz, Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University, Jerusalem 91120, Israel
Eran Israeli, Department of Gastroenterology and Liver Diseases, Hadassah-Hebrew University, Jerusalem 91120, Israel
Ehud Melzer, Gastrointestinal and Liver Diseases Institute, Kaplan Medical Center, Rehovot 76100, Israel
Nitsan Maharshak, Bacteriotherapy Clinic, Tel Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
Author contributions: All authors helped to perform the research; Greenberg SA contributed to collecting data, data analysis and writing the manuscript; Youngster I, Livovsky DM, Melzer E and Paz K contributed to performing procedures and data collection; Cohen NA contributed to data collection and writing the manuscript; Strahilevitz J contributed to data collection; Israeli E contributed to performing procedures; Fliss-Isakov N contributed to data analysis; Maharshak N contributed to drafting conception and design, performing procedures, writing the manuscript and data collection.
Institutional review board statement: This study was approved by the institutional review board of Tel Aviv Sourasky Medical Center.
Informed consent statement: Informed consent was obtained from the patients.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have checked the manuscript according to STROBE checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author to: Nitsan Maharshak, MD, Chief Doctor, Director, Doctor, Senior Lecturer, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv 6423906, Israel.
Telephone: +972-3-6947305 Fax: +972-3-6974184
Received: August 10, 2018
Peer-review started: August 10, 2018
First decision: October 24, 2018
Revised: November 26, 2018
Accepted: December 6, 2018
Article in press: December 6, 2018
Published online: December 21, 2018
Research background

The incidence of Clostridium difficile infection (CDI) is rising, and the increase is associated with significant morbidity and mortality rates. Fecal microbiota transplantation (FMT) is a promising and safe treatment. FMT has been performed in 5 medical centers in Israel since 2013, but its efficacy and safety had not yet been assessed.

Research motivation

To summarize all the FMT procedures performed in Israel for CDI between 2013-2017 and provide a detailed report on its current status, success rates, safety, and modes of administration.

Research objectives

The main objectives were to assess FMT success and failure rates as well as predictors of success with respect to mode of administration.

Research methods

This multi-center retrospective study included all the patients who were treated with FMT for CDI in Israel between January 2013 and October 2017. Clinical data were obtained from medical records, and they included epidemiologic information, risk factors for CDI, Charlson co-morbidity scores, and follow-up information up to 6 mo post-FMT. The Student t test was used for normally distributed variables and the Mann-Whitney U test was applied for non-normally distributed variables. We also used the χ2 test to assess associations among categorical variables. Multivariate logistic regression analysis tested the association between patient and FMT characteristics and successful FMT, controlling for potential confounders.

Research results

A total of 111 CDI patients were included. The median age of the 111 participating patients was 70 years [interquartile range (IQR): 53-82], 47 (42%) of the patients were males, and the median 1-year Charlson comorbidity score for the entire cohort was 6 (IQR: 3-7 points; expected one-year survival of 79% ± 9%). Seventy-eight (70%) of the FMT procedures were performed in an ambulatory setting. FMT was performed through the lower gastrointestinal route (LGI) in 50 patients (45%), followed by capsules in 37 patients (33%), and through the upper GI route (UGI) in 24 patients (22%). A total of 97 (87.4%) patients achieved clinical remission (79% UGI, 88% LGI, and 92% capsules, P = 0.338). Multiple FMT infusions were rare and unsuccessful. The multi-variance analysis revealed that severe disease and inpatient status were independently inversely related to FMT success, with an OR of 0.14 and 0.19, respectively. Patients younger than 60 years (n = 35, 32%) had higher percentages of background inflammatory bowel disease (IBD; 14/35, 40%) compared patients older than 60 years (6/76, 8%, P < 0.01), and waited much longer to undergo the FMT procedure (time between diagnosis of CDI to FMT of 102 d for the older group and 198 d for the younger group, P < 0.05). Eleven patients who died during the study period (no death was attributed to the FMT procedure) were much older (84 years compared with 62 years, P < 0.01), and had higher Charlson comorbidity index scores (8 compared with 4.5, P < 0.01).

Research conclusions

This is the first comprehensive description of the FMT experience in Israel since the procedure was introduced in 2013. This study shows FMT success rates which are similar to other reports worldwide, and provides the information about the efficacy and safety of the procedure, with respect to different administration routes. Predictors of FMT failure were CDI-related (severe disease and inpatient status) but not patient-related (as reflected by the Charlson comorbidity score). Concomitant IBD did not affect clinical outcomes. FMT through capsules was an efficient mode of FMT administration, and emerged as being a safe and well-tolerated alternative to endoscopy.

Research perspectives

FMT is a safe and effective treatment for CDI. The association between severe CDI with higher FMT failure rates raises the need for the future investigation of other approaches. FMT through capsules seems to be at least as good as FMT by means of endoscopies and its potential as a primary route should be investigated.