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Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic ReviewFecal Microbiota Transplantation for Clostridium difficile Infection

Dimitri Drekonja, MD, MS; Jon Reich, MD; Selome Gezahegn, MD; Nancy Greer, PhD; Aasma Shaukat, MD, MPH; Roderick MacDonald, MS; Indy Rutks, BS; and Timothy J. Wilt, MD, MPH
[+] Article, Author, and Disclosure Information

From Center for Chronic Disease Outcomes Research, Minneapolis Veterans Affairs Health Care System, and University of Minnesota School of Medicine, Minneapolis, Minnesota.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs or the U.S. government.

Grant Support: By the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

Disclosures: Dr. Drekonja reports grants under review from the U.S. Department of Veterans Affairs (VA) Cooperative Studies Program and personal fees from Rebiotix during the conduct of the study. Dr. Shaukat reports grants from the VA Office of Research and Development during the conduct of the study. Dr. Greer reports grants from the VA Office of Research and Development Quality Enhancement Research Initiative during the conduct of the study. Mr. MacDonald reports grants from the VA Office of Research and Development Quality Enhancement Research Initiative during the conduct of the study. Dr. Wilt reports funding from the VA Evidence Synthesis Program to conduct this review and that he is the Minneapolis Evidence Synthesis Program director and principal contract recipient. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2693.

Requests for Single Reprints: Dimitri Drekonja, MD, MS, Minneapolis Veterans Affairs Health Care System, 1 Veterans Drive, Mail Code 111-F, Minneapolis, MN 55417; e-mail, drek0002@umn.edu.

Current Author Addresses: Dr. Drekonja: Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Mail Code 111-F, Minneapolis, MN 55417.

Drs. Reich and Shaukat: Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Mail Code 111-D, Minneapolis, MN 55417.

Dr. Gezahegn: Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Mail Code 111, Minneapolis, MN 55417.

Dr. Greer: Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Mail Code 152, Minneapolis, MN 55417.

Mr. MacDonald: Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Mail Code 151, Minneapolis, MN 55417.

Mr. Rutks: Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Mail Code 151/152, Minneapolis, MN 55417.

Dr. Wilt: Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Mail Code 111-O, Minneapolis, MN 55417.

Author Contributions: Conception and design: D. Drekonja, S. Gezahegn, N. Greer, A. Shaukat, T.J. Wilt.

Analysis and interpretation of the data: D. Drekonja, J. Reich, S. Gezahegn, N. Greer, A. Shaukat, R. MacDonald, T.J. Wilt.

Drafting of the article: D. Drekonja, J. Reich, A. Shaukat.

Critical revision of the article for important intellectual content: D. Drekonja, S. Gezahegn, N. Greer, A. Shaukat, T.J. Wilt.

Final approval of the article: D. Drekonja, S. Gezahegn, N. Greer, A. Shaukat, I. Rutks, T.J. Wilt.

Provision of study materials or patients: N. Greer, I. Rutks.

Statistical expertise: R. MacDonald, T.J. Wilt.

Obtaining of funding: T.J. Wilt.

Administrative, technical, or logistic support: N. Greer, I. Rutks, T.J. Wilt.

Collection and assembly of data: D. Drekonja, J. Reich, S. Gezahegn, N. Greer, A. Shaukat, R. MacDonald, I. Rutks.


Ann Intern Med. 2015;162(9):630-638. doi:10.7326/M14-2693
Text Size: A A A

Background: The role of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is not well-known.

Purpose: To assess the efficacy, comparative effectiveness, and harms of FMT for CDI.

Data Sources: MEDLINE (1980 to January 2015), Cochrane Library, and ClinicalTrials.gov, followed by hand-searching references from systematic reviews and identified studies.

Study Selection: Any study of FMT to treat adult patients with CDI; case reports were only used to report harms.

Data Extraction: Data were extracted by 1 author and verified by another; 2 authors independently assessed risk of bias and strength of evidence.

Data Synthesis: Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. A high proportion of treated patients had symptom resolution; however, the role of previous antimicrobials is unclear. One RCT comparing FMT with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and 23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively (P < 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20) reported no difference between groups (60% in the nasogastric tube group and 80% in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases. In 7 case-series studies of patients with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients treated with FMT for initial CDI, results were mixed.

Limitation: Most studies were uncontrolled case-series studies; only 2 RCTs were available for analysis.

Conclusion: Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT for refractory or initial CDI treatment and on whether effects vary by donor, preparation, or delivery method.

Primary Funding Source: U.S. Department of Veterans Affairs.

Figures

Grahic Jump Location
Figure.

Summary of evidence search and selection.

CDI = Clostridium difficile infection; FMT = fecal microbiota transplantation; RCT = randomized, controlled trial.

* Included 1 RCT.

Grahic Jump Location

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Fecal microbiota transplantation for C. difficile infection: better to cast a glance?
Posted on May 14, 2015
Giovanni Cammarota, Gianluca Ianiro
Department of Internal Medicine and Gastroenterology, Catholic University, A. Gemelli Hospital, Rome, Italy. E-mail address: gcammarota@rm.unicatt.it
Conflict of Interest: None Declared
Dear Sir,
we have read with interest the sistematic review by Drekonja et al (1) about the efficacy of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI). As not did before, authors focused on the role of FMT not only for recurrent CDI but also for initial and refractory disease.
We were impressed by the 55% overall success rate of FMT for refractory disease. These results, although higher than those of standard medical therapy, are extremely far from the excellent (85%) resolution rates achieved by FMT for recurrent disease. Since recurrences may lead the patient to the risk of severe complications and the need for surgery by themselves (2), such a disparity cannot be explained only by the burdensome nature of refractory disease.
After going over the subgroup of patients with refractory disease reviewed by authors, two main findings came out. First, studies reporting disease activity included only patients with severe CDI. This is not unexpected, since resistance to therapies leads to the clinical progression of the disease, and refractory CDI often arises as a severe disease (3). More strikingly, the overall 55% resolution rate achieved by single-infusion FMT raised to 87% when multiple infusions were administered.
Recently, we did a randomized controlled trial comparing colonoscopic FMT with standard vancomycin regimen for recurrent CDI (4). During the colonoscopy, we diagnosed pseudomembranous colitis (PMC) in 7 of the 20 patients in the FMT arm (35%). After the failure of a single infusion in the first 2 of them, we decided to provide repeated infusions every 3 days to all subsequent subjects with PMC and observed a progressive, terrific disappearance of pseudomembranes and clinical resolution of the disease in the further 5 patients.
Although colonoscopy may be riskier and more expensive than other routes, it allows the identification of PMC, which is indicative of severe CDI. According to our and the above mentioned evidences, it is plausible that severe CDI may benefit by sustained and repeated infusions to be resolved. From this point of view, therefore, colonoscopic FMT appears not only to provide slightly higher resolution rates than other routes (5), but, more than anything, to have the potential to drive the therapeutic strategy against the disease. If managed with adequate expertise, colonoscopic FMT may be a step ahead of other routes, and its dissemination is warranted for a better management of CDI.

References
1. Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, et al. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015;162:630-8. [PMID: 25938992] doi: 10.7326/M14-2693.
2. Kelly CP, LaMont JT. Clostridium difficile – more difficult than ever. N Engl J Med. 2008;359:1932–40. [PMID: 18971494] doi: 10.1056/NEJMra0707500.
3. Surawicz CM, Alexander J. Treatment of refractory and recurrent Clostridium difficile infection. Nat Rev Gastroenterol Hepatol. 2011;8:330-9. [PMID: 21502971] doi: 10.1038/nrgastro.2011.59
4. Cammarota G, Masucci L, Ianiro G, Bibbò S, Dinoi G, Costamagna G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015;41:835-43. PMID: [25728808] doi: 10.1111/apt.13144.
5. 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. PMID: 25340496] doi: 10.1097/MD.0000000000000097.
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