Systematic Review of Intestinal Microbiota Transplantation (Fecal Bacteriotherapy) for Recurrent Clostridium difficile Infection

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Abstract

Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.

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Effect of antimicrobial agents on the ecological balance of human microflora.

A. Sullivan, C Edlund, C E Nord (2001)

The normal microflora acts as a barrier against colonisation of potentially pathogenic microorganisms and against overgrowth of already present opportunistic microorganisms. Control of growth of opportunistic microorganisms is termed colonisation resistance. Administration of antimicrobial agents, therapeutically or as prophylaxis, causes disturbances in the ecological balance between the host and the normal microflora. Most studies on the impact of antimicrobial agents on normal microflora have been carried out on the intestinal flora. Less is known on the effects on oropharyngeal, skin, and vaginal microflora. Disturbances in the microflora depend on the properties of the agents as well as of the absorption, route of elimination, and possible enzymatic inactivation and/or binding to faecal material of the agents. The clinically most common disturbances in the intestinal microflora are diarrhoea and fungal infections that usually cease after the end of treatment. A well-balanced microflora prevents establishment of resistant microbial strains. By using antimicrobial agents that do not disturb colonisation resistance, the risk of emergence and spread of resistant strains between patients and dissemination of resistant determinants between microorganisms is reduced. In this article, the potential ecological effects of administration of antimicrobial agents on the intestinal, oropharyngeal, and vaginal microflora are summarised. The review is based on clinical studies published during the past 10 years.

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Treatment with monoclonal antibodies against Clostridium difficile toxins.

Israel Lowy, Deborah Molrine, Brett Leav … (2010)

New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection. We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo. Among the 200 patients who were enrolled (101 in the antibody group and 99 in the placebo group), the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies (7% vs. 25%; 95% confidence interval, 7 to 29; P<0.001). The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8% for the antibody group and 32% for the placebo group (P=0.06); among patients with more than one previous episode of C. difficile infection, recurrence rates were 7% and 38%, respectively (P=0.006). The mean duration of the initial hospitalization for inpatients did not differ significantly between the antibody and placebo groups (9.5 and 9.4 days, respectively). At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group (P=0.09). The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection. (ClinicalTrials.gov number, NCT00350298.) 2010 Massachusetts Medical Society

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Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes.

Stuart Johnson (2009)

Episodes of recurrent Clostridium difficile infection (CDI) are difficult to treat for several reasons. Foremost, data are lacking to support any particular treatment strategy. In addition, treatment of recurrent episodes is not always successful, and repeated, prolonged treatment is often necessary. Identification of subgroups at risk for recurrent CDI may aid in diagnosing and treating these patients. Two likely mechanistic factors increasing the risk of recurrent CDI are an inadequate immune response to C. difficile toxins and persistent disruption of the normal colonic flora. Important epidemiologic risk factors include advanced age, continuation of other antibiotics, and prolonged hospital stays. Current guidelines recommend that the first recurrent episode be treated with the same agent (i.e., metronidazole or vancomycin) used for the index episode. However, if the first recurrence is characterized as severe, vancomycin should be used. A reasonable strategy for managing a subsequent episode involves tapering followed by pulsed doses of vancomycin. Other potentially effective strategies for recurrent CDI include vancomycin with adjunctive treatments, such as Saccharomyces boulardii, rifaximin "chaser" therapy after vancomycin, nitazoxanide, fecal transplantation, and intravenous immunoglobulin. New treatment agents that are active against C. difficile, but spare critical components of the normal flora, may decrease the incidence of recurrent CDI.

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Author and article information

Journal

Title: Clinical Infectious Diseases

Publisher: Oxford University Press (OUP)

ISSN (Print): 1058-4838

ISSN (Electronic): 1537-6591

Publication date Created: November 15 2011

Publication date (Print): November 15 2011

Publication date (Electronic): November 15 2011

Volume: 53

Issue: 10

Pages: 994-1002

Article

DOI: 10.1093/cid/cir632

PubMed ID: 22002980

SO-VID: 73b26bd7-7155-4660-b0b4-8b3fc360001d

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