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      Clostridioides difficile therapeutics: guidelines and beyond

      review-article
      ,
      Therapeutic Advances in Infectious Disease
      SAGE Publications
      C. difficile, FMT, guidelines, treatment

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          Abstract

          Clostridioides difficile infection (CDI) has become an increasingly common infection both within and outside of the hospital setting. The management of this infection has been evolving as we learn more about the role of the human microbiota in protecting us from this gastrointestinal opportunist. For many years the focus of treatment had been on eradication of the vegetative, toxin-producing form of the organism, with little regard for its collateral impact on the host’s microbiota or risk of recurrence. With the marked increase in C. difficile disease, and, particularly, recurrent disease in the last decade, new guidelines are more focused on targeting and reducing collateral damage to the colonic microbiota. Immune-based strategies that manipulate the microbiota and provide a humoral response to toxins have now become mainstream. Newer strategies are needed to look beyond simply resolving the primary episode but are focused on delayed outcomes such as cure at 90 days, reduced morbidity and mortality, and patient quality of life. The purpose of this review is to familiarize readers with the most recent evidence-based guidelines for C. difficile management, and to describe the role of newer antimicrobials, immunological-, and microbiota-based therapeutics to prevent recurrence and improve the outcomes of people with CDI.

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          Most cited references56

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          Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

          A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.
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            Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection.

            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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              Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.

              Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use.
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                Author and article information

                Contributors
                Journal
                Ther Adv Infect Dis
                Ther Adv Infect Dis
                TAI
                sptai
                Therapeutic Advances in Infectious Disease
                SAGE Publications (Sage UK: London, England )
                2049-9361
                2049-937X
                13 August 2019
                Jan-Dec 2019
                : 6
                : 2049936119868548
                Affiliations
                [1-2049936119868548]Division of Infectious Diseases, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA
                [2-2049936119868548]Division of Infectious Diseases, Mayo Clinic Arizona, Phoenix, AZ, USA
                Author notes
                Author information
                https://orcid.org/0000-0001-5210-1258
                Article
                10.1177_2049936119868548
                10.1177/2049936119868548
                6693025
                afeafc1b-f691-446a-a554-9da54643ef56
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 6 March 2019
                : 17 July 2019
                Categories
                Review
                Custom metadata
                January-December 2019

                c. difficile,fmt,guidelines,treatment
                c. difficile, fmt, guidelines, treatment

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