Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this "organ" has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.

Gut Microbiota in Health and Disease

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.

/pdf/clinical-practice-guidelines-for-clostridium-difficile-4hs0j01jnf.pdf

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)

https://www.themedlab.com/wp-content/uploads/2014/01/ACG_Guideline_Cdifficile_April_2013.pdf

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)60002-1/pdf

European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for 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.

Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection.

Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD. In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; ). No serious adverse reactions were observed in these patients. ComP p .05

The Search for a Better Treatment for Recurrent Clostridium difficile Disease: Use of High-Dose Vancomycin Combined with Saccharomyces boulardii

Clostridium difficile is the leading cause of nosocomial gastrointestinal illness in adult patients in hospitals. Even though C. difficile disease in adults has been well studied, research on pediatric C. difficile disease is still in its infancy. For many years it has been believed that C. difficile was a disease that affected only adults and was not a problem for children. This erroneous belief arose from the observation that neonates acquire C. difficile quickly (within 48 hours of birth) but show no intestinal symptoms (1–4). More recent evidence has been documented in case reports of pediatric C. difficile and outbreaks of C. difficile disease in pediatric populations (5– 7). Pediatric C. difficile disease has also been associated with the occurrence of severe complications and high mortality rates (8–10). The cascade of events in the pathogenesis of C. difficile disease is similar in children and adults. Normal intestinal microflora are disrupted by antibiotic exposure, medications, or surgery. If the child is then exposed to C. difficile (or its spores), colonization may occur, with production of toxins A and B. These toxins act on enterocytes, causing an inflammatory response and morphologic changes that lead to diarrhea or colitis. Host factors (age, diet, immune response) play an important role in determining whether C. difficile develops into asymptomatic carriage or active disease. Treatment for pediatric C. difficile disease usually relies on metronidazole or vancomycin, but clinical guidelines have not been defined for the pediatric population (11). As in adults, recurrent C. difficile disease that does not respond to conventional therapy develops in a proportion of children treated with antibiotic therapy.

Sally A. Brandmarker

Papers

The Search for a Better Treatment for Recurrent Clostridium difficile Disease: Use of High-Dose Vancomycin Combined with Saccharomyces boulardii

Pediatric Clostridium difficile: a phantom menace or clinical reality?

Invited Review Pediatric Clostridium difficile: A Phantom Menace or Clinical Reality?