Probiotics and Fecal Microbiota Transplant for Primary and Secondary Prevention of Clostridium difficile Infection

Abstract

Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea and is associated with an increased risk of mortality. The use of probiotics and fecal microbiota transplantation (FMT) has been studied to reduce the incidence and severity of this infection, but variable efficacy and safety data have been reported. Probiotics are hypothesized to be effective in the management of CDI through a number of mechanisms that include maintenance of normal gastrointestinal flora, antimicrobial and antitoxin properties, and immunomodulatory effects. Despite promising results in small trials and meta-analyses, prospective, randomized, controlled trials have not demonstrated probiotics to be effective in the primary prevention of C. difficile-associated diarrhea (CDAD). Probiotics may be effective for secondary prevention in patients with recurrent CDI, but guidelines acknowledge the lack of compelling evidence. Trials are limited by the use of varying types of strains, numbers of strains, and doses of probiotics, as well the definitions of CDI and CDAD. FMT has been proposed as a method for restoring gut microbiota and has been shown to significantly increase the rate of cure in patients with recurrent CDI. Current studies have demonstrated minimal adverse effects, with no reports of transmission of infectious diseases; however, the optimal delivery method, sample preparation, and donor selection remain unclear. In this review, findings from recent literature are highlighted, and guideline recommendations for the use of these agents in the primary and secondary prevention of CDI are summarized.

Prevention of Clostridium difficile Infection in Critically Ill Adults

“…One single‐center randomized open‐label study of adults with recurrent CDI demonstrated an 81% CDI cure rate with no relapse at 10 weeks using FMT versus 31% with oral vancomycin . Most studies regarding FMT do not include important details related to contribution of ICU patients, nor is there a comparative study that included FMT as a first‐line prevention strategy . The lack of FMT data for CDI prevention in the ICU is unfortunate because there is a signal of added benefit when implemented early, and gut diversity persists for several months after transplantation .…”

“…The diverse microbiome of a healthy gastrointestinal environment provides colonization resistance against C. difficile and nourishment of endothelial cells by fatty acid production. 59 Disruption of the gut microbiota, typically from antibiotics active against anaerobic bacteria, compromises these defense mechanisms and enables overgrowth of microorganisms that induce diarrhea. The term antibiotic-associated diarrhea describes this common adverse effect of antibiotic treatment (5-30%), with CDI the most notable form of antibiotic-associated diarrhea.…”

“…To address this controversy, one review summarized the published literature describing the utility of probiotics for primary or secondary prevention of CDI and concluded that probiotics in these scenarios cannot be supported. 59 The 2017 SHEA/IDSA CDI guideline made no recommendation related to primary prevention outside of clinical trials due to the lack of conclusive evidence. Regarding secondary prevention, the guideline described the promise of both Saccharomyces boulardii and Lactobacillus species but refrained from making a recommendation.…”

“…59 The lack of FMT data for CDI prevention in the ICU is unfortunate because there is a signal of added benefit when implemented early, and gut diversity persists for several months after transplantation. 11,59 A proof-of-concept study of FMT for primary CDI in Norway was recently conducted, with a phase III trial under way (ClinicalTrials.gov identifier NCT03562741). Whether FMT will be a standard of care for primary or secondary prevention of CDI is unknown.…”

Traditional Chinese Medicine Prescriptions Decrease Diarrhea Rate by Relieving Colonic Inflammation and Ameliorating Caecum Microbiota in Piglets

“…Gut probiotics may be effective for secondary prevention in patients with recurrent Clostridium difficileassociated diarrhea through maintenance of the normal gastrointestinal flora [39]. As reported, Bulleidia could ferment glucose and anti-inflammatory products acetate, lactate, and trace amounts of succinate were the end products of fermentation [40]. A few studies demonstrated that Eubacterium and Bifidobacteria were able to use carbohydrate for the production of short-chain fatty acids, which can inhibit inflammatory responses in the gut [41,42].…”