Decreased Diversity of the Fecal Microbiome in Recurrent<i>Clostridium difficile</i>–Associated Diarrhea

Chang, Ju Young; Antonopoulos, Dionysios A.; Kalra, Apoorv; Tonelli, Adriano R.; Khalife, Walid; Schmidt, Thomas M.; Young, Vincent B.

doi:10.1086/525047

Cited by 927 publications

(712 citation statements)

References 14 publications

(22 reference statements)

Supporting

Mentioning

654

Contrasting

Unclassified

Order By: Relevance

“…A study of the colonic microbiota in normal controls, individuals with one episode of CDI and patients with RCDI, showed that those with RCDI had a marked decrease in the diversity of the fl ora compared with the other two groups ( 84 ). Moreover, therapy that puts healthy donor stool into the stomach, small intestine, or colon of patients with RCDI (fecal microbiota transplant (FMT)) has the highest rate of success ( ≥ 90 % ) compared with results of other therapies ( 85 ).…”

Section: Management Of Rcdimentioning

confidence: 99%

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

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,465

1,408

View full text Add to dashboard Cite

Clostridium diffi cile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratifi ed depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mildto-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classifi cation of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI. Am J Gastroenterol 2013; 108:478-498; doi: 10.1038/ajg.2013 12. In patients in whom oral antibiotics cannot reach a segment of the colon, such as with Hartman's pouch, ileostomy, or colon diversion, vancomycin therapy delivered via enema should be added to treatments above until the patient improves. (Conditional recommendation, low-quality evidence)13. The use of anti-peristaltic agents to control diarrhea from confi rmed or suspected CDI should be limited or avoided, as they may obscure symptoms and precipitate complicated disease. Use of anti-peristaltic agents in the setting of CDI must always be accompanied by medical therapy for CDI. (Strong recommendation, low-quality evidence) Management of severe and complicated CDI14. Supportive care should be delivered to all patients and includes intravenous fl uid resuscitation, electrolyte replacement, and pharmacological venous thromboembolism prophylaxis. Furthermore, in the absence of ileus or signifi cant abdominal distention, oral or enteral feeding should be continued. 17. Vancomycin delivered orally (500 mg four times per day) and per rectum (500 mg in a volume of 500 ml four times a day) plus intravenous metronidazole (500 mg three times a day) is the treatment of choice for patients with complicated CDI with ileus or toxic colon and / or signifi cant abdominal distention. (Strong recommendation, low-quality evidence)18. Surgical consult should be obtained in all patients with complicated CDI. Surgical therapy should be considered in patients with any one of the following attributed to CDI: hypotension requiring vasopressor therapy; clinical signs of sepsis and organ dysfunction (renal and pulmonary); mental status changes; white blood cell count ≥ 50,000 cells / μ l, lactate ≥ 5 mmol / l; or failure to improve on medical therapy after 5 days. (Strong recommendation, moderate-quality evidence) Management of recurrent CDI (RCDI)19. The fi rst recurrence of CDI can be treated ...

show abstract

Section: Management Of Rcdimentioning

confidence: 99%

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

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,465

1,408

View full text Add to dashboard Cite

show abstract

“…Recurrent CDI is thought to be the result of an inability of the intestinal microbiota to rehabilitate and re-establish itself after the initial antibiotic insult, thereby rendering the host susceptible to either a relapse with the same C. difficile strain or new re-infection with different strains of C. difficile [32,33]. In the case of the former, a major mechanism for rCDI is believed to be C. difficile spore recrudescence or persistence from the initial infection.…”

Section: Recurrent C Difficile Infection (Rcdi)mentioning

confidence: 99%

“…Our knowledge of the microbial composition of the intestinal microbiota is evolving, largely due to technical advances in metagenomic analyses. Numerous studies have demonstrated decreased intestinal microbial diversity among patients with rCDI compared to those with only one episode of CDI that does not recur [33], and diversity is reduced in patients with primary or rCDI compared to those with asymptomatic colonization [33,37,38]. Other studies have shown lower proportions of the family Clostridiales Incertae Sedis XI in patients who developed CDI compared to those who did not [39][40][41].…”

Section: Recurrent C Difficile Infection (Rcdi)mentioning

confidence: 99%

Recurrent Clostridium difficile infection and the microbiome

2015

View full text Add to dashboard Cite

The diverse and densely populated gastrointestinal microbiota is essential for the regulation of host physiology and immune function. As our knowledge of the composition and function of the intestinal microbiota continues to expand, there is new interest in using these developments to tailor fecal microbiota transplantation (FMT) and microbial ecosystem therapeutics (MET) for a variety of diseases. The potential role of FMT and MET in the treatment of Clostridium difficile infection (CDI)-currently the leading nosocomial gastrointestinal infection-has proven highly effective for recurrent CDI, and has emerged as a paradigm shift in the treatment of this disease. The current review will serve as a summary of the key aspects of CDI, and will introduce the essential framework and challenges of FMT, as is currently practiced. MET represents the progression of conventional bacteriotherapy that fundamentally capitalizes on the restorative properties of intestinal bacterial communities and may be viewed as the culmination of a rationally designed therapeutic modality. As our understanding of the composition and function of the intestinal microbiota evolves, it will likely drive next-generation microbiota therapies for a range of medical conditions, such as inflammatory bowel disease, obesity, and metabolic syndrome.

show abstract

“…Patients with CDI harbour an intestinal microbiota with a characteristic reduced diversity owing to antibiotic use (Chang et al, 2008;Shahinas et al, 2012). We hypothesized that patients with recurrent CDI also show a composition favourable for the overgrowth of C. difficile, lacking specific signature microbes that prevent them to return to a sustainable homeostatic status after infection, resulting in recurrences.…”

Section: Introductionmentioning

confidence: 99%

Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

et al. 2014

View full text Add to dashboard Cite

Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time.Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.

show abstract

Decreased Diversity of the Fecal Microbiome in RecurrentClostridium difficile–Associated Diarrhea

Cited by 927 publications

References 14 publications

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

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

Recurrent Clostridium difficile infection and the microbiome

Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

Contact Info

Product

Resources

About