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Concept: Clostridium


In 1958, doctors in Denver administered feces by enema to their patients with fulminant, life-threatening pseudomembranous enterocolitis.(1) The goal of this infusion of donor feces (also termed fecal microbiota transplantation [FMT]) was to “re-establish the balance of nature” within the intestinal flora to correct the disruption caused by antibiotic treatment. They reported “immediate and dramatic” responses and concluded that “this simple yet rational therapeutic method should be given more extensive clinical evaluation.” During the ensuing 50 years, the association between Clostridium difficile infection and pseudomembranous enterocolitis was established, and effective antimicrobial treatments were identified. Despite these advances, C. difficile became . . .

Concepts: Bacteria, Gut flora, Antibiotic, Metronidazole, Probiotic, Clostridium difficile, Pseudomembranous colitis, Clostridium


To the Editor: Lessa et al. (Feb. 26 issue)(1) estimate the incidence of community-acquired Clostridium difficile infection at 30 to 120 cases per 100,000 persons per year in the United States. The investigators used active laboratory surveillance without correction for underestimation. We recently estimated the true incidence of C. difficile infection in the Netherlands in the community by testing 12,714 submitted stool samples for C. difficile regardless of whether such a report was requested by physicians.(2) After correction for cases in which the patient did not visit a general practitioner or that were not diagnosed owing to the lack of . . .

Concepts: Gut flora, European Union, Infection, United States, Poverty in the United States, Clostridium difficile, Clostridium, Clostridia


Background The magnitude and scope of Clostridium difficile infection in the United States continue to evolve. Methods In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥1 year of age). Cases were classified as community-associated or health care-associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection. Results A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care-associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care-associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001) Conclusions C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.).

Concepts: Epidemiology, Disease, Infection, United States, Incidence, Prevalence, Clostridium difficile, Clostridium


Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI) develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.

Concepts: Bacteria, Gut flora, Microbiology, Infection, Antibiotic resistance, Vancomycin, Clostridium difficile, Clostridium


We have isolated Clostridium perfringens type B, an epsilon toxin-secreting bacillus, from a young woman at clinical presentation of Multiple Sclerosis (MS) with actively enhancing lesions on brain MRI. This finding represents the first time that C. perfringens type B has been detected in a human. Epsilon toxin’s tropism for the blood-brain barrier (BBB) and binding to oligodendrocytes/myelin makes it a provocative candidate for nascent lesion formation in MS. We examined a well-characterized population of MS patients and healthy controls for carriage of C. perfringens toxinotypes in the gastrointestinal tract. The human commensal Clostridium perfringens type A was present in approximately 50% of healthy human controls compared to only 23% in MS patients. We examined sera and CSF obtained from two tissue banks and found that immunoreactivity to ETX is 10 times more prevalent in people with MS than in healthy controls, indicating prior exposure to ETX in the MS population. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation since these lesions are characterized by BBB permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate.

Concepts: Magnetic resonance imaging, Multiple sclerosis, Cerebrospinal fluid, Gram positive bacteria, Clostridium, Clostridium perfringens, Gas gangrene, Clostridia


IMPORTANCE Health care-associated infections (HAIs) account for a large proportion of the harms caused by health care and are associated with high costs. Better evaluation of the costs of these infections could help providers and payers to justify investing in prevention. OBJECTIVE To estimate costs associated with the most significant and targetable HAIs. DATA SOURCES For estimation of attributable costs, we conducted a systematic review of the literature using PubMed for the years 1986 through April 2013. For HAI incidence estimates, we used the National Healthcare Safety Network of the Centers for Disease Control and Prevention (CDC). STUDY SELECTION Studies performed outside the United States were excluded. Inclusion criteria included a robust method of comparison using a matched control group or an appropriate regression strategy, generalizable populations typical of inpatient wards and critical care units, methodologic consistency with CDC definitions, and soundness of handling economic outcomes. DATA EXTRACTION AND SYNTHESIS Three review cycles were completed, with the final iteration carried out from July 2011 to April 2013. Selected publications underwent a secondary review by the research team. MAIN OUTCOMES AND MEASURES Costs, inflated to 2012 US dollars. RESULTS Using Monte Carlo simulation, we generated point estimates and 95% CIs for attributable costs and length of hospital stay. On a per-case basis, central line-associated bloodstream infections were found to be the most costly HAIs at $45 814 (95% CI, $30 919-$65 245), followed by ventilator-associated pneumonia at $40 144 (95% CI, $36 286-$44 220), surgical site infections at $20 785 (95% CI, $18 902-$22 667), Clostridium difficile infection at $11 285 (95% CI, $9118-$13 574), and catheter-associated urinary tract infections at $896 (95% CI, $603-$1189). The total annual costs for the 5 major infections were $9.8 billion (95% CI, $8.3-$11.5 billion), with surgical site infections contributing the most to overall costs (33.7% of the total), followed by ventilator-associated pneumonia (31.6%), central line-associated bloodstream infections (18.9%), C difficile infections (15.4%), and catheter-associated urinary tract infections (<1%). CONCLUSIONS AND RELEVANCE While quality improvement initiatives have decreased HAI incidence and costs, much more remains to be done. As hospitals realize savings from prevention of these complications under payment reforms, they may be more likely to invest in such strategies.

Concepts: Health care, Kidney, Medicine, Nosocomial infection, Urinary tract infection, Infection, Clostridium difficile, Clostridium


The use of glyphosate modifies the environment which stresses the living microorganisms. The aim of the present study was to determine the real impact of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro. The presented results evidence that the highly pathogenic bacteria as Salmonella Entritidis, Salmonella Gallinarum, Salmonella Typhimurium, Clostridium perfringens and Clostridium botulinum are highly resistant to glyphosate. However, most of beneficial bacteria as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lactobacillus spp. were found to be moderate to highly susceptible. Also Campylobacter spp. were found to be susceptible to glyphosate. A reduction of beneficial bacteria in the gastrointestinal tract microbiota by ingestion of glyphosate could disturb the normal gut bacterial community. Also, the toxicity of glyphosate to the most prevalent Enterococcus spp. could be a significant predisposing factor that is associated with the increase in C. botulinum-mediated diseases by suppressing the antagonistic effect of these bacteria on clostridia.

Concepts: Bacteria, Gut flora, Microbiology, Pathogen, Enterococcus, Clostridium, Firmicutes, Clostridium botulinum


Diagnosis of Clostridium difficile infection is controversial because of many laboratory methods, compounded by two reference methods. Cytotoxigenic culture detects toxigenic C difficile and gives a positive result more frequently (eg, because of colonisation, which means that individuals can have the bacterium but no free toxin) than does the cytotoxin assay, which detects preformed toxin in faeces. We aimed to validate the reference methods according to clinical outcomes and to derive an optimum laboratory diagnostic algorithm for C difficile infection.

Concepts: Bacteria, Gut flora, Infection, Antibiotic resistance, Clostridium difficile, Diarrhea, Clostridium, Clostridia


Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.

Concepts: Medicine, Clinical trial, Gut flora, Clinical research, Implementation, Probiotic, Clostridium difficile, Clostridium


The incidence, severity, and associated costs of Clostridium difficile (C. difficile) infection (CDI) have dramatically increased in hospitals over the past decade, indicating an urgent need for strategies to prevent transmission of C. difficile. This article describes a multifaceted collaborative approach to reduce hospital-onset CDI rates in 35 acute care hospitals in the New York metropolitan region. Hospitals participated in a comprehensive CDI reduction intervention and formed interdisciplinary teams to coordinate their efforts. Standardized clinical infection prevention and environmental cleaning protocols were implemented and monitored using checklists. Monthly data reports were provided to hospitals for facility-specific performance evaluation and comparison to aggregate data from all participants. Hospitals also participated in monthly teleconferences to review data and highlight successes, challenges, and strategies to reduce CDI. Incidence of hospital-onset CDI per 10,000 patient days was the primary outcome measure. Additionally, the incidence of nonhospital-associated, community-onset, hospital-associated, and recurrent CDIs were measured. The use of a collaborative model to implement a multifaceted infection prevention strategy was temporally associated with a significant reduction in hospital-onset CDI rates in participating New York metropolitan regional hospitals.

Concepts: Gut flora, Infection, New York City, Clostridium difficile, Clostridium, New York metropolitan area, Clostridia, Amtrak