Clostridium difficile infection (CDI) has steadily increased in incidence since the 1990s, with an associated increase in recurrence and severity, which has in turn lead to more intensive care unit ...(ICU) admissions. The development of recurrent CDI, in particular, has been associated with increasing patient morbidity and mortality as well as an immense financial burden on the health care system. Recently, fecal microbiota transplantation (FMT) has received much publicity as an effective means of treatment for recurrent CDI. The goal of this review is to provide evidence-based recommendations for the diagnosis and management of CDI, with a particular focus on FMT and its utilization in the ICU.
Clostridium difficile and the microbiota Seekatz, Anna M; Young, Vincent B
The Journal of clinical investigation,
10/2014, Letnik:
124, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Clostridium difficile infection (CDI) is the leading health care-associated illness. Both human and animal models have demonstrated the importance of the gut microbiota's capability of providing ...colonization resistance against C. difficile. Risk factors for disease development include antibiotic use, which disrupts the gut microbiota, leading to the loss of colonization resistance and subsequent CDI. Identification of the specific microbes capable of restoring this function remains elusive. Future studies directed at how microbial communities influence the metabolic environment may help elucidate the role of the microbiota in disease development. These findings will improve current biotherapeutics for patients with CDI, particularly those with recurrent disease.
Clostridium difficile is one of the main etiological agents causing antibiotic-associated diarrhea. This study investigated the genetic diversity of 70 toxigenic C. difficile isolates from two Korean ...hospitals by employing toxinotyping, ribotyping, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Toxin gene amplification resulted in 68 A⁺B⁺ and two A-B+ isolates. Most isolates (95.7-100%) were susceptible to daptomycin, metronidazole, and vancomycin. Seventy C. difficile isolates were classified into five toxinotypes, 19 ribotypes, 16 sequence types (STs), and 33 arbitrary pulsotypes. All C. difficile isolates of ribotype 018 (n = 38) were classified into ST17, which was the most prevalent ST in both hospitals. However, C. difficile isolates of ST17 (ribotype 018) exhibited pulsotypes that differed by hospital. ST2 (ribotype 014/020), 8 (ribotypes 002), 17 (ribotype 018), and 35 (ribotypes 015) were detected in both hospitals, whereas other STs were unique to each hospital. Statistical comparison of the different typing methods revealed that ribotyping and PFGE were highly predictive of STs. In conclusion, our epidemiological study indicates that C. difficile infections in both hospitals are associated with the persistence of endemic clones coupled with the emergence of many unique clones. A combination of MLST with PFGE or ribotyping could be useful for monitoring epidemic C. difficile strains and the emergence of new clones in hospitals.
Objective. To evaluate the accuracy of real-time polymerase chain reaction (PCR) for Clostridium difficile–associated disease (CDAD) detection, after hospital CDAD rates significantly increased ...following real-time PCR initiation for CDAD diagnosis.
Design. Hospital-wide surveillance study following examination of CDAD incidence density rates by interrupted time series design.
Setting. Large university-based hospital.
Participants. Hospitalized adult patients.
Methods. CDAD rates were compared before and after real-time PCR implementation in a university hospital and in the absence of physician and infection control practice changes. After real-time PCR introduction, all hospitalized adult patients were screened for C. difficile by testing a fecal specimen by real-time PCR, toxin enzyme-linked immunosorbent assay, and toxigenic culture.
Results. CDAD hospital rates significantly increased after changing from cell culture cytotoxicity assay to a real-time PCR assay. One hundred ninety-nine hospitalized subjects were enrolled, and 101 fecal specimens were collected. C. difficile was detected in 18 subjects (18%), including 5 subjects (28%) with either definite or probable CDAD and 13 patients (72%) with asymptomatic C. difficile colonization.
Conclusions. The majority of healthcare-associated diarrhea is not attributable to CDAD, and the prevalence of asymptomatic C. difficile colonization exceeds CDAD rates in healthcare facilities. PCR detection of asymptomatic C. difficile colonization among patients with non-CDAD diarrhea may be contributing to rising CDAD rates and a significant number of CDAD false positives. PCR may be useful for CDAD screening, but further study is needed to guide interpretation of PCR detection of C. difficile and the value of confirmatory tests. A gold standard CDAD diagnostic assay is needed.
Clostridium difficile infection (CDI) is a major cause of health care-associated infection worldwide, and new preventive strategies are urgently needed. Current control measures do not target ...asymptomatic carriers, despite evidence that they can contaminate the hospital environment and health care workers' hands and potentially transmit C difficile to other patients.
To investigate the effect of detecting and isolating C difficile asymptomatic carriers at hospital admission on the incidence of health care-associated CDI (HA-CDI).
We performed a controlled quasi-experimental study between November 19, 2013, and March 7, 2015, in a Canadian acute care facility. Admission screening was conducted by detecting the tcdB gene by polymerase chain reaction on a rectal swab. Carriers were placed under contact isolation precautions during their hospitalization.
Changes in HA-CDI incidence level and trend during the intervention period (17 periods of 4 weeks each) were compared with the preintervention control period (120 periods of 4 weeks each) by segmented regression analysis and autoregressive integrated moving average (ARIMA) modeling. Concomitant changes in the aggregated HA-CDI incidence at other institutions in Québec City, Québec (n = 6) and the province of Québec (n = 94) were also examined.
Overall, 7599 of 8218 (92.5%) eligible patients were screened, among whom 368 (4.8%) were identified as C difficile carriers. During the intervention, 38 patients (3.0 per 10 000 patient-days) developed an HA-CDI compared with 416 patients (6.9 per 10 000 patient-days) during the preintervention control period (P < .001). There was no immediate change in the level of HA-CDIs on implementation (P = .92), but there was a significant decrease in trend over time of 7% per 4-week period (rate ratio, 0.93; 95% CI, 0.87-0.99 per period; P = .02). ARIMA modeling also detected a significant effect of the intervention, represented by a gradual progressive decrease in the HA-CDI time series by an overall magnitude of 7.2 HA-CDIs per 10 000 patient-days. We estimated that the intervention had prevented 63 of the 101 (62.4%) expected cases. By contrast, no significant decrease in HA-CDI rates occurred in the control groups.
Detecting and isolating C difficile carriers was associated with a significant decrease in the incidence of HA-CDI. If confirmed in subsequent studies, this strategy could help prevent HA-CDI.
Clostridium difficile is a predominant cause of antibiotic-associated diarrhoea. It is increasingly difficult to treat C. difficile infection efficiently owing to its multidrug resistance. In the ...present study, 60 clinical C. difficile isolates were collected and analysed for their genotype, antimicrobial susceptibility and resistance mechanisms. Tandem repeat sequence typing (TRST) generated 21 types, including the epidemic clone tr017. Antimicrobial susceptibility testing of eight antibiotics was performed by the agar dilution method. Rifampicin, metronidazole and vancomycin remained the most potent agents in vitro, whilst the resistance rates of other agents such as ciprofloxacin, cefoxitin, clindamycin, tetracycline and moxifloxacin varied from 30% to 100%. 73.33% of the strains were multiresistant to at least three classes of antibiotics, and tr017 strains made up the greatest proportion of multidrug resistance. By further investigating the resistance mechanisms, amino acid substitutions in target enzymes encoded by gyrA/gyrB and rpoB were observed in fluoroquinolone- and rifampicin-resistant strains, respectively. The erm(B) gene was the most prevalent in macrolide–lincosamide–streptogramin B (MLSB)-resistant strains, and the ErmB determinant ‘Erj2’, a novel genetic organisation identified in this study, plays a central role in conferring resistance, especially in epidemic strains. Moreover, transposon Tn916 carrying the tet(M) gene is more common than Tn5397 in tetracycline resistance.
Background. The National Action Plan to Combat Antibiotic Resistant Bacteria calls for all US hospitals to improve antibiotic prescribing as a key prevention strategy for resistance and clostridium ...difficile. Antibiotic stewardship programs (ASPs) will be important in this effort but implementation is not well understood. Methods. We analyzed the 2014 National Healthcare Safety Network Annual Hospital Survey to describe ASPs in US acute care hospitals as defined by the Center for Disease Control and Prevention's (CDC) Core Elements for Hospital ASPs. Univariate analyses were used to assess stewardship infrastructure and practices by facility characteristics and a multivariate model determined factors associated with meeting all ASP core elements. Results. Among 4184 US hospitals, 39% reported having an ASP that met all 7 core elements. Although hospitals with greater than 200 beds (59%) were more likely to have ASPs, 1 in 4 (25%) of hospitals with less than 50 beds reported achieving all 7 CDC-defined core elements of a comprehensive ASP. The percent of hospitals in each state that reported all seven elements ranged from 7% to 58%. In the multivariate model, written support (adjusted relative risk RR 7.2 95% confidence interval CI, 6.2–8.4; P < .0001) or salary support (adjusted RR 1.5 95% CI, 1.4–1.6; P < .0001) were significantly associated with having a comprehensive ASP. Conclusions. Our findings show that ASP implementation varies across the United States and provide a baseline to monitor progress toward national goals. Comprehensive ASPs can be established in facilities of any size and hospital leadership support for antibiotic stewardship appears to drive the establishment of ASPs.
C. difficile enterocolitis (CDAC) is the most common hospital infection, burdened by an increased incidence of coagulation-related complications such as deep vein thrombosis (DVT) and disseminated ...intravascular coagulation (DIC) as well as a significant sepsis-related mortality. In this review, we analyzed the available data concerning the correlation between coagulation complications related to C. difficile infection (CDI) and inflammasome activation, in particular the pyrin-dependent one. The little but solid available preclinical and clinical evidence shows that inflammasome activation increases the risk of venous thromboembolism (VTE). As proof of this, it has been observed that in vitro inhibition of the molecules (e.g., tissue factor) mainly involved in coagulation activation could block the process. In vivo studies show that it could be possible to reduce the incidence of complications associated with C. difficile infection (CDI) and mortality due to a state of hypercoagulability. A personalized therapeutic approach to reduce the inflammatory activity and prevent thromboembolic complications could be preliminarily defined to reduce mortality.
Probiotics may prevent Clostridium difficile infection (CDI), a leading healthcare-associated infection in the United States. However, prior studies were limited by heterogeneity in products and ...patient populations. Recent clinical evidence and new approaches to probiotic development are reviewed.
Probiotic use may reduce incident CDI in high-risk populations by as much as 50%, though prior clinical trials have yielded conflicting results. Combining probiotics with prebiotics improves growth and engraftment in the host. Bacillus clausii and Lactobacillus reuteri secrete compounds that directly inhibit C. difficile. Organisms that produce secondary bile acids, such as Clostridium scindens, enhance C. difficile colonization resistance. Nontoxigenic C. difficile, which provides nutritional niche competition, may prevent CDI. Refinements to fecal microbiota transplantation (FMT) blur the line between probiotics and FMT. These include a quality-controlled stool product (RBX2660), purified Firmicutes spores (SER-109) and sterile fecal filtrate. Bacteriophages may treat CDI but have unknown safety and efficacy in humans.
There have been a number of advances in probiotics and our understanding of their role in prevention of CDI, but a number of important safety and efficacy questions remain. An improved understanding of the native microbiota structure and function will allow for continued development of rationally designed probiotic therapy to provide enhanced protection against CDI.
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