Risk factors for contagious gastroenteritis in adult patients with diarrhoea in the emergency department - a prospective observational multicentre study.

BACKGROUND: Infectious gastroenteritis is common in the emergency department (ED). Patients infected with either Norovirus or toxigenic Clostridium difficile require special isolation procedures. The aims were to describe the aetiology of infectious gastroenteritis in the ED, evaluate whether current isolation procedures, based on clinical judgement are sufficient, and to identify information that might be used to identify patients requiring isolation. METHODS: Prospective, observational, multicentre study. We collected information on symptoms, vital signs, travel history, the recent use of antibiotics, and infectious contacts and tested faecal samples for Norovirus, C. difficile, and enteropathogenic bacteria. RESULTS: The study enrolled 227 patients, of whom 163 (71%) delivered a faecal sample for Norovirus analysis (13% positive), 171 (74%) for C. difficile (13% positive), and 173 (76%) for enteropathogenic bacteria (16% positive). In total 71% of the patients were isolated using strict precautions, 29% of the isolated patient and 14% of the patients who were not isolated had had a highly contagious GE. Risk factors for Norovirus included frequent vomiting (OR 5.5), recent admission of another patient with Norovirus (OR 2.6), and a short duration of diarrhoea. Risk factors for C. difficile infections included older age (OR 6.0), longer duration of diarrhoea (OR 5.2), mucus in stool (OR 3.5), and previous antibiotic use (OR 23.4). CONCLUSION: Highly contagious GE occurs in » of the GE patients in the EDs, isolation based on clinical judgement is not very efficient. Several risk factors can predict the presence of Norovirus or toxigenic Clostridium difficile. It is uncertain whether this knowledge can improve isolation practices in ED settings. TRIAL REGISTRATION: This study was retrospectively registered in the Clinical Trials Data Base ( NCT02685527 ) and prospectively approved by the Regional Committees on Health Research Ethics for Southern Denmark (project ID S20140200) and Ethics Committee at the Medical Association of Schleswig-Holstein ["Ethikkommission bei der Ärztekammer Schleswig-Holstein", project ID 120/15(I)] and registered with the Danish Data Protection Agency (project ID nr. 2008-58-0035/ 1608).

Wild mice in and around the city of Utrecht, the Netherlands, are carriers of Clostridium difficile but not ESBL-producing Enterobacteriaceae, Salmonella spp. or MRSA.

Mice in buildings are a hygiene hazard because they harbour several zoonoses and animal diseases. The aim of this study was to gather information on specific bacteria in house mice caught in the urban environment. Mice caught in snap traps during pest control activities were collected in and around the city of Utrecht, the Netherlands, during May-June 2014, October-November 2015 and September-November 2016. The gut contents were analysed for ESBL/AmpC-producing Enterobacteriaceae, Salmonella spp., and Clostridium difficile and the buccal cavities were swabbed for methicillin-resistant S. aureus (MRSA). In total, 109 house mice (Mus musculus) and 22 wood mice (Apodemus sylvaticus) were examined. One mouse was found positive for Enterobacter spp. Salmonella spp. and MRSA were not found. Of n = 80 mice, 35·0% carried C. difficile (ribotypes in descending order of frequency: 014/020, 258, 002, 005, 013, 056, 081 and two unknown ribotypes). In conclusion, mouse droppings are a hazard for transmission of C. difficile to humans and their environment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that mice in buildings can carry Clostridium difficile ribotypes that are associated with clinical disease in humans. Whether the mice are the source or whether they picked up these bacteria from the human environment has not been investigated. Either way, mouse droppings in the indoor environment are a hazard for transmission of C. difficile to humans.

Optimal control of vaccination rate in an epidemiological model of Clostridium difficile transmission.

The spore-forming, gram-negative bacteria Clostridium difficile can cause severe intestinal illness. A striking increase in the number of cases of C. difficile infection (CDI) among hospitals has highlighted the need to better understand how to prevent the spread of CDI. In our paper, we modify and update a compartmental model of nosocomial C. difficile transmission to include vaccination. We then apply optimal control theory to determine the time-varying optimal vaccination rate that minimizes a combination of disease prevalence and spread in the hospital population as well as cost, in terms of time and money, associated with vaccination. Various hospital scenarios are considered, such as times of increased antibiotic prescription rate and times of outbreak, to see how such scenarios modify the optimal vaccination rate. By comparing the values of the objective functional with constant vaccination rates to those with time-varying optimal vaccination rates, we illustrate the benefits of time-varying controls.

Clostridium difficile Infection Among US Emergency Department Patients With Diarrhea and No Vomiting.

STUDY OBJECTIVE: The incidence of Clostridium difficile infection has increased and has been observed among persons from the community who have not been exposed to antibiotics or health care settings. Our aims are to determine prevalence of C difficile infection among emergency department (ED) patients with diarrhea and the prevalence among patients without traditional risk factors. METHODS: We conducted a prospective observational study of patients aged 2 years or older with diarrhea (≥3 episodes/24 hours) and no vomiting in 10 US EDs (2010 to 2013). We confirmed C difficile infection by positive stool culture result and toxin assay. C difficile infection risk factors were antibiotic use or overnight health care stay in the previous 3 months or previous C difficile infection. We typed strains with pulsed-field gel electrophoresis. RESULTS: Of 422 participants, median age was 46 years (range 2 to 94 years), with median illness duration of 3.0 days and 43.4% having greater than or equal to 10 episodes of diarrhea during the previous 24 hours. At least one risk factor for C difficile infection was present in 40.8% of participants; 25.9% were receiving antibiotics, 26.9% had health care stay within the previous 3 months, and 3.3% had previous C difficile infection. Forty-three participants (10.2%) had C difficile infection; among these, 24 (55.8%) received antibiotics and 19 (44.2%) had health care exposure; 17 of 43 (39.5%) lacked any risk factor. Among participants without risk factors, C difficile infection prevalence was 6.9%. The most commonly identified North American pulsed-field gel electrophoresis (NAP) strains were NAP type 1 (23.3%) and NAP type 4 (16.3%). CONCLUSION: Among mostly adults presenting to US EDs with diarrhea and no vomiting, C difficile infection accounted for approximately 10%. More than one third of patients with C difficile infection lacked traditional risk factors for the disease. Among participants without traditional risk factors, prevalence of C difficile infection was approximately 7%.

Transmissibility of Clostridium difficile Without Contact Isolation: Results From a Prospective Observational Study With 451 Patients.

Background: Contact precautions are recommended by health authorities in Europe and the United States for patients with Clostridium difficile infection (CDI). Recently, the significance of nosocomial transmission has been challenged by screening on admission studies and whole-genome sequencing, providing evidence for an endogenous source of C. difficile. We discontinued contact precautions for patients with CDI, except for patients infected with hypervirulent ribotypes or with stool incontinence, to determine the rate of transmission. Methods: From January 2004 to December 2013, contacts of each index case with CDI were screened for toxigenic C. difficile by culturing rectal swabs. Transmission was defined as possible if toxigenic C. difficile was detected in contacts, as probable if the identical polymerase chain reaction ribotype was identified in index­contact pairs, and as confirmed if next-generation sequencing (NGS) revealed clonality of strains. Results: Four hundred fifty-one contacts were exposed to 279 index patients nursed in 2-to 4-bed rooms. Toxigenic C. difficile was detected in 6.0% (27/451) after a median contact time of 5 days. Identical ribotypes were identified in 6 index­contact pairs, accounting for probable transmission in 1.3% (6/451). NGS was performed for 4 of 6 pairs with identical strains, and confirmed transmission in 2 contact patients. Conclusions: The rate of transmission of toxigenic, predominantly nonhypervirulent C. difficile, was low and no outbreaks were recorded over a 10-year period after discontinuing contact precautions for patients with CDI who were not severely incontinent and who used dedicated toilets. As contact precautions may lead to lower levels of care, their implementation needs to be balanced against the risk of nosocomial transmission.

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation.

BACKGROUND: Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. METHODS: We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. RESULTS: Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. CONCLUSIONS: CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics.

Bringing the Dynamic Microbiome to Life with Animations.

Our bodies and natural environment contain complex microbial communities, colloquially termed microbiomes. We previously created a web-based application, EMPeror, for visualizing ordinations derived from comparisons of these microbiome communities. We have now improved EMPeror to create interactive animations that connect successive samples to highlight patterns over time.

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology.

Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era.

Antimicrobial Stewardship and Environmental Decontamination for the Control of Clostridium difficile Transmission in Healthcare Settings.

We implement an agent-based model for Clostridium difficile transmission in hospitals that accounts for several processes and individual factors including environmental and antibiotic heterogeneity in order to evaluate the efficacy of various control measures aimed at reducing environmental contamination and mitigating the effects of antibiotic use on transmission. In particular, we account for local contamination levels that contribute to the probability of colonization and we account for both the number and type of antibiotic treatments given to patients. Simulations illustrate the relative efficacy of several strategies for the reduction of nosocomial colonizations and nosocomial diseases.

Nosocomial transmission of Clostridium difficile ribotype 027 in a Chinese hospital, 2012-2014, traced by whole genome sequencing.

BACKGROUND: The rapid spread of Clostridium difficile NAP1/BI/027 (C. difficile 027) has become one of the leading threats of healthcare-associated infections worldwide. However, C. difficile 027 infections have been rarely reported in Asia, particularly in China. RESULTS: In this study, we identified a rare C. difficile bloodstream infection (BSI) from three isolates of a patient during repeated hospital admission. This finding triggered a retrospective epidemiological study to scan all cases and strains emerged from this ward during the past three years. Using medical personnel interviews, medical record reviews and the genomic epidemiology, two outbreaks in 2012 and 2013-2014 were identified. Through using whole genome sequencing, we succeeded to trace the origin of the BSI strain. Surprisingly, we found the genome sequences were similar to C. difficile 027 strain R20291, indicating the occurrence of a rare C. difficile 027 strain in China. Integrated epidemiological investigation and whole genome sequencing of all strains, we constructed a nosocomial transmission map of these two C. difficile 027 outbreaks and traced the origin of the infection. CONCLUSIONS: By genome sequencing, spatio-temporal analysis and field epidemiology investigation, we can estimate their complex transform network and reveal the possible modes of transmission in this ward. Based on their genetic diversity, we can assume that the toilets, bathroom, and janitor's equipment room may be contaminated area, which may be suggested to improve infection control measures in the following health care.

Zoonotic potential of the Clostridium difficile RT078 family in Taiwan.

Clostridium difficile is the major cause of nosocomial diarrhea. We have previously demonstrated that in southern Taiwan, severe C. difficile-associated diarrhea (CDAD) cases were due to the C. difficile RT 126 strain infection, indicating the arrival of an epidemic C. difficile clone in southern Taiwan. RT126 has a close genetic relationship with RT078. However, the RT078 family is the predominant strain of C. difficile in animals worldwide, particularly in swine. In this study, we surveyed C. difficile strains isolated from swine at several farms in Taiwan from August 2011 to March 2015. We found that all swine strains, namely RT078 (32.5%, 37 of 114), RT126 (28.9%, 33 of 114) and RT127 (37.7%, 43 of 114), belonged to the toxigenic RT078 family. All strains had high gyrA mutation rate (57.9%, 66/114), which was linked to quinolone resistance. Notably, Rep-PCR revealed that 3 RT078 animal strains had the same fingerprint as human RT078 clinical isolates; their phylogenic relationship was closely related to the whole gene sequences of tcdB, thus suggesting zoonotic potential for C. difficile infection in Taiwan.

Clostridium difficile in Food and Animals: A Comprehensive Review.

Zoonoses are infections or diseases that can be transmitted between animals and humans through direct contact, close proximity or the environment. Clostridium difficile is ubiquitous in the environment, and the bacterium is able to colonise the intestinal tract of both animals and humans. Since domestic and food animals frequently test positive for toxigenic C. difficile, even without showing any signs of disease, it seems plausible that C. difficile could be zoonotic. Therefore, animals could play an essential role as carriers of the bacterium. In addition, the presence of the spores in different meats, fish, fruits and vegetables suggests a risk of foodborne transmission. This review summarises the current available data on C. difficile in animals and foods, from when the bacterium was first described up to the present.

An Economic Analysis of Strategies to Control Clostridium Difficile Transmission and Infection Using an Agent-Based Simulation Model.

BACKGROUND: A number of strategies exist to reduce Clostridium difficile (C. difficile) transmission. We conducted an economic evaluation of "bundling" these strategies together. METHODS: We constructed an agent-based computer simulation of nosocomial C. difficile transmission and infection in a hospital setting. This model included the following components: interactions between patients and health care workers; room contamination via C. difficile shedding; C. difficile hand carriage and removal via hand hygiene; patient acquisition of C. difficile via contact with contaminated rooms or health care workers; and patient antimicrobial use. Six interventions were introduced alone and "bundled" together: (a) aggressive C. difficile testing; (b) empiric isolation and treatment of symptomatic patients; (c) improved adherence to hand hygiene and (d) contact precautions; (e) improved use of soap and water for hand hygiene; and (f) improved environmental cleaning. Our analysis compared these interventions using values representing 3 different scenarios: (1) base-case (BASE) values that reflect typical hospital practice, (2) intervention (INT) values that represent implementation of hospital-wide efforts to reduce C. diff transmission, and (3) optimal (OPT) values representing the highest expected results from strong adherence to the interventions. Cost parameters for each intervention were obtained from published literature. We performed our analyses assuming low, normal, and high C. difficile importation prevalence and transmissibility of C. difficile. RESULTS: INT levels of the "bundled" intervention were cost-effective at a willingness-to-pay threshold of $100,000/quality-adjusted life-year in all importation prevalence and transmissibility scenarios. OPT levels of intervention were cost-effective for normal and high importation prevalence and transmissibility scenarios. When analyzed separately, hand hygiene compliance, environmental decontamination, and empiric isolation and treatment were the interventions that had the greatest impact on both cost and effectiveness. CONCLUSIONS: A combination of available interventions to prevent CDI is likely to be cost-effective but the cost-effectiveness varies for different levels of intensity of the interventions depending on epidemiological conditions such as C. difficile importation prevalence and transmissibility.

Possible Interplay Between Hospital and Community Transmission of a Novel Clostridium Difficile Sequence Type 295 Recognized by Next-Generation Sequencing.

OBJECTIVE To use next-generation sequencing (NGS) analysis to enhance epidemiological information to identify and resolve a Clostridium difficile outbreak and to evaluate its effectiveness beyond the capacity of current standard PCR ribotyping. METHODS NGS analysis was performed as part of prospective surveillance of all detected C. difficile isolates at a university hospital. An outbreak of a novel C. difficile sequence type (ST)-295 was identified in a hospital and a community hostel for homeless adults. Phylogenetic analysis was performed of all ST-295 and closest ST-2 isolates. Epidemiological details were obtained from hospital records and the public health review of the community hostel. RESULTS We identified 7 patients with C. difficile ST-295 infections between June 2013 and April 2015. Of these patients, 3 had nosocomial exposure to this infection and 3 had possible hostel exposure. Current Society for Healthcare Epidemiology of America (SHEA)- Infectious Diseases Society of America (IDSA) surveillance definitions (2010) were considered in light of our NGS findings. The initial transmission was not detectable using current criteria, because of 16 weeks between ST-295 exposure and symptoms. We included 3 patients with hostel exposure who met surveillance criteria of hospital-acquired infection due to their hospital admissions. CONCLUSION NGS analysis enhanced epidemiological information and helped identify and resolve an outbreak beyond the capacity of standard PCR ribotyping. In this cluster of cases, NGS was used to identify a hostel as the likely source of community-based C. difficile transmission. Infect Control Hosp Epidemiol 2016;37:680-684.

Quantifying Transmission of Clostridium difficile within and outside Healthcare Settings.

To quantify the effect of hospital and community-based transmission and control measures on Clostridium difficile infection (CDI), we constructed a transmission model within and between hospital, community, and long-term care-facility settings. By parameterizing the model from national databases and calibrating it to C. difficile prevalence and CDI incidence, we found that hospitalized patients with CDI transmit C. difficile at a rate 15 (95% CI 7.2-32) times that of asymptomatic patients. Long-term care facility residents transmit at a rate of 27% (95% CI 13%-51%) that of hospitalized patients, and persons in the community at a rate of 0.1% (95% CI 0.062%-0.2%) that of hospitalized patients. Despite lower transmission rates for asymptomatic carriers and community sources, these transmission routes have a substantial effect on hospital-onset CDI because of the larger reservoir of hospitalized carriers and persons in the community. Asymptomatic carriers and community sources should be accounted for when designing and evaluating control interventions.

Mechanisms of hypervirulent Clostridium difficile ribotype 027 displacement of endemic strains: an epidemiological model.

Following rapid, global clonal dominance of hypervirulent ribotypes, Clostridium difficile now constitutes the primary infectious cause of nosocomial diarrhoea. Evidence indicates at least three possible mechanisms of hypervirulence that facilitates the successful invasion of these atypical strains: 1) increased infectiousness relative to endemic strains; 2) increased symptomatic disease rate relative to endemic strains; and 3) an ability to outcompete endemic strains in the host's gut. Stochastic simulations of an infection transmission model demonstrate clear differences between the invasion potentials of C. difficile strains utilising the alternative hypervirulence mechanisms, and provide new evidence that favours certain mechanisms (1 and 2) more than others (3). Additionally, simulations illustrate that direct competition between strains (inside the host's gut) is not a prerequisite for the sudden switching that has been observed in prevailing ribotypes; previously dominant C. difficile strains can be excluded by hypervirulent ribotypes through indirect (exploitative) competition.

Environmental transmission of Clostridium difficile: association between hospital room size and C. difficile Infection.

OBJECTIVE: To evaluate the association between hospital room square footage and acquisition of nosocomial Clostridium difficile infection (CDI). METHODS: A case-control study was conducted at a university hospital during the calendar year of 2011. Case patients were adult inpatients with nosocomial CDI. Control patients were hospitalized patients without CDI and were randomly selected and matched to cases in a 2:1 ratio on the basis of hospital length of stay in 3-day strata. A multivariate model was developed using conditional logistic regression to evaluate risk factors for nosocomial CDI. RESULTS: A total of 75 case patients and 150 control patients were included. On multivariate analyses, greater square footage of the hospital room was associated with a significantly increased risk of acquiring CDI (odds ratio for every 50 ft² increase, 3.00; 95% CI, 1.75-5.16; P<.001). Other factors associated with an increased risk of CDI were location in a single room (odds ratio, 3.43; 95% CI, 1.31-9.05; P=.01), malignant tumor (4.56; 1.82-11.4; P=.001), and receipt of cefepime (2.48; 1.06-5.82; P=.04) or immunosuppressants (6.90; 2.07-23.0; P=.002) within the previous 30 days. CONCLUSIONS: Greater room square footage increased the risk of acquisition of CDI in the hospital setting, likely owing to increased environmental contamination and/or difficulty in effective disinfection. Future studies are needed to determine feasible and effective cleaning protocols based on patient and room characteristics.

Asymptomatic carriers of toxigenic C. difficile in long-term care facilities: a meta-analysis of prevalence and risk factors.

BACKGROUND: The impact of Clostridium difficile colonization in C. difficile infection (CDI) is inadequately explored. As a result, asymptomatic carriage is not considered in the development of infection control policies and the burden of carrier state in long-term care facilities (LTCFs) is unknown. PURPOSE: To explore the epidemiology of C. difficile colonization in LTCFs, identify predisposing factors and describe its impact on healthcare management. DATA SOURCES: PubMed, Embase and Web of Science (up to June 2014) without language restriction, complemented by reference lists of eligible studies. STUDY SELECTION: All studies providing extractable data on the prevalence of toxigenic C. difficile colonization among asymptomatic residents in LTCFs. DATA EXTRACTION: Two authors extracted data independently. STATISTICAL METHODS: The pooled colonization estimates were calculated using the double arcsine methodology and reported along with their 95% random-effects confidence intervals (CIs), using DerSimonian-Laird weights. We assessed the impact of patient-level covariates on the risk of colonization and effects were reported as odds ratios (OR, 95% CI). We used the colonization estimates to simulate the effective reproduction number R through a Monte Carlo technique. RESULTS: Based on data from 9 eligible studies that met the specified criteria and included 1,371 subjects, we found that 14.8% (95%CI 7.6%-24.0%) of LTCF residents are asymptomatic carriers of toxigenic C. difficile. Colonization estimates were significantly higher in facilities with prior CDI outbreak (30.1% vs. 6.5%, p = 0.01). Patient history of CDI (OR 6.07; 95% CI 2.06-17.88; effect derived from 3 studies), prior hospitalization (OR 2.11; 95% CI 1.08-4.13; derived from 3 studies) and antimicrobial use within previous 3 months (OR 3.68; 95% CI 2.04-6.62; derived from 4 studies) were associated with colonization. The predicted colonization rate at admission was 8.9%. CONCLUSION: Asymptomatic carriage of toxigenic C. difficile represents a significant burden in LTCFs and is associated with prior CDI outbreaks in the facility, a history of CDI, prior hospitalization and antimicrobial use. These findings can impact infection control measures at LTCFs.