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1.  A multicenter study of Clostridium difficile infection-related colectomy, 2000–2006 
Background
The incidence of Clostridium difficile infection (CDI) has been increasing. Previous studies report that the number of colectomies for CDI is also rising. Outside of a few notable outbreaks, there are few published data documenting increasing severity of CDI. The specific aims of this multiyear, multicenter study were to assess CDI-related colectomy rates and compare CDI-related colectomy rates by CDI surveillance definition.
Methods
Cases of CDI and patients who underwent colectomy were identified electronically from 5 US tertiary-care centers from July 2000 through June 2006. Chart review was performed to determine if a colectomy was for CDI. Monthly CDI-related colectomy rates were calculated as the number of CDI-related colectomies per 1,000 CDI cases. Data between observational groups were compared using χ2 and Mann-Whitney U tests. Logistic regression was performed to evaluate risk factors for CDI-related colectomy.
Results
8569 cases of CDI were identified and 75 patients had CDI-related colectomy. The overall colectomy rate was 8.7/1,000 CDI cases. The CDI-related colectomy rate ranged from 0 to 23 per 1,000 CDI episodes across hospitals. The colectomy rates for healthcare facility (HCF)-onset CDI was 4.3/1000 CDI cases and 16.5 /1000 CDI cases for community-onset CDI (p <.05). There were significantly more CDI-related colectomies at hospitals B and C (p<.05).
Conclusions
The overall CDI-related colectomy rate was low, and there was no significant change in the CDI-related colectomy rate over time. Onset of disease outside of the study hospital was an independent risk factor for colectomy.
doi:10.1086/665318
PMCID: PMC3657463  PMID: 22476273
2.  Predictors of Clostridium difficile infection severity in patients hospitalised in medical intensive care 
AIM: To describe and analyse factors associated with Clostridium difficile infection (CDI) severity in hospitalised medical intensive care unit patients.
METHODS: We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit (MICU) at a French university hospital. We include patients hospitalised between January 1, 2007 and December 31, 2011. Data on demographics characteristics, past medical history, CDI description was collected. Exposure to risk factors associated with CDI within 8 wk before CDI was recorded, including previous hospitalisation, nursing home residency, antibiotics, antisecretory drugs, and surgical procedures.
RESULTS: All included cases had their first episode of CDI. The mean incidence rate was 12.94 cases/1000 admitted patients, and 14.93, 8.52, 13.24, 19.70, and 8.31 respectively per 1000 admitted patients annually from 2007 to 2011. Median age was 62.9 [interquartile range (IQR) 55.4-72.40] years, and 13 (32.5%) were women. Median length of MICU stay was 14.0 d (IQR 5.0-22.8). In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. The duration of diarrhoea was 13.0 (8.0-19.5) d. In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. Prior to CDI, 38 patients (95.0%) were exposed to antibiotics, and 12 (30%) received at least 4 antibiotics. Fluoroquinolones, 3rd generation cephalosporins, coamoxiclav and tazocillin were prescribed most frequently (65%, 55%, 40% and 37.5%, respectively). The majority of cases were hospital-acquired (n = 36, 90%), with 5 cases (13.9%) being MICU-acquired. Fifteen patients had severe CDI. The crude mortality rate within 30 d after diagnosis was 40% (n = 16), with 9 deaths (9 over 16; 56.3%) related to CDI. Of our 40 patients, 15 (37.5%) had severe CDI. Multivariate logistic regression showed that male gender [odds ratio (OR): 8.45; 95%CI: 1.06-67.16, P = 0.044], rising serum C-reactive protein levels (OR = 1.11; 95%CI: 1.02-1.21, P = 0.021), and previous exposure to fluoroquinolones (OR = 9.29; 95%CI: 1.16-74.284, P = 0.036) were independently associated with severe CDI.
CONCLUSION: We report predictors of severe CDI not dependent on time of assessment. Such factors could help in the development of a quantitative score in ICU’s patients.
doi:10.3748/wjg.v19.i44.8034
PMCID: PMC3848151  PMID: 24307797
Clostridium difficile; Health-care associated infection; Hospital-acquired infection; Intensive care unit; Nosocomial infection; Severe Clostridium difficile infection
3.  Frequent Hospital Readmissions for Clostridium difficile Infection and the Impact on Estimates of Hospital-Associated C. difficile Burden 
Background
Clostridium difficile infection (CDI) is associated with medical care and may cause readmission following hospitalization for any reason. The incidence of readmissions due to CDI is not well known.
Design
Retrospective cohort study of adult inpatients in one county from 2000–2007, using mandatory hospital discharge data.
Setting
All hospitals in Orange County, California
Patients
All adult inpatients readmitted with new-onset Clostridium difficile infection within 12 weeks of discharge.
Measurements
We assessed trends in hospital-associated CDI (HA-CDI) incidence, with and without inclusion of post-discharge CDI (PD-CDI) events resulting in re-hospitalization within 12 weeks of discharge. We measured the effect of including PD-CDI events on hospital-specific CDI incidence, a mandatory reporting measure in California, and on relative hospital ranks by CDI incidence.
Results
From 2000 to 2007, countywide hospital-onset CDI (HO-CDI) incidence increased from 15/10,000 to 22/10,000 admissions. When including PD-CDI events, HA-CDI incidence doubled (29/10,000 in 2000 and 52/10,000 in 2007). Overall, including PD-CDI events resulted in significantly higher hospital-specific CDI incidence, although hospitals had disproportionate amounts of HA-CDI occurring post-discharge. This resulted in substantial shifts in some hospitals’ rankings by CDI incidence. In multivariate models, both HO and PD-CDI were associated with increasing age, higher length of stay, and select comorbidities. Race and Hispanic ethnicity were predictive of PD-CDI but not HO-CDI.
Limitations
PD-CDI incidence may be underestimated since outpatient events were not evaluated. Inaccuracies in claims data may cause under or over-estimation of CDI cases. Whether C. difficile was acquired in the hospital or community post-discharge for PD-CDI is not known.
Conclusions
PD-CDI events associated with re-hospitalization are increasingly common. The majority of HA-CDI cases now may be occurring post-discharge, raising important questions about both accurate reporting and effective prevention strategies. Some risk factors for PD-CDI may be different than those for HO-CDI, allowing additional identification of high-risk groups before discharge.
doi:10.1086/663209
PMCID: PMC3657466  PMID: 22173518
4.  Healthcare Resource Utilization for Recurrent Clostridium difficile Infection in a Large University Hospital in Houston, Texas 
PLoS ONE  2014;9(7):e102848.
Background
There are limited data examining healthcare resource utilization in patients with recurrent Clostridium difficile infection (CDI).
Methods
Patients with CDI at a tertiary-care hospital in Houston, TX, were prospectively enrolled into an observational cohort study. Recurrence was assessed via follow-up phone calls. Patients with one or more recurrence were included in this study. The location at which healthcare was obtained by patients with recurrent CDI was identified along with hospital length of stay. CDI-attributable readmissions, defined as a positive toxin test within 48 hours of admission and a primary CDI diagnosis, were also assessed.
Results
372 primary cases of CDI were identified of whom 64 (17.2%) experienced at least one CDI recurrence. Twelve of 64 patients experienced 18 further episodes of CDI recurrence. Of these 64 patients, 33 (50.8%) patients with recurrent CDI were readmitted of which 6 (18.2%) required ICU care, 29 (45.3%) had outpatient care only, and 2 (3.1%) had an ED visit. Nineteen (55.9%) readmissions were defined as CDI-attributable. For patients with CDI-attributable readmission, the average length of stay was 6±6 days.
Conclusion
Recurrent CDI leads to significant healthcare resource utilization. Methods of reducing the burden of recurrent CDI should be further studied.
doi:10.1371/journal.pone.0102848
PMCID: PMC4109955  PMID: 25057871
5.  Incidence of and risk factors for community-associated Clostridium difficile infection: A nested case-control study 
BMC Infectious Diseases  2011;11:194.
Background
Clostridium difficile is the most common cause of nosocomial infectious diarrhea in the United States. However, recent reports have documented that C. difficile infections (CDIs) are occurring among patients without traditional risk factors. The purpose of this study was to examine the epidemiology of CA-CDI, by estimating the incidence of CA-CDI and HA-CDI, identifying patient-related risk factors for CA-CDI, and describing adverse health outcomes of CA-CDI.
Methods
We conducted a population-based, retrospective, nested, case-control study within the University of Iowa Wellmark Data Repository from January 2004 to December 2007. We identified persons with CDI, determined whether infection was community-associated (CA) or hospital-acquired (HA), and calculated incidence rates. We collected demographic, clinical, and pharmacologic information for CA-CDI cases and controls (i.e., persons without CDI). We used conditional logistic regression to estimate the odds ratios (ORs) for potential risk factors for CA-CDI.
Results
The incidence rates for CA-CDI and HA-CDI were 11.16 and 12.1 cases per 100,000 person-years, respectively. CA-CDI cases were more likely than controls to receive antimicrobials (adjusted OR, 6.09 [95% CI 4.59-8.08]) and gastric acid suppressants (adjusted OR, 2.30 [95% CI 1.56-3.39]) in the 180 days before diagnosis. Controlling for other covariates, increased risk for CA-CDI was associated with use of beta-lactam/beta-lactamase inhibitors, cephalosporins, clindamycin, fluoroquinolones, macrolides, and penicillins. However, 27% of CA-CDI cases did not receive antimicrobials in the 180 days before their diagnoses, and 17% did not have any traditional risk factors for CDI.
Conclusions
Our study documented that the epidemiology of CDI is changing, with CA-CDI occurring in populations not traditionally considered "high-risk" for the disease. Clinicians should consider this diagnosis and obtain appropriate diagnostic testing for outpatients with persistent or severe diarrhea who have even remote antimicrobial exposure.
doi:10.1186/1471-2334-11-194
PMCID: PMC3154181  PMID: 21762504
6.  Characterisation of Clostridium difficile Hospital Ward–Based Transmission Using Extensive Epidemiological Data and Molecular Typing 
PLoS Medicine  2012;9(2):e1001172.
A population-based study in Oxfordshire (UK) hospitals by Sarah Walker and colleagues finds that in an endemic setting with good infection control, ward-based contact cannot account for most new cases of Clostridium difficile infection.
Background
Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea and is endemic in hospitals, hindering the identification of sources and routes of transmission based on shared time and space alone. This may compromise rational control despite costly prevention strategies. This study aimed to investigate ward-based transmission of C. difficile, by subdividing outbreaks into distinct lineages defined by multi-locus sequence typing (MLST).
Methods and Findings
All C. difficile toxin enzyme-immunoassay-positive and culture-positive samples over 2.5 y from a geographically defined population of ∼600,000 persons underwent MLST. Sequence types (STs) were combined with admission and ward movement data from an integrated comprehensive healthcare system incorporating three hospitals (1,700 beds) providing all acute care for the defined geographical population. Networks of cases and potential transmission events were constructed for each ST. Potential infection sources for each case and transmission timescales were defined by prior ward-based contact with other cases sharing the same ST. From 1 September 2007 to 31 March 2010, there were means of 102 tests and 9.4 CDIs per 10,000 overnight stays in inpatients, and 238 tests and 15.7 CDIs per month in outpatients/primary care. In total, 1,276 C. difficile isolates of 69 STs were studied. From MLST, no more than 25% of cases could be linked to a potential ward-based inpatient source, ranging from 37% in renal/transplant, 29% in haematology/oncology, and 28% in acute/elderly medicine to 6% in specialist surgery. Most of the putative transmissions identified occurred shortly (≤1 wk) after the onset of symptoms (141/218, 65%), with few >8 wk (21/218, 10%). Most incubation periods were ≤4 wk (132/218, 61%), with few >12 wk (28/218, 13%). Allowing for persistent ward contamination following ward discharge of a CDI case did not increase the proportion of linked cases after allowing for random meeting of matched controls.
Conclusions
In an endemic setting with well-implemented infection control measures, ward-based contact with symptomatic enzyme-immunoassay-positive patients cannot account for most new CDI cases.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Hospital-acquired infections are common and occur when patients are infected with an organism found in the hospital or health-care environment. Hospital-acquired infections can sometimes cause no symptoms but often lead to illness or even death. A leading hospital-acquired infection is with the anaerobic bacterium Clostridium difficile, which causes gastrointestinal problems, including diarrhea, leading to severe illness and even death, especially in older patients or patients who are already seriously ill. Between 7% and 26% of elderly adult inpatients in hospitals may be asymptomatic carriers of C. difficile, and the spores that are formed by this organism can live outside of the human body for long periods of time and are notoriously resistant to most routine surface-cleaning methods. Following major hospital-associated outbreaks around the world, C. difficile infection has become a prime target for expensive prevention and infection control strategies.
Why Was This Study Done?
Prevention strategies and infection control measures have contributed to reducing the incidence of C. difficile infection, however, to date, there have not been any robust evaluations of the impact of such strategies in reducing the spread of infection at the individual level. In order to implement improved, cost-effective policies, and to work out how to reduce incidence even further, a better understanding of person-to-person spread is crucial, especially as infection with C. difficile depends on a combination of factors, such as antibiotic exposure and host susceptibility. Therefore, the researchers conducted this study to examine in detail the transmission of C. difficile in hospital wards in order to give more insight and information on the nature of person-to-person spread.
What Did the Researchers Do and Find?
The researchers used a population-based study in Oxfordshire, UK, to investigate hospital ward–based transmission of defined C. difficile strains from symptomatic patients by identifying C. difficile infection from routine clinical microbiological samples from 1 September 2007 to 31 March 2010. Throughout this period, Oxfordshire hospitals operated a rigorous infection control policy monitored by infection control staff, in which stool samples for C. difficile testing were taken from admitted patients with persistent diarrhea, and from patients with any diarrhea who were 65 years or older. The researchers tested all stool samples for C. difficile toxins by enzyme immunoassay, cultured positive samples, and genotyped C. difficile isolates by using multi-locus sequence typing (to identify strains, that is, sequence types), and finally, constructed networks of cases and potential transmissions (by tracing contacts for up to 26 weeks) for each sequence type identified.
In order to show which ward-based contacts potentially incorporated direct person-to-person spread and indirect transmission via the environment during shared ward exposure, the researchers analysed links (ward contacts) between the first case (the donor) and the second case (the recipient) for all pairs of cases with the same sequence type. The researchers then calculated the minimum infectious period by measuring the time between the first infected stool sample from the donor and ward contact with the recipient, and calculated the incubation period as the time between this ward contact and the first infected stool sample in the recipient. To reduce the possibility of shared ward contacts occurring by chance, the researchers used patients with negative enzyme immunoassay stool samples as controls to estimate how often such ward contacts reflected actual transmission rather than chance.
Over the study period, almost 30,000 stool samples from almost 15,000 patients were tested for C. difficile, with 4.4% (1,282) found positive for C. difficile in enzyme immunoassay and culture. With genotyping, the researchers identified 69 strains (sequence types) of C. difficile. The researchers found that the majority (66%) of cases of C. difficile infection were not linked to known cases, and only 23% had a credible ward-based donor sharing the same sequence type of C. difficile. Furthermore, the researchers found that most probable transmissions occurred less than one week after the onset of symptoms, with a minority (10%) occurring after eight weeks. Most incubation periods were less than four weeks, but a few (13%) were more than 12 weeks. Importantly, even after allowing for the random meeting of matched controls and for persistent ward contamination, the proportion of linked cases did not increase following ward discharge of a C. difficile infection case.
What Do These Findings Mean?
These findings show that in an endemic setting with well-implemented infection control measures, ward-based contact with symptomatic, enzyme-immunoassay-positive patients cannot account for most new cases of C. difficile infection. Crucially, these findings mean that C. difficile infection might not be effectively controlled by current strategies to prevent person-to-person spread. Although the researchers were able to distinguish different strains of C. difficile, there were insufficient numbers of these different strains to deduce whether the results they obtained might be different if there was a different combination of strain types, that is, if some strains were spreading more in hospitals than others. Finally, in order to determine what other types of control interventions are required to reduce the spread of C. difficile, a better understanding of other routes of transmission and reservoirs of infectivity is needed.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001172.
This study is further discussed in a PLoS Medicine Perspective by Stephan Harbarth and Matthew Samore
The US Centers for Disease Control and Prevention provides information about C. difficile infection, as does the UK Health Protection Agency
The World Health Organization has published a guide for preventing hospital-acquired infections
doi:10.1371/journal.pmed.1001172
PMCID: PMC3274560  PMID: 22346738
7.  Performance of severity of illness classification for Clostridium difficile infection to predict need-for-colectomy or inpatient death 
Background
In current state of practice, disease severity assessment for Clostridium difficile infection (CDI) lacks consensus between different organizations. In the latest guidelines for management of CDI, authors have proposed a new disease severity classification. This classification has been derived from expert opinion and includes previously reported patient related factors that predict unfavorable outcome in CDI.
Objective
To evaluate the performance of new disease severity classification to predict CDI-related colectomy or in-patient deaths.
Methods
This observational study was performed at a 300-bed community hospital catering to a suburban population. All the adult patients discharged during October 2005 through September 2012 and diagnosed with CDI were included in the study. Cases of CDI were identified using the billing database. Demographic and clinical characteristics of CDI cases were extracted from medical chart reviews performed by two physician researchers. Cases were classified as mild-to-moderate, severe, or severe and complicated CDI. Major outcomes measured were in-patient deaths and colectomy attributed to CDI. For risk stratification, each variable of severe and complicated CDI was counted.
Results
In total, 59,897 patients were discharged from our hospital during the study period; 894 of them were diagnosed with CDI. Mean age of CDI cases was 74 years (standard deviation 15 years), 345 (39%) were male, and median length of hospital stay was 7 days (interquartile range 4–13). One hundred ninety-one patients (21%) were classified as mild-to-moderate, 93 patients (10%) as severe, and 610 patients (68%) as severe and complicated. In total, 14 patients underwent colectomy for CDI and 53 patients expired. In 35 of these patients, the cause of death was thought to be CDI. The combined outcome (CDI-related colectomy and/or death in hospital) occurred in 47 patients. None of the patients in mild-to-moderate disease or severe disease had combined outcome. On severe and complicated cases, as the score increased, rate of combined outcome increased significantly (z−12.7, p<0.0001). On plotting receiver-operating curve, the simple variable count had area under the curve of 0.91.
Conclusion
The newly proposed disease severity classification for CDI categorized more than two-thirds of patients as severe and complicated. Increase in number of severe and complicated classifying variables increases the chance of adverse outcomes significantly. Patients meeting only one variable could be potentially treated as a severe case instead of severe and complicated. This data needs to validated prospectively before could be used in clinical practice.
doi:10.3402/jchimp.v4.24711
PMCID: PMC4120135  PMID: 25147642
Clostridium difficile infection; Severity of Illness; Need for colectomy; inpatient mortality
8.  Mortality and Clostridium difficile infection: a review 
Background
Clostridium difficile infection (CDI) is a common cause of diarrhoea in hospitalised patients. Around the world, the incidence and severity of CDI appears to be increasing, particularly in the northern hemisphere. The purpose of this integrative review was to investigate and describe mortality in hospitalised patients with CDI.
Methods
A search of the literature between 1 January 2005 and 30 April 2011 focusing on mortality and CDI in hospitalised patients was conducted using electronic databases. Papers were reviewed and analysed individually and themes were combined using integrative methods.
Results
All cause mortality at 30 days varied from 9% to 38%. Three studies report attributable mortality at 30 days, varying from 5.7% to 6.9%. In hospital mortality ranged from 8% to 37.2%
Conclusion
All cause 30 day mortality appeared to be high, with 15 studies indicating a mortality of 15% or greater. Findings support the notion that CDI is a serious infection and measures to prevent and control CDI are needed. Future studies investigating the mortality of CDI in settings outside of Europe and North America are needed. Similarly, future studies should include data on patient co-morbidities.
doi:10.1186/2047-2994-1-20
PMCID: PMC3533881  PMID: 22958425
Clostridium difficile infection; Clostridium difficile associated diarrhoea; Mortality; Death
9.  Clostridium difficile and inflammatory bowel disease: Role in pathogenesis and implications in treatment 
Clostridium difficile (C. difficile) is the leading cause of antibiotic associated colitis and nosocomial diarrhea. Patients with inflammatory bowel disease (IBD) are at increased risk of developing C. difficile infection (CDI), have worse outcomes of CDI-including higher rates of colectomy and death, and experience higher rates of recurrence. However, it is still not clear whether C. difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment. The burden of CDI has increased dramatically over the past decade, with severe outbreaks described in many countries, which have been attributed to a new and more virulent strain. A parallel rise in the incidence of CDI has been noted in patients with IBD. IBD patients with CDI tend be younger, have less prior antibiotic exposure, and most cases of CDI in these patients represent outpatient acquired infections. The clinical presentation of CDI in these patients can be unique-including diversion colitis, enteritis and pouchitis, and typical findings on colonoscopy are often absent. Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation, and the prognostic implications of CDI in these patients, it is recommended to test all IBD patients hospitalized with a disease flare for C. difficile. Treatment includes general measures such as supportive care and infection control measures. Antibiotic therapy with either oral metronidazole, vancomycin, or the novel antibiotic-fidaxomicin, should be initiated as soon as possible. Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI. The aim of this paper is to review recent data on CDI in IBD: role in pathogenesis, diagnostic methods, optional treatments, and outcomes of these patients.
doi:10.3748/wjg.v19.i43.7577
PMCID: PMC3837256  PMID: 24282348
Clostridium difficile; Diarrhea; Inflammatory bowel disease; Pathogenesis; Treatment
10.  Defining acute renal dysfunction as a criterion for the severity of Clostridium difficile infection in patients with community-onset vs hospital-onset infection 
The Journal of hospital infection  2013;83(4):294-299.
SUMMARY
Background
Acute renal dysfunction can be used to define severe Clostridium difficile infection (CDI). The Society for Healthcare Epidemiology of America (SHEA) and Infectious Disease Society of America (IDSA) guidelines define acute renal dysfunction as serum creatinine (SrCr) ≥1.5 times the premorbid level.
Aim
To determine the ability to assess premorbid SrCr in hospitalized patients with CDI, stratified into community-onset CDI (CO-CDI) and hospital-onset CDI (HO-CDI); and to evaluate differing definitions for premorbid SrCr as a criterion for acute renal dysfunction.
Methods
Hospitalized patients with CDI were stratified into CO-CDI and HO-CDI. The ability to assess premorbid SrCr was determined, and the incidence of acute renal dysfunction and the severity of CDI were compared using varying definitions of premorbid SrCr.
Findings
In total, 293 patients with CDI were evaluated; of these, 135 (46%) had CO-CDI and 158 (54%) had HO-CDI. Premorbid SrCr data were not available for 37 (27%) patients with CO-CDI and one (<1%) patient with HO-CDI (P < 0.0001). Depending on the definition of premorbid SrCr used, acute renal dysfunction ranged from 17% to 24% for patients with CO-CDI (P = 0.26), and from 13% to 14% for HO-CDI (P = 0.81). The severity of CDI could not be determined for 43 out of 293 (15%) patients, primarily due to the lack of premorbid SrCr data (N = 38).
Conclusion
Assessment of acute renal dysfunction and the severity of CDI was not possible for many patients with CO-CDI using the current SHEA/IDSA guidelines. Given the increasing incidence of CO-CDI, an alternative definition of acute renal dysfunction may be required.
doi:10.1016/j.jhin.2012.12.011
PMCID: PMC3984400  PMID: 23433867
Healthcare-associated infections; Guideline development; Severity scoring systems; Clostridium difficile infection
11.  Detection of Clostridium difficile infection clusters, using the temporal scan statistic, in a community hospital in southern Ontario, Canada, 2006–2011 
BMC Infectious Diseases  2014;14:254.
Background
In hospitals, Clostridium difficile infection (CDI) surveillance relies on unvalidated guidelines or threshold criteria to identify outbreaks. This can result in false-positive and -negative cluster alarms. The application of statistical methods to identify and understand CDI clusters may be a useful alternative or complement to standard surveillance techniques. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting CDI clusters and determine if there are significant differences in the rate of CDI cases by month, season, and year in a community hospital.
Methods
Bacteriology reports of patients identified with a CDI from August 2006 to February 2011 were collected. For patients detected with CDI from March 2010 to February 2011, stool specimens were obtained. Clostridium difficile isolates were characterized by ribotyping and investigated for the presence of toxin genes by PCR. CDI clusters were investigated using a retrospective temporal scan test statistic. Statistically significant clusters were compared to known CDI outbreaks within the hospital. A negative binomial regression model was used to identify associations between year, season, month and the rate of CDI cases.
Results
Overall, 86 CDI cases were identified. Eighteen specimens were analyzed and nine ribotypes were classified with ribotype 027 (n = 6) the most prevalent. The temporal scan statistic identified significant CDI clusters at the hospital (n = 5), service (n = 6), and ward (n = 4) levels (P ≤ 0.05). Three clusters were concordant with the one C. difficile outbreak identified by hospital personnel. Two clusters were identified as potential outbreaks. The negative binomial model indicated years 2007–2010 (P ≤ 0.05) had decreased CDI rates compared to 2006 and spring had an increased CDI rate compared to the fall (P = 0.023).
Conclusions
Application of the temporal scan statistic identified several clusters, including potential outbreaks not detected by hospital personnel. The identification of time periods with decreased or increased CDI rates may have been a result of specific hospital events. Understanding the clustering of CDIs can aid in the interpretation of surveillance data and lead to the development of better early detection systems.
doi:10.1186/1471-2334-14-254
PMCID: PMC4030047  PMID: 24885351
Clostridium difficile infection; Temporal scan statistic; Clusters; Community hospital; Ribotype 027
12.  Proton Pump Inhibitors and Risk for Recurrent Clostridium Difficile Infection Among Inpatients 
Objectives
Observational studies suggest that proton pump inhibitors (PPIs) are a risk factor for incident Clostridium difficile infection (CDI). Data also suggest an association between PPIs and recurrent CDI, although large-scale studies focusing solely on hospitalized patients are lacking. We therefore performed a retrospective cohort analysis of inpatients with incident CDI to assess receipt of PPIs as a risk factor for CDI recurrence in this population.
Methods
Using electronic medical records, we identified hospitalized adult patients between December 1, 2009 and June 30, 2012 with incident CDI, defined as a first positive stool test for C. difficile toxin B and who received appropriate treatment. Electronic records were parsed for clinical factors including receipt of PPIs, other acid suppression, non-CDI antibiotics, and comorbidities. The primary exposure was in-hospital PPIs given concurrently with C. difficile treatment. Recurrence was defined as a second positive stool test 15 to 90 days after the initial positive test. C. difficile recurrence rates in the PPI exposed and unexposed groups were compared with the log-rank test. Multivariable Cox proportional hazards modeling was performed to control for demographics, comorbidities, and other clinical factors.
Results
We identified 894 inpatients with incident CDI. The cumulative incidence of CDI recurrence in the cohort was 23%. Receipt of PPIs concurrent with CDI treatment was not associated with C. difficile recurrence (HR 0.82; 95% CI 0.58–1.16). Black race (HR 1.66, 95% CI 1.05–2.63), increased age (HR 1.02, 95% CI 1.01–1.03), and increased comorbidities (HR 1.09, 95% CI 1.04–1.14) were associated with CDI recurrence. In light of a higher 90-day mortality seen among those who received PPIs (log-rank p = 0.02), we also analyzed the subset of patients who survived to 90 days of follow-up. Again, there was no association between PPIs and CDI recurrence (HR 0.87; 95% CI 0.60–1.28). Finally, there was no association between recurrent CDI and increased duration or dose of PPIs.
Conclusions
Among hospitalized adults with C. difficile, receipt of PPIs concurrent with C. difficile treatment was not associated with CDI recurrence. Black race, increased age, and increased comorbidities significantly predicted recurrence. Future studies should test interventions to prevent CDI recurrence among high risk inpatients.
doi:10.1038/ajg.2013.333
PMCID: PMC3966060  PMID: 24060760
13.  Clostridium difficile Infection Is Associated With Increased Risk of Death and Prolonged Hospitalization in Children 
Clostridium difficile infection (CDI) is associated with increased mortality, prolonged hospitalization, and higher costs among a multicenter cohort of hospitalized children matched by important demographic and clinical characteristics. The impact of CDI is most significant among children with hospital-onset disease.
Background Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children.
Methods A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI (propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects.
Results We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2–13 years) for exposed and 8 years (IQR, 3–14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77–12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54–6.56 days) and $18 900 (95% CI, $15 100–$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29–23.90 days) and $93 600 (95% CI, $80 000–$107 200) for HO-CDI.
Conclusions Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children.
doi:10.1093/cid/cit155
PMCID: PMC3669523  PMID: 23532470
C. difficile infection; pediatrics; outcomes; epidemiology
14.  Clostridium difficile Infection in Patients With Chronic Kidney Disease 
Mayo Clinic Proceedings  2012;87(11):1046-1053.
Objective
To examine the rate of Clostridium difficile infection (CDI) and hospital-associated outcomes in a national cohort of hospitalized patients with chronic kidney disease (CKD) and assess the impact of long-term dialysis on outcome in these patients.
Patients and Methods
Data for January 1, 2005, through December 31, 2009 were obtained from the National Hospital Discharge Survey, which includes information on patient demographics, diagnoses, procedures, and discharge types. Data collected and analyzed for this study included age, sex, race, admission type (urgent or emergent combined vs elective), any colectomy diagnosis, length of stay, type of discharge, and mortality. International Classification of Diseases, Ninth Revision, Clinical Modification codes were utilized to identify CKD patients and CDI events. Weighted analysis was performed using JMP version 9.
Results
An estimated 162 million adults were hospitalized during 2005-2009, and 8.03 million (5%) had CKD (median age, 71 years). The CDI rate in CKD patients was 1.49% (0.119 million) compared with 0.70% (1.14 million) in patients without CKD (P<.001). Patients with CKD who were undergoing long-term dialysis were more than 2 times as likely to develop CDI than non-CKD patients and 1.33 times more likely than CKD patients not undergoing dialysis (all P<.001). In a weighted multivariate analysis adjusting for sex and comorbidities, patients with CKD and CDI had longer hospitalization, higher colectomy rate (adjusted odds ratio [aOR], 2.30; 95% confidence interval [CI], 2.14-2.47), dismissal to a health care facility (aOR, 2.22; 95% CI, 2.19-2.25), and increased in-hospital mortality (aOR, 1.55; 95% CI, 1.52-1.59; all P<.001) as compared with CKD patients without CDI. Patients with CKD who were undergoing long-term dialysis did not have worse outcomes as compared with CKD patients who were not undergoing long-term dialysis.
Conclusion
These data suggest that patients with CKD have a higher risk of CDI and increased hospital-associated morbidity and mortality. Future prospective studies are needed to confirm these findings and to identify effective CDI prevention in CKD patients, who appear to have an increased risk of CDI acquisition.
doi:10.1016/j.mayocp.2012.05.025
PMCID: PMC3541867  PMID: 23127731
AKI, acute kidney injury; CDI, Clostridium difficile infection; CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; NHDS, National Hospital Discharge Survey; OR, odds ratio
15.  Risk factors for recurrent Clostridium difficile infection (CDI) hospitalization among hospitalized patients with an initial CDI episode: a retrospective cohort study 
BMC Infectious Diseases  2014;14:306.
Background
Recurrent Clostridium difficile infection (rCDI) is observed in up to 25% of patients with an initial CDI episode (iCDI). We assessed risk factors for rCDI among patients hospitalized with iCDI.
Methods
We performed a retrospective cohort study at Barnes-Jewish Hospital from 1/1/03 to 12/31/09. iCDI was defined as a positive toxin assay for C. difficile with no CDI in previous 60 days, and rCDI as a repeat positive toxin ≤42 days of stopping iCDI treatment. Three demographic, 13 chronic and 12 acute disease characteristics, and 21 processes of care were assessed for association with rCDI. Cox modeling identified independent risk factors for rCDI.
Results
425 (10.1%) of 4,200 patients enrolled developed rCDI. Of the eight risk factors for rCDI on multivariate analyses, the strongest three were 1) high-risk antimicrobials following completion of iCDI treatment (HR 2.95, 95% CI 2.25-3.86), 2) community-onset healthcare-associated iCDI (HR 1.80, 95% CI 1.41-2.29) and 3) fluoroquinolones after completion of iCDI treatment (HR 1.56, 95% CI 1.63-2.08). Other risk factors included gastric acid suppression, ≥2 hospitalizations within prior 60 days, age, and IV vancomycin after iCDI treatment ended.
Conclusions
The rCDI rate was 10.1%. Recognizing such modifiable risk factors as certain antimicrobial treatments and gastric acid suppression may help optimize prevention efforts.
doi:10.1186/1471-2334-14-306
PMCID: PMC4050409  PMID: 24898123
C. difficile; Risk factors; Recurrence
16.  “Outcomes in community–acquired clostridium difficile infection” 
SUMMARY
Background
Community-acquired Clostridium difficile infection (CA-CDI) is an increasingly appreciated condition. It is being described in populations lacking traditional predisposing factors that have been previously considered at low-risk for this infection. As most studies of CDI are hospital-based, outcomes in these patients are not well known.
Aim
To examine outcomes and their predictors in patients with CA-CDI.
Methods
A sub-group analysis of a population-based epidemiological study of CDI in Olmsted County, Minnesota from 1991-2005 was performed. Data regarding outcomes, including severity, treatment response, need for hospitalization and recurrence were analyzed.
Results
Of 157 CA-CDI cases, the median age was 50 years and 75.3% were female. Among all CA-CDI cases, 40% required hospitalization, 20% had severe and 4.4% had severe-complicated infection, 20% had treatment failure and 28% had recurrent CDI. Patients who required hospitalization were significantly older (64 vs 44 years, p<0.001), more likely to have severe disease (33.3% vs 11.7%, p=0.001), and had higher mean Charlson comorbidity index scores (2.06 vs 0.84, p=0.001). They had similar treatment failure and recurrence rates as patients who did not require hospitalization.
Conclusions
CA-CDI can be associated with complications and poor outcomes, including hospitalization and severe CDI. As the incidence of CA-CDI increases, clinicians should be aware of risk factors (increasing age, comorbid conditions and disease severity) that predict the need for hospitalization and complications in patients with CA-CDI.
doi:10.1111/j.1365-2036.2011.04984.x
PMCID: PMC3293482  PMID: 22229532
Clostridium difficile infection; community-acquired; outcomes; predictors of hospitalization
17.  A Time-Series Analysis of Clostridium difficile and Its Seasonal Association with Influenza 
OBJECTIVE
To characterize the temporal progression of the monthly incidence of Clostridium difficile infections (CDIs) and to determine whether the incidence of CDI is related to the incidence of seasonal influenza.
DESIGN
A retrospective study of patients in the Nationwide Inpatient Sample during the period from 1998 through 2005.
METHODS
We identified all hospitalizations with a primary or secondary diagnosis of CDI with use of International Classification of Diseases, 9th Revision, Clinical Modification codes, and we did the same for influenza. The incidence of CDI was modeled as an autoregression about a linear trend. To investigate the association of CDI with influenza, we compared national and regional CDI and influenza series data and calculated cross-correlation functions with data that had been prewhitened (filtered to remove temporal patterns common to both series). To estimate the burden of seasonal CDI, we developed a proportional measure of seasonal CDI.
RESULTS
Time-series analysis of the monthly number of CDI cases reveals a distinct positive linear trend and a clear pattern of seasonal variation (R2 = 0.98). The cross-correlation functions indicate that influenza activity precedes CDI activity on both a national and regional basis. The average burden of seasonal (ie, winter) CDI is 23%.
CONCLUSIONS
The epidemiologic characteristics of CDI follow a pattern that is seasonal and associated with influenza, which is likely due to antimicrobial use during influenza seasons. Approximately 23% of average monthly CDI during the peak 3 winter months could be eliminated if CDI remained at summer levels.
doi:10.1086/651095
PMCID: PMC3024857  PMID: 20175682
18.  Temporal phenome analysis of a large electronic health record cohort enables identification of hospital-acquired complications 
Objective
To develop methods for visual analysis of temporal phenotype data available through electronic health records (EHR).
Materials and methods
24 580 adults from the multiparameter intelligent monitoring in intensive care V.6 (MIMIC II) EHR database of critically ill patients were analyzed, with significant temporal associations visualized as a map of associations between hospital length of stay (LOS) and ICD-9-CM codes. An expanded phenotype, using ICD-9-CM, microbiology, and computerized physician order entry data, was defined for hospital-acquired Clostridium difficile (HA-CDI). LOS, estimated costs, 30-day post-discharge mortality, and antecedent medication provider order entry were evaluated for HA-CDI cases compared to randomly selected controls.
Results
Temporal phenome analysis revealed 191 significant codes (p value, adjusted for false discovery rate, ≤0.05). HA-CDI was identified in 414 cases, and was associated with longer median LOS, 20 versus 9 days, and adjusted HR 0.33 (95% CI 0.28 to 0.39). This prolongation carries an estimated annual incremental cost increase of US$1.2–2.0 billion in the USA alone.
Discussion
Comprehensive EHR data have made large-scale phenome-based analysis feasible. Time-dependent pathological disease states have dynamic phenomic evolution, which may be captured through visual analytical approaches. Although MIMIC II is a single institutional retrospective database, our approach should be portable to other EHR data sources, including prospective ‘learning healthcare systems’. For example, interventions to prevent HA-CDI could be dynamically evaluated using the same techniques.
Conclusions
The new visual analytical method described in this paper led directly to the identification of numerous hospital-acquired conditions, which could be further explored through an expanded phenotype definition.
doi:10.1136/amiajnl-2013-001861
PMCID: PMC3861919  PMID: 23907284
Electronic Health Records; Phenotype; Data Mining; Computing Methodologies; Computer Graphics
19.  Clostridium difficile Infection in Hospitalized Liver Transplant Patients: A Nationwide Analysis 
Liver Transplantation  2012;18(8):972-978.
Introduction
Incidence of Clostridium difficile infection (CDI) is increasing among hospitalized patients. Liver transplant patients are at higher risk for acquiring CDI. Small, single-center studies, but no nation-wide analyses, have assessed this association.
Methods
We used the Healthcare Cost and Utilization Project- Nationwide Inpatient Sample (HCUP-NIS) from years 2004–2008 for this retrospective cross sectional study. Patients with any discharge diagnosis of liver transplant comprised the study population and were identified using ICD-9-CM codes. Those with a discharge diagnosis of CDI were considered cases. Our primary outcomes were prevalence of CDI and effect of CDI on inpatient mortality. Our secondary outcomes included length of stay and hospitalization charges. Regression analysis was used to derive odds ratios adjusted for potential confounders.
Results
There were 193,714 discharges with a diagnosis of liver transplant from 2004–2008. Prevalence of CDI was 2.7% in liver transplant population compared to 0.9% in non liver transplant population (p <0.001). Most of the liver transplant patients were in the 50–64 age group. Liver transplant patients were at higher odds of developing CDI (OR 2.88, 95% CI 2.68–3.10). Increasing age, increasing comorbidity, IBD and NG tube placement were also independent risk factors for CDI. CDI in liver transplant was associated with a higher mortality, 5.5% as compared to 2.3% in liver transplant only population (adjusted OR 1.7, 95% CI 1.3–2.2).
Conclusions
Liver transplant patients have a higher prevalence of CDI as compared to non liver transplant patients (2.7% vs. 0.9%).CDI was an independent risk factor for mortality in liver transplant population.
doi:10.1002/lt.23449
PMCID: PMC3405162  PMID: 22505356
Solid organ transplant; complications; outcomes research; cross sectional
20.  Impact of Clostridium difficile infection on inflammatory bowel disease outcome: A review 
World Journal of Gastroenterology : WJG  2014;20(33):11736-11742.
Although a considerable number of studies support a substantial increase in incidence, severity, and healthcare costs for Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD), only few evaluate its impact on IBD outcome. Medline and several other electronic databases from January 1993 to October 2013 were searched in order to identify potentially relevant literature. Most of the studies showed that IBD patients with CDI present a greater proportion of worse outcomes than those without CDI. These patients have longer length of hospital stay, higher rates of colectomies, and increased mortality. Patients with ulcerative colitis are more susceptible to CDI and have more severe outcomes than those with Crohn’s disease. However, studies reported variable results in both short- and long-term outcomes. Contrasting results were also found between studies using nationwide data and those reporting from single-center, or between some North-American and European studies. An important limitation of all studies analyzed was their retrospective design. Due to contrasting data often provided by retrospective studies, further prospective multi-center studies are necessary to evaluate CDI impact on IBD outcome. Until then, a rapid diagnosis and adequate therapy of infection are of paramount importance to improve IBD patients’ outcome. The aim of this article is to provide up to date information regarding CDI impact on outcome in IBD patients.
doi:10.3748/wjg.v20.i33.11736
PMCID: PMC4155363  PMID: 25206277
Clostridium difficile infection; Ulcerative colitis; Crohn's disease; Outcome
21.  Clostridium difficile in a HIV-Infected Cohort: Incidence, Risk Factors, and Clinical Outcomes 
AIDS (London, England)  2013;27(17):10.1097/01.aids.0000432450.37863.e9.
Objective
C. difficile is the most commonly reported infectious diarrhea in HIV-infected patients in the United States. We set out to determine the incidence, risk factors, and clinical presentation of C. difficile infections (CDI) in a cohort of HIV-infected subjects.
Design
We performed a nested, case-control analysis with four non-CDI controls randomly selected for each case.
Methods
We assessed the incidence of CDI in the Johns Hopkins HIV Clinical Cohort between July 1, 2003 and December 31, 2010. Incident cases were defined as first positive C. difficile cytotoxin assay or PCR for toxin B gene. We used conditional logistic regression models to assess risk factors for CDI. We abstracted data on the clinical presentation and outcomes from case chart review.
Results
We identified 154 incident CDI cases for an incidence of 8.3 cases/1000 patient years. No unique clinical features of HIV-associated CDI were identified. In multivariate analysis, risk of CDI was independently increased for: CD4 count ≤50 cells/mm3 (Adjusted Odds Ratio (AOR) 20.7, 95% CI 2.8–151.4), hospital onset CDI (AOR 26.7 [3.1–231.2]), and use of clindamycin (AOR 27.6 [2.2–339.4]), fluoroquinolones (AOR 4.5 [1.2–17.5]), macrolides (AOR 6.3 [1.8–22.1]), gastric acid suppressants (AOR 3.1 [1.4–6.9]), or immunosuppressive agents (AOR 6.8 [1.2–39.6]).
Conclusions
The incidence of CDI in HIV-infected patients was twice that previously reported. Our data show compromised cellular immunity, as defined by CD4 ≤50 cells/ mm3is a risk factor for CDI. Clinicians should be aware of the increased CDI risk, particularly in those with severe CD4 count suppression.
doi:10.1097/01.aids.0000432450.37863.e9
PMCID: PMC3880635  PMID: 23842125
case-control; Clostridium difficile; HIV; incidence; risk factors
22.  Epidemiology of Clostridium difficile infection in two tertiary-care hospitals in Perth, Western Australia: a cross-sectional study 
The epidemiology of Clostridium difficile infection (CDI) has changed over time and between countries. It is therefore essential to monitor the characteristics of patients at risk of infection and the circulating strains to recognize local and global trends, and improve patient management. From December 2011 to May 2012 we conducted a prospective, observational epidemiological study of patients with laboratory-confirmed CDI at two tertiary teaching hospitals in Perth, Western Australia to determine CDI incidence and risk factors in an Australian setting. The incidence of CDI varied from 5.2 to 8.1 cases/10 000 occupied bed days (OBDs) at one hospital and from 3.9 to 16.3/10 000 OBDs at the second hospital. In total, 80 patients with laboratory-confirmed CDI met eligibility criteria and consented to be in the study. More than half (53.8%) had hospital-onset disease, 28.8% had community-onset and healthcare facility-associated disease and 7.5% were community-associated infections according to the definitions used. Severe CDI was observed in 40.0% of these cases but the 30-day mortality rate for all cases was only 2.5%. Besides a shorter length of stay among cases of community-onset CDI, no characteristics were identified that were significantly associated with community-onset or severe CDI. From 70 isolates, 34 different ribotypes were identified. The predominant ribotypes were 014 (24.3%), 020 (5.7%), 056 (5.7%) and 070 (5.7%). Whereas this study suggests that the characteristics of CDI cases in Australia are not markedly different from those in other developed countries, the increase in CDI rate observed emphasizes the importance of surveillance.
doi:10.1002/nmi2.43
PMCID: PMC4184660  PMID: 25356346
Community-associated Clostridium difficile infection; healthcare facility-associated Clostridium difficile infection; molecular epidemiology; ribotype 244
23.  Outcome of ICU patients with Clostridium difficile infection 
Critical Care  2012;16(6):R215.
Introduction
As data from Clostridium difficile infection (CDI) in intensive care unit (ICU) are still scarce, our objectives were to assess the morbidity and mortality of ICU-acquired CDI.
Methods
We compared patients with ICU-acquired CDI (watery or unformed stools occurring ≥ 72 hours after ICU admission with a stool sample positive for C. difficile toxin A or B) with two groups of controls hospitalized at the same time in the same unit. The first control group comprised patients with ICU-acquired diarrhea occurring ≥ 72 hours after ICU admission with a stool sample negative for C. difficile and for toxin A or B. The second group comprised patients without any diarrhea.
Results
Among 5,260 patients, 512 patients developed one episode of diarrhea. Among them, 69 (13.5%) had a CDI; 10 (14.5%) of them were community-acquired, contrasting with 12 (17.4%) that were hospital-acquired and 47 (68%) that were ICU-acquired. A pseudomembranous colitis was associated in 24/47 (51%) ICU patients. The median delay between diagnosis and metronidazole administration was one day (25th Quartile; 75th Quartile (0; 2) days). The case-fatality rate for patients with ICU-acquired CDI was 10/47 (21.5%), as compared to 112/443 (25.3%) for patients with negative tests. Neither the crude mortality (cause specific hazard ratio; CSHR = 0.70, 95% confidence interval; CI 0.36 to 1.35, P = 0.3) nor the adjusted mortality to confounding variables (CSHR = 0.81, 95% CI 0.4 to 1.64, P = 0.6) were significantly different between CDI patients and diarrheic patients without CDI. Compared to the general ICU population, neither the crude mortality (SHR = 0.64, 95% CI 0.34 to 1.21, P = 0.17), nor the mortality adjusted to confounding variables (CSHR = 0.71, 95% confidence interval (CI) 0.38 to 1.35, P = 0.3), were significantly different between the two groups. The estimated increase in the duration of stay due to CDI was 8.0 days ± 9.3 days, (P = 0.4) in comparison to the diarrheic population, and 6.3 days ± 4.3 (P = 0.14) in comparison to the general ICU population.
Conclusions
If treated early, ICU-acquired CDI is not independently associated with an increased mortality and impacts marginally the ICU length of stay.
doi:10.1186/cc11852
PMCID: PMC3672590  PMID: 23127327
24.  Severe clinical outcome is uncommon in Clostridium difficile infection in children: a retrospective cohort study 
BMC Pediatrics  2014;14:28.
Background
Clostridium difficile infection (CDI) is the most common cause of health care–associated diarrhea in children and adults. Although serious complications of CDI have been reported to be increasing in adults, this trend has not yet been demonstrated in children. The purpose of this study was to examine the features of CDI in a pediatric population, with special attention to the occurrence of CDI-related severe outcomes.
Methods
A chart review was conducted for patients with C. difficile infection detected by cytotoxin assay between August, 2008 and July, 2012. Basic demographics, mode of acquisition (nosocomial versus community), laboratory and clinical features, treatment, and outcome data were collected. Pulsed-field gel electrophoresis and polymerase chain reaction detection of toxin A (tcdA), toxin B (tcdB), binary toxin (cdtB) and tcdC genes were performed on isolates from nosocomial cases by the National Microbiology Laboratory, Winnipeg, Manitoba.
Results
Ninety percent of children with CDI experienced resolution of symptoms by 30 days after disease onset and 2% experienced a severe outcome. There were no cases where colectomy was performed for CDI, and only one case where CDI contributed to death. Various combinations of clinical and laboratory features were not predictive of a severe outcome. Seventy-four percent of cases were nosocomial-associated. Among all cultured strains, the NAP4 strain occurred most frequently (24%), followed by NAP1 (11%). There was no association between strain type and clinical outcome; however, relapses were significantly more frequent in NAP4-infected children.
Conclusions
Severe outcomes due to CDI are uncommon in children compared to adults. Further prospective pediatric studies on CDI in community and hospital settings are required to better understand risk factors, optimal treatment and the significance of NAP4 in pediatric CDI.
doi:10.1186/1471-2431-14-28
PMCID: PMC3912344  PMID: 24485120
Clostridium difficile; North American pulsed-field type; Pediatrics; Child
25.  genetic risk factors for clostridium difficile infection in Ulcerative Colitis 
Introduction
Patients with inflammatory bowel disease (IBD) are at higher risk for Clostridium difficile infection (CDI). Disruption of gut microbiome and interaction with the intestinal immune system are essential mechanisms for pathogenesis of both CDI and IBD. Whether genetic polymorphisms associated with susceptibility to IBD are also associated with risk of CDI is unknown.
Methods
We used a prospective registry of patients from a tertiary referral hospital. Medical record review was performed to identify all ulcerative colitis (UC) patients within the registry with a history of CDI. All patients were genotyped on the Immunochip. We examined the association between the 163 risk loci for IBD and risk of CDI using a dominant genetic model. Model performance was examined using receiver operating characteristics curves.
Results
The study included 319 patients of whom 29 developed CDI (9%). Female gender and pancolitis were associated with increased risk while use of anti-TNF was protective against CDI. Six genetic polymorphisms including those at TNFRSF14 (Odds ratio (OR) 6.0, p-value 0.01) were associated with increased risk while 2 loci were inversely associated. On multivariate analysis, none of the clinical parameters retained significance after adjusting for genetics. Presence of at least one high risk locus was associated with an increase in risk for CDI (20% vs. 1%) (p=6 × 10−9). Compared to 11% for a clinical model, the genetic loci explained 28% of the variance in CDI risk and had a greater AUROC.
Conclusion
Host genetics may influence susceptibility to CDI in patients with ulcerative colitis.
doi:10.1111/apt.12425
PMCID: PMC3755009  PMID: 23848254
Clostridium difficile; ulcerative colitis; tumor necrosis factor; colectomy; genetics

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