Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.

Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.

Development and Validation of a Risk Score for Clostridium difficile Infection in Medicare Beneficiaries: A Population-Based Cohort Study.

OBJECTIVES: To create a risk stratification score for Clostridium difficile infection (CDI) in elderly adults. DESIGN: A sample from the Medicare 5% data set linked to Medicaid and Minimum Data Set (MDS) files from 2008 to 2009. Risk score was derived via a split-cohort through logistic regression model used to assign numerical values to each retained covariate. Score characteristics were tested using a threshold analysis. SETTING: Community, long-term, and acute care settings. PARTICIPANTS: Population-based sample Medicare beneficiaries aged 65 and older on January 1, 2008, with continuous Medicare coverage from January 1, 2008, through December 31, 2009. MEASUREMENTS: The primary outcome was incident CDI, defined as International Classification of Diseases, Ninth Revision, Clinical Modification code 008.45 or CDI according to the MDS, and no CDI in the preceding 12 months. RESULTS: The cohort consisted of 6,838 participants with CDI and 1,158,327 without. Logistic regression modeling (hospitalization, nursing home stay, or antibiotics in prior year; inflammatory bowel, chronic liver, chronic kidney, or cardiac disease; aged ≥75, Northeast residence; c-statistic = 0.858) was used to determine to a score out of 22 possible points. A score of seven points (found in 18.8% of the total population) had a negative predictive value of 98.7%. CONCLUSION: CDI risk is high and age dependent in the population aged 65 and older. By stratifying risk, this score should help ensure efficient allocation of prevention resources.

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.

Economic evaluation of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection in Australia.

BACKGROUND AND AIM: Clostridium difficile is the most common cause of hospital-acquired diarrhea in Australia. In 2013, a randomized controlled trial demonstrated the effectiveness of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The aim of this study is to evaluate the cost-effectiveness of fecal microbiota transplantation-via either nasoduodenal or colorectal delivery-compared with vancomycin for the treatment of recurrent CDI in Australia. METHODS: A Markov model was developed to compare the cost-effectiveness of fecal microbiota transplantation compared with standard antibiotic therapy. A literature review of clinical evidence informed the structure of the model and the choice of parameter values. Clinical effectiveness was measured in terms of quality-adjusted life years. Uncertainty in the model was explored using probabilistic sensitivity analysis. RESULTS: Both nasoduodenal and colorectal FMT resulted in improved quality of life and reduced cost compared with vancomycin. The incremental effectiveness of either FMT delivery compared with vancomycin was 1.2 (95% CI: 0.1, 2.3) quality-adjusted life years, or 1.4 (95% CI: 0.4, 2.4) life years saved. Treatment with vancomycin resulted in an increased cost of AU$4094 (95% CI: AU$26, AU$8161) compared with nasoduodenal delivery of FMT and AU$4045 (95% CI: -AU$33, AU$8124) compared with colorectal delivery. The mean difference in cost between colorectal and nasoduodenal FMT was not significant. CONCLUSIONS: If FMT, rather than vancomycin, became standard care for recurrent CDI in Australia, the estimated national healthcare savings would be over AU$4000 per treated person, with a substantial increase in quality of life.

Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.

Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the U.S. health care system and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges because the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New experimental treatments including vaccines, monoclonal antibodies, and nontoxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed.

[New methodological advances: algorithm proposal for management of Clostridium difficile infection]. / Nuevos avances metodológicos: propuesta de algoritmo para el manejo de la infección por Clostridium difficile.

INTRODUCTION: Clostridium difficile infection (CDI) is considered the most common cause of health care-associated diarrhea and also is an etiologic agent of community diarrhea. The aim of this study was to assess the potential benefit of a test that detects glutamate dehydrogenase (GDH) antigen and C. difficile toxin A/B, simultaneously, followed by detection of C. difficile toxin B (tcdB) gene by PCR as confirmatory assay on discrepant samples, and to propose an algorithm more efficient. MATERIAL AND METHODS: From June 2012 to January 2013 at Hospital Infantil Universitario Niño Jesús, Madrid, the stool samples were studied for the simultaneous detection of GDH and toxin A/B, and also for detection of toxin A/B alone. When results between GDH and toxin A/B were discordant, a single sample for patient was selected for detection of C. difficile toxin B (tcdB) gene. RESULTS: A total of 116 samples (52 patients) were tested. Four were positive and 75 negative for toxigenic C. difficile (Toxin A/B, alone or combined with GDH). C. difficile was detected in the remaining 37 samples but not toxin A/B, regardless of the method used, except one. Twenty of the 37 specimens were further tested for C. difficile toxin B (tcdB) gene and 7 were positive. DISCUSSION: The simultaneous detection of GDH and toxin A/B combined with PCR recovered undiagnosed cases of CDI. In accordance with our data, we propose a two-step algorithm: detection of GDH and PCR (in samples GDH positive). This algorithm could provide a superior cost-benefit ratio in our population.

Identification of Recurrent Clostridium difficile Infection Using Administrative Codes: Accuracy and Implications for Surveillance.

OBJECTIVE: To develop an algorithm using administrative codes, laboratory data, and medication data to identify recurrent Clostridium difficile infection (CDI) and to examine the sensitivity, specificity, positive and negative predictive values, and performance of this algorithm. METHODS: We identified all patients with 2 or more International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes for CDI (008.45) from January 1 through December 31, 2013. Information on number of diagnosis codes, stool toxin assays (enzyme immunoassay or polymerase chain reaction), and unique prescriptions for metronidazole and vancomycin was identified. Logistic regression was used to identify independent predictors of recurrent CDI and a predictive model was developed. RESULTS: A total of 591 patients with at least 2 ICD-9 codes for CDI were included (median age, 66 years). The derivation cohort consisted of 157 patients among whom 43 (27%) had recurrent CDI. Presence of 3 or more ICD-9 codes for CDI (odds ratio, 2.49), 2 or more stool tests (odds ratio, 2.88), and 2 or more prescriptions for vancomycin (odds ratio, 5.87) were independently associated with confirmed recurrent CDI. A classifier incorporating 2 or more prescriptions for vancomycin and either 2 or more stool tests or 3 or more ICD-9-CM codes had a positive predictive value of 41% and negative predictive value of 90%. The area under the receiver operating characteristic curve for this combined classifier was modest (0.69). CONCLUSION: Identification of recurrent episodes of CDI in administrative data poses challenges. Accurate assessment of burden requires individual case review to confirm diagnosis.

Long-term outcomes of an antimicrobial stewardship program implemented in a hospital with low baseline antibiotic use.

OBJECTIVE: To evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use. DESIGN: Quasi-experimental, interrupted time-series study. SETTING: Public safety net hospital with 525 beds. INTERVENTION: Implementation of a formal ASP in July 2008. METHODS: We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008-September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005-June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures. RESULTS: During the preintervention period, total antibacterial and antipseudomonal use were declining (-9.2 and -5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (-3.7 and -2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (-$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes. CONCLUSION: In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.

Predicting the risk for hospital-onset Clostridium difficile infection (HO-CDI) at the time of inpatient admission: HO-CDI risk score.

OBJECTIVE: To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission DESIGN: Retrospective data analysis SETTING: Six US acute care hospitals PATIENTS: Adult inpatients METHODS: We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations. RESULTS: Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001). CONCLUSION: Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

Validation of the 3-day rule for stool bacterial tests in Japan.

OBJECTIVE: Stool cultures are expensive and time consuming, and the positive rate of enteric pathogens in cases of nosocomial diarrhea is low. The 3-day rule, whereby clinicians order a Clostridium difficile (CD) toxin test rather than a stool culture for inpatients developing diarrhea >3 days after admission, has been well studied in Western countries. The present study sought to validate the 3-day rule in an acute care hospital setting in Japan. METHODS: Stool bacterial and CD toxin test results for adult patients hospitalized in an acute care hospital in 2008 were retrospectively analyzed. Specimens collected after an initial positive test were excluded. The positive rate and cost-effectiveness of the tests were compared among three patient groups. PATIENTS: The adult patients were divided into three groups for comparison: outpatients, patients hospitalized for ≤3 days and patients hospitalized for ≥4 days. RESULTS: Over the 12-month period, 1,597 stool cultures were obtained from 992 patients, and 880 CD toxin tests were performed in 529 patients. In the outpatient, inpatient ≤3 days and inpatient ≥4 days groups, the rate of positive stool cultures was 14.2%, 3.6% and 1.3% and that of positive CD toxin tests was 1.9%, 7.1% and 8.5%, respectively. The medical costs required to obtain one positive result were 9,181, 36,075 and 103,600 JPY and 43,200, 11,333 and 9,410 JPY, respectively. CONCLUSION: The 3-day rule was validated for the first time in a setting other than a Western country. Our results revealed that the "3-day rule" is also useful and cost-effective in Japan.

Evaluation of the diagnostic performance of the xpert Clostridium difficile assay and its comparison with the toxin A/B enzyme-linked fluorescent assay and in-house real-time PCR assay used for the detection of toxigenic C. difficile.

BACKGROUND: Clostridium difficile genes or toxin can be detected using several laboratory techniques. In this study, we compared the performance of the Xpert C. difficile assay with that of a toxin A/B enzyme-linked fluorescent immunoassay (ELFA) and an in-house real-time PCR assay for the tcdB gene. METHODS: From April 2011 through January 2012, 138 soft or liquid stool samples from 138 adult patients at Paik Hospital were tested using the toxin A/B ELFA, in-house real-time PCR assay, and Xpert C. difficile assay to detect toxigenic C. difficile. Specimens were considered true positives if results were positive in both the in-house real-time PCR for tcdB gene and Xpert C. difficile assays. RESULTS: Sensitivity of the toxin A/B ELFA, in-house tcdB gene real-time PCR, and Xpert C. difficile assay were 67.6%, 97.3%, and 100.0%, respectively. The specificity of the in-house tcdB gene real-time PCR assay was 100%, while the specificity was 98.0% for the other two methods. The turnaround time (TAT) was 50 min for the Xpert C. difficile assay, 75 min for the toxin A/B ELFA, and 160 min for the in-house real-time PCR assay. CONCLUSION: The Xpert C. difficile assay and the in-house real-time PCR assay had higher sensitivity than the toxin A/B ELFA; however, the specificities of the three assays were similar. Considering its rapid TAT and high sensitivity, use of the Xpert C. difficile assay is highly recommended for rapid and accurate diagnosis of C. difficile infection.

Active surveillance for carbapenem-resistant Enterobacteriaceae using stool specimens submitted for testing for Clostridium difficile.

Active surveillance to identify asymptomatic carriers of carbapenem-resistant Enterobacteriaceae (CRE) is a recommended strategy for CRE control in healthcare facilities. Active surveillance using stool specimens tested for Clostridium difficile is a relatively low-cost strategy to detect CRE carriers. Further evaluation of this and other risk factor-based active surveillance strategies is warranted.

Impact of toxigenic Clostridium difficile polymerase chain reaction testing on the clinical microbiology laboratory and inpatient epidemiology.

Conversion from Clostridium difficile toxin A/B EIA to tcdB polymerase chain reaction for diagnosis of C. difficile infection (CDI) resulted in significant decreases in laboratory testing volume and largely unchanged C. difficile toxin detection rates. Decreases in healthcare-associated CDI rates (P ≤ 0.05) reflected a clinical practice benefit of this conversion.

Policy development for Clostridium difficile.

The Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection (ARHAI) was created at the height of the incidence of Clostridium difficile infection (CDI). This article describes the role of ARHAI in the evaluation of laboratory testing for CDI, a related consultation on the legal requirements for manufacturers of in vitro diagnostic medical devices, a CDI healthcare bundle and surveillance of CDI in children.

Vital signs: preventing Clostridium difficile infections.

BACKGROUND: Clostridium difficile infection (CDI) is a common and sometimes fatal health-care-associated infection; the incidence, deaths, and excess health-care costs resulting from CDIs in hospitalized patients are all at historic highs. Meanwhile, the contribution of nonhospital health-care exposures to the overall burden of CDI, and the ability of programs to prevent CDIs by implementing CDC recommendations across a range of hospitals, have not been demonstrated previously. METHODS: Population-based data from the Emerging Infections Program were analyzed by location and antecedent health-care exposures. Present-on-admission and hospital-onset, laboratory-identified CDIs reported to the National Healthcare Safety Network (NHSN) were analyzed. Rates of hospital-onset CDIs were compared between two 8-month periods near the beginning and end of three CDI prevention programs that focused primarily on measures to prevent intrahospital transmission of C. difficile in three states (Illinois, Massachusetts, and New York). RESULTS: Among CDIs identified in Emerging Infections Program data in 2010, 94% were associated with receiving health care; of these, 75% had onset among persons not currently hospitalized, including recently discharged patients, outpatients, and nursing home residents. Among CDIs reported to NHSN in 2010, 52% were already present on hospital admission, although they were largely health-care related. The pooled CDI rate declined 20% among 71 hospitals participating in the CDI prevention programs. CONCLUSIONS: Nearly all CDIs are related to various health-care settings where predisposing antibiotics are prescribed and C. difficile transmission occurs. Hospital-onset CDIs were prevented through an emphasis on infection control. IMPLICATIONS FOR PUBLIC HEALTH: More needs to be done to prevent CDIs; major reductions will require antibiotic stewardship along with infection control applied to nursing homes and ambulatory-care settings as well as hospitals. State health departments and partner organizations have shown leadership in preventing CDIs in hospitals and can prevent more CDIs by extending their programs to cover other health-care settings.

[Assessment of the usefulness of chromogenic medium for the isolation of Clostridium difficile from the gastrointestinal tract of children with diarrhoea]. / Ocena przydatnosci podloza chromogennego do izolacji Clostridium difficile z przewodu pokarmowego dzieci z biegunka.

INTRODUCTION: Clostridium difficile is well known as an important cause of nosocomial infection. Laboratory diagnostics have included bacterial culture or more commonly, direct detection of preformed toxin in stool samples using different assays. The aim of this study was to evaluate and compare two selecitve media to isolation of C. difficile from paediatric diarrhoeal stool samples. METHODS: Fifty nine stool samples, collected from 43 children with diarrhoea, were examined for routine laboratory diagnosis of C. difficile infection. Commercially available tests for detection of A/B toxins of C. difficile were performed. The same stool samples were cultured on two selective media for strain isolation: CLO and CDIFF (bioMerieux S.A., France) and incubated 48h and 24h respectively. RESULTS: Twenty two samples gave positive results for toxins A/B C. difficile. From 24 samples inoculated on selective media C. difficile strains were cultured: from 8 samples on CLO medium and from 16 samples on CDIFF medium. CONCLUSIONS: CDIFF medium is more effective for isolation of C. difficile strains from stool samples collected from children with diarrhoea.

Pathology consultation on detection of Clostridium difficile.

Laboratory methods for detecting Clostridium difficile have undergone considerable evolution since the organism's etiologic association with antibiotic-associated diarrhea and colitis was established. Clearly, familiarity with the advantages and shortcomings of the various assays is essential for the laboratory director when choosing among these tests. For the consulting pathologist, furthermore, an understanding of the laboratory's role in securing a diagnosis of C difficile infection (CDI) is also required to identify requests for unnecessary testing that may be costly and potentially misleading. The purpose of this article is to highlight the major differences in laboratory test methods for CDI and to review a few commonly encountered provider ordering scenarios.