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Objective To reduce health care facility–onset (HCFO) Clostridioides difficile infection (CDI) incidence by improving diagnostic stewardship and reducing the inappropriate testing of C difficile assays. Patients and Methods A multidisciplinary team conducted a quality improvement initiative from January 1, 2020, through March 31, 2021. Clostridioides difficile infection and inappropriate testing were identified via electronic health records using predefined criteria related to stool quantity/caliber, confounding medications, and laboratory data. An intervention bundle was designed including (1) provider education, (2) implementation of an appropriate testing algorithm, (3) expert review of C difficile orders, and (4) batch testing of assays to facilitate review and cancellation if inappropriate. Results Compared with a baseline period from January to September 2020, implementation of our intervention bundle from December 2020 to March 2021 resulted in an 83.6% reduction in inappropriate orders tested and a 41.7% reduction in HCFO CDI incidence. Conclusion A novel prevention bundle improved C difficile diagnostic stewardship and HCFO CDI incidence by reducing testing of inappropriate orders. Such initiatives targeting HCFO CDI may positively affect patient safety and hospital reimbursement.

Clostridioides difficile has become the most common healthcare-associated pathogen in the United States, leading the US Centers for Disease Control and Prevention (CDC) to classify C. difficile as an “urgent” public health threat that requires “urgent and aggressive action.” This call to action has led to new discoveries that have advanced our understanding of Clostridioides difficile infection (CDI) immunology and clinical development of immunologic-based therapies for CDI prevention. However, CDI immunology research has been limited in pediatric populations, and several unanswered questions remain regarding the function of host immune response in pediatric CDI pathogenesis and the potential role of immunologic-based therapies in children. This review summarizes the innate and adaptive immune responses previously characterized in animals and humans and provides a current update on clinical development of immunologic-based therapies for CDI prevention in adults and children. These data inform the future research needs for children.

The article presents an analytical review of the works of domestic and foreign authors on the problem of studying the peculiarities of the formation of the intestinal microbiota and risk factors for the development of microdysbiosis in newborns with the activation of opportunistic bacteria, including C. difficile. Special attention is paid to the effect of antibiotics on the state of the intestinal microbiota and the activation of toxigenic strains of C. difficile. Divergent views on the role of toxigenic strains of C. difficile in the development of infectious pathology of newborns are presented.

Article Summary: This multicenter study focusing on critically ill patients showed a strong relationship between hemolysis and mortality., Usually responsible for soft tissue infections, Clostridioides species can also cause bacteremia, life-threatening infections often requiring intensive care unit (ICU) admission. We conducted a multicenter retrospective study to investigate Clostridioides bacteremia in ICUs to describe the clinical and biologic characteristics and outcomes in critically ill patients. We identified 135 patients with Clostridioides bacteremia, which occurred almost exclusively (96%) in patients with underlying conditions. Septic shock and digestive symptoms were the hallmarks of Clostridioides bacteremia in the ICU. We identified 16 different species of Clostridioides, among which C. perfringens accounted for 31% of cases. Despite the high sensitivity of Clostridioides to common antimicrobial drugs, mortality rates were high: 52% for ICU patients and 71% overall at 3 months. In multivariate analysis, the most important factor associated with increased risk for death was the presence of hemolysis. Clostridioides bacteremia often leads to multiple organ failures, which have high mortality rates.

Objective:To determine the impact of electronic health record (EHR)–based interventions and test restriction on Clostridioides difficile tests (CDTs) and hospital-onset C. difficile infection (HO-CDI).Design:Quasi-experimental study in 3 hospitals.Setting:957-bed academic (hospital A), 354-bed (hospital B), and 175-bed (hospital C) academic-affiliated community hospitals.Interventions:Three EHR-based interventions were sequentially implemented: (1) alert when ordering a CDT if laxatives administered within 24 hours (January 2018); (2) cancellation of CDT orders after 24 hours (October 2018); (3) contextual rule-driven order questions requiring justification when laxative administered or lack of EHR documentation of diarrhea (July 2019). In February 2019, hospital C implemented a gatekeeper intervention requiring approval for all CDTs after hospital day 3. The impact of the interventions on C. difficile testing and HO-CDI rates was estimated using an interrupted time-series analysis.Results:C. difficile testing was already declining in the preintervention period (annual change in incidence rate [IR], 0.79; 95% CI, 0.72–0.87) and did not decrease further with the EHR interventions. The laxative alert was temporally associated with a trend reduction in HO-CDI (annual change in IR from baseline, 0.85; 95% CI, 0.75–0.96) at hospitals A and B. The gatekeeper intervention at hospital C was associated with level (IRR, 0.50; 95% CI, 0.42-0.60) and trend reductions in C. difficile testing (annual change in IR, 0.91; 95% CI, 0.85–0.98) and level (IRR 0.42; 95% CI, 0.22–0.81) and trend reductions in HO-CDI (annual change in IR, 0.68; 95% CI, 0.50–0.92) relative to the baseline period.Conclusions:Test restriction was more effective than EHR-based clinical decision support to reduce C. difficile testing in our 3-hospital system.

Objectives We analyzed test volume data to identify low-value test utilization. We subsequently tracked the efficacy of interventions to improve test utilization by decreasing low-value testing. Methods Test volume data for analytes included in the Choosing Wisely guidelines were analyzed to identify population outliers. Outliers were defined by test volume ratios of either analyte to sodium or paired analytes to correct for variation in patient volumes at each site. Interventions to improve test utilization were targeted to outlier sites. Relative efficacy in reducing low-value testing was tracked at those sites. Results After appropriate data cleaning, test volume ratios for 17 analytes paired with sodium and 8 pairs of analytes were acquired from 108 national sites. A site with abnormally high Clostridium difficile/sodium ratio was selected for intervention, leading to a 71% decrease in C difficile tests. Two different interventions to decrease creatine kinase MB isoform (CKMB) testing were performed at two unique sites with abnormally high CKMB/troponin ratios. These interventions decreased CKMB by 11% and 98% at the different sites, showing the efficacy of the different kinds of interventions. Conclusions Test volume ratio analysis and benchmarking enable identification of low-value test utilization.

Clostridioides difficile infection (CDI) has become a threatening public health problem in the developed world. In the kingdom of Saudi Arabia, prevalence of CDI is still unknown due to limited surveillance protocols and diagnostic resources. We used a two-step procedure to study and confirm C. difficile cases. We also studied toxin profiles of these isolates. Stool samples were collected from symptomatic patients and clinically suspected of CDI for almost 12 months. Isolates were confirmed by culture method followed by 16S rRNA sequencing. Multiplex PCR was performed for the identification of toxin A, toxin B and binary toxin genes and compared to Gene Expert results. Out of the 47 collected samples, 27 were successfully grown on culture media. 18 samples were confirmed as C. difficile by both culture and 16S rRNA sequencing. Interestingly, the rest of the isolates (9 species) belonged to different genera. Our results showed 95% of samples were positive for both toxin A and B (tcdA, tcdB) and all samples exhibited the toxin gene regulator tcdC. All samples were confirmed negative for the binary toxin gene ctdB and 11% of the isolates were positive for ctdA gene. Interestingly, one isolate harbored the binary toxin gene (cdtA+) and tested negative for both toxins A and B. We believe that combining the standard culture method with molecular techniques can make the detection of C. difficile more accurate.

Clostridioides difficile is the single most deadly bacterial pathogen in the United States, and its global prevalence and outsized health impacts underscore the need for more effective therapeutic options. Towards this goal, a novel group of modified peptidoglycan hydrolases with significant in vitro bactericidal activity have emerged as potential candidates for treating C. difficile infections (CDI). To date, discovery and development efforts directed at these CDI-specific lysins have been limited, and in particular there has been no systematic comparison of known or newly discovered lysin candidates. Here, we detail bioinformatics-driven discovery of six new anti-C. difficile lysins belonging to the amidase-3 family of enzymes, and we describe experimental comparison of their respective catalytic domains (CATs) with highly active CATs from the literature. Our quantitative analyses include metrics for expression level, inherent antibacterial activity, breadth of strain selectivity, killing of germinating spores, and structural and functional measures of thermal stability. Importantly, prior studies have not examined stability as a performance metric, and our results show that the panel of eight enzymes possess widely variable thermal denaturation temperatures and resistance to heat inactivation, including some enzymes that exhibit marginal stability at body temperature. Ultimately, no single enzyme dominated with respect to all performance measures, suggesting the need for a balanced assessment of lysin properties during efforts to find, engineer, and develop candidates with true clinical potential.

Background Published bundles to reduce Clostridioides difficile Infection (CDI) frequently lack information on compliance with individual elements. We piloted a computerized clinical decision support-based intervention bundle and conducted detailed evaluation of several intervention-related measures. Methods A quasi-experimental study of a bundled intervention was performed at 2 acute care community hospitals in Maryland. The bundle had five components: (1) timely placement in enteric precautions, (2) appropriate CDI testing, (3) reducing proton-pump inhibitor (PPI) use, (4) reducing high-CDI risk antibiotic use, and (5) optimizing use of a sporicidal agent for environmental cleaning. Chi-square and Kruskal-Wallis tests were used to compare measure differences. An interrupted time series analysis was used to evaluate impact on hospital-onset (HO)-CDI. Results Placement of CDI suspects in enteric precautions before test results did not change. Only hospital B decreased the frequency of CDI testing and reduced inappropriate testing related to laxative use. Both hospitals reduced the use of PPI and high-risk antibiotics. A 75% decrease in HO-CDI immediately postimplementation was observed for hospital B only. Conclusion A CDI reduction bundle showed variable impact on relevant measures. Hospital-specific differential uptake of bundle elements may explain differences in effectiveness, and emphasizes the importance of measuring processes and intermediate outcomes.

Objective To evaluate whether Clostridioides (formerly Clostridium) difficile–contaminated stethoscope diaphragms remained aseptic by the placement of an aseptic diaphragm barrier. Methods On November 1, 2019, fresh cultures of C difficile were diluted to 107 colony-forming units (CFU)/mL and used to inoculate 16 stethoscope diaphragms; 8 had an aseptic diaphragm barrier applied and 8 served as nonbarrier controls. Contaminated stethoscopes were anaerobically incubated, then swabbed at 15 and 30 minutes, 2 and 4 hours, and 1, 2, 3, and 7 days after inoculation and subsequently plated onto blood, chocolate, and cycloserine-cefoxitin fructose agar. Plates were incubated for 48 hours and on November 9, 2019, the resulting colonies were manually counted. Statistical analyses (RStudio, version 1.0.153) used analysis of variance with post hoc Tukey honestly significant difference. Results Overall, mean colony count was 33 CFU on stethoscopes without barriers vs zero on those with barriers (P≤.05). Growth was greatest at 48 hours, with colony counts as high as 160 CFU. The presence of the barrier resulted in no growth in 100% of stethoscope diaphragms for up to 1 week. Conclusion We found that stethoscope diaphragm barriers provide an aseptic patient contact point, thus reducing the potential for transmission of C difficile during the physical examination. In critical care environments, in which many hospitals use acoustically inferior disposable stethoscopes, the option of a disposable aseptic stethoscope barrier may allow high-quality auscultation while reducing the potential for pathogen transmission.

The survival of Clostridioides difficile (previously Clostridium difficile) vegetative cells and endospores was compared at different levels of indigenous microflora using autoclaved and unautoclaved dairy composts with different moisture contents (MCs).Both types of composts adjusted to 20, 30 and 40% MCs were inoculated with a suspension of C. difficile that contained both vegetative cells (c. 5-6 log CFU per gram) and endospores (c. 5·0 CFU per gram), and then stored aerobically inside a humidity-controlled chamber at room temperature 22·5 ± 0·8°C for 1 year. The level of indigenous microflora was very stable during the storage after day 7 in both types of compost. The greatest reductions of C. difficile vegetative cell counts occurred during the first 24 h of storage in autoclaved and unautoclaved composts, which had 4·7 and 5·5 log CFU per gram with 20% MC, 1·8 and 2·1 log CFU per gram with 30% MC, and 2·3 and 1·3 log CFU per gram with 40% MC, respectively. Both MC and the duration of storage have significant (P 0·05) effects on the survival of vegetative cells for first 120 days of storage. The slow inactivation of C. difficile vegetative cells at higher MCs during aerobic storage was confirmed by exponentially decaying modelling data during the early stage of aerobic exposure. The reduction of endospore counts (1·0 log CFU per gram) during the storage for both types of compost at all MCs was not significant (P 0·05) except for the autoclaved compost with 30% MC.The highly resistant C. difficile endospores to the unfavourable environmental conditions survived for more than a year while vegetative cells died off exponentially upon the initial aerobic exposure.The long-term survival of C. difficile endospores in contaminated compost may transmit the pathogen to fresh produce, animals or water in pre-harvest conditions.

Introduction: Updated international guidelines recommend the use of a two-step algorithm (glutamate dehydrogenase [GDH] or nucleic-acid amplification test [NAAT] plus toxin) rather than NAAT alone for the diagnosis of Clostridioides difficile (formerly Clostridium difficile) infections. The goal of our project was to evaluate the impact of a new bundle on the rate of hospital-acquired C. difficile infections (CDIs), hospital-acquired CDI standardized infection ratio (SIR), antibiotic days of therapy (DOT), and financial cost. Materials and Methods: The new bundle was implemented in April 2018. This bundle was implemented across five hospitals in Catholic Health Initiatives (CHI) Texas Division. The bundle included a switch from NAAT to a two-step process (GDH and toxin). We placed the new test in an order panel which included enteric isolation and required indications for C. difficile testing. We used quarterly data pre- and post-intervention to calculate SIR and DOT. Results: In the pre-intervention period, 15.5% of the total 3513 C. difficile NAAT was positive. In the post-intervention period, 5.7% of a total of 2845 GDH and toxin assays was positive for both GDH and toxin (P < 0.0001). SIR, which adjusts for denominator and change in testing methodology, also dropped from 1.02 to 0.43. The estimated cost associated with positive C. difficile cases dropped from 1,932,150 USD to 1,113,800 USD with an estimated yearly cost saving of 794,150 USD. Compliance with enteric isolation improved from 73.1% to 92.5% (P = 0.008). Conclusion: The new testing bundle led to a marked reduction in hospital-acquired CDI and unnecessary treatment, reduction in C. difficile testing, an increase in compliance with enteric isolation, and significant cost savings.

Objective : We assessed the cost-effectiveness of establishing a fecal microbial transplant (FMT) unit in Canada for the treatment of recurrent CDI. Design : We performed a cost-effectiveness analysis to determine the number of patients with recurrent CDI needed to treat (NNT) annually to make establishing a FMT unit cost-effective. We compared treating patients for their second recurrence of CDI with FMT in a jurisdiction with a FMT unit, compared to being treated with antibiotics; then sent to a medical center with FMT available for the third recurrence. We used a willingness to pay threshold of $50,000 per quality-adjusted-life-year gained. Results : The minimum annual NNT was 15 for FMT via colonoscopy, 17 for FMT via capsule, and 44 for FMT via enema compared with vancomycin, and 16, 18, and 47 compared with fidaxomicin, respectively. A medical center's minimum catchment area when establishing a FMT unit would have to be 56,849 if using FMT via colonoscopy, or 64,429 if using capsules. Conclusion : We report the minimum number of patients requiring treatment annually with FMT to achieve cost-effectiveness, when including start-up and ongoing costs. FMT is cost-effective in Canada in populations with a sufficient number of eligible patients, ranging from 15 to 47 depending on the FMT modality used. This is crucial for medical jurisdictions making decisions about establishing a FMT unit for the treatment of recurrent CDI. The cost-effectiveness can be generalized in other countries.

Spore formation and germination are essential for the bacterial pathogen Clostridioides difficile to transmit infection. Despite the importance of these developmental processes to the infection cycle of C. difficile, the molecular mechanisms underlying how this obligate anaerobe forms infectious spores and how these spores germinate to initiate infection were largely unknown until recently. Work in the last decade has revealed that C. difficile uses a distinct mechanism for sensing and transducing germinant signals relative to previously characterized spore formers. The C. difficile spore assembly pathway also exhibits notable differences relative to Bacillus spp., where spore formation has been more extensively studied. For both these processes, factors that are conserved only in C. difficile or the related Peptostreptococcaceae family are employed, and even highly conserved spore proteins can have differential functions or requirements in C. difficile compared to other spore formers. This review summarizes our current understanding of the mechanisms controlling C. difficile spore formation and germination and describes strategies for inhibiting these processes to prevent C. difficile infection and disease recurrence.

BACKGROUND: Clostridium difficile infection is one of the most common causes of diarrhea in healthcare facilities. More studies are needed to identify patients at high risk of C difficile infection in our community. OBJECTIVES: Estimate the prevalence of C difficile infection among adult patients and evaluate the risk factors associated with infection. DESIGN: Retrospective record review. SETTING: Tertiary academic medical center in Jeddah. PATIENTS AND METHODS: Eligible patients were adults (≥18 years old) with confirmed C difficile diagnosis between January 2013 and May 2018. MAIN OUTCOME MEASURES: Prevalence rate and types of risk factors. SAMPLE SIZE: Of 1886 records, 129 patients had positive lab results and met the inclusion criteria. RESULTS: The prevalence of C difficile infection in our center over five years was 6.8%. The mean (SD) age was 56 (18) years, and infection was more prevalent in men (53.5%) than in women (46.5%). The most common risk factors were use of proton-pump inhibitors (PPI) and broad-spectrum antibiotics. The overlapping exposure of both PPIs and broad-spectrum antibiotics was 56.6%. There was no statistically significant difference between the type of PPI ( P =.254) or antibiotic ( P =.789) and the onset of C difficile infection. CONCLUSION: The overall C difficile infection prevalence in our population was low compared to Western countries. The majority of the patients who developed C difficile infection were using PPIs and/or antibiotics. No differences were observed in the type of antibiotic or PPI and the onset of C difficile infection development. Appropriate prescribing protocols for PPIs and antibiotics in acute settings are needed. LIMITATIONS: Single center and retrospective design. CONFLICT OF INTEREST: None.

OBJECTIVES: Diagnosing Clostridioides difficile infections in young children with high asymptomatic colonization is challenging. We compared the frequency of C difficile detection by polymerase chain reaction (PCR) in healthy control (HC) children with those with acute gastroenteritis (AGE) and evaluated fecal-lactoferrin and organism load as possible indicators of true C difficile infection disease. METHODS: Stool was collected from children RESULTS: Of 524 stools collected from 524 children (250 with AGE, 274 HCs), C difficile was detected less in children with AGE (14%, 36 of 250) than in HCs (28%, 76 of 274) stools (P < .0001). Among infants CONCLUSIONS: HC children

Objectives: To determine the effectiveness of erythritol and xylitol in the inhibition of gut bacteria possibly associated with Autism Spectrum Disorder (ASD) and Clostridium difficile Infection (CDI). Methods: Seven bacterial strains associated with ASD, or with CDI and a control probiotic were tested for polyol inhibitory activity: Clostridium histolyticum, Bacteroides vulgatus, Bifidobacterium longham, and two strains each of Clostridium bolteae and difficile. Each strain was grown in brain heart infusion/sucrose media with polyol concentrations varying from 0% to 15% for erythritol and 0% -30 % for xylitol. Growth of Clostridium histolyticum and Bifidobacterium longham was measured after 24 hours while all other strains were evaluated at 48 hours to permit additional growth. Optical density was measured using a spectrophotometer and the plates were read at 620 nm. Results: All strains had results indicating polyol inhibition of growth. Clostridium histolyticum (Chis), Bifidobacterium longham (Blof), and both Clostridium bolteae (Cbol) strains showed reduced growth with increasing polyol concentration with an inflection point of about 4% for both xylitol and erythritol (complete or near complete inhibition relative to control wells). Bacteroides vulgatus (Bvul) grew very lightly in the BHI/sucrose. This strain has visible growth but very low OD values. Inhibition of growth with increasing polyol concentrations was observed but assessing the polyol inhibition break point was difficult with this strain. Conclusions: Xylitol and erythritol at sufficient concentrations were able to inhibit the growth of bacterial strains that have been associated with the development of Autism Spectrum Disorder in recently published studies.

Bezlotoxumab is a fully human monoclonal antibody that binds and neutralizes Clostridium difficile toxin B. This analysis investigated the potential of bezlotoxumab to induce immunogenicity in healthy phase 1 trial participants and in phase 2/3 trial participants receiving oral antibacterial therapy for primary or recurrent C difficile infection. Immunogenicity to bezlotoxumab was evaluated following a single intravenous dose (≤20 mg/kg) or 2 consecutive doses (10 mg/kg) given 84 days apart in healthy participants across 3 phase 1 trials (Protocol MK-3415A-004, N = 30; Protocol CA-GCDX-05-01, N = 54; Protocol MK-3415A-006, N = 12) and following a single 10 mg/kg dose in 1 phase 2 trial (Protocol CA-GCDX-06-02, ClinicalTrials.gov identifier: NCT00350298; N = 97) and 2 phase 3 trials (Protocols MK-3415A-001 and MK-3415A-002, ClinicalTrials.gov identifiers: NCT01241552 and NCT01513239; N = 1414). No treatment-emergent antidrug antibodies were observed following single or repeated dosing of bezlotoxumab. No phase 1 participants and only 1 phase 2 participant tested positive before bezlotoxumab exposure (non-treatment-emergent positive). Nine participants tested non-treatment-emergent positive in phase 3 trials, 1 of whom was neutralizing antibody-positive. Overall, the immunogenicity potential of bezlotoxumab is considered to be low.

Introduction: Clostridium difficile infection (CDI) is the most common infectious cause of diarrhoea in hospitalised patients. It is a severe issue with increasing incidence in healtcare facilities and commmunities. Early and appropriate testing of CDI is very imortant. There are many different approaches that can be used in the CDI laboratory diagnostics. Recently performed studies evaluated diagnostic algorithms to optimize laboratory CDI diagnostics. The aim of the work was to implement an optimal algorithm of testing methods in CDI diagnostics. Materials and methods: The retrospective analysis of patients’ samples suspected on CDI was carried out in 2017. The data was analysed from the Laboratory Klinicka Biochemia in Zilina. The application of ESCMID re -commendation criteria for algorithm of testing, together with procedures in laboratory practice was carried out. Results: The analysis of the data showed that the applied algorithm or testing in CDI and highlighted the importance of preanalytic phase, and the evaluation of testing methods and results, together with clinical findings. Two- and three- step algorithm together with cultivation methods were applied. 87,6% of samples could be eva -luated with positive or negative results according to the 2-step algorhitm. Further samples were assessed and tested by ELISA test or PCR method. Conclusion: CDI represents a significant burden in healthcare facilities. An early diagnostics and interpretation helps to start the early treatment and helps in surveillence of the infection.

Background:Cohorting of patients and staff is a control strategy often used to prevent the spread of infection in healthcare institutions. However, a comprehensive evaluation of cohorting as a prevention approach is lacking.Methods:We performed a systematic review of studies that used cohorting as part of an infection control strategy to reduce hospital-acquired infections. We included studies published between 1966 and November 30, 2019, on adult populations hospitalized in acute-care hospitals.Results:In total, 87 studies met inclusion criteria. Study types were quasi-experimental “before and after” (n = 35), retrospective (n = 49), and prospective (n = 3). Case-control analysis was performed in 7 studies. Cohorting was performed with other infection control strategies in the setting of methicillin-resistantStaphylococcus aureus(MRSA, n = 22),Clostridioides difficileinfection (CDI, n = 6), vancomycin-resistantEnterococcus(VRE, n = 17), carbapenem-resistant Enterobacteriaceae infections (CRE, n = 22),A. baumannii(n = 15), and other gram-negative infections (n = 5). Cohorting was performed either simultaneously (56 of 87, 64.4%) or in phases (31 of 87, 35.6%) to help contain transmission. In 60 studies, both patients and staff were cohorted. Most studies (77 of 87, 88.5%) showed a decline in infection or colonization rates after a multifaceted approach that included cohorting as part of the intervention bundle. Hand hygiene compliance improved in approximately half of the studies (8 of 15) during the respective intervention.Conclusion:Cohorting of staff, patients, or both is a frequently used and reasonable component of an enhanced infection control strategy. However, determining the effectiveness of cohorting as a strategy to reduce transmission of MDRO andC. difficileinfections is difficult, particularly in endemic situations.

Significance Clostridioides difficile is a bacterial pathogen of global importance that is a major cause of hospital-acquired diarrhea. Antibiotic-mediated disruptions to the gut microbiota and associated metabolome promote C. difficile growth and infection through mechanisms that are poorly understood. Here, we show that intestinal bile acids, which are known to play a role in C. difficile germination and outgrowth, also directly bind and inhibit TcdB toxin, the primary virulence determinant of C. difficile . Bile acid binding induces a major conformational change in TcdB structure that prevents receptor binding and uptake into cells. In addition to suggesting a role for bile acids in protecting against C. difficile pathogenesis, these findings highlight an approach to block C. difficile virulence.

Objective:Clostridioides difficile infection (CDI) is rapidly increasing in children’s hospitals nationwide. Thus, we aimed to compare the effectiveness of 9 infection prevention interventions and 6 multiple-intervention bundles at reducing hospital-onset CDI and asymptomatic C. difficile colonization.Design:Agent-based simulation model of C. difficile transmission.Setting:Computer-simulated, 80-bed freestanding, tertiary-care pediatric hospital, including 8 identical wards with 10 single-bed patient rooms each.Participants:The model includes 5 distinct agent types: patients, visitors, caregivers, nurses, and physicians.Interventions:Daily and terminal environmental disinfection, screening at admission, reduced intrahospital patient transfers, healthcare worker (HCW), visitor, and patient hand hygiene, and HCW and visitor contact precautions.Results:The model predicted that daily environmental disinfection with sporicidal product, combined with screening for asymptomatic C. difficile at admission, was the most effective 2-pronged infection prevention bundle, reducing hospital-onset CDI by 62.0% and asymptomatic colonization by 88.4%. Single-intervention strategies, including daily disinfection, terminal disinfection, asymptomatic screening at admission, HCW hand hygiene, and patient hand hygiene, as well as decreasing intrahospital patient transfers, all also reduced both hospital-onset CDI and asymptomatic colonization in the model. Visitor hand hygiene and visitor and HCW contact precautions were not effective at reducing either measure.Conclusions:Hospitals can achieve substantial reduction in hospital-onset CDIs by implementing a small number of highly effective interventions.

Background: After publication of the Clostridioides difficile infection (CDI) guidelines by the Infectious Disease Society of America (IDSA) in early 2018, we identified that many prescribers at our institution continued to practice using the older guidelines. Objective: This study aimed to determine whether the implementation of an electronic order set for CDI would increase prescriber compliance to current IDSA recommendations for CDI management. Methods: This was a single-center, prospective cohort study of adult inpatients with a confirmed CDI. The study was conducted between March 1, 2018, and April 1, 2019. Patients were stratified into a preintervention and postintervention group before and after order set implementation. The primary outcome was a composite of appropriate CDI therapy selection and discontinuation of nonessential antimicrobials and acid-suppressive agents. The secondary outcome evaluated appropriate CDI therapy medications prescribed at hospital discharge. Results: Of the 149 patients included in this study, 96 were included in a preintervention group and 53 included in a postintervention group. The primary outcome was met in 45% of patients in the preintervention group and 66% of patients in the postintervention group ( P = .01). The secondary outcome occurred in 86% of patients in the preintervention group and 100% of patients in the postintervention group ( P = .02). Conclusion: Implementation of a CDI electronic order set and alert bundle was associated with enhanced prescriber adherence to guideline-directed therapy. Our results suggest that order sets not only improve inpatient compliance to guidelines but may also improve medication-related adherence to guideline recommendations upon discharge.

Background: Mount Sinai Beth Israel is a 350-bed, acute-care hospital located on Manhattan’s Lower East Side. In 2014, the hospital had reached a high (9.8 cases per 10,000 patient days ) hospital-onset (HO) C. difficile rate. By 2015, this rate had decreased to 5.6 cases per 10,000 patient days because of compliance with established C.difficile bundle practices performed by nursing and environmental services. Despite these interventions, HO C. difficile events continued to occur. We realized that more had to be done to gain control over our rates. To determine areas for further improvement, infection prevention held an RCA meeting for every positive hospital-onset result. We discovered from these RCAs that many C. difficile tests were ordered without a valid indication. We believed that measures could be taken to ensure that only C. difficile tests with a valid indication would be ordered. Methods: We used the Plan-Do-Study-Act (PDSA) model to look at what changes could be made to reduce our rate and to sustain this reduction. Multidisciplinary meetings of leaders and frontline staff were held to determine why patients were being tested for C. difficile. The following indications were revealed: repeat tests for same patient to “catch” a positive result after the first test was negative; inclusion as part of patient “pan-culturing”; testing patients who had diarrhea after receiving laxatives; and C. difficile cultures for patients who were asymptomatic. Starting in 2016, 3 consecutive interventions were implemented in fairly rapid succession. First, a C. difficile testing algorithm was developed. Second, a C. difficile test order protocol with a “hard stop” to prevent inappropriate indications was placed in the EMR. Last, a multidisciplinary form, called the C. difficile Team Huddle Form, was created for use by all members of the patient’s team. This form gave MDs, RNs, and PCAs a framework to decide together whether the test was indicated for the patient. If the team agreed to test, the ID physician on service was called for approval. Results: These 3 interventions yielded a sustained and statistically significant decrease (P = 0.0007) in the facility-wide hospital-onset C. difficile from a preintervention rate of 5.6 cases per 10,000 patient days in 2015 to 0.4 in 2019. Conclusions: Multidisciplinary use of the C. difficile testing interventions led to further reduction of the hospital-onset C. difficile infection rate. To sustain this rate reduction over time, infection prevention specialists must work with providers and frontline staff on an ongoing basis.Funding: NoneDisclosures: None

Background:Clostridioides difficile is a major cause of antibiotic-associated colitis and the most common healthcare-associated pathogen in the United States. Interrupting the known transmission mechanisms of C. difficile in hospitals requires appropriate hand hygiene, disinfection of potentially contaminated surfaces, and patient equipment. However, only limited data are available on the effectiveness of germicides against various strains of C. difficile, with and without fetal calf serum, and at multiple exposure times. For this reason, we undertook the following evaluation to determine the effectiveness of germicides. Methods: The effectiveness of the sporicidal activity of the germicides against 5 strains of C. difficile was evaluated using a quantitative carrier test, a standard of ASTM International developed by Sattar et al. In this protocol, metal carriers (1 cm diameter 0.7 mm thick) were inoculated with 10 L spore suspension, containing ~103 or 106 C. difficile spores, and we then exposed them to 50 L germicide for 1, 5, 10, or 20 minutes. The following C. difficile strains were used in these studies: ATCC strains 9689; J9; BI-9; 630; and CF-4. To determine whether C. difficile spore susceptibility was similar to other spores, we also tested Bacillus atrophaeus spores, ATCC strain 19659. Fetal calf serum (FCS) was used to simulate organic matter. Results: In general, high-level disinfectants (eg, OPA, glutaraldehyde), chemical sterilants (eg, peracetic acid), and high concentrations of chlorine (>5,000 ppm) were generally sporicidal (>3 log10 reduction) in 5–10 minutes (and sometimes 1 minute). This level of sporicidal activity was demonstrated for the various strains of C. difficile spores and B. atrophaeus spores (Table 1). There did not appear to be any significant differences in inactivation of C. difficile spores (BI-9 strain) in the presence or absence of FCS (Table 2). Discussion: The sporicidal activity of disinfectants is critical because such formulations are routinely used to eliminate the risk associated with noncritical and semicritical instruments and environmental surfaces. Our data suggest that immersion in most (but not all) high-level disinfectants for 10 minutes is likely to be successful in eradicating C. difficile spores (>4 log10 reduction) from semicritical equipment (eg, endoscopes). Additionally, high concentrations of chlorine and some high-level disinfectants will kill C. difficile spores in 1 or 2 minutes.Funding: NoneDisclosures: Drs. Rutala and Weber are consultants to PDI (Professional Disposable International)

Previous decades have witnessed a change in the epidemiology of Clostridium difficile infections. This study aimed to determine temporal trends in the incidence of C difficile infection across geographic regions.An initial search of the relevant literature was conducted from date inception to October 2018 without language restriction. We estimated the pooled incidences using logit transformation, weighted by inverse variance. The Joinpoint Regression Analysis Program was used to explore its temporal trend.Globally, the estimated incidence of C difficile infection increased from 6.60 per 10,000 patient-days in 1997 to 13.8 per 10,000 patient-days in 2004. Thereafter, a significant downward trend was observed, at -8.75% annually until 2015. From 2005 to 2015, the incidences in most European countries decreased at a rate between 1.97% and 4.11% per annum, except in France, where an increasing incidence was observed (β = 0.16; P.001). The incidences have stabilized in North America over the same period; however, in Asia, the incidence increased significantly from 2006 to 2014 (annualized percentage change = 14.4%; P.001). The increase was greatest in Western Asian countries, including Turkey and Israel (β0.10; P.004).This study revealed rapid changes in the incidence of C difficile infection. This meta-analysis should inform the allocation of resources for controlling C difficile infection and future surveillance efforts in countries where epidemiologic information on C difficile infection remains sparse.

BackgroundClostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.MethodsWe reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.ResultsWe included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0–47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3–20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.ConclusionsFew patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

Background:Clostridium difficile infection (CDI) is a reportable hospital metric associated with significant healthcare expenditures. The epidemiology of CDI is pivotal to the implementation of preventative measures.Objective:To portray temporal CDI trends in Veterans Health Administration (VA) hospitals.Design:A retrospective analysis of veterans who had stool testing for C. difficile.Setting:VA acute-care hospitals within the continental United States.Methods:Data were mined from the VA’s Corporate Data Warehouse. CDI is reported per 10,000 patient days.Results:From 2006 to 2016, 472,346 patients had C. difficile testing. Overall, decreases in incidence of total CDI (16.81 to 13.66) and hospital-onset healthcare facility-associated (HO-HCFA) CDI (10.87 to 6.41) were observed. Temporal increases in the incidence of total and HO-HCFA CDI were associated with the increased use of molecular testing (P < .0001). Decreased use of fluoroquinolones (P < .0001), clindamycin (P = .0006), and third-generation cephalosporins (P = .0002) correlated with decreased rates of CDI, but VA mandatory reporting did not influence CDI rates (P = .24). The overall crude 30-day mortality of patients with CDI decreased from 2.17 deaths per 10,000 patient days in 2006 to 1.41 in 2016. The frequency of International Classification of Disease, Ninth/Tenth Revision (ICD-9/10) discharge diagnosis for CDI was 73.3%.Conclusion:Molecular testing was associated with increased incidence of CDI. Controlling CDI is likely multifactorial. Although the VA initiative to report cases of hospital-acquired CDI was not significant in our model, the advent of stewardship programs throughout the VA and reductions in the use of third-generation cephalosporins, fluoroquinolones, and clindamycin were significantly associated with reduced rates of CDI.

Purpose: Clostridium difficile spores are extremely resilient to high temperatures. Sublethal temperatures are associated with the ‘reactivation’ of dormant spores, and are utilized to maximize C. difficile spore recovery. Spore eradication is of vital importance to the food industry. The current study seeks to elucidate the transient and persisting effects of heating C. difficile spores at various temperatures. Methods: Spores of five C. difficile strains of different ribotypes (001, 015, 020, 027 and 078) were heated at 50, 60 and 70–80 °C for 60 min in phosphate-buffered saline (PBS) and enumerated at 0, 15, 30, 45 and 60 min. GInaFiT was used to model the kinetics of spore inactivation. In subsequent experiments, spores were transferred to enriched brain heart infusion (BHI) broths after 10 min of 80 °C heat treatment in PBS; samples were enumerated at 90 min and 24 h. Results: The spores of all strains demonstrated log-linear inactivation with tailing when heated for 60 min at 80 °C [(x=7.54±0.04 log10 vs 4.72±0.09 log10 colony-forming units (c.f.u.) ml− 1; P