Epidemiology Of Clostridioides Difficile Infection Research Articles

Predominance of Clostridioides difficile PCR ribotype 181 in northern Greece, 2016–2019

ObjectivesThe epidemiology of Clostridioides difficile infection (CDI) has undergone many changes since the beginning of this century and continues to evolve based on recent studies. Here, we performed a molecular analysis of C. difficile isolates in northern Greece across 10 health-care facilities, spanning from 2016 to 2019. Methods221 C. difficile isolates were cultured from stool samples of hospitalized patients with diarrhea and screened by PCR for the presence of the toxin A (tcdA), toxin B (tcdB), the binary toxin (cdtA and cdtB) genes and the regulating gene of tcdC. PCR ribotyping of the cultured isolates was performed by a standardized protocol for capillary gel-based PCR ribotyping and an international database with well-documented reference strains. ResultsThirty-five different PCR ribotypes were identified. The most common RTs identified were: 181 (36%, 80/221), 017 (10%, 21/221), 126 (9%, 19/221), 078 (4%, 9/221) and 012 (4%, 8/221). Notably, the predominant RT181, with toxin profile tcdA+tcdB+cdtA+cdtB+, was identified in seven out of ten participating hospitals. ConclusionsMultiple C. difficile ribotypes have been circulating in the northern Greece region with RTs 181 (closely related to 027), 017, 126 and 078 being predominant.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Evaluation of the genomic epidemiology and transmission of Clostridioides difficile infection across a community

Background:Clostridioides difficile infection (CDI) is a major cause of morbidity and healthcare costs in the United States. The epidemiology of CDI has recently shifted, with healthcare-associated (HCA) CDI trending downward and community-associated (CA)-CDI becoming more prominent. The cause of this shift is not well understood but may be related to changing genomic epidemiology. We assessed C. difficile strains across a CDC Emerging Infections Program (EIP) site in Western New York, including strains from both HCA-CDI and CA-CDI cases to characterize predominating strains and putative transmission across epidemiological classifications and between index and recurrent cases. Methods: In total, 535 isolates of C. difficile were collected over a 6-month period in 2018 from the Monroe Country, New York, EIP site and were analyzed using whole-genome sequencing (WGS). Standard epidemiological definitions were used to classify cases as hospital onset (HO-CDI); community associated (CA-CDI); community onset, healthcare associated (CO-HCFA-CDI); or long-term care onset (LTCO-CDI). Recurrent cases were defined as those diagnosed within 8 weeks of an initial positive test. Multilocus sequence types (MLSTs) were assigned according to PUBMLST and single-nucleotide polymorphisms (SNPs) were determined using a modified CFSAN analytical pipeline. Cases resulting from putative transmission were defined as those separated by 0–1 core SNPs. Results: Of 535 isolates, 454 were from index and 81 were from recurrent cases. The index cases were comprised of CA-CDI (47.4%), CO-HCFA-CDI (24%), LTCO-CDI (8.1%), and HO-CDI (19.3%). Cases with recurrent disease mirrored the epidemiological distribution of the larger set. Common MLSTs included ST2 (12.3%), ST8 (10.5%), ST42 (7.9%), ST58 (4.9%), ST43 (4.5%), and ST11 (4.3%). The previously widespread epidemic strain, NAP1/ST1/RT027 accounted for Conclusions: The genomic epidemiology of C. difficile across this large community cohort demonstrated a diverse group of strain types that was similarly distributed across epidemiological classifications and between index and recurrent cases. SNP analysis indicated that direct transmission between cases was uncommon.Funding: NoneDisclosures: None

Clostridioides difficile infection (CDI) epidemiology and patient characteristics in Switzerland

ObjectivesClostridioides difficile infection (CDI) is a disease with high morbidity and mortality rates. The objective of this study was to describe CDI epidemiology and patient characteristics over a 5-year period in Switzerland and assess risk factors for mortality, recurrence and severe CDI. Patients and methodsWe retrospectively included all consecutive CDI cases having occurred in adult patients hospitalized in two tertiary centers: the Lausanne University Hospital (1000 beds) and the University Hospital of Zurich (900 beds), between 2014 and 2018. Suspected cases of CDI were identified from the microbiology laboratory database on the basis of a positive test and confirmed by records review. ResultsDuring first CDI episodes, the median age was 67 years and the median Charlson comorbidity index (CCI) score was 5. All in all, 299 out of 826 patients (36.2%) had severe infection based on the Infectious Diseases Society of America criteria. In the multivariable analysis, CCI was associated with increased risk of mortality. None of the factors recorded on admission were significantly associated with increased risk of recurrence. In the multivariable analysis, male sex and CCI were associated with severity, while immunosuppression was associated with less severe presentation. ConclusionsIf we did not identify any criteria on admission that could be predictive of recurrences, this could be explained the retrospective nature of the study. A higher comorbidity index is a key driver for severe CDI and mortality. Reporting of CDI is not mandatory in Switzerland; structuration of CDI reporting should be a short-term priority.

Epidemiology of Clostridioides difficile infection in hospitalized patients in Spain: An eight-year review (2012–2019)

BackgroundClostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data. MethodsPoint prevalence survey data on infections of hospitalized patients for years 2012–2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI. ResultsThe prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08–1.15) and 1.09% (CI 95% 1.04–1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age. ConclusionIn Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making.

Clostridioides (Clostridium) difficile isolated from paediatric patients in Western Australia 2019–2020

Less is understood about the epidemiology of Clostridioides difficile infection (CDI) in children compared to adults, and its impact is complicated by variations in the natural development of infection in paediatric patients. The interplay of rising CDI incidence in hospitalised paediatric patients, emergence of hypervirulent strains and community associated CDI (CA-CDI) in the past decade is a potential threat in both hospital and community settings. Research in Australia regarding paediatric CDI is limited. Here, we report the molecular characterisation of C.difficile isolated from paediatric patients at a tertiary hospital in Perth, Western Australia. A total of 427 stool samples was collected from patients aged from <1 to 17 years being investigated for diarrhoea from July 2019 to June 2020. Stool specimens were cultured and isolates of C.difficile characterised by ribotyping and toxin gene profiling. Clostridioides difficile was recovered from 84/427 (19.7%) samples tested. The most prevalent PCR ribotypes (RTs) were RT 002 (12.4%), a toxigenic strain, and RT 009 (15.7%), a non-toxigenic strain. Interestingly, C.difficile RT 078 and RT 017, strains that are not endemic in Australia, were isolated from a 1- and 4-year-old child, respectively. Clostridioides difficile RT 106, a strain of emerging importance in Australia, was recovered from two cases (5.3%). Resistance to metronidazole, fidaxomicin, amoxicillin, rifaximin and meropenem was not detected, however, 45 isolates (50.6%) showed resistance to at least one agent, and multidrug resistance was observed in 13.3% of the resistant isolates (6/45). This study provides a baseline for future surveillance of paediatric CDI in Australia. Given that young children can be asymptomatically colonised with toxigenic C.difficile strains, they represent a potential reservoir of strains causing CDI in adults.

Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.

The US Centers for Disease Control and Prevention (CDC) classified Clostridioides 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 C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence. Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children. This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.

Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy.

Clostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000 C. difficile genomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, and pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI-III. The emergence of these three novel genomospecies predates clades C1-5 by millions of years, rewriting the global population structure of C. difficile specifically and taxonomy of the Peptostreptococcaceae in general. These genomospecies all show unique and highly divergent toxin gene architecture, advancing our understanding of the evolution of C. difficile and close relatives. Beyond the taxonomic ramifications, this work may impact the diagnosis of CDI.

Epidemiologic and Clinical Characteristics of Clostridioides difficile Infections in Hospitalized and Outpatient Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

The epidemiology and clinical course of Clostridioides difficile infection (CDI) in children, especially with cancer, are poorly defined. We aim to describe the epidemiology, clinical features and outcomes of CDI and to identify risk factors for recurrence in a pediatric oncology center. This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by positive C. difficile test in symptomatic patients. CDI episodes were classified as incident, duplicate or recurrent and community-onset, hospital-onset or community-onset healthcare facility-associated. Data about clinical course and outcomes were abstracted. Risk factors for CDI recurrence were assessed by logistic regression. One hundred seventy-eight patients 1 year of age and older developed 291 CDI episodes; 78% were incident and 22% recurrent. Underlying diagnoses were leukemia/lymphoma (57%) and solid/brain tumors (41%); 30% were HSCT recipients. Antibiotics, chemotherapy, antacids, steroids and laxatives were received by 96%, 82%, 70%, 47% and 15%, respectively. Half of the patients were neutropenic. Twenty-two percent of outpatients with CDI required hospitalization. Chemotherapy was delayed in 25%. There were no intensive care unit admissions nor deaths due to CDI. Exposure to H2-antagonists was identified as an independent risk factor for CDI recurrence. Although CDI in pediatric oncology and HSCT patients was associated with chemotherapy delay and hospitalization in approximately a quarter of patients, it was not associated with morbidity or mortality because patients had no attributable intensive care unit admission nor death. H2-antagonists are independent risk factors for CDI recurrence.

Epidemiology of Clostridioides difficile infection in hospitalized patients in Spain: An eight-year review (2012–2019)

BackgroundClostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data. MethodsPoint prevalence survey data on infections of hospitalized patients for years 2012–2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI. ResultsThe prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08–1.15) and 1.09% (CI 95% 1.04–1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age. ConclusionIn Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making.

Burden of Clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI

BackgroundClostridioides difficile is a Gram-positive anaerobic bacterium, which causes Clostridioides difficile infection (CDI). It has been recognised as a leading cause of healthcare-associated infections and a considerable threat to public health globally. This systematic literature review (SLR) summarises the current evidence on the epidemiology and clinical burden of CDI.MethodsA SLR was conducted to identify CDI and recurrent CDI (rCDI) epidemiology studies, to evaluate patient and disease characteristics, incidence rates, epidemiological findings and risk factors. Embase, MEDLINE and the Cochrane Library databases were searched for English articles from 2009 to 2019. Included territories were the United Kingdom, France, Germany, Italy, Spain, Poland, US, Canada, Australia, Japan and China.ResultsOf 11,243 studies identified, 165 fulfilled the selection criteria. An additional 20 studies were identified through targeted review of grey literature. The most widely reported findings were incidence and risk factors for CDI and rCDI.Among key studies reporting both healthcare-associated (HA-CDI) and community-associated CDI (CA-CDI) incidence rates for each country of interest, incidence rates per 10,000 patient days in the US were 8.00 and 2.00 for HA-CDI and CA-CDI, respectively. The highest incidence in Europe was reported in Poland (HA-CDI: 6.18 per 10,000 patient days, CA-CDI: 1.4 per 10,000 patient days), the lowest from the UK, at 1.99 per 10,000 patient days and 0.56 per 10,000 patient days for HA-CDI and CA-CDI, respectively.No clear trend for incidence over time emerged, with most countries reporting stable rates but some either a decrease or increase.Rates of recurrent CDI varied based on geographical setting. The rate of recurrence was lower in community-associated disease compared to healthcare-associated disease.Independent CDI risk factors identified common to both initial CDI and recurrent CDI included increasing age, antibiotic use, recent hospitalisation, and proton pump inhibitor (PPI) use. In addition, leukocyte count, length of hospital stays, and Charlson comorbidity index score featured as statistically significant risk factors for recurrent CDI, but these are not reported among the most common statistically significant risk factors for initial CDI.ConclusionsDespite considerable heterogeneity, evidence suggests substantial incidence of recurrent and primary CDI, even after considerable efforts in the last decade.

Establishment of a French surveillance system of Clostridiodes difficile infection: Comparison of patient’s characteristics with other national and European data

IntroductionThe magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies. MethodsDIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions.A literature review of studies conducted in Western Europe on CDI and published between January 2008 and May 2018 was done to compare their data with those included in the DIFTEC™ database. ResultsFrom January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%).The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study.Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies. DiscussionThese results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings.

Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection.

In the United States, Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infection, affecting nearly half a million people and resulting in more than 20,000 in-hospital deaths every year. It is therefore imperative to better characterize the intricate interplay between C. difficile microbial factors, host immunologic signatures, and clinical features that are associated with adverse outcomes of severe CDI. In this narrative review, we discuss the implications of C. difficile genetics and virulence factors in the molecular epidemiology of CDI, and the utility of early biomarkers in predicting the clinical trajectory of patients at risk of developing severe CDI. Furthermore, we identify associations between host immune factors and CDI outcomes in both animal models and human studies. Next, we highlight clinical factors including renal dysfunction, aging, blood biomarkers, level of care, and chronic illnesses that can affect severe CDI diagnosis and outcome. Finally, we present our perspectives on two specific treatments pertinent to patient outcomes: metronidazole administration and surgery. Together, this review explores the various venues of CDI research and highlights the importance of integrating microbial, host, and clinical data to help clinicians make optimal treatment decisions based on accurate prediction of disease progression.

Tube Feeding: A Risk Factor for Clostridioides difficile Infection Among Long-Term Care Facility Residents Hospitalized at a Tertiary-Care Hospital in Detroit

Objective: We investigated the epidemiology of Clostridioides difficile infection (CDI) in long-term care facility (LTCF) patients admitted to a tertiary-care center in Detroit. Methods: A retrospective case-control study was conducted of LTCF residents who were hospitalized with CDI at the Detroit Medical Center between January 1, 2009, and December 31, 2016. Case patients (LTCF residents admitted with CDI) were compared to 2 sets of inpatient controls. The first set of controls included inpatients presenting from the same LTCFs without CDI (control A). Second set included inpatients admitted from non-LTCF (home, community, hospital) who acquired CDI &gt; 48 hours after admission or those who acquired CDI within 48 hours of admission but were exposed to an acute-care hospital within 4 weeks prior to admission (control B). Cases were matched (1:3 ratio) to the 2 sets of controls (control A and control B) based on year of admission. Matched multivariable analyses using conditional logistic regression were performed to identify independent predictors of CDI. Results: In total, 85 cases were matched to 2 sets of controls. For the first multivariate logistic regression model performed on cases and control A (n1 = 255), significant risk factors identified included tube feeding (OR, 3.60; 95% CI, 1.43–9.02; P = .006) and albumin ≤2.5 g/dL (OR, 4.98; 95% CI, 2.02–12.31; P &lt; .001). For the second multivariate logistic regression model performed on cases and control B (n2 = 255), significant risk factors identified included Charlson comorbidity index score (OR, 1.25; 95% CI, 1.12–1.40; P &lt; .001), tube feeding (OR, 3.63; 95% CI, 1.81–7.25; P &lt; .001), prior use of PPI (OR, 0.37; 95% CI, 0.20–0.68; P = .001), prior use of H2 blockers (OR, 0.34; 95% CI, 0.16–0.69; P = .003), and prior use of antibiotics (OR, 0.12; 95% CI, 0.06–0.24; P &lt; .001). Cases were more likely to have complicated CDI (OR, 7.02; P &lt; .001) and recurrent CDI (OR, 2.63; P =.02) when compared to control B. Conclusions: Patients who acquired CDI at LTCFs experienced more severe CDI and were at greater risk for recurrent CDI than patients with other healthcare-associated CDI. For the regression model performed on cases and control A as well as that performed on cases and control B, tube feeding was the only variable that consistently predicted CDI among LTCF patients.Funding: This study was supported by Pfizer Inc (Collegeville, PA).Disclosures: None

Temporal Change of Risk Factors in Hospital-Acquired Clostridioides difficile Infection Using Time-Trend Analysis

Background: In the past few decades, the epidemiology of Clostridioides difficile infection (CDI) has evolved. Given recent changes in the incidence of CDI and prevention efforts, we investigated temporal changes over a period of 8 years (2009–2016) in the incidence of and risk factors for CDI. Methods: Both pediatric and adult inpatients discharged from hospitals in metropolitan New York City were included. Individual and environmental (eg, pharmacological) risk factors were identified through a matched case-control by the length of stay at a ratio of 1:4. A Cochran–Armitage test or Mann-Kendall test was used to investigate trends of incidence and risk factors. Results: During the study period, 6,038 of 694,849 (0.87%) patients had a positive test for C. difficile during their hospitalization. Of these, 2,659 of 6,038 (44.04%) were identified as hospital-acquired CDI (HA-CDI) and just over half (3,379 of 6,038, 55.96%) were identified as community-acquired CDI (CA-CDI). There were no trends in total CDI incidence rates; rather, we detected downward trends in HA-CDI and upward trends in CA-CDI (Ptrend &lt; .05). Younger patients and patients with lower risk of illness had HA-CDI over time (Ptrend &lt; .05). Antibiotics were administered to more patients over time and in longer cumulative days (+3% and +3.1% per year). We detected a reduction in the receipt of high-risk antibiotics in all cohorts (−0.12% per year) and a decrease in cumulative days of high-risk antibiotics in the cohort with HA-CDI (−1.1% per year). When stratified by the type of high-risk antibiotics, the use of carbapenem, cephalosporins, clindamycin, and monobactam increased (+0.53%, +1.8%, +0.5%, and +0.39% per year, respectively), whereas the use of broad-spectrum penicillins and glycylcycline significantly decreased over time in all cohorts (−1.8% and −0.22% per year). Among the cohorts with HA-CDI, only cephalosporins showed a significant upward trend (+ 5.7% per year) and only fluoroquinolones showed a significant downward trend (−2.2% per year). Lastly, a reduction of proton pump inhibitors and an increased use of histamine-2 blockers were detected in all cohorts (−3.8% and +7.3% per year) (all Ptrend &lt; .05). Conclusions: Although the incidence of HA-CDI decreased, more effort to decrease all antibiotics use and cumulative days should be emphasized as part of antibiotic stewardship. The downward trends of high-risk antibiotics might have been associated with the decrease in the trend of HA-CDI; however, the impact of the trends of risk factors on the trend of HA-CDI should be further investigated.Funding: NoneDisclosures: None

Epidemiological and Molecular Characterization of Clostridioides difficile Infection in Canadian Outpatient Settings, 2015–2019

Background: Healthcare services are increasingly shifting from inpatient to outpatient settings. Outpatient settings such as emergency departments (EDs), oncology clinics, dialysis clinics, and day surgery often involve invasive procedures with the risk of acquiring healthcare-associated infections (HAIs). As a leading cause of HAI, Clostridioides difficile infection (CDI) in outpatient settings has not been sufficiently described in Canada. The Canadian Nosocomial Infection Surveillance Program (CNISP) aims to describe the epidemiology, molecular characterization, and antimicrobial susceptibility of outpatient CDI across Canada. Methods: Epidemiologic data were collected from patients diagnosed with CDI from a network of 47 adult and pediatric CNISP hospitals. Patients presenting to an outpatient setting such as the ED or outpatient clinics were considered as outpatient CDI. Cases were considered HAIs if the patient had had a healthcare intervention within the previous 4 weeks, and they were considered community-associated if there was no history of hospitalization within the previous 12 weeks. Clostridioides difficile isolates were submitted to the National Microbiology Laboratory for testing during an annual 2-month targeted surveillance period. National and regional rates of CDI were stratified by outpatient location. Results: Between January 1, 2015, and June 30, 2019, 2,691 cases of outpatient-CDI were reported, and 348 isolates were available for testing. Most cases (1,475 of 2,691, 54.8%) were identified in outpatient clinics, and 72.8% (1,960 of 2,691) were classified as community associated. CDI cases per 100,000 ED visits were highest in 2015, at 10.3, and decreased to 8.1 in 2018. Rates from outpatient clinics decreased from 3.5 in 2016 to 2.7 in 2018 (Fig. 1). Regionally, CDI rates in the ED declined in Central Canada and increased in the West after 2016. Rates in outpatient clinics were &gt;2 times higher in the West compared to other regions. RT027 associated with NAP1 was most common among ED patients (26 of 195, 13.3%), whereas RT106 associated with NAP11 was predominant in outpatient clinics (22 of 189, 11.6%). Overall, 10.4% of isolates were resistant to moxifloxacin, 0.5% were resistant to rifampin, and 24.2% were resistant to clindamycin. No resistance was observed for metronidazole, vancomycin, or tigecycline. Compared to CNISP inpatient CDI data, outpatients with CDI were younger (51.8 ± 23.3 vs 64.2 ± 21.6; P &lt; .001), included more females (56.4% vs 50.9%; P &lt; .001), and were more often treated with metronidazole (63.0% vs 56.1%; P &lt; .001). Conclusions: For the first time, CDI cases identified in outpatient settings were characterized in a Canadian context. Outpatient CDI rates are decreasing overall, but they vary by region. Predominant ribotypes vary based on outpatient location. Outpatients with CDI are younger and are more likely female than inpatients with CDI.Funding: NoneDisclosures: Susy Hota reports contract research for Finch Therapeutics.

Time trends and predictors of laboratory-confirmed recurrent and severe Clostridioides difficile infections in Manitoba: a population-based study.

Many previous studies of Clostridioides difficile infection (CDI) epidemiology have used hospital discharge data codes, which can have limited accuracy. We used a data set of laboratory-confirmed cases of CDI in the province of Manitoba, Canada, to describe the epidemiology of CDI over a decade. We conducted a population-based historical cohort study using Manitoba Health's population-wide laboratory-based CDI data set linked to administrative health databases. All individuals living in Manitoba and experiencing a CDI episode between 2005 and 2015 were included (n = 8471) and followed up from CDI diagnosis. We assessed time trends of CDI, incidence and predictors of recurrence and severe outcomes, and health care encounters after CDI diagnosis. CDI episodes were stratified by community versus hospital site of acquiring CDI. Between 2005 and 2009, overall CDI diagnoses decreased by an average of 12.6% per year (95% confidence interval [CI] -4.4 to -20.0), with no statistically significant change from 2010 to 2015. In stratified analysis, incident and recurrent CDI had a similar decrease in the initial study time period and then stabilized. The proportion of community-associated CDI cases increased by an average of 4.8% per year (95% CI 2.8 to 6.8) during the study period. CDI acquired in a health care facility had a higher recurrence rate and more severe outcomes. Recurrence of CDI increased the likelihood of admission to hospital. Between 2005 and 2015, the rates of overall laboratory-confirmed CDI, incident CDI, recurrent CDI and severe outcomes following CDI initially decreased before stabilizing, and an increasing proportion of CDI cases were community-associated. There is an increasing need to test for CDI among outpatients with diarrhea and to increase efforts to prevent recurrent CDI.

Multicenter study of the epidemiology of Clostridioides difficile infection and recurrence in southern Brazil

Clostridioides (Clostridium) difficile is the main etiology underlying antibiotic-associated diarrhea (AAD). Still, few Brazilian data are available on this infection. The aims of this multicenter study were to identify the prevalence, clinical characteristics, and outcomes of C. difficile infection (CDI) in patients with antibiotic associated diarrhea at eight hospitals in Curitiba, southern Brazil, during the years 2017–2019. Stool samples were tested using enzyme immunoassay for glutamate dehydrogenase antigen (GDH) and A/B toxins. Positive GDH samples were further evaluated by real-time polymerase chain reaction (PCR) for the presence of genes encoding toxin B (tcdB), binary toxin (cdt), and marker of hypervirulent C. difficile strain (tcdC deletion). The prevalence of CDI in 351 patients with AAD included in the study was 17.7% (n = 62). Among the CDI cases, tcdB was positive in all 62 stool samples, while cdt was positive in 10 samples, and tcdC deletion was positive in only two. Carriage of carbapenem-resistant Gram-negative bacilli, previous hospitalization, and use of broad-spectrum cephalosporin and carbapenem were associated with CDI. Among patients with CDI, 64.5% presented with severe diarrhea, and 8% (5/62) progressed with colitis and required intensive care. The 30-day mortality was 24% (15/62), and the CDI-associated mortality was 4.8% (3/62). Overall, 83.8% (52/62) of the patients achieved primary cure, and 20.8% of the evaluated patients (10/48) presented CDI recurrence. The treatment administered was not significantly associated with the 60-day recurrence or mortality. In conclusion, we reported in this study data of prevalence and recurrence rates of CDI in patients with AAD and evaluated the number of severe cases and infection-related mortality, which were up to now unknown in Southern Brazilian hospitals.

Hospital acquired Clostridioides difficile infection and risk factors for severity in a university hospital: A prospective study

Clostridioides difficile infection (CDI) is a well-known cause of health care-associated diarrhea. Data about CDI epidemiology of Turkey is limited. This study investigates CDI incidence, clinical characteristics, and factors associated with severe CDI in a tertiary care center university hospital. This is a case control study was conducted between 2012 and 2016. We included all patients, 18 years of age or more, with CDI diagnosis. For each patient diagnosed with CDI, information was collected concerning the severity of disease, treatment regimen, treatment response, disease recurrence, 30-day case fatality. Cases defined as severe hospital acquired CDI (HA-CDI) and controls defined as non-severe CDI patients. We identified 100 cases of HA-CDI out of 111 patients. Total CDI incidence was 1.19/10,000 patient-days. The incidence decreased 32.5% during the study period. We identified severe CDI in 24% of patients. Age and admission to intensive care unit were independent risk factors for severe CDI. This study reports a 5-year prospective epidemiology of CDI in a tertiary care center in Istanbul, Turkey. The findings of this study suggest that HA-CDI incidence and proportion of severe CDI is low compared to European and US literature. We believe that CDI is underreported, neglected but still an important health care associated infection in Turkey.

Temporal change of risk factors in hospital-acquired Clostridioides difficile infection using time-trend analysis.

Given recent changes in the epidemiology of Clostridioides difficile infection (CDI) and prevention efforts, we investigated temporal changes over a period of 11 years (2006-2016) in incidence and risk factors for CDI. Retrospective matched case-control study. Pediatric and adult inpatients (n = 694,849) discharged from 3 hospitals (tertiary and quaternary care, community, and pediatric) in a large, academic health center in New York City. Risk factors were identified in cases and controls matched by length of stay at a ratio of 1:4. A Cochran-Armitage or Mann-Kendall test was used to investigate trends of incidence and risk factors. Of 694,849 inpatients, 6,038 (0.87%) had CDI: 44% of these cases were hospital acquired (HA-CDI) and 56% were community acquired (CA-CDI). We observed temporal downward trends in HA-CDI (-0.03% per year) and upward trends in CA-CDI (+0.04% per year). Over time, antibiotics were administered to more patients (+3% per year); the use of high-risk antibiotics declined (-1.2% per year); and antibiotic duration increased in patients with HA-CDI (+4.4% per year). Fewer proton-pump inhibitors and more histamine-2 blockers were used (-3.8% and +7.3% per year, respectively; all Ptrend <.05). Although the incidence of HA-CDI decreased over time, CA-CDI simultaneously increased. Continued efforts to assure judicious use of antibiotics in inpatient and community settings is clearly vital. Measuring the actual the level of exposure of an antibiotic (incidence density) should be used for ongoing surveillance and assessment.