Epidemiology Of Clostridioides Difficile Infection Research Articles

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.

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) wereidentified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.

Clostridioides difficile Infections in Adult and Pediatric Intestinal and Multivisceral Transplant Patients

Background Solid organ transplant (SOT) recipients are at increased risk of Clostridioides difficile infection (CDI). Studies addressing the epidemiology of CDI in intestinal and multivisceral transplant are limited. Since 2013, our center greatly expanded its intestinal and multivisceral transplant program, providing the consummate opportunity to examine CDI in this vulnerable population. Methods We conducted a retrospective study of all intestinal and multivisceral transplant recipients between 2009 and 2018. Results We identified 86 patients who underwent a total of 94 transplants. There were 60 isolated intestinal transplants (64%), 21 intestine/pancreas/liver (22%), 10 intestine/pancreas (11%), 2 intestine/pancreas/liver/kidney (2%), and 1 intestine/kidney transplant (1%). All but 3 patients received perioperative metronidazole. Four patients (5%) had CDI before transplant, but none experienced recurrence in the first 6 months posttransplant. Five patients suffered 7 mild-moderate episodes of early CDI (attack rate, 5.9%). Three patients (60%) with early CDI developed rejection, similar to the observed incidence (70%) in patients without CDI. Two patients with early CDI developed recurrent infection; both of these patients underwent intestinal retransplant. Overall, 1-year mortality was similar (20% among patients with early CDI vs. 23% among those without early CDI). Conclusions For certain solid organ transplant recipients, an association between CDI and allograft loss, rejection, and mortality has been shown. Although limited by sample size, we observed that early CDI was not associated with those outcomes in the present investigation. Multicenter studies are merited to explore risk factors for CDI and associations with transplant-related outcomes in intestinal and multivisceral transplant recipients.

Recommendations and guidelines for the treatment of Clostridioides difficile infection in Taiwan.

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided.

Incidence of Clostridioides difficile infection in peripartum women: a retrospective cohort study.

Background:The incidence of Clostridioides difficile infection (CDI) is increasing in the general population. Data on the epidemiology of CDI in peripartum women – a highly vulnerable patient population – is scarce. The objective of this study was to report the incidence of CDI in peripartum women.Methods:A single-center retrospective cohort study was conducted in peripartum women from 1997 to 2017. Peripartum CDI was defined as definite CDI (watery diarrhea for >24 h with positive stool assay) during pregnancy, or within 6 weeks postpartum. Incidence was reported per 100,000 pregnancies and time trends in incidence were analyzed using Poisson regression. Analyses were done separately for time trends before and after 2007, when CDI testing strategy changed to polymerase chain reaction.Results:From 1997 to 2017, 80 patients with peripartum CDI (47 during pregnancy, 33 postpartum) out of 125,683 pregnancies (0.064%) were identified. Incidence of CDI increased 3.4 fold (95% confidence interval 1.5–7.4, p = 0.005) over the 21 year period. Time trends were evident after (p = 0.054), but not before 2007 (p = 0.97).Conclusion:Incidence of CDI in peripartum women increased over the 21 year study period. The rise in incidence is concerning, and calls for heightened surveillance for CDI in this highly vulnerable population.

Foodborne transmission of Clostridioides difficile: a review.

The epidemiology of Clostridioides difficile infection (CDI) is changing, with increasing rates of community-acquired infections. In light of recent advances in understanding C. difficile transmission networks with whole-genome sequencing, new routes of spread outside the hospital need to be considered. This review examines the evidence behind food as a driver of C. difficile dissemination. Recently published studies adding to the existing body of literature supporting C. difficile as a foodborne pathogen are discussed. Specifically, new evidence on the presence of C. difficile in root vegetables is reviewed. Whole genome sequencing studies delineating local and global transmission networks, in which the food chain may play a large role, are presented. Additional research implicating trehalose in the food industry and C. difficile is examined. Genomic studies show that a new approach to studying C. difficile transmission is needed. Further research on C. difficile epidemiology should shift from a primarily nosocomial setting to include the community and environment at large, and attention given to implications of the food chain in the spread of this pathogen.

Clostridioides difficile ribotypes 001 and 126 were predominant in Tehran healthcare settings from 2004 to 2018: a 14-year-long cross-sectional study

ABSTRACT Clostridioides difficile infection (CDI) remains a major healthcare problem worldwide, however, little is known about CDI epidemiology in Iran. Between December 2004 and November 2018, 3649 stool samples were collected from patients in 69 hospitals and medical centres in Tehran and were cultured for the presence of C. difficile; isolates were characterized by PCR ribotyping and toxin genes detection. A total of 582 C. difficile isolates were obtained and the overall CDI prevalence was 15.9%; 290 (49.8%) cases were healthcare-associated (HA) and 292 (50.2%) cases were community-associated (CA). Of these, DNA of 513 isolates submitted for ribotyping. The ribotype and/or WEBRIBO type could be assessed in 366 (62.9%) isolates. The most frequent RTs were 001 (n = 75, 12.9%), 126 (n = 65, 11.2%) and 084 (n = 19, 3.3%); the toxin gene profile tcdA + B + /cdtA + B + (n = 112, 19.2%) was the most common. Fifteen C. difficile isolates (2.6%) did not carry any toxin genes. There was no difference between frequently found RTs in HA-CDI and CA-CDI, except for RT 029 which was more likely to be associated with healthcare origin (12/15, p-value = 0.02). No isolate of RTs 027 or 078 was identified. Importantly, RTs 031, 038, 039, 084, 085 reported previously as RTs with an absence of toxin genes, revealed the presence of toxin genes in our study. Using Simpson’s reciprocal index of diversity, we found that RT diversity decreased as the prevalence of the RT 084 increased (R = −0.78, p-value = 0.041). Different patterns in CDI epidemiology underscore the importance of local surveillance and infection control measures in Tehran healthcare settings.

2368. Molecular Epidemiology of Clostridioides difficile Infections in Pediatric Oncology and Transplant Patients

BackgroundThe incidence of Clostridioides difficile infection (CDI) has been rising among children, both in the community and hospital setting. The genomic variability and molecular epidemiology of CDI in children, especially with cancer are poorly understood. We aim to evaluate the molecular epidemiology and relatedness of C. difficile isolates among inpatient and outpatient pediatric oncology and stem cell transplant patients (POTP) using whole-genome sequencing (WGS).MethodsThis was a retrospective cohort study of CDI in POTP in 2016. CDI cases were identified by electronic medical record search for positive C. difficile toxin PCR tests. Retrieved residual stool specimens were cultured anaerobically using pre-reduced CCMB-TAL broth (Anaerobe Systems, Inc.), toxin-producing C. difficile isolates were determined using a cell culture cytotoxicity assay with neutralization (TechLab, Inc.), and WGS was performed, followed by core genome MLST (cgMLST). Variability of the isolates was summarized by strain type (ST), and a minimum spanning tree was constructed, defining clusters of genomically related isolates as those with < 7 alleles difference. Plausible epidemiologic links among the closely related strains such as receiving care on the same inpatient unit on the same day or on the same unit but on different days within 8 weeks before CDI were evaluated to identify potential transmission events.ResultsAmong 141 CDI episodes in 89 patients; 103 stool samples were cultured, and 101 (98%) isolates were sequenced identifying 23 different strain types in 81 (80%) isolates. 34 (38%) patients had multiple episodes of CDI. 16 clusters of related isolates were identified (figure), 10 (62%) of which involved only multiple specimens from the same patient. For the 6 clusters involving multiple patients, epidemiologic investigation revealed only 2 (33%) potential transmission events.ConclusionWGS identified a highly diverse group of C. difficile isolates among POTP with CDI. Although WGS identified clusters of closely related isolates in multiple patients, epidemiologic investigation of shared inpatient exposures identified potential transmission in only two clusters. C. difficile transmission was uncommon. DisclosuresRandall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board.

2404. Molecular Epidemiology of Clostridioides difficile in the United States, 2017

BackgroundIn 2009, the Centers for Disease Control and Prevention (CDC) implemented Clostridioides difficile infection (CDI) surveillance through the Emerging Infections Program (EIP) to monitor the incidence and evolving epidemiology of CDI in the United States. Since 2012, ribotypes (RTs) 027, 106, 002, 014, and 020 have constituted the top five strain types among both US community- and healthcare-associated isolates. Here we describe the changes in molecular epidemiology of C. difficile isolates collected in the United States in 2017.MethodsIn 2017, CDI surveillance was conducted at 10 EIP sites (CA, CO, CT, GA, MD, MN, NM, NY, OR, and TN). A convenience sample of clinical laboratories across EIP sites submitted C. difficile-positive stool specimens to the MN Department of Health Public Health Laboratory and Hines VA Hospital (IL) for culture. Isolates were forwarded to CDC and characterized by capillary-based PCR-ribotyping and PCR detection of tcdA, tcdB, cdtA, cdtB, and deletions in tcdC.ResultsIn 2017, 1,051 C. difficile isolates were submitted; the total number of isolates received from each site ranged from 11 to 286 with a median of 85.5. In total, 143 RTs were observed, with the majority of isolates harboring toxin genes tcdA and tcdB (95%) and a wild-type tcdC sequence (71%). Among 556 healthcare-associated isolates, RT 027 was the most prevalent and the top RT at 5 sites (CA, GA, MD, NM, TN). Ribotype 106 was the most prevalent among 495 community-associated CA isolates and the top RT at 6 sites (CO, CT, GA, MD, MN, TN). Ribotype 027 significantly decreased from 2012 to 2017 among both healthcare-associated (21% vs 15%; p = 0.02) and community-associated isolates (17% vs 6%; P < 0.0001). Among healthcare-associated isolates, RT 076, which was observed in 8 EIP sites, increased from 2% in 2016 to 5% in 2017 (p = 0.05) and replaced RT 020 as one of the top 5 healthcare-associated RTs in 2017.ConclusionDespite an overall decline since 2012, RT 027 remained the most prevalent RT among healthcare-associated isolates submitted in 2017. The increased frequency of RT 076 among healthcare-associated isolates submitted in 2017 highlights the evolving molecular epidemiology of C. difficile and the need for continued surveillance to monitor potential emerging strains.Disclosures All authors: No reported disclosures.

Risk factors for Clostridioides difficile infection in hospitalized patients and associated mortality in Japan: a multi-centre prospective cohort study

Although population characteristics and antimicrobial prescribing practices suggest that the hospitalized population in Japan is at high risk of Clostridioides difficile infection (CDI), the epidemiology of CDI in Japan is poorly understood. This prospective cohort study aimed to investigate the epidemiology of CDI at 12 hospitals in Japan. Patients with clinically significant diarrhoea (CSD) were enrolled. Stool specimens were tested for C.difficile by toxin A and/or B enzyme immunoassay (EIA) in the hospital laboratories, and a toxigenic culture and nucleic acid amplification tests were performed at a central laboratory. The risk factors of CDI and the impact of CDI on mortality were investigated. In total, 566 patients with CSD were included in the analyses. A total of 152 patients received the diagnosis of CDI by Toxin A/B EIA, toxigenic culture, or nucleic acid amplification test. Factors associated with CDI included low albumin (adjusted odds ratio (aOR): 1.56; 95% confidence interval (CI): 1.03-2.34) and length of hospital stay before stool collection >18 days (aOR: 1.73; 95% CI: 1.09-2.75). CDI was associated with an increased mortality on univariate analysis (OR: 1.6, 95% CI: 1.0-2.6) but was not associated with an increased risk of mortality on multivariable analysis. Risk factors for CDI in Japan were similar to those identified in the USA and Europe. However, CDI was not associated with an increased risk of mortality in this population of patients with CSD.

Epidemiology of Clostridioides difficile infection in Canada: A six-year review to support vaccine decision-making.

Two vaccines against Clostridioides difficile infections (CDI) are currently in phase III trials. To enable decision-making on their use in public health programs, national disease epidemiology is necessary. To determine the epidemiology of hospital-acquired CDI (HA-CDI) and community-associated CDI (CA-CDI) in Canada using provincial surveillance data and document discrepancies in CDI-related definitions among provincial surveillance programs. Publicly-available CDI provincial surveillance data from 2011 to 2016 that distinguished between HA-CDI and CA-CDI were included and the most common surveillance definitions for each province were used. The HA-, CA-CDI incidence rates and CA-CDI proportions (%) were calculated for each province. Both HA- and CA-CDI incidence rates were examined for trends. Types of disparities were summarized and detailed discrepancies were documented. Canadian data were analyzed from nine provinces. The HA-CDI rates ranged from 2.1/10,000 to 6.5/10,000 inpatient-days, with a decreasing trend over time. Available data on CA-CDI showed that both rates and proportions have been increasing over time. Discrepancies among provincial surveillance definitions were documented in CDI case classifications, surveillance populations and rate calculations. In Canada overall, the rate of HA-CDI has been decreasing and the rate of CA-CDI has been increasing, although this calculation was impeded by discrepancies in CDI-related definitions among provincial surveillance programs. Nationally-adopted common definitions for CDI would enable better comparisons of CDI rates between provinces and a calculation of the pan-Canadian burden of illness to support vaccine decision-making.

Epidemiology of Clostridioides difficile infection in Canada: A six-year review to support vaccine decision-making

Epidemiology of Clostridioides difficile infection in Canada: A six-year review to support vaccine decision-making

Multilocus Variable-Number Tandem-Repeat Analysis of Clostridioides difficile Clusters in Ribotype 027 Isolates and Lack of Association with Clinical Outcomes.

The epidemiology of Clostridioides difficile infection (CDI) has drastically changed since the emergence of the epidemic strain BI/NAP1/027, also known as ribotype 027 (R027). However, the relationship between the infecting C. difficile strain and clinical outcomes is still debated. We hypothesized that certain subpopulations of R027 isolates could be associated with unfavorable outcomes. We applied high-resolution multilocus variable-number tandem-repeat analysis (MLVA) to characterize C. difficile R027 isolates collected from confirmed CDI patients recruited across 10 Canadian hospitals from 2005 to 2008. PCR ribotyping was performed first to select R027 isolates that were then analyzed by MLVA (n = 450). Complicated CDI (cCDI) was defined by the occurrence of any of admission to an intensive care unit, colonic perforation, toxic megacolon, colectomy, and if CDI was the cause or contributed to death within 30 days after enrollment. Three major MLVA clusters were identified, MC-1, MC-3, and MC-10. MC-1 and MC-3 were exclusive to Quebec centers, while MC-10 was found only in Ontario. Fewer cases infected with MC-1 developed cCDI (4%) than those infected with MC-3 and MC-10 (15% and 16%, respectively), but a statistically significant difference was not reached. Our data did not identify a clear association between subpopulations of R027 and different clinical outcomes; however, the data confirmed the utility of MLVA's higher discrimination potential to better characterize CDI populations in an epidemiological analysis. For a patient with CDI, the progression toward an unfavorable outcome is a complex process that probably includes several interrelated strain and host characteristics.

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.

471. Prevalence and Characteristics of Clostridioides difficile Infection in Bangladesh

BackgroundThe estimated prevalence of Clostridioides difficile infection (CDI) in several South Asian countries is 10.5%, similar to that in North America and Europe. However, the epidemiology of CDI in Bangladesh is unknown. We aimed to assess the prevalence of CDI and assess hospital environmental contamination of toxigenic C. difficile in Bangladesh.MethodsThis was a prospective observational cohort study at two large tertiary care centers in Dhaka, Bangladesh, conducted from January 2017 to December 2017. Stool samples were collected from hospitalized adults with diarrhea (≥3 loose stools in a 24-hour period) and antimicrobial exposure within the past 30 days. Hospital environmental samples were collected by swabbing surfaces of common areas in the hospital. All samples underwent toxigenic culture. C. difficile isolates were tested for toxins A and B and PCR-ribotyped.ResultsOf 204 stool samples collected, 16 (7.8%) were positive for toxigenic C. difficile. Patients with CDI shared a room with significantly more patients (Table 1). Of 392 environmental samples, 48 (12.2%) were positive for toxigenic C. difficile, which was more common in patient care vs. nonpatient care areas (14.4% vs. 7.8%, P = 0.057). Twelve clinical stool isolates and 42 environmental isolates were ribotyped. Ribotypes identified in stool isolates were F017 (50%), FP053-163 (17%), FP435 (17%), F106 (8%), and F014-020 (8%). With the exception of FP435, these were also the most common ribotypes in environmental isolates: F017 (24%), FP053-163 (12%), F106 (26%), and F014-020 (10%).ConclusionFor the first time, we report the prevalence of CDI and ribotypes in at risk patients in Bangladesh. Rates and ribotypes are similar to other resource-rich or resource-limited countries.Table 1: Demographic Data for All Stool SamplesVariableNo toxigenic C. difficile (n = 188)Toxigenic C. difficile (n = 16) P Female sex, n (%)77 (41)9 (56)0.234Age, years, median (IQR)46 (32–58)39 (25–53)0.212Hospital A, n (%)149 (79)13 (81)>0.99Length of prior hospital stay, days, median (IQR)13 (7–23)14 (8–32)0.798Duration of previous antibiotics, days, median (IQR)10 (7–17)12 (6–20)0.687Number of patients in the same room, median (IQR)13 (7–19)19 (14–20)0.009Disclosures K. W. Garey, Merck & Co.: Grant Investigator, Grant recipient.