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Clostridium difficile infection is the most common infectious cause of health care-associated diarrhea among hospital-admitted patients in developed countries and can lead to substantial morbidity and mortality. (1,2) In 2002, [...], BACKGROUND: The clinical and molecular epidemiology of health care-associated Clostridium difficile infection in nonepidemic settings across Canada has evolved since the first report of the virulent North American pulsed-field gel electrophoresis type 1 (NAP1) strain more than 15 years ago. The objective of this national, multicentre study was to describe the evolving epidemiology and molecular characteristics of health care-associated C. difficile infection in Canada during a post-NAP1epidemic period, particularly patient outcomes associated with the NAP1 strain. METHODS: Adult inpatients with C. difficile infection were prospectively identified, using a standard definition, between 2009 and 2015 through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 64 acute care hospitals. Patient demographic characteristics, severity of infection and outcomes were reviewed. Molecular testing was performed on isolates, and strain types were analyzed against outcomes and epidemiologic trends. RESULTS: Over a 7-year period, 20 623 adult patients admitted to hospital with health care-associated C. difficile infection were reported to CNISP, and microbiological data were available for 2690 patients. From 2009 to 2015, the national rate of health care-associated C. difficile infection decreased from 5.9 to 4.3 per 10000 patient-days. NAP1 remained the dominant strain type, but infection with this strain has significantly decreased over time, followed by an increasing trend of infection with NAP4 and NAP11 strains. The NAP1 strain was significantly associated with a higher rate of death attributable to C. difficile infection com pared with non-NAP1 strains (odds ratio 1.91, 95% confidence interval [CI] 1.292.82). Isolates were universally susceptible to metronidazole; one was nonsusceptible to vancomycin. The proportion of NAP1 strains within individual centres predicted their rates of health careassociated C. difficile infection; for every 10% increase in the proportion of NAP1 strains, the rate of health care-associated C. difficile infection increased by 3.3% (95% CI 1.7%-4.9%). INTERPRETATION: Rates of health care-associated C. difficile infection have decreased across Canada. In nonepidemic settings, NAP4 has emerged as a common strain type, but NAP1, although decreasing, continues to be the predominant circulating strain and remains significantly associated with higher attributable mortality.

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficileinfection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Background:The clinical and molecular epidemiology of health care–associated Clostridium difficileinfection in nonepidemic settings across Canada has evolved since the first report of the virulent North American pulsed-field gel electrophoresis type 1 (NAP1) strain more than 15 years ago. The objective of this national, multicentre study was to describe the evolving epidemiology and molecular characteristics of health care–associated C. difficileinfection in Canada during a post-NAP1-epidemic period, particularly patient outcomes associated with the NAP1 strain.Methods:Adult inpatients with C. difficileinfection were prospectively identified, using a standard definition, between 2009 and 2015 through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 64 acute care hospitals. Patient demographic characteristics, severity of infection and outcomes were reviewed. Molecular testing was performed on isolates, and strain types were analyzed against outcomes and epidemiologic trends.Results:Over a 7-year period, 20 623 adult patients admitted to hospital with health care–associated C. difficileinfection were reported to CNISP, and microbiological data were available for 2690 patients. From 2009 to 2015, the national rate of health care–associated C. difficileinfection decreased from 5.9 to 4.3 per 10 000 patient-days. NAP1 remained the dominant strain type, but infection with this strain has significantly decreased over time, followed by an increasing trend of infection with NAP4 and NAP11 strains. The NAP1 strain was significantly associated with a higher rate of death attributable to C. difficileinfection compared with non-NAP1 strains (odds ratio 1.91, 95% confidence interval [CI] 1.29–2.82). Isolates were universally susceptible to metronidazole; one was nonsusceptible to vancomycin. The proportion of NAP1 strains within individual centres predicted their rates of health care–associated C. difficileinfection; for every 10% increase in the proportion of NAP1 strains, the rate of health care–associated C. difficileinfection increased by 3.3% (95% CI 1.7%–4.9%).Interpretation:Rates of health care–associated C. difficileinfection have decreased across Canada. In nonepidemic settings, NAP4 has emerged as a common strain type, but NAP1, although decreasing, continues to be the predominant circulating strain and remains significantly associated with higher attributable mortality.

ABSTRACTThe prevalence of Clostridium difficileinfections has increased due to the emergence of epidemic variants from diverse genetic lineages. Here we describe the emergence of a novel variant during an outbreak in a Costa Rican hospital that was associated with severe clinical presentations. This C. difficilevariant elicited higher white blood cell counts and caused disease in younger patients than did other strains isolated during the outbreak. Furthermore, it had a recurrence rate, a 30-day attributable disease rate, and disease severity as great as those of the epidemic strain NAP1. Pulsed-field gel electrophoresis genotyping indicated that the outbreak strains belong to a previously undescribed variant, designated NAPCR1. Whole-genome sequencing and ribotyping indicated that the NAPCR1variant belongs to C. difficileribotype 012 and sequence type 54, as does the reference strain 630. NAPCR1strains are resistant to fluoroquinolones due to a mutation in gyrA, and they possess an 18-bp deletion in tcdCthat is characteristic of the epidemic, evolutionarily distinct, C. difficileNAP1 variant. NAPCR1genomes contain 10% more predicted genes than strain 630, most of which are of hypothetical function and are present on phages and other mobile genetic elements. The increased virulence of NAPCR1was confirmed by mortality rates in the hamster model and strong inflammatory responses induced by bacteria-free supernatants in the murine ligated loop model. However, NAPCR1strains do not synthesize toxin A and toxin B at levels comparable to those in NAP1 strains. Our results suggest that the pathogenic potential of this emerging C. difficilevariant is due to the acquisition of hypothetical functions associated with laterally acquired DNA.

ABSTRACTEnterococcus faecalisG1-0247 (vancomycin MIC, 16 μg/ml) was found to harbor a vanGoperon 99% identical to the vanGoperon in E. faecalisBM4518. E. faecalisN03-0233 (vancomycin MIC, 16 μg/ml) was found to harbor a novel vanGoperon, vanG2, on an element in a different chromosomal location than the vanG-harboring elements in G1-0247 and BM4518.

ABSTRACTA questionnaire relating to Clostridium difficiledisease incidence and diagnostic practices was sent to 380 Canadian hospitals (all with >50 beds). The national questionnaire response rate was 63%. In-house testing was performed in 17.6, 61.5, and 74.2% of the hospitals with <300, 300 to 500, and >500 beds, respectively. The average test positivity rates were 17.2, 15.3, and 13.2% for hospitals with <300, 300 to 500, and >500 beds, respectively. The average disease incidences were 23.5, 30.8, and 40.3 cases per 100,000 patient days in the hospitals with <300, 300 to 500, and >500 beds, respectively. In the 81 hospitals where in-house testing was performed, cytotoxin testing utilizing tissue culture was most common (44.4%), followed by enzyme-linked immunosorbent assay (38.3%), culture for toxigenic C. difficile(32.1%), and latex agglutination (13.6%). The clinical criteria for C. difficiletesting were variable, with 85% of hospitals indicating that a test was done automatically if ordered by a doctor. Our results show that C. difficile-associated diarrhea is a major problem in hospitals with =200 beds. Despite a lower disease incidence in smaller hospitals, there was a higher diagnostic test positivity rate. This may reflect the preference of smaller hospitals for culture and latex agglutination tests.

The aim of the present study was to determine whether Clostridium difficile was present in uncooked retail ground beef and ground pork products sold in Winnipeg, Manitoba. Using an alcohol treatment protocol and inoculation of cultures on C difficile Moxalactam Norfloxacin (CDMN), toxigenic C difficile was found in 6.3% of 48 meat samples. The C difficile isolates belonged to different pulsotypes, all of which had been previously isolated from the stool of Manitoba patients with C difficile disease. Because cooking of meat will not eradicate C difficile spores, this raises a concern regarding potential foodborne transmissibility of this organism.

Clostridium difficile is the etiological agent of antibiotic-associated diarrhea; the most common form of nosocomial infectious diarrhea. The basis for the shock-like systemic symptoms observed in severe cases of this infection are not known. It is hypothesized that the invasion of C difficile toxins A and/or B from the gut mucosa may contribute to these symptoms.A polarized tissue culture model employing Caco-2 cells grown on transwell inserts was established to study the translocation of purified C difficile toxins A and B. C difficile toxins were 125I labelled and inoculated onto confluent polarized Caco-2 cell monolayers to study translocation dynamics. Electrical resistance measurements were used to monitor monolayer confluence and tight junction integrity. Samples were taken from the apical and basal sides of the insert, as well as the insert itself, and tested using the human foreskin fibroblasts cell cytotoxicity assay to monitor partitioning of the radiolabelled toxins.Toxin A produced a 50% reduction in electrical resistance in 3 h whereas the same concentration of toxin B required at least 7 h to achieve the same effect. Both toxins A and B were able to translocate across confluent monolayers of Caco-2 cells. The combination of toxin A and B together was synergistic with respect to promoting the translocation of toxin B. Although the addition of toxin A resulted in a 100% increase in the amount of toxin B able to translocate, no increases in toxin A translocation were observed. These findings suggest a model of pathogenesis in which C difficile toxin A facilitates the translocation of toxin B from the gut into submucosal areas where it may play a role in inflammatory damage.