CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 308 SURVEILLANCE Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2016–2020 Canadian Nosocomial Infection Surveillance Program1* Abstract Background: Canadians experience increased morbidity, mortality and healthcare costs due to healthcare-associated infections (HAIs) and antimicrobial resistance (AMR). The Canadian Nosocomial Infection Surveillance Program (CNISP) collects and utilizes epidemiologic and laboratory surveillance data to inform infection prevention and control and antimicrobial stewardship programs and policies. The objective of this report is to describe the epidemiologic and laboratory characteristics and trends of HAIs and AMR from 2016 to 2020 using surveillance data provided by Canadian hospitals participating in the CNISP. Methods: Data were collected from 87 Canadian sentinel acute care hospitals between January 1, 2016, and December 31, 2020, for Clostridioides difficile infection (CDI), methicillin- resistant Staphylococcus aureus (MRSA) bloodstream infections, vancomycin-resistant Enterococci (VRE) bloodstream infections and carbapenemase-producing Enterobacterales (CPE). Case counts, rates, outcome data, molecular characterization and antimicrobial resistance profiles are presented. Results: From 2016 to 2020, increases in rates per 10,000 patient days were observed for MRSA bloodstream infections (33%; 0.84–1.12, p=0.037), VRE bloodstream infections (72%; 0.18–0.31, p=0.327), and CPE infections (67%, 0.03–0.05, p=0.117) and colonizations (86%, 0.14–0.26, p=0.050); however, CDI rates decreased by 8.5% between 2016 and 2020 (from 5.77–5.28, p=0.050). Conclusion: Surveillance findings from a national network of Canadian acute care hospitals indicate that rates of MRSA and VRE bloodstream infections, CPE infections and colonizations have increased substantially between 2016 and 2020 while rates of CDI have decreased. The collection of detailed, standardized surveillance data and the consistent application of infection prevention and control practices in acute care hospitals are critical in reducing the burden of HAIs and AMR infections in Canada. Further investigations into the impact of coronavirus disease 2019 and associated public health measures are underway. This work is licensed under a Creative Commons Attribution 4.0 International License. Affiliation 1 Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, ON *Correspondence: cnisp-pcsin@phac-aspc.gc.ca Suggested citation: Canadian Nosocomial Infection Surveillance Program. Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2016–2020. Can Commun Dis Rep 2022;48(7/8):308–24. https://doi.org/10.14745/ccdr.v48i78a03 Keywords: healthcare-associated infections, community-associated infections, antimicrobial resistance, surveillance, Clostridioides difficile infection, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci, carbapenemase-producing Enterobacterales, Escherichia coli, Canadian Nosocomial Infection Surveillance Program file:C:\Users\WPATTERS\1%20-%20USB%20Stick%20DOCS\Issue%2047%20DTP\Source%20Graphics\CCBY.png https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ mailto:cnisp-pcsin%40phac-aspc.gc.ca?subject= SURVEILLANCE CCDR • July/August 2022 • Vol. 48 No. 7/8Page 309 Introduction Healthcare-associated infections (HAIs), including those caused by antimicrobial resistant organisms (AROs), are an ongoing threat to the health and safety of patients. The morbidity and mortality caused by HAIs place significant burden on patients and healthcare resources (1–5). A 2017 Canadian point- prevalence survey estimated that 7.9% of patients had at least one HAI; results comparable to those reported by the European Centre for Disease Prevention and Control where HAI prevalence among tertiary hospitals was estimated to be 7.1% (6,7). A similar 2015 point-prevalence study in the United States estimated that there were 687,000 HAIs in acute care hospitals (8). During the coronavirus disease 2019 (COVID-19) pandemic that was declared on March 11, 2020 (9), changes in hospital infection prevention and control and antimicrobial stewardship efforts may have had impacts on rates of HAIs and AMR (10). Antimicrobial resistance (AMR) has been recognized as a growing danger to global health (11). Worldwide, an estimated 700,000 people die of resistant infections each year (12). In Canada, it is estimated that 1 in 19 deaths are attributable to resistant bacterial infections. The cost of AMR to the healthcare sector is $1.4 billion per year and is projected to increase to $7.6 billion per year by 2050 (13). Global surveillance, improved antibiotic stewardship, enhanced infection prevention and control and public awareness are vital to curbing existing and emerging infections and identifying patterns of antimicrobial resistance. In Canada, the Public Health Agency of Canada collects national data on various HAIs and AMR through the Canadian Nosocomial Infection Surveillance Program (CNISP). Established in 1994, CNISP is a collaboration between the Public Health Agency of Canada, the Association of Medical Microbiology and Infectious Disease Canada and sentinel hospitals from across Canada. The goal of CNISP is to facilitate and inform the prevention, control and reduction of HAIs and AROs in Canadian acute care hospitals through active surveillance and reporting. Consistent with the World Health Organization’s core components of infection prevention and control (10), CNISP performs consistent, standardized surveillance to reliably estimate HAI burden, establish benchmark rates for national and international comparison, identify potential risk factors and assess and inform specific interventions to improve patient health outcomes. Data provided by CNISP directly supports the collaborative goals outlined in the 2017 Pan-Canadian Framework for Action for tackling antimicrobial resistance and antimicrobial use (11). In this report, we describe the most recent HAI and AMR surveillance data collected from CNISP participating hospitals between 2016 and 2020. Methods Design The Canadian Nosocomial Infection Surveillance Program conducts prospective, sentinel surveillance for HAIs (including AROs). Case definitions Standardized case definitions for healthcare-associated (HA) and community-associated (CA) infections were used. Refer to Annex A for full case definitions. Data sources Between January 1, 2016, and December 31, 2020, participating hospitals submitted epidemiologic data on cases meeting the respective case definitions for Clostridioides difficile infection (CDI), methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA BSI), vancomycin-resistant Enterococci bloodstream infections (VRE BSI) and carbapenemase-producing Enterobacterales (CPE) infections and colonizations. In 2020, 87 hospitals across Canada participated in HAI surveillance and are further described in Table 1. In 2020, nearly half of patient admissions captured in CNISP HAI surveillance were from medium-sized adult (sites=21, 27%) and mixed hospitals (sites=14, 22%) (Supplemental file Figure S1). Epidemiologic (demographic, clinical and outcome data) and denominator data (patient days and patient admissions) were collected and submitted by participating hospitals through the Canadian Network for Public Health Intelligence platform, a secure online data platform. Reviews of standardized protocols and case definitions were conducted annually by established infectious disease expert working groups and training for data submission was provided as required. Data quality for each surveillance project was periodically evaluated (14,15). Laboratory data Patient-linked laboratory isolates (stool samples for CDI cases) were sent to the Public Health Agency of Canada’s National Microbiology Laboratory for molecular characterization and susceptibility testing. The MRSA BSI, VRE BSI, CPE and paediatric CDI isolates were submitted year-round. Adult CDI isolates were submitted annually during a targeted two-month period (March 1 to April 30). Statistical analysis Rates of HAI were calculated and represent infections and/ or colonizations identified in patients admitted to CNISP participating hospitals. The HAI rates were calculated by dividing the total number of cases by the total number of patient admissions (multiplied by 1,000) or patient days (multiplied by 10,000). The HAI rates are reported nationally and by region (Western: British Columbia, Alberta, Saskatchewan and CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 310 SURVEILLANCE Manitoba; Central: Ontario and Québec; Eastern: Nova Scotia, New Brunswick, Prince Edward Island and Newfoundland and Labrador; Northern: Nunavut). Sites that were unable to provide case data were excluded from rate calculations and missing denominator data were estimated, where applicable. Missing epidemiological and molecular data were excluded from analysis. The Mann-Kendall test was used to test trends over time. Significance testing was two-tailed and differences were considered significant at p≤0.05. Where available, attributable and all-cause mortality were reported for HAIs. Attributable mortality rate was defined as the number of deaths per 100 HAI cases where the HAI was the direct cause of death or contributed to death within 30 days after the date of the first positive laboratory or histopathology specimen, as determined by physician review. All-cause mortality rate was defined as the number of deaths per 100 HAI cases 30 days following positive culture. Results Clostridioides difficile infection Between 2016 and 2020, overall CDI rates significantly decreased by 8.5% (5.77–5.28 infections per 10,000 patient days, p=0.050); however, a similar increase of 8.0% in CDI rates (4.89–5.28 per 10,000 patient days) was observed in 2020 compared to 2019 (Table 2). Stratified by source of infection, the incidence of HA- CDI significantly decreased by 13.4% from 4.39–3.80 infections per 10,000 patient days (p=0.050) (Table S1.1). Community- associated-CDI (Annex A) rates have decreased 3.0% when comparing 2016 to 2020 rates per 1,000 patient admission; however, the decreasing trend was not considered significant (p=0.327). Both HA and CA-CDI rates increased in 2020 compared to 2019 (5.0% and 11.1%, respectively). Regionally, HA-CDI rates have steadily decreased across all regions except in the East where rates have remained relatively consistent. For CA-CDI, Eastern and Central region rates have decreased between 2016 and 2020 while Western rates have remained the same. Overall CDI attributable mortality remained low and fluctuated (range: 1.3–2.7 deaths per 100 cases) from 2016 to 2020 (p=0.801) (Table 2). The proportion of C. difficile isolates resistant to moxifloxacin decreased by 9.1% between 2016 (15.7%, n=103/657) and 2020 (6.6%, n=28/426). Since 2016, moxifloxacin resistance decreased significantly among HA-CDI isolates (11.0%, p=0.050) while a smaller non-significant decrease was observed among CA-CDI (3.4%, p=0.624) (Table S1.2). All tested C. difficile isolates were susceptible to vancomycin and tigecycline. There was a single case of metronidazole resistance in 2018. From 2016 to 2020, the prevalence of ribotype 027 associated with NAP1 decreased for both HA and CA-CDI (5.3% vs. 5.9%, respectively) (Table S1.3). Methicillin-resistant Staphylococcus aureus bloodstream infections Between 2016 and 2019, overall MRSA BSI rates significantly increased by 33.3% (0.84–1.12 infections per 10,000 patient days, p=0.037), and remained stable in 2020 during the COVID-19 pandemic (Table 3). Stratified by case type, a continued steady increase (75%, p=0.023) was observed from 2016 to 2020 in CA-MRSA BSI (Annex A) compared to HA- MRSA BSI, which fluctuated over time (Table S2.1). In 2020, HA- MRSA BSI and CA-MRSA BSI rates were highest in Western Table 1: Summary of hospitals participating in the Canadian Nosocomial Infection Surveillance Program, by region, 2020 Details of participating hospitals Westerna Centralb Easternc Northernd Total Total number of hospitals 28 32 26 1 87 Hospital type Adulte 12 21 16 0 49 Mixed 12 7 9 1 29 Paediatric 4 4 1 0 9 Hospital size Small (1–200 beds) 10 8 18 1 37 Medium (201–499 beds) 11 17 8 0 36 Large (500+ beds) 7 7 0 0 14 Admissions and discharge Total number of beds 9,617 12,130 3,302 22 25,071 Total number of admissions 424,296 494,428 133,894 2,271 1,054,889 Total number of patient days 3,137,774 3,721,010 933,042 6,085 7,797,911 a Western refers to British Columbia, Alberta, Saskatchewan and Manitoba b Central refers to Ontario and Québec c Eastern refers to Nova Scotia, New Brunswick, Prince Edward Island and Newfoundland and Labrador d Northern refers to Nunavut e Seven hospitals classified as “adult” had a neonatal intensive care unit SURVEILLANCE CCDR • July/August 2022 • Vol. 48 No. 7/8Page 311 Table 2: Clostridioides difficile infection data, Canada, 2016–2020a C. difficile infection data Year 2016 2017 2018 2019 2020 Number of infections and incidence rates Number of C. difficile infection cases 4,008 4,012 3,842 3,595 3,645 Rate per 1,000 patient admissions 4.34 4.28 4.13 3.71 3.92 Rate per 10,000 patient days 5.77 5.67 5.39 4.89 5.28 Number of reporting hospitals 67 68 68 73 82 Attributable mortality rate per 100 cases (%)b 2.4 2.3 1.3 2.3 2.7 Antimicrobial resistancec n % n % n % n % n % Clindamycin 145 22.1 149 22.0 307 48.6 219 40.0 66 15.5 Moxifloxacin 103 15.7 114 16.9 70 11.1 64 11.7 28 6.6 Rifampin 9 1.4 14 2.1 10 1.6 5 0.9 4 0.9 Metronidazole 0 0.0 0 0.0 1 0.2 0 0.0 0 0 Total number of isolates testedd 657 N/A 676 N/A 632 N/A 547 N/A 426 N/A Abbreviations: C. difficile, Clostridioides difficile; N/A, not applicable a All C. difficile isolates from 2016 to 2020 submitted to National Microbiology Laboratory were susceptible to tigecycline and vancomycin b Deaths where C. difficile infection was the direct cause of death or contributed to death 30 days after the date of the first positive lab specimen or positive histopathology specimen. Mortality data are collected during the two-month period (March and April of each year) for adults (age 18 years and older) and year-round for children (age 1 year to younger than 18 years old). Among paediatric patients, there was no death attributable to healthcare-associated C. difficile infection c C. difficile infection isolates are collected for resistance testing during the two-month period (March and April of each year) for adults (age 18 years and older) and year-round for children (age 1 year to younger than 18 years old) from admitted patients only d Total number reflects the number of isolates tested for each of the antibiotics listed above Table 3: Methicillin-resistant Staphylococcus aureus bloodstream infections data, Canada, 2016–2020 MRSA BSI data Year 2016 2017 2018 2019 2020 Number of infections and incidence rates Number of MRSA bloodstream infections 604 606 767 881 845 Rate per 1,000 patient admissions 0.61 0.61 0.78 0.84 0.83 Rate per 10,000 patient days 0.84 0.84 1.05 1.12 1.12 Number of reporting hospitals 64 65 62 69 80 All-cause mortality ratea Number of deaths 111 99 144 144 146 All-cause mortality rate per 100 cases 19.1 16.4 18.8 16.4 17.4 Antimicrobial resistanceb n % n % n % n % n % Erythromycin 418 78.7 455 81.0 531 75.6 511 75.6 447 72.3 Ciprofloxacin 411 77.4 432 76.9 504 71.8 473 70.0 404 65.4 Clindamycin 230 43.3 239 42.5 290 41.3 144 21.3 202 32.7 Tetracycline 31 5.8 35 6.2 50 7.1 48 7.1 39 6.3 Trimethoprim/sulfamethoxazole 11 2.1 8 1.4 14 2.0 10 1.5 14 2.3 Rifampin 10 1.9 9 1.6 6 0.9 7 1.0 6 1.0 Tigecycline 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 Daptomycin 5 0.9 5 0.9 0 0.0 0 0.0 4 0.6 Total number of isolates testedc,d 531 N/A 562 N/A 702 N/A 676 N/A 618 N/A Abbreviations: MRSA, methicillin-resistant S. aureus; MRSA BSI, methicillin-resistant S. aureus bloodstream infection; N/A, not applicable a Based on the number of cases with associated 30-day outcome data b All MRSA isolates from 2016 to 2020 submitted to National Microbiology Laboratory were susceptible to linezolid and vancomycin c In some years, the number of isolates tested for resistance varied by antibiotic d Total number reflects the number of isolates tested for each of the antibiotics listed above CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 312 SURVEILLANCE Canada (0.46 and 0.79 infections per 10,000 patient days, respectively). Among hospital types, HA and CA-MRSA BSI rates have generally remained highest among adult and mixed hospitals. Stratified by hospital size, HA-MRSA BSI rates were highest among large hospitals (500+ beds) since 2018 while CA-MRSA BSI rates have remained highest among medium size hospitals (201–499 beds) since 2019. All-cause mortality decreased 1.7% from 2016 to 2020 (19.1%–17.4%, p=0.449) (Table 3). In 2020, all-cause mortality was higher among those with HA-MRSA (19.9%) compared to those with CA-MRSA (15.9%) (data not shown). Clindamycin resistance among MRSA isolates decreased by 10.6% between 2016 (43.3%, n=230/531) and 2020 (32.7%, n=202/618) (Table 3). Since 2016, the proportion of MRSA isolates with erythromycin and ciprofloxacin resistance has decreased, yet remains high (72.3% and 65.4% in 2020, respectively). Between 2016 and 2020, daptomycin resistance was detected in 14 isolates. All tested MRSA isolates from 2016 to 2020 were susceptible to linezolid and vancomycin. Stratified by case type, clindamycin resistance among HA-MRSA isolates (45.8%) was, on average, consistently higher from 2016 to 2020 compared to CA-MRSA isolates (34.1%) during the same period (Table S2.2). There were no other notable differences in antibiotic resistance patterns by MRSA BSI case type. Between 2016 and 2020, the proportion of epidemic types identified as CMRSA2 (USA100/800) and most commonly associated with MRSA infections acquired in a hospital or healthcare setting continued to decrease; from 33.6% of all isolates in 2016 to 21.2% in 2020. The proportion of epidemic types identified as CMRSA7 (USA400) and CMRSA10 (USA300) and most commonly associated with MRSA infections acquired in the community continued to increase and account for the largest proportion of all isolates from 2016 (52.8%) to 2020 (63.8%). The CMRSA10 (USA300) was the most common epidemic type identified from 2016 to 2020, with 50.2% identified in 2020 (n=311/620) (Table S2.3). Vancomycin-resistant Enterococci bloodstream infections From 2016 to 2020, VRE BSI rates increased 72.2%, from 0.18 to 0.31 infections per 10,000 patient days, with the highest rate of 0.35 infections per 10,000 patient days observed in 2018 (Table 4). During the COVID-19 pandemic in 2020, VRE BSI rates in the CNISP network remained stable compared to 2019. Regionally, VRE BSI rates were highest in Western and Central Canada (0.36 and 0.33 infections per 10,000 patient days in 2019, respectively) with few VRE BSIs reported in Eastern Canada (range: 0–0.03 infections per 10,000 patient days) (Table S3.1). In 2020 compared to 2019, VRE BSI rates decreased among large (500+ beds) and small (1–200 beds) hospitals while increasing by 28.6% (0.28–0.36 infections per 10,000 patient days) among medium (201–499 beds) hospitals. Vancomycin-resistant Enterococci bloodstream infections were predominantly healthcare-associated, as 93.2% (n=887/952) reported from 2016 to 2020 were acquired in a healthcare facility (Table S3.2). All-cause mortality remained high (32.7%) from 2016 to 2020. Between 2016 and 2020, high-level gentamycin resistance among VRE BSI isolates (Enterococcus faecium) increased from 13.2% to 26.1%; however, a 7.0% decrease was observed more recently between 2019 and 2020. Daptomycin non-susceptibility was first identified in 2016 (n=7/91, 7.7%) and decreased to 3.5% (n=4/115) in 2020 (Table 4). Since 2016, the majority (98.4%– 100%) of VRE BSI isolates were identified as Enterococcus faecium; however, in 2018, three E. faecalis VRE BSI isolates were identified (Table S3.3). Among E. faecium isolates, the proportion identified as sequence type 1478 was highest in 2018 (38.7%, n=70/181) and decreased in 2020 (17.6%, n=21/119; p<0.001) (Table S3.4). Carbapenemase-producing Enterobacterales From 2016 to 2020, CPE infection rates have remained low but increased from 0.03 to 0.05 infections per 10,000 patient days (p=0.117), while a significant increase (85.7%) was observed in CPE colonization rates (from 0.14 to 0.26 colonizations per 10,000 patient days, p=0.050) (Table 5). Both CPE infections and colonizations rates decreased in 2020 compared to 2019 (16.7% and 10.3%, respectively). From 2016 to 2020, the majority of CPE infections (97.5%) were identified in Central (50.0%, n=80/160) and Western Canada (47.5%, n=76/160) while few infections were identified in the East (2.5%; n=4/160) (Table S4.1). During this same period, most CPE colonizations were identified in Central Canada (80.4%; n=600/746), followed by Western Canada (19.1%, n=143/746), while only three colonizations were reported in Eastern Canada (Table S4.2). From 2016 to 2020, large hospitals (500+ beds) reported the highest rates of CPE infections (0.04–0.09 infections per 10,000 patient days); however, small hospitals (1–200 beds) reported the highest CPE infection rates in 2019 (0.10 infections per 10,000 patient days). The CPE colonization rates remained highest among large hospitals from 2016 to 2020 (range: 0.25– 0.35 infections per 10,000 patient days). Thirty day all-cause mortality was 15.2% (n=22/145) among CPE- infected patients. Among all CPE cases reported from 2016 to 2020, 39.2% (n=312/795) reported travel outside of Canada and of those, 83.3% (n=240/288) received medical care while abroad. From 2016 to 2020, the prevalence of amikacin and gentamicin resistance among CPE isolates decreased by 18.5% and 9.4%, respectively, while trimethoprim-sulfamethoxazole resistance increased by 12.8% (Table 5). The predominant carbapenemases identified in Canada were Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), and Oxacillinase-48 (OXA-48), accounting for 91.9% of identified carbapenemases in 2020. SURVEILLANCE CCDR • July/August 2022 • Vol. 48 No. 7/8Page 313 Table 4: Vancomycin-resistant Enterococci bloodstream infections data, Canada, 2016–2020 VRE BSI data Year 2016 2017 2018 2019 2020 Vancomycin-resistant Enterococci bloodstream infections data Number of VRE BSI infections 121 154 246 247 207 Rate per 1,000 patient admissions 0.13 0.16 0.26 0.23 0.24 Rate per 10,000 patient days 0.18 0.23 0.35 0.32 0.31 Number of reporting hospitals 59 59 59 68 62 Antimicrobial resistance of Enterococcus faecium isolates n % n % n % n % n % Ampicillin 91 100 116 100 181 100 169 100 112 97.4 Chloramphenicol 2 2.2 11 9.5 4 2.2 28 16.6 22 19.1 Ciprofloxacin 91 100 116 100 181 100 169 100 113 98.3 Daptomycina 7 7.7 10 8.6 12 6.6 7 4.1 4 3.5 Erythromycin 83 91.2 108 93.1 173 95.6 162 95.9 108 93.9 High-level gentamicin 12 13.2 45 38.8 77 42.5 56 33.1 30 26.1 Levofloxacin 91 100 116 100 179 98.9 169 100 112 97.4 Linezolid 1 1.1 0 0 2 1.1 3 1.8 0 0 Nitrofurantoin 35 38.5 52 44.8 55 30.4 68 40.2 40 34.8 Penicillin 91 100 116 100 181 100.0 169 100 113 98.3 Quinupristin/Dalfopristin 9 9.9 8 6.9 18 9.9 18 10.7 8 7.0 Rifampicin 85 93.4 110 94.8 163 90.1 155 91.7 98 85.2 High-level streptomycin 32 35.2 39 33.6 60 33.1 43 25.4 23 20.0 Tetracycline 46 50.5 66 56.9 108 59.7 119 70.4 72 62.6 Tigecycline 0 0 0 0 1 0.6 0 0 0 0 Vancomycin 88 96.7 111 95.7 176 97.2 166 98.2 110 95.7 Total number of isolates testedb 91 N/A 116 N/A 181 N/A 169 N/A 115 N/A Abbreviations: VRE BSI, vancomycin-resistant Enterococci bloodstream infection; N/A, not applicable a Daptomycin does not have intermediate or resistant breakpoints in 2016, 2017 & 2018. Clinical and Laboratory Standards Institute (CLSI) resistance breakpoints came into effect in 2019 b Total number reflects the number of isolates tested for each of the antibiotics listed above Note: Aggregate mortality data reported in-text due to fluctuations in the small numbers of VRE BSI deaths reported each year Among submitted isolates from 2016 to 2020, the proportion of carbapenemase-producing pathogens identified as Escherichia coli increased 11.9% while those identified as K. pneumoniae and Acinetobacter baumannii decreased by 10.9% each (Table S5). Discussion Surveillance data collected via CNISP have shown that between 2016 and 2020 infection rates (including both HA and CA- cases) in Canada have decreased 8.5% for CDI, but increased for MRSA BSI and VRE BSI (33.3% and 72.2%, respectively). The CPE infection rates increased, but remained low; however, colonizations increased 85.7%. The COVID-19 pandemic has potentially had mixed impacts on the rates of HAIs in Canada and in the United States (16). Further investigation is required to assess the influence of pandemic-related factors that may be attributed to the changes in observed rates of HAIs, such as public health measures implemented in both the hospital and the community, population travel and mobility, changes in infection control practices, screening, laboratory testing and antimicrobial stewardship (10). The CDI rates in Canada declined and followed similar trends observed globally; however, rates remained higher in North America relative to other regions (17). In Canada, rates of CDI during the 2020 COVID-19 pandemic were higher than those observed in 2019 and contrast with results seen in the United States where CDI rates have continued to decline (16). The CDI moxifloxacin resistance decreased in Canada to 6.6% in 2020 and remained lower than previously published weighted pooled resistance data for North America (44.0%) and Asia (33.0%) and corresponds to the declining prevalence of ribotype 027 (18,19). The overall reduction in CDI rates across Canada suggests improvements in infection prevention and CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 314 SURVEILLANCE Table 5: Carbapenemase-producing Enterobacterales data, Canada, 2016–2020a CPE data Year 2016 2017 2018 2019 2020 Number of infections and incidence rates Number of CPE infections 21 20 36 48 35 Infection rate per 1,000 patient admissions 0.02 0.02 0.04 0.05 0.04 Infection rate per 10,000 patient days 0.03 0.03 0.05 0.06 0.05 Number of CPE colonizations 88 112 142 214 190 Colonization rate per 1,000 patient admissions 0.10 0.12 0.16 0.21 0.20 Colonization rate per 10,000 patient days 0.14 0.18 0.22 0.29 0.26 Number of reporting hospitals 55 56 57 64 72 Drugs tested for antimicrobial resistance Antibioticsb,c n % n % n % n % n % Piperacillin-Tazobactam 116 72.0 159 85.0 210 92.1 237 90.8 184 87.6 Ceftriaxone 149 92.5 173 92.5 212 93.0 250 95.8 186 88.6 Ceftazidime 139 86.3 160 85.6 192 84.2 233 89.3 173 82.4 Meropenem 140 87.0 159 85.0 198 86.8 190 72.8 130 61.9 Ciprofloxacin 133 82.6 138 73.8 158 69.3 183 70.1 150 71.4 Amikacin 42 26.1 32 17.1 44 19.3 23 8.8 16 7.6 Gentamicin 62 38.5 64 34.2 80 35.1 86 33.0 61 29.1 Tobramycin 75 46.6 71 38.0 101 44.3 121 46.4 78 37.1 Trimethoprim-sulfamethoxazole 102 63.4 113 60.4 143 62.7 193 73.9 160 76.2 Tigecycline 32 19.9 18 9.6 30 13.2 36 13.8 0 0 Total number of isolates testedd 161 N/A 187 N/A 228 N/A 261 N/A 210 N/A Carbapenemases identified KPC 84 52.2 86 46.0 122 53.5 127 48.7 82 39.1 NDM 45 28.0 53 28.3 59 25.9 74 28.4 66 31.4 OXA-48 20 12.4 33 17.6 30 13.2 40 15.3 45 21.4 SMEe 4 2.5 2 1.1 4 1.8 1 0.4 2 1 NDM/OXA-48 4 2.5 5 2.7 6 2.6 10 3.8 7 3.3 GES 1 0.6 1 0.5 1 0.4 2 0.8 0 0 IMP 0 0.0 0 0.0 3 1.3 1 0.4 1 0.5 NMC 2 1.2 4 2.1 2 0.9 4 1.5 6 2.9 VIM 2 1.2 3 1.6 3 1.3 3 1.1 0 0 Other 0 0.0 0 0.0 0 0.0 0 0.0 0 0 Total number of isolates testedf 161 N/A 187 N/A 228 N/A 261 N/A 210 N/A Abbreviations: CPE, carbapenemase-producing Enterobacterales; GES, Guiana extended-spectrum β-lactamase; IMP, active-on-imipenem; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; NMC, not metalloenzyme carbapenemase; OXA-48, Oxacillinase-48; N/A, not applicable; SME, Serratia marcescens enzymes; VIM, Verona integron-encoded metallo-β- lactamase a Includes data for all CPE isolates submitted b All isolates were resistant to ampicillin, and all but one to cefazolin. All carbapenemase-producing organism isolates were screened for the mcr-type gene which is an acquired gene associated with colistin resistance c The denominator for some drugs were adjusted as minimum inhibitory concentration values were not given in all cases due to VITEK® algorithms d Total number reflects the number of isolates tested for each of the antibiotics listed above e Only found in Serratia marcescens f Some isolates contain multiple carbapenemases therefore the total number of isolates tested and the number of carbapenemases indicated may not match Note: Aggregate mortality data reported in-text due to fluctuations in the small numbers of CPE deaths reported each year SURVEILLANCE CCDR • July/August 2022 • Vol. 48 No. 7/8Page 315 control practices and quality-improvement initiatives such as hand hygiene compliance, environmental cleaning, improved diagnostic techniques and antibiotic stewardship (20,21). The decline of RT027 from 2016 to 2020 may also have influenced the decline in CDI rates among CNISP hospitals as this ribotype has been associated with increased virulence and fluoroquinoline resistance (22). The rise in MRSA BSI rates in Canada, attributed to the increase in CA-MRSA BSI rates, is concerning due to the severe clinical outcomes, increased length of hospital stays and increased healthcare costs associated with BSI’s among admitted patients (23–26). A reduction in clindamycin resistance from 2016 to 2019 is most likely associated with the decrease in the proportion of CMRSA2 epidemic type identified among tested isolates (27). Compared to the increase observed in MRSA BSI rates in Canada, MRSA BSI rates in select large Australian tertiary care hospitals were lower and fluctuated between 2016 and 2019 (28). Similarly, in England, a plateau in MRSA BSI rates has been observed since 2015 (1.4–1.5 per 100,000 population and 0.8–0.9 hospital-onset cases per 100,000 bed days) (29). Both globally and in Canada, the prevalence of CA-MRSA is increasing and may provide a reservoir that could contribute to the increasing number of patients identified with CA-MRSA admitted to hospitals (30,31). The increasing rate of patients hospitalized with MRSA BSI acquired in the community observed in CNISP data suggests that further strategies to reduce or prevent MRSA infections in the community may be needed. Although beyond the scope of CNISP, studies at the broader population level to identify the prevalence of MRSA in the community, especially among populations at increased risk of contracting CA-MRSA, such as children, athletes, incarcerated populations, people who live in crowded conditions or people who inject drugs, may be worthwhile and could help to inform prevention strategies in the community (32). The increasing rates of VRE BSI in Canadian acute care hospitals are of concern as this infection is associated with a high mortality and increased hospital burden (33–35). The increase in VRE BSI rates observed among CNISP hospitals may be linked to changes in infection control policies, specifically the discontinuation of VRE screening and isolation programs in some Canadian acute care hospitals (36). Additionally, the rise in VRE BSI rates from 2013 to 2018 and subsequent decrease in 2019 and 2020 coincides with the emergence and decline of the pstS-null sequence type 1478 (ST1478) (37). The ST1478 sequence type is associated with daptomycin non-susceptibility and high- level gentamicin resistance, and the resistance patterns among VRE BSI isolates for these two antibiotics correspond to the trend in ST1478. It is important to note that the observed VRE BSI trends are, for the most part, being driven by a limited number of hospitals that have experienced outbreaks while caring for high risk patients (e.g. bone marrow transplants, solid organ transplants, cancer patients, etc.) (38). Similarly, increasing trends in prevalence of VRE BSI have also been observed in Europe (39– 42), which may be associated, in part, with the introduction and spread of a new clone and gaps in infection prevention practices (37,41). The CPE infections are of clinical significance and public health concern as they are associated with significant morbidity and mortality, limited treatment options and an ability to spread rapidly in healthcare settings (43–47). The incidence of CPE infection in Canada remains low; however, an 85.7% increase in CPE colonization rates was observed over the same period of time. Recent decreases in CPE infection and colonization rates in 2020 require further research to investigate the impact of changes in previously identified risk factors such as travel and receipt of healthcare in high-risk areas, as well as changes to infection control practices such as patient screening (44,48–50). Data on the incidence of CPE in other countries remains limited (51); however, a few countries have also reported a low but increasing incidence of CPE (52,53). Increased awareness and changes in screening and testing practices may reflect the increase in CPE colonization. Coordinated public health action, including strict implementation of infection control measures such as enquiry regarding travel, and enhanced surveillance are essential in reducing the transmission of CPE in Canadian acute care hospitals. Strengths and limitations The CNISP collects standardized and detailed epidemiological and laboratory-linked data from 87 sentinel hospitals across Canada to provide national HAI and AMR trends that can be used for benchmarking hospital infection prevention and control practices in serving to reduce HAIs and AROs in Canadian acute care hospitals. It is important to note that data included in this report include the COVID-19 pandemic, and 2020 rates of HAI’s and AMR may be impacted by changes in hospital admissions, mobility and national, regional, local and hospital-based infection prevention and control measures. The epidemiologic data collected by CNISP were limited to the information available in patient charts. Turnover of hospital staff reviewing medical charts may affect the consistent application of CNISP definitions and data quality over time; however, these data are collected by experienced and training infection prevention and control staff who receive periodic training with respect to CNISP methods and definitions. Data quality assessments are also conducted to maintain and improve data quality. The CNISP network may not fully represent the general inpatient population in Canada; however, efforts in recruitment have increased representation and coverage of Canadian acute care beds from 27% to 30% from 2016 to 2020, particularly among Northern, rural communities and Indigenous populations. Next steps Continued recruitment of Canadian acute care hospitals to increase acute care bed coverage from all ten provinces and three territories is ongoing in order to improve the quality and representativeness of Canadian HAI estimates. Furthermore, CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 316 SURVEILLANCE an enhanced hospital screening practice survey is conducted annually to better understand changes in HAI rates across Canada. In recent years, CNISP has initiated surveillance for new and emerging pathogens, such as Candida auris, and epidemiologic and laboratory-led working groups were formed to further investigate new pathogens such as VRE BSI ST1478 and extensively drug-resistant CPE. In 2019, CNISP re-established viral respiratory infection surveillance to collect and report detailed epidemiologic information on patients hospitalized with viral respiratory infections. This surveillance was expanded in 2020 to include patients hospitalized with COVID-19. The CNISP continues to support the national public health response to the COVID-19 pandemic. Future studies aim to analyze the impact of the COVID-19 pandemic on HAI rates and AMR. Conclusion Findings from surveillance conducted by a national network of Canadian acute care hospitals indicate that rates of MRSA BSI, VRE BSI and CPE infections and colonizations substantially increased between 2016 and 2020 while rates of CDI decreased. Ongoing surveillance and reporting of epidemiologic and laboratory data are essential to inform infection prevention and control and antimicrobial stewardship policies to help reduce the burden of HAI and impact of AMR in Canadian acute care hospitals. Authors’ statement Canadian Nosocomial Infection Surveillance Program hospitals provided expertise in the development of protocols in addition to the collection and submission of epidemiological data and lab isolates. The National Microbiology Laboratory completed the laboratory analyses and contributed to the interpretation and revision of the paper. Epidemiologists from Public Health Agency of Canada were responsible for the conception, analysis, interpretation, drafting and revision of the article. Competing interests None. Acknowledgements We gratefully acknowledge the contribution of the physicians, epidemiologists, infection control practitioners and laboratory staff at each participating hospital: Vancouver General Hospital (VGH), Vancouver, British Columbia (BC); Richmond General Hospital, Richmond, BC; UBC Hospital, Vancouver, BC; Lion’s Gate, North Vancouver, BC; Powell River General Hospital, Powell River, BC; Sechelt Hospital (formerly St. Mary’s), Sechelt, BC; Squamish General Hospital, Squamish, BC; BC Children’s Hospital, Vancouver, BC; Peter Lougheed Centre, Calgary, Alberta (AB); Rockyview General Hospital, Calgary, AB; South Health Campus, Calgary, AB; Foothills Medical Centre, Calgary, AB; Alberta Children’s Hospital, Calgary, AB; University of Alberta Hospital, Edmonton, AB; Stollery Children’s Hospital, Edmonton, AB; Health Sciences Centre-Winnipeg, Winnipeg, Manitoba (MB); University of Manitoba Children’s Hospital, Winnipeg, MB; Children’s Hospital of Western Ontario, London, Ontario (ON); St. Michael’s Hospital, Toronto, ON; Victoria Hospital, London, ON; University Hospital, London, ON; Toronto General Hospital, Toronto, ON; Toronto Western Hospital, Toronto, ON; Princess Margaret, Toronto, ON; Mount Sinai Hospital, Toronto, ON; Bridgepoint Active Healthcare, Toronto, ON; Sunnybrook Hospital, Toronto, ON; Kingston General Hospital, Kingston, ON; SMBD - Jewish General Hospital, Montréal, Québec (QC); Lachine General Hospital, Lachine, QC; The Moncton Hospital, Moncton, New Brunswick (NB); Halifax Infirmary, Halifax, Nova Scotia (NS); Victoria General, Halifax, NS; Rehabilitation Centre, Halifax, NS; Veterans Memorial Building, Halifax, NS; Dartmouth General Hospital, Halifax, NS; IWK Health Centre, Halifax, NS; Hospital for Sick Children, Toronto, ON; Montreal Children’s Hospital, Montréal, QC; Royal University Hospital, Saskatoon, Saskatchewan (SK); Moose Jaw Hospital, SK; St. Paul’s Hospital, Saskatoon, SK; General Hospital & Miller Centre, St. John’s, Newfoundland and Labrador (NL); Burin Peninsula Health Care Centre, Burin, NL; Carbonear General Hospital, Carbonear, NL; Dr. G.B. Cross Memorial Hospital, Clarenville, NL; Janeway Children’s Hospital and Rehabilitation Centre, St. John’s, NL; St. Clare’s Mercy Hospital, St. John’s, NL; Sir Thomas Roddick Hospital, Stephenville, NL; McMaster Children’s Hospital, Hamilton, ON; St Joseph’s Healthcare, Hamilton, ON; Jurvinski Hospital and Cancer Center, Hamilton, ON; General Site, Hamilton, ON; Civic Campus, Ottawa, ON; General Campus, Ottawa, ON; University of Ottawa Heart Institute, Ottawa, ON; Hôpital Maisonneuve- Rosemont, Montréal, QC; Victoria General Hospital, Victoria, BC; Royal Jubilee, Victoria, BC; Nanaimo Regional General Hospital, Nanaimo, BC; Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON; BC Women’s Hospital, Vancouver, BC; Hôtel-Dieu de Québec, QC; Centre hospitalier de l’Université de Montréal, Montréal, QC; Montreal General Hospital, Montréal, QC; Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC; Royal Victoria Hospital, Montréal, QC; Montreal Neurological Institute, Montréal, QC; North York General Hospital, Toronto, ON; Kelowna General Hospital, Kelowna, BC; Queen Elizabeth Hospital, Charlottetown, Prince Edward Island (PE); Prince County Hospital, Summerside, PE; Western Memorial Regional Hospital, Corner Brook, NL; Regina General Hospital, Regina, SK; Pasqua Hospital, Regina, SK; Sudbury Regional Hospital, Sudbury, ON; University Hospital of Northern BC, Prince George, BC; Qikiqtani General Hospital, Nunavut. 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DOI https://www.cdc.gov/mmwr/volumes/68/wr/mm6809e1.htm https://www.cdc.gov/mrsa/community/index.html https://doi.org/10.3390/antibiotics10020105 https://doi.org/10.1017/ice.2015.228 https://doi.org/10.1016/S1473-3099(18)30605-4 https://doi.org/10.1093/cid/ciaa009 https://doi.org/10.3201/eid2609.201576 https://doi.org/10.1016/j.ajic.2018.05.003 https://doi.org/10.1016/j.ajic.2018.05.003 https://doi.org/10.2807/1560-7917.ES.2020.25.35.1900575 https://doi.org/10.1186/s13756-019-0466-x https://doi.org/10.1080/22221751.2020.1769500 https://doi.org/10.1017/ice.2015.163 https://doi.org/10.1111/j.1469-0691.2012.03821.x. https://doi.org/10.1016/S1473-3099(13)70190-7 https://doi.org/10.1016/S1473-3099(17)30228-1 CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 320 SURVEILLANCE 47. 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Carbapenemase-producing Enterobacteriaceae in the UK: A national study (EuSCAPE-UK) on prevalence, incidence, laboratory detection methods and infection control measures. J Antimicrob Chemother 2017;72(2):596–603. DOI 53. Zhao S, Kennedy S, Perry MR, Wilson J, Chase-Topping M, Anderson E, Woolhouse MEJ, Lockhart M. Epidemiology of and risk factors for mortality due to carbapenemase- producing organisms (CPO) in healthcare facilities. J Hosp Infec 2021;110:184–93. DOI https://doi.org/10.1016/S1473-3099(18)30605-4 https://doi.org/10.1093/jac/dks214 https://doi.org/10.1093/infdis/jiw282 https://doi.org/10.3201/eid2409.180164 https://doi.org/10.1080/21505594.2016.1222343 https://doi.org/10.1093/jac/dkw414 https://doi.org/10.1016/j.jhin.2021.01.028 SURVEILLANCE CCDR • July/August 2022 • Vol. 48 No. 7/8Page 321 Annex A: Surveillance case definitions and eligibility criteria, 2020 Clostridioides difficile infection A “primary” episode of Clostridioides difficile infection (CDI) is defined either as the first episode of CDI ever experienced by the patient or a new episode of CDI that occurs greater than eight weeks after the diagnosis of a previous episode in the same patient. A patient is identified as having CDI if: • The patient has diarrhea or fever, abdominal pain and/or ileus AND a laboratory confirmation of a positive toxin assay or positive polymerase chain reaction (PCR) for C. difficile (without reasonable evidence of another cause of diarrhea) OR • The patient has a diagnosis of pseudomembranes on sigmoidoscopy or colonoscopy (or after colectomy) or histological/pathological diagnosis of CDI OR • The patient is diagnosed with toxic megacolon (in adult patients only) Diarrhea is defined as one of the following: • More watery/unformed stools in a 36-hour period OR • More watery/unformed stools in a 24-hour period and this is new or unusual for the patient (in adult patients only) Exclusion: • Any patients younger than one year • Any paediatric patients (aged one year to younger than 18 years) with alternate cause of diarrhea found (i.e. rotavirus, norovirus, enema or medication, etc.) are excluded even if C. difficile diagnostic test result is positive CDI case classification Once a patient has been identified with CDI, the infection will be classified further based on the following criteria and the best clinical judgment of the healthcare and/or infection prevention and control practitioner. Healthcare-associated (acquired in your facility) CDI case definition • Related to the current hospitalization: o The patient’s CDI symptoms occur in your healthcare facility three or more days (or 72 hours or longer) after admission • Related to a previous hospitalization: o Inpatient: the patient’s CDI symptoms occur less than three days after the current admission (or fewer than 72 hours) AND the patient had been previously hospitalized at your healthcare facility and discharged within the previous four weeks o Outpatient: the patient presents with CDI symptoms at your emergency room (ER) or outpatient location AND the patient had been previously hospitalized at your healthcare facility and discharged within the previous four weeks • Related to a previous healthcare exposure at your facility: o Inpatient: the patient’s CDI symptoms occur less than three days after the current admission (or fewer than 72 hours) AND the patient had a previous healthcare exposure at your facility within the previous four weeks o Outpatient: the patient presents with CDI symptoms at your ER or outpatient location AND the patient had a previous healthcare exposure at your facility within the previous four weeks Healthcare-associated (acquired in any other healthcare facility) CDI case definition • Related to a previous hospitalization at any other healthcare facility: o Inpatient: the patient’s CDI symptoms occur less than three days after the current admission (or fewer than 72 hours) AND the patient is known to have been previously hospitalized at any other healthcare facility and discharged/transferred within the previous four weeks o Outpatient: the patient presents with of CDI symptoms at your ER or outpatient location AND the patient is known to have been previously hospitalized at any other healthcare facility and discharged/transferred within the previous four weeks • Related to a previous healthcare exposure at any other healthcare facility o Inpatient: the patient’s CDI symptoms occur less than three days after the current admission (or fewer than 72 hours) AND the patient is known to have a previous healthcare exposure at any other healthcare facility within the previous four weeks o Outpatient: the patient presents with CDI symptoms at your ER or outpatient location AND the patient is known to have a previous healthcare exposure at any other healthcare facility within the previous four weeks Healthcare-associated CDI but unable to determine which facility The patient with CDI DOES meet both definitions of healthcare- associated (acquired in your facility) and healthcare-associated (acquired in any other healthcare facility), but unable to determine to which facility the case is primarily attributable to. CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 322 SURVEILLANCE Community-associated CDI case definition • Inpatient: the patient’s CDI symptoms occur less than three days (or fewer than 72 hours) after admission, with no history of hospitalization or any other healthcare exposure within the previous 12 weeks • Outpatient: the patient presents with CDI symptoms at your ER or outpatient location with no history of hospitalization or any other healthcare exposure within the previous 12 weeks Indeterminate CDI case definition The patient with CDI does NOT meet any of the definitions listed above for healthcare-associated or community-associated CDI. The symptom onset was more than four weeks but fewer than 12 weeks after the patient was discharged from any healthcare facility or after the patient had any other healthcare exposure. Methicillin-resistant Staphylococcus aureus (MRSA) infection MRSA bloodstream infection (BSI) case definition: • Isolation of Staphylococcus aureus from blood AND • Patient must be admitted to the hospital AND • Is a “newly identified S. aureus infection” at a Canadian Nosocomial Infection Surveillance Program (CNISP) hospital at the time of hospital admission or identified during hospitalization. Infection inclusion criteria • Methicillin-susceptible Staphylococcus aureus (MSSA) or MRSA BSIs identified for the first time during this current hospital admission • MSSA or MRSA BSIs that have already been identified at your site or another CNISP site but are new infections Criteria to determine NEW MSSA or MRSA BSI • Once the patient has been identified with a MSSA or MRSA BSI, they will be classified as a new MSSA or MRSA if they meet the following criteria: more than 14 days since previously treated MSSA or MRSA BSI and in the judgment of infection control physicians and practitioners represents a new infection Infection exclusion criteria • Emergency, clinic, or other outpatient cases who are NOT admitted to the hospital Healthcare-associated (HA) case definition: Healthcare-associated is defined as an inpatient who meets the following criteria and in accordance with the best clinical judgment of the healthcare and/or infection prevention and control practitioner: • Patient is on or beyond calendar day 3 of their hospitalization (calendar day 1 is the day of hospital admission) OR • Has been hospitalized in your facility in the last 7 days or up to 90 days depending on the source of the infection OR • Has had a healthcare exposure at your facility that would have resulted in this bacteremia (using best clinical judgment) OR • Any patient who has a bacteremia not acquired at your facility that is thought to be associated with any other healthcare exposure (e.g. another acute-care facility, long- term care, rehabilitation facility, clinic or exposure to a medical device) Healthcare-associated (HA) case definition (newborn): • The newborn is on or beyond calendar day 3 of their hospitalization (calendar day 1 is the day of hospital admission) • The mother was NOT known to have MRSA on admission and there is no epidemiological reason to suspect that the mother was colonized prior to admission, even if the newborn is fewer than 48 hours of age • In the case of a newborn transferred from another institution, MSSA or MRSA BSI may be classified as HA your acute-care facility if the organism was NOT known to be present and there is no epidemiological reason to suspect that acquisition occurred prior to transfer Community-associated case definition: • No exposure to healthcare that would have resulted in this bacteremia (using best clinical judgment) and does not meet the criteria for a healthcare-associated BSI SURVEILLANCE CCDR • July/August 2022 • Vol. 48 No. 7/8Page 323 Vancomycin-resistant Enterococci (VRE) infection VRE BSI case definition: • Isolation of Enterococcus faecalis or faecium from blood AND • Vancomycin MIC at least 8 µg/ml AND • Patient must be admitted to the hospital AND • Is a “newly” identified VRE BSI at a CNISP facility at the time of hospital admission or identified during hospitalization A newly identified VRE BSI is defined as a positive VRE blood isolate more than 14 days after completion of therapy for a previous infection and felt to be unrelated to previous infection in accordance with best clinical judgment by Infection Control physicians and practitioners. Exclusion criteria: • Emergency, clinic, or other outpatient cases who are not admitted to the hospital Healthcare-associated (HA) case definition: Healthcare-associated is defined as an inpatient who meets the following criteria and in accordance with the best clinical judgment of the healthcare and/or infection prevention and control practitioner: • Patient is on or beyond calendar day 3 of their hospitalization (calendar day 1 is the day of hospital admission) OR • Has been hospitalized in your facility in the last 7 days or up to 90 days depending on the source of the infection OR • Has had a healthcare exposure at your facility that would have resulted in this bacteremia (using best clinical judgment) OR • Any patient who has a bacteremia not acquired at your facility that is thought to be associated with any other healthcare exposure (e.g. another acute-care facility, long- term care, rehabilitation facility, clinic or exposure to a medical device) Carbapenemase-producing Enterobacterales (CPE) infection Case eligibility: • Patient is admitted to a CNISP hospital or presents to a CNISP hospital emergency department or a CNISP hospital- based outpatient clinic • Laboratory confirmation of carbapenem resistance or carbapenemase production in Enterobacterales spp. Following molecular testing, only isolates determined to be harbouring a carbapenemase are included in surveillance. If multiple isolates are submitted for the same patient in the same surveillance year, only the isolate from the most invasive site is included in epidemiological results (e.g. rates and outcome data). However, antimicrobial susceptibility testing results represent all CPE isolates (including clinical and screening isolates from inpatients and outpatients) submitted between 2016 and 2020; duplicates (i.e. isolates from the same patient where the organism and the carbapenemase were the same) were excluded. CCDR • July/August 2022 • Vol. 48 No. 7/8 Page 324 SURVEILLANCE Annex B: List of supplementary figure and tables These documents can be accessed on the Supplemental material file. Figure S1: Number and proportion of patient admissions included in the Canadian Nosocomial Infection Surveillance Program by hospital type and size, 2020 Table S1.1: Cases and incidence rates of healthcare-associated and community-associated Clostridioides difficile infection by region, hospital type and hospital size, Canada, 2016–2020 Table S1.2: Antimicrobial resistance of healthcare-associated and community-associated Clostridioides difficile infection isolates, Canada, 2016–2020 Table S1.3: Number and proportion of common ribotypes of healthcare-associated and community-associated Clostridioides difficile infection cases, Canada, 2016–2020 Table S2.1: Cases and incidence rates of healthcare-associated and community-associated methicillin-resistant Staphylococcus aureus bloodstream infections by region, hospital type and hospital size, 2016–2020 Table S2.2: Antimicrobial resistance of healthcare-associated and community-associated methicillin-resistant Staphylococcus aureus bloodstream infection isolates, Canada, 2016–2020 Table S2.3: Number and proportion of select methicillin-resistant Staphylococcus aureus epidemic types identified Table S3.1: Number of vancomycin-resistant Enterococci bloodstream infections incidence rates by region, hospital type and hospital size, 2016–2020 Table S3.2: Number of healthcare-associated vancomycin-resistant Enterococci bloodstream infections and incidence rates by region, hospital type and hospital size, 2016–2020 Table S3.3: Number and proportion of vancomycin-resistant Enterococci bloodstream infections isolate types identified, 2016–2020 Table S3.4: Distribution of vancomycin-resistant Enterococci bloodstream (Enterococcus faecium) sequence type, 2016–2020 Table S4.1: Number of carbapenemase-producing Enterobacterales infections and incidence rates by region, hospital type and hospital size, 2016–2020 Table S4.2: Number of carbapenemase-producing Enterobacterales colonizations and incidence rates by region, hospital type and hospital size, 2016–2020 Table S5: Number and proportion of main carbapenemase-producing pathogens identified https://www.canada.ca/content/dam/phac-aspc/documents/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2022-48/issue-7-8-july-august-2022/ccdrv48i78a03s-eng.pdf