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-NAP1-epidemic 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 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. difficile infection 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. 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.

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Background Healthcare acquired infections (HAI) are an important public health problem in developed countries, but comprehensive data on trends over time are lacking. Prevalence surveys have been used as a surrogate for incidence studies and can be readily repeated. Methods The Canadian Nosocomial Infection Surveillance Program conducted prevalence surveys in 2002 and 2009 in a large network of major Canadian acute care hospitals. NHSN definitions of HAI were used. Use of isolation precautions on the survey day was documented. Results In 2009, 9,953 acute care inpatients were surveyed; 1,234 infections (124/1000) were found, compared to 111/1000 in 2002, ( p < 0.0001). There was increased prevalence of urinary tract infection (UTI) and Clostridium difficile , offset by decreases in pneumonia and bloodstream infection. Use of isolation precautions increased from 77 to 148 per 1000 patients ( p < 0.0001), attributable to increased use of contact precautions in patients infected or colonized with antimicrobial resistant organisms. Conclusion Between 2002 and 2009 HAI prevalence increased by 11.7 % in a network of major Canadian hospitals due to increases in Clostridium difficile and urinary tract infection. The use of isolation precautions increased by 92.2 % attributable to increased contact isolation. National prevalence surveys are useful tools to assess evolving trends in HAI.

ABSTRACT Carbapenemase-producing Enterobacteriaceae (CPE) are increasing globally; here we report on the investigation of CPE in Canada over a 5-year period. Participating acute care facilities across Canada submitted carbapenem-nonsusceptible Enterobacteriaceae from 1 January 2010 to 31 December 2014 to the National Microbiology Laboratory. All CPE were characterized by antimicrobial susceptibilities, pulsed-field gel electrophoresis, multilocus sequence typing, and plasmid restriction fragment length polymorphism analysis and had patient data collected using a standard questionnaire. The 5-year incidence rate of CPE was 0.09 per 10,000 patient days and 0.07 per 1,000 admissions. There were a total of 261 CPE isolated from 238 patients in 58 hospitals during the study period. blaKPC-3 (64.8%) and blaNDM-1 (17.6%) represented the highest proportion of carbapenemase genes detected in Canadian isolates. Patients who had a history of medical attention during international travel accounted for 21% of CPE cases. The hospital 30-day all-cause mortality rate for the 5-year surveillance period was 17.1 per 100 CPE cases. No significant increase in the occurrence of CPE was observed from 2010 to 2014. Nosocomial transmission of CPE, as well as international health care, is driving its persistence within Canada.

BACKGROUND Bloodstream infection (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA) is associated with considerable morbidity and mortality. OBJECTIVE To determine the incidence of MRSA BSI in Canadian hospitals and to identify variables associated with increased mortality. METHODS Prospective surveillance for MRSA BSI conducted in 53 Canadian hospitals from January 1, 2008, through December 31, 2012. Thirty-day all-cause mortality was determined, and logistic regression analysis was used to identify variables associated with mortality. RESULTS A total of 1,753 patients with MRSA BSI were identified (incidence, 0.45 per 1,000 admissions). The most common sites presumed to be the source of infection were skin/soft tissue (26.6%) and an intravascular catheter (22.0%). The most common spa types causing MRSA BSI were t002 (USA100/800; 55%) and t008 (USA300; 29%). Thirty-day all-cause mortality was 23.8%. Mortality was associated with increasing age (odds ratio, 1.03 per year [95% CI, 1.02–1.04]), the presence of pleuropulmonary infection (2.3 [1.4–3.7]), transfer to an intensive care unit (3.2 [2.1–5.0]), and failure to receive appropriate antimicrobial therapy within 24 hours of MRSA identification (3.2 [2.1–5.0]); a skin/soft-tissue source of BSI was associated with decreased mortality (0.5 [0.3–0.9]). MRSA genotype and reduced susceptibility to vancomycin were not associated with risk of death. CONCLUSIONS This study provides additional insight into the relative impact of various host and microbial factors associated with mortality in patients with MRSA BSI. The results emphasize the importance of ensuring timely receipt of appropriate antimicrobial agents to reduce the risk of an adverse outcome. Infect. Control Hosp. Epidemiol. 2016;37(4):390–397

BACKGROUNDHip and knee arthroplasty infections are associated with considerable healthcare costs. The merits of reducing the postoperative surveillance period from 1 year to 90 days have been debated.OBJECTIVESTo report the first pan-Canadian hip and knee periprosthetic joint infection (PJI) rates and to describe the implications of a shorter (90-day) postoperative surveillance period.METHODSProspective surveillance for infection following hip and knee arthroplasty was conducted by hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) using standard surveillance definitions.RESULTSOverall hip and knee PJI rates were 1.64 and 1.52 per 100 procedures, respectively. Deep incisional and organ-space hip and knee PJI rates were 0.96 and 0.71, respectively. In total, 93% of hip PJIs and 92% of knee PJIs were identified within 90 days, with a median time to detection of 21 days. However, 11%–16% of deep incisional and organ-space infections were not detected within 90 days. This rate was reduced to 3%–4% at 180 days post procedure. Anaerobic and polymicrobial infections had the shortest median time from procedure to detection (17 and 18 days, respectively) compared with infections due to other microorganisms, including Staphylococcus aureus.CONCLUSIONSPJI rates were similar to those reported elsewhere, although differences in national surveillance systems limit direct comparisons. Our results suggest that a postoperative surveillance period of 90 days will detect the majority of PJIs; however, up to 16% of deep incisional and organ-space infections may be missed. Extending the surveillance period to 180 days could allow for a better estimate of disease burden.Infect Control Hosp Epidemiol 2017;38:147–153

BACKGROUND: Increasing antimicrobial resistance has been identified as an important global health threat. Antimicrobial use is a major driver of resistance, especially in the hospital sector. Understanding the extent and type of antimicrobial use in Canadian hospitals will aid in developing national antimicrobial stewardship priorities. METHODS: In 2002 and 2009, as part of one-day prevalence surveys to quantify hospital-acquired infections in Canadian Nosocomial Infection Surveillance Program hospitals, data were collected on the use of systemic antimicrobial agents in all patients in participating hospitals. Specific agents in use (other than antiviral and antiparasitic agents) on the survey day and patient demographic information were collected. RESULTS: In 2002, 2460 of 6747 patients (36.5%) in 28 hospitals were receiving antimicrobial therapy. In 2009, 3989 of 9953 (40.1%) patients in 44 hospitals were receiving antimicrobial therapy (P<0.001). Significantly increased use was observed in central Canada (37.4% to 40.8%) and western Canada (36.9% to 41.1%) but not in eastern Canada (32.9% to 34.1%). In 2009, antimicrobial use was most common on solid organ transplant units (71.0% of patients), intensive care units (68.3%) and hematology/oncology units (65.9%). Compared with 2002, there was a significant decrease in use of first-and second-generation cephalosporins, and significant increases in use of carbapenems, antifungal agents and vancomycin in 2009. Piperacillin-tazobactam, as a proportion of all penicillins, increased from 20% in 2002 to 42.8% in 2009 (P<0.001). There was a significant increase in simultaneous use of >1 agent, from 12.0% of patients in 2002 to 37.7% in 2009. CONCLUSION: From 2002 to 2009, the prevalence of antimicrobial agent use in Canadian Nosocomial Infection Surveillance Program hospitals significantly increased; additionally, increased use of broad-spectrum agents and a marked increase in simultaneous use of multiple agents were observed.

BACKGROUND: Increasing antimicrobial resistance has been identified as an important global health threat. Antimicrobial use is a major driver of resistance, especially in the hospital sector. Understanding the extent and type of antimicrobial use in Canadian hospitals will aid in developing national antimicrobial stewardship priorities. METHODS: In 2002 and 2009, as part of one-day prevalence surveys to quantify hospital-acquired infections in Canadian Nosocomial Infection Surveillance Program hospitals, data were collected on the use of systemic antimicrobial agents in all patients in participating hospitals. Specific agents in use (other than antiviral and antiparasitic agents) on the survey day and patient demographic information were collected. RESULTS: In 2002, 2460 of 6747 patients (36.5%) in 28 hospitals were receiving antimicrobial therapy. In 2009, 3989 of 9953 (40.1%) patients in 44 hospitals were receiving antimicrobial therapy (P 1 agent, from 12.0% of patients in 2002 to 37.7% in 2009. CONCLUSION: From 2002 to 2009, the prevalence of antimicrobial agent use in Canadian Nosocomial Infection Surveillance Program hospitals significantly increased; additionally, increased use of broadspectrum agents and a marked increase in simultaneous use of multiple agents were observed.

Children with healthcare-associated Clostridium difficile infection were identified. The incidence increased from 3.2/10,000 patient days in 2007 to 5.2/10,000 patient days in 2011 ( p < 0.001). Of 169 isolates, the most common North American Pulsed-Field (NAP) types were NAP4 (n = 43; (25.4%), and NAP1 (n = 25;14.8%) while 55 (32.6%) were non-assigned NAP types.

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Objective.To determine trends, patient characteristics, and outcome of patients with healthcare-associated influenza in Canadian hospitals.Design.Prospective surveillance of laboratory-confirmed influenza among hospitalized adults was conducted from 2006 to 2012. Adults with positive test results at or after admission to the hospital were assessed. Influenza was considered to be healthcare associated if symptom onset was equal to or more than 96 hours after admission to a facility or if a patient was readmitted less than 96 hours after discharge or admitted less than 96 hours after transfer from another facility. Baseline characteristics of influenza patients were collected. Patients were reassessed at 30 days to determine the outcome.Setting.Acute care hospitals participating in the Canadian Nosocomial Infection Surveillance Program.Results.A total of 570 (17.3%) of 3,299 influenza cases were healthcare associated; 345 (60.5%) were acquired in a long-term care facility (LTCF), and 225 (39.5%) were acquired in an acute care facility (ACF). There was year-to-year variability in the rate and proportion of cases that were healthcare associated and variability in the proportion that were acquired in a LTCF versus an ACF. Patients with LTCF-associated cases were older, had a higher proportion of chronic heart disease, and were less likely to be immunocompromised compared with patients with ACF-associated cases; there was no significant difference in 30-day all-cause and influenza-specific mortality.Conclusions.Healthcare-associated influenza is a major component of the burden of disease from influenza in hospitals, but the proportion of cases that are healthcare associated varies markedly from year to year, as does the proportion of healthcare-associated infections that are acquired in an ACF versus an LTCF.

To the Editor—We read with interest the article by Taylor et al regarding healthcare-associated influenza in Canadian hospitals from 2006 to 2012. The data represent appealing information on viral nosocomial infections, which are often less investigated than hospital-acquired bacterial infections. We think that the definition of healthcare-associated influenza would gain from discussion, particularly concerning the time period between hospitalization and influenza onset. In the Taylor et al study, hospital-acquired influenza was defined as symptom onset at least 96 hours after admission or readmission, with a positive influenza test result less than 96 hours after discharge or a positive test result less than 96 hours after patient transfer from another facility. In other clinical investigations, the time period considered varied greatly, ranging from 48 hours to 7 days. We previously applied the criterion of 48 hours after hospitalization. The incubation period should serve to define the optimal cutoff differentiating communityand hospital-acquired influenza. A previous review estimated that the median incubation periods of influenza A and B were 1.4 and 0.6 days, respectively, with 95% of patients infected by influenza A and B developing symptoms by 2.8 and 1.1 days, respectively, after infection. Of note, these results were based on 6 and 2 experimental studies of influenza A and B, respectively. The mechanisms of infection were inhalation, nasal spray, and nasal drops. The sole observational study included in this review of influenza A demonstrated that 37 airline passengers became symptomatic 12–84 hours after exposure to a single individual with influenza (median 38 hours). Nevertheless, experimental infection and natural experiments may present incubation periods different from normal exposures. The incubation period for influenza in real-life conditions could be defined by analyzing the results of outbreak investigations via epidemiological and molecular approaches. Epidemiological analyses usually provide the time period between at-risk contact or exposure and onset of symptoms in cases. Molecular analyses provide strict similarity of strains. Combining the 2 approaches could specify an incubation period for influenza. There are still only a few studies in this field, but they could become the standard in the future. The criteria for definition based on time period between hospitalization and onset are important to discuss for the following reasons. First, attack rate calculations will be affected by the definition. Indeed, longer time intervals lead to underestimation of the burden of healthcare-associated influenza. However, incubation periods differ by influenza serotype. Short time periods between patient entry and onset might evoke misclassification of late-onset communityacquired cases as hospital-acquired cases. Second, sources of exposure might differ regarding this time period (ie, family, other patients, healthcare workers, or visitors). Information on documented or reported influenza sources in the family or neighborhood might then be considered in the definition of healthcare-associated influenza. Third, patient characteristics will change by time periods adopted for diagnosis, and then comparisons between communityand hospitalacquired influenza might fluctuate accordingly. Finally, in case of legalities, hospital-attributable risk can be questioned, depending on the definition adopted. The Taylor et al study provides interesting new findings and raises the need for a standardized definition of healthcareacquired influenza. A standardized definition would allow better comparability between observational and interventional investigations into healthcare-associated influenza.

Background Clostridium difficile is an anaerobic, Gram-positive bacterium that has been implicated as the leading cause of antibiotic-associated diarrhea. Metronidazole is currently the first-line treatment for mild to moderate C. difficile infections. Our laboratory isolated a strain of C. difficile with a stable resistance phenotype to metronidazole. A shotgun proteomics approach was used to compare differences in the proteomes of metronidazole-resistant and -susceptible isolates. Methodology/Principal Findings NAP1 C. difficile strains CD26A54_R (Met-resistant), CD26A54_S (reduced- susceptibility), and VLOO13 (Met-susceptible) were grown to mid-log phase, and spiked with metronidazole at concentrations 2 doubling dilutions below the MIC. Peptides from each sample were labeled with iTRAQ and subjected to 2D-LC-MS/MS analysis. In the absence of metronidazole, higher expression was observed of some proteins in C. difficile strains CD26A54_S and CD26A54_R that may be involved with reduced susceptibility or resistance to metronidazole, including DNA repair proteins, putative nitroreductases, and the ferric uptake regulator (Fur). After treatment with metronidazole, moderate increases were seen in the expression of stress-related proteins in all strains. A moderate increase was also observed in the expression of the DNA repair protein RecA in CD26A54_R. Conclusions/Significance This study provided an in-depth proteomic analysis of a stable, metronidazole-resistant C. difficile isolate. The results suggested that a multi-factorial response may be associated with high level metronidazole-resistance in C. difficile, including the possible roles of altered iron metabolism and/or DNA repair.

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The usefulness of carbapenems for gram-negative infections is becoming compromised by organisms harboring carbapenemases, enzymes which can hydrolyze the drug. Currently KPC (class A), NDM (class B), and OXA-48 types (class D) are the most globally widespread carbapenemases. However, among the GES-type class A extended-spectrum β-lactamases (ESBLs) there are variants that hydrolyze carbapenems, with blaGES-5 being the most common. Two Escherichia coli and two Serratia marcescens harboring blaGES-5 on plasmids were isolated by the Canadian Nosocomial Infection Surveillance Program (CNISP) from four different patients in a single hospital over a 2-year period. Complete sequencing of the blaGES-5 plasmids indicated that all four had nearly identical backbones consisting of genes for replication, partitioning, and stability, but contained variant accessory regions consisting of mobile elements and antimicrobial resistance genes. The plasmids were of a novel replicon type, but belonged to the MOBQ1 group based on relaxase sequences, and appeared to be mobilizable, but not self-transmissible. Considering the time periods of bacterial isolation, it would appear the blaGES-5 plasmid has persisted in an environmental niche for at least 2 years in the hospital. This has implications for infection control and clinical care when it is transferred to clinically relevant gram-negative organisms.