Artificial Intelligence You Can Trust: What Matters Beyond Performance When Applying Artificial Intelligence to Renal Histopathology?

Although still in its infancy, artificial intelligence (AI) analysis of kidney biopsy images is anticipated to become an integral aspect of renal histopathology. As these systems are developed, the focus will understandably be on developing ever more accurate models, but successful translation to the clinic will also depend upon other characteristics of the system.In the extreme, deployment of highly performant but "black box" AI is fraught with risk, and high-profile errors could damage future trust in the technology. Furthermore, a major factor determining whether new systems are adopted in clinical settings is whether they are "trusted" by clinicians. Key to unlocking trust will be designing platforms optimized for intuitive human-AI interactions and ensuring that, where judgment is required to resolve ambiguous areas of assessment, the workings of the AI image classifier are understandable to the human observer. Therefore, determining the optimal design for AI systems depends on factors beyond performance, with considerations of goals, interpretability, and safety constraining many design and engineering choices.In this article, we explore challenges that arise in the application of AI to renal histopathology, and consider areas where choices around model architecture, training strategy, and workflow design may be influenced by factors beyond the final performance metrics of the system.

Antimicrobial use in Canadian acute-care hospitals: Findings from three national point-prevalence surveys between 2002 and 2017.

OBJECTIVES: The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use. METHODS: Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%. RESULTS: In each survey, 28-47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%-37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%-41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%-40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60). CONCLUSIONS: The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.

Patients in hospital with laboratory-confirmed COVID-19 in a network of Canadian acute care hospitals, Mar. 1 to Aug. 31, 2020: a descriptive analysis.

BACKGROUND: Information on the epidemiology of patients in hospital with laboratory-confirmed coronavirus disease 2019 (COVID-19) in Canadian acute care hospitals is needed to inform infection prevention and control strategies and public health measures. The aim of this surveillance was to describe the epidemiology of patients in hospital with laboratory-confirmed COVID-19 in a network of Canadian acute care hospitals between Mar. 1 and Aug. 31, 2020. METHODS: Through prospective surveillance, we identified adult and pediatric patients in hospital with laboratory-confirmed COVID-19 using a standard definition between Mar. 1 and Aug. 31, 2020, through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 78 hospitals. Patient demographic and clinical characteristics and data on treatment, interventions and outcomes were reviewed and described. RESULTS: As of Aug. 31, 2020, the CNISP had received data for 1906 patients in hospital with COVID-19 in 49 sentinel hospitals in 9 provinces. The majority of patients in hospital with COVID-19 were older (median age 71 yr) and had underlying medical conditions (85.8%). Few children with COVID-19 were admitted to a participating hospital (n = 37, 1.9%). Acquisition of COVID-19 in hospitals was infrequent (6.4% of all cases). A total of 32.8% of patients were admitted from a long-term care facility or retirement home. Health care workers constituted 10.6% of adult patients aged 18-65 years in hospital with COVID-19. Thirty-day attributable mortality was 16.2%. Hospital admission rates peaked in mid-April and were highest in Ontario and Quebec. INTERPRETATION: Surveillance findings indicate that a high proportion of Canadian patients in hospital with COVID-19 during the first 6 months of the pandemic were older adults with underlying medical conditions. Active surveillance of patients in hospital with COVID-19 is critical to enhancing our knowledge of the epidemiology of COVID-19 and to identifying populations at risk for severe outcomes, which will help guide Canada's response in the coming months.

Interpreting ancient food practices: stable isotope and molecular analyses of visible and absorbed residues from a year-long cooking experiment.

Chemical analyses of carbonized and absorbed organic residues from archaeological ceramic cooking vessels can provide a unique window into the culinary cultures of ancient people, resource use, and environmental effects by identifying ingredients used in ancient meals. However, it remains uncertain whether recovered organic residues represent only the final foodstuffs prepared or are the accumulation of various cooking events within the same vessel. To assess this, we cooked seven mixtures of C3 and C4 foodstuffs in unglazed pots once per week for one year, then changed recipes between pots for the final cooking events. We conducted bulk stable-isotope analysis and lipid residue analysis on the charred food macro-remains, carbonized thin layer organic patina residues and absorbed lipids over the course of the experiment. Our results indicate that: (1) the composition of charred macro-remains represent the final foodstuffs cooked within vessels, (2) thin-layer patina residues represent a mixture of previous cooking events with bias towards the final product(s) cooked in the pot, and (3) absorbed lipid residues are developed over a number of cooking events and are replaced slowly over time, with little evidence of the final recipe ingredients.

Trends in health care-associated infections in acute care hospitals in Canada: an analysis of repeated point-prevalence surveys.

BACKGROUND: Health care-associated infections are a common cause of patient morbidity and mortality. We sought to describe the trends in these infections in acute care hospitals, using data from 3 national point-prevalence surveys. METHODS: The Canadian Nosocomial Infection Surveillance Program (CNISP) conducted descriptive point-prevalence surveys to assess the burden of health care-associated infections on a single day in February of 2002, 2009 and 2017. Surveyed infections included urinary tract infection, pneumonia, Clostridioides difficile infection, infection at surgical sites and bloodstream infections. We compared the prevalence of infection across the survey years and considered the contribution of antimicrobial-resistant organisms as a cause of these infections. RESULTS: We surveyed 28 of 33 (response rate 84.8%) CNISP hospitals (6747 patients) in 2002, 39 of 55 (response rate 71.0%) hospitals (8902 patients) in 2009 and 47 of 66 (response rate 71.2%) hospitals (9929 patients) in 2017. The prevalence of patients with at least 1 health care-associated infection increased from 9.9% in 2002 (95% confidence interval [CI] 8.4%-11.5%) to 11.3% in 2009 (95% CI 9.4%-13.5%), and then declined to 7.9% in 2017 (95% CI 6.8%-9.0%). In 2017, device-associated infections accounted for 35.6% of all health care-associated infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 3.9% of all organisms identified from 2002 to 2017; other antibiotic-resistant organisms were uncommon causes of infection for all survey years. INTERPRETATION: In CNISP hospitals, there was a decline in the prevalence of health care-associated infection in 2017 compared with previous surveys. However, strategies to prevent infections associated with medical devices should be developed. Apart from MRSA, few infections were caused by antibiotic-resistant organisms.

Results from the Canadian Nosocomial Infection Surveillance Program for detection of carbapenemase-producing Acinetobacter spp. in Canadian hospitals, 2010-16.

Objectives: Globally there is an increased prevalence of carbapenem-resistant Acinetobacter spp. (CRAs) and carbapenemase-producing Acinetobacter spp. (CPAs) in the hospital setting. This increase prompted the Canadian Nosocomial Infection Surveillance Program (CNISP) to conduct surveillance of CRA colonizations and infections identified from patients in CNISP-participating hospitals between 2010 and 2016. Methods: Participating acute care facilities across Canada submitted CRAs from 1 January 2010 to 31 December 2016. Patient data were collected from medical records using a standardized questionnaire. WGS was conducted on all CRAs and data underwent single nucleotide variant analysis, resistance gene detection and MLST. Results: The 7 year incidence rate of CRA was 0.02 per 10 000 patient days and 0.015 per 1000 admissions, with no significant increase observed over the surveillance period (P > 0.73). Ninety-four CRA isolates were collected from 58 hospitals, of which 93 (98.9%) were CPA. Carbapenemase OXA-235 group (48.4%) was the most common due to two separate clusters, followed by the OXA-23 group (41.9%). Patients with a travel history were associated with 38.8% of CRA cases. The all-cause 30 day mortality rate for infected cases was 24.4 per 100 CRA cases. Colistin was the most active antimicrobial agent (95.8% susceptibility). Conclusions: CRA remains uncommon in Canadian hospitals and the incidence did not increase from 2010 to 2016. Almost half of the cases were from two clusters harbouring OXA-235-group enzymes. Previous medical treatment during travel outside of Canada was common.

The evolving epidemiology of Clostridium difficile infection in Canadian hospitals during a postepidemic period (2009-2015).

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.

Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network).

BACKGROUND: Ongoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons. METHODS: The Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death. RESULTS: Overall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4-48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4-47.8%) and 48.0% (95% CI: 37.5-56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8-65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0-88.4%). CONCLUSIONS: While effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability. ClinicalTrials.gov Identifier: NCT01517191.

Environmental scan of infection prevention and control practices for containment of hospital-acquired infectious disease outbreaks in acute care hospital settings across Canada.

BACKGROUND: Ward closure is a method of controlling hospital-acquired infectious diseases outbreaks and is often coupled with other practices. However, the value and efficacy of ward closures remains uncertain. PURPOSE: To understand the current practices and perceptions with respect to ward closure for hospital-acquired infectious disease outbreaks in acute care hospital settings across Canada. METHODS: A Web-based environmental scan survey was developed by a team of infection prevention and control (IPC) experts and distributed to 235 IPC professionals at acute care sites across Canada. Data were analyzed using a mixed-methods approach of descriptive statistics and thematic analysis. RESULTS: A total of 110 completed responses showed that 70% of sites reported at least 1 outbreak during 2013, 44% of these sites reported the use of ward closure. Ward closure was considered an "appropriate," "sometimes appropriate," or "not appropriate" strategy to control outbreaks by 50%, 45%, and 5% of participants, respectively. System capacity issues and overall risk assessment were main factors influencing the decision to close hospital wards following an outbreak. DISCUSSION: Results suggest the use of ward closure for containment of hospital-acquired infectious disease outbreaks in Canadian acute care health settings is mixed, with outbreak control methods varying. The successful implementation of ward closure was dependent on overall support for the IPC team within hospital administration.

Results from the Canadian Nosocomial Infection Surveillance Program on Carbapenemase-Producing Enterobacteriaceae, 2010 to 2014.

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.

Assessing the magnitude and trends in hospital acquired infections in Canadian hospitals through sequential point prevalence surveys.

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.

Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review.

BACKGROUND: Though often used to control outbreaks, the efficacy of ward closure is unclear. This systematic review sought to identify studies defining and describing ward closure in outbreak control and to determine impact of ward closure as an intervention on outbreak containment. METHODS: We searched these databases with no language restrictions: MEDLINE, 1946 to 7 July 2014; EMBASE, 1974 to 7 July 2014; CINAHL, 1937 to 8 July 2014; and Cochrane Database of Systematic Reviews, 2005 to May 2014. We also searched the following: IndMED; LILACS; reference lists from retrieved articles; conference proceedings; and websites of the CDCP, the ICID, and the WHO. We included studies of patients hospitalized in acute care facilities; used ward closure as a control measure; used other control measures; and discussed control of the outbreak(s) under investigation. A component approach was used to assess study quality. RESULTS: We included 97 English and non-English observational studies. None included a controlled comparison between ward closure and other interventions. We found that ward closure was often used as part of a bundle of interventions but could not determine its direct impact separate from all the other interventions whether used in parallel or in sequence with other interventions. We also found no universal definition of ward closure which was widely accepted. CONCLUSIONS: With no published controlled studies identified, ward closure for control of outbreaks remains an intervention that is not evidence based and healthcare personnel will need to continue to balance the competing risks associated with its use, taking into consideration the nature of the outbreak, the type of pathogen and its virulence, mode of transmission, and the setting in which it occurs. Our review has identified a major research gap in this area.

The molecular epidemiology of incident methicillin-resistant Staphylococcus aureus cases among hospitalized patients in Alberta, Canada: a retrospective cohort study.

BACKGROUND: Infection Prevention and Control (IPC) surveillance for incident methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized patients is performed in a complete provincial surveillance network of all acute care facilities in Alberta, Canada. IPC surveillance is centralized using a web-based data entry platform so that each patient is counted only once. All diagnostic laboratories submit the first clinical MRSA isolate associated with a patient without previous MRSA positive clinical cultures in the preceding year to the Provincial Laboratory for Public Health (ProvLab) for molecular typing. This study will investigate the relationship between the IPC epidemiological classification based on time of detection following admission to hospital (Hospital Acquired and Community Associated) and the matched laboratory MRSA surveillance data using a retrospective cohort study design. METHODS: Incident IPC MRSA cases were classified according to IPC epidemiologic definitions. DNA sequencing of the Staphylococcus protein A (spa) gene and pulsed-field gel electrophoresis (PFGE) typing was performed. IPC MRSA surveillance data were matched to the ProvLab molecular surveillance data. Univariate comparisons of proportions were performed for categorical variables and the Student's t test for continuous variables. RESULTS: MRSA molecular typing data were available for matching for 46.7 % (2248/4818) of incident IPC cases. There was agreement in definitions for traditional nosocomial clones (USA100/CMRSA2) with Hospital Acquired (HA)-MRSA (65.1 % of all IPC HA-MRSA) and traditional community clones (USA400/CMRSA7 and USA300/CMRSA10) with Community Acquired (CA)-MRSA (62.4 % of CA-MRSA). However, we observed discordance for both traditional nosocomial/CA-MRSA (30.4 % of CA-MRSA) and for traditional community/HA-MRSA (26.9 % of HA-MRSA). CONCLUSIONS: We note agreement between traditional nosocomial clones and HA-MRSA, and traditional community clones and CA-MRSA. However, approximately one-quarter of HA-MRSA are those of traditional community clones while approximately one-third of CA-MRSA are those of traditional nosocomial clones. Collaborative provincial MRSA surveillance is important as the distinction between IPC case attribution in acute care settings and the historical definitions of MRSA clones as community- or healthcare-associated have blurred.

Prevalence of antimicrobial use in a network of Canadian hospitals in 2002 and 2009.

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.

HISTORIQUE: La résistance antimicrobienne croissante est une menace importante pour la santé dans le monde. L'utilisation d'antimicrobiens est un moteur de résistance majeur, particulièrement dans le milieu hospitalier. Il faut comprendre la portée et le type d'utilisation des antimicrobiens dans les hôpitaux canadiens pour établir les priorités nationales en matière de gouvernance antimicrobienne. MÉTHODOLOGIE: En 2002 et 2009, dans le cadre de sondages de prévalence d'une journée visant à quantifier les infections nosocomiales dans les hôpitaux du Programme canadien de surveillance des infections nosocomiales, les chercheurs ont colligé des données sur l'utilisation des antimicrobiens systémiques par tous les patients des hôpitaux participants. Le jour du sondage, ils ont recueilli les agents précis utilisés (à part les antiviraux et les antiparasitaires) et l'information démographique relative aux patients. RÉSULTATS: En 2002, 2 460 des 6 747 patients (36,5 %) de 28 hôpitaux recevaient un traitement antimicrobien. En 2009, 3 989 des 9 953 patients (40,1 %) de 44 hôpitaux recevaient un tel traitement (P<0,001). L'utilisation avait beaucoup augmenté au centre du Canada (37,4 % à 40,8 %) et dans l'Ouest canadien (36,9 % à 41,1 %), mais pas dans l'Est canadien (32,9 % à 34,1 %). En 2009, l'utilisation d'antimicrobiens était plus courante dans les unités de transplantation d'organes pleins (71,0 % des patients), les unités de soins intensifs (68,3 %) et les unités d'hématologie-oncologie (65,9 %). Par rapport à 2002, on constatait en 2009 une diminution importante des céphalosporines de première et seconde générations et des augmentations marquées de carbapénèmes, d'antifongiques et de vancomycine. L'utilisation de piperacilline-tazobactam, en proportion de toutes les pénicillines, est passée de 20 % en 2002 à 42,8 % en 2009 (P<0,001). L'utilisation simultanée de plus d'un agent a également connu une hausse importante, passant de 12,0 % des patients en 2002 à 37,7 % en 2009. CONCLUSION: De 2002 à 2009, la prévalence d'utilisation d'antimicrobiens dans les hôpitaux du Programme canadien de surveillance des infections nosocomiales a considérablement augmenté. De plus, les chercheurs ont constaté une augmentation marquée d'agents à large spectre et d'utilisation simultanée de multiples agents.

A consensus development conference model for establishing health policy for surveillance and screening of antimicrobial-resistant organisms.

The Canadian Consensus Development Conference on Surveillance and Screening for Antimicrobial-Resistant Organisms (AROs) was sponsored by the Alberta Ministry of Health to provide evidence to update policies for ARO screening in acute care settings. A rigorous evidence-based literature review completed before the conference concluded that that neither universal nor targeted screening of patients was associated with a reduction in hospital-acquired ARO colonization, infection, morbidity, or mortality. Leading international clinicians, scientists, academics, policy makers, and administrators presented current evidence and clinical experience, focusing on whether and how hospitals should screen patients for AROs as part of broader ARO control strategies. An unbiased and independent "jury" with a broad base of expertise from complementary disciplines considered the evidence and released a consensus statement of 22 recommendations. Policy highlights included developing an integrated "One Health" strategy, fully resourcing basic infection control practices, not performing universal screening, and focusing original research to determine what works.

Complete Sequence of Four Multidrug-Resistant MOBQ1 Plasmids Harboring blaGES-5 Isolated from Escherichia coli and Serratia marcescens Persisting in a Hospital in Canada.

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 ß-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.

Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing.

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.