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Background The role of antibiotics in preventing urinary tract infection (UTI) in older adults is unknown. We sought to quantify the benefits and risks of antibiotic prophylaxis among older adults. Methods We conducted a matched cohort study comparing older adults (≥66 years) receiving antibiotic prophylaxis, defined as antibiotic treatment for ≥30 days starting within 30 days of a positive culture, with patients with positive urine cultures who received antibiotic treatment but did not receive prophylaxis. We matched each prophylaxis recipient to 10 nonrecipients based on organism, number of positive cultures, and propensity score. Outcomes included (1) emergency department (ED) visit or hospitalization for UTI, sepsis, or bloodstream infection within 1 year; (2) acquisition of antibiotic resistance in urinary tract pathogens; and (3) antibiotic-related complications. Results Overall, 4.7% (151/3190) of UTI prophylaxis patients and 3.6% (n = 1092/30 542) of controls required an ED visit or hospitalization for UTI, sepsis, or bloodstream infection (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.12–1.57). Acquisition of antibiotic resistance to any urinary antibiotic (HR, 1.31; 95% CI, 1.18–1.44) and to the specific prophylaxis agent (HR, 2.01; 95% CI, 1.80–2.24) was higher in patients receiving prophylaxis. While the overall risk of antibiotic-related complications was similar between groups (HR, 1.08; 95% CI, .94–1.22), the risk of Clostridioidesdifficile and general medication adverse events was higher in prophylaxis recipients (HR [95% CI], 1.56 [1.05–2.23] and 1.62 [1.11–2.29], respectively). Conclusions Among older adults with UTI, the harms of long-term antibiotic prophylaxis may outweigh their benefits.

This paper summarizes COVID-19 disease epidemiology in Canada in the pre-vaccine era—from January through to December 2020. Canadian case numbers, risk factors, disease presentations (including severe and critical disease), and outcomes are described. Differences between provinces and territories in geography, population size and density, health demographics, and pandemic impact are highlighted. Key concepts in public health response and mitigation are reviewed, including masking, physical distancing, hand washing, and the promotion of outdoor interactions. Adequate investment in public health infrastructure is stressed, and regional differences in screening and testing strategies are highlighted. The spread of COVID-19 in Canadian workplaces, long-term care homes, and schools is described and lessons learned emphasized. The impact of COVID-19 on vulnerable populations in Canada—including Indigenous Peoples, ethnic minorities and newcomers, people who use drugs, people who are homeless, people who are incarcerated, and people with disabilities—is described. Sex and gender disparities are also highlighted. Author recommendations include strategies to reduce transmission (such as test–trace–isolate), the establishment of nationally standardized definitions and public reporting, the protection of high risk and vulnerable populations, and the development of a national strategy on vaccine allocation.

Objectives:An accurate estimate of the average number of hand hygiene opportunities per patient hour (HHO rate) is required to implement group electronic hand hygiene monitoring systems (GEHHMSs). We sought to identify predictors of HHOs to validate and implement a GEHHMS across a network of critical care units.Design:Multicenter, observational study (10 hospitals) followed by quality improvement intervention involving 24 critical care units across 12 hospitals in Ontario, Canada.Methods:Critical care patient beds were randomized to receive 1 hour of continuous direct observation to determine the HHO rate. A Poisson regression model determined unit-level predictors of HHOs. Estimates of average HHO rates across different types of critical care units were derived and used to implement and evaluate use of GEHHMS.Results:During 2,812 hours of observation, we identified 25,417 HHOs. There was significant variability in HHO rate across critical care units. Time of day, day of the week, unit acuity, patient acuity, patient population and use of transmission-based precautions were significantly associated with HHO rate. Using unit-specific estimates of average HHO rate, aggregate HH adherence was 30.0% (1,084,329 of 3,614,908) at baseline with GEHHMS and improved to 38.5% (740,660 of 1,921,656) within 2 months of continuous feedback to units (P < .0001).Conclusions:Unit-specific estimates based on known predictors of HHO rate enabled broad implementation of GEHHMS. Further longitudinal quality improvement efforts using this system are required to assess the impact of GEHHMS on both HH adherence and clinical outcomes within critically ill patient populations.

We evaluated the impact of discontinuing vancomycin-resistant Enterococcus (VRE) screening and use of contact precautions on the incidence of health care-associated Clostridioides difficile infection (HA-CDI) in acute teaching hospitals in Ontario, Canada. Among hospitals that stopped VRE screening and contact precaution measures, there was a significant change in HA-CDI rates after the discontinuation of practices (incidence rate ratios, 1.11; 95% confidence interval, 1.01-1.22). No change in rate was observed among hospitals that continued VRE control practices. Screening and use of contact precautions for VRE may provide hospitals additional advantages for broadened HA-CDI control and prevention.

Background Influenza causes significant annual morbidity and mortality, particularly in older adults, for whom influenza vaccine effectiveness (VE) is also lower. Immunizing one group (e.g., children) against influenza may indirectly protect another group (e.g., older adults) against influenza and its complications. Methods We updated previous systematic reviews on indirect protection against influenza by searching MEDLINE and EMBASE for relevant human studies published until January 4, 2017. We abstracted and critically appraised English language publications that reported or provided information to calculate indirect VE against influenza, as a percentage, in non-institutional settings. We developed a term called ‘estimated actual protection’ to explore the relationship between indirect protection and the product of direct VE and relative vaccine coverage. We calculated estimated actual protection for a subset of studies that reported coverage and indirect VE for: laboratory-confirmed influenza; outpatient care for respiratory illness; influenza-associated emergency visits; or influenza-associated hospitalizations. We ran linear mixed models to compare estimated actual protection against indirect VE for the four outcomes, and graphed the data. Results Of 2320 unique records identified, we abstracted and appraised 26 articles describing 24 studies. The majority of included studies reported at least one outcome suggesting that immunizing one group reduced influenza-related outcomes in another group. Critical appraisal of the abstracted studies identified recurring methodological weaknesses, such as lack of laboratory-confirmed influenza. Our exploratory analyses of 18 studies indicated a positive but not statistically significant relationship between estimated actual protection and indirect protection for each of the four outcomes. Conclusions Our systematic review and exploratory analyses suggest influenza immunization provides some level of indirect protection. However, our critical appraisal highlights the need for a standardized and consistently applied approach to measuring indirect protection against influenza to fill existing knowledge gaps. Additionally, the concept of estimated actual protection requires validation.

Background Vancomycin-resistant enterococci (VRE) are a serious antimicrobial resistant threat in the healthcare setting. We assessed the cost-effectiveness of VRE screening and isolation for patients at high-risk for colonisation on a general medicine ward compared to no VRE screening and isolation from the healthcare payer perspective. Methods We developed a microsimulation model using local data and VRE literature, to simulate a 20-bed general medicine ward at a tertiary-care hospital with up to 1000 admissions, approximating 1 year. Primary outcomes were accrued over the patient’s lifetime, discounted at 1.5%, and included expected health outcomes (VRE colonisations, VRE infections, VRE-related bacteremia, and deaths subsequent to VRE infection), quality-adjusted life years (QALYs), healthcare costs, and incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) and scenario analyses were conducted to assess parameter uncertainty. Results In our base-case analysis, VRE screening and isolation prevented six healthcare-associated VRE colonisations per 1000 admissions (6/1000), 0.6/1000 VRE-related infections, 0.2/1000 VRE-related bacteremia, and 0.1/1000 deaths subsequent to VRE infection. VRE screening and isolation accrued 0.0142 incremental QALYs at an incremental cost of $112, affording an ICER of $7850 per QALY. VRE screening and isolation practice was more likely to be cost-effective (> 50%) at a cost-effectiveness threshold of $50,000/QALY. Stochasticity (randomness) had a significant impact on the cost-effectiveness. Conclusion VRE screening and isolation can be cost-effective in majority of model simulations at commonly used cost-effectiveness thresholds, and is likely economically attractive in general medicine settings. Our findings strengthen the understanding of VRE prevention strategies and are of importance to hospital program planners and infection prevention and control.

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAPSpn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAPSpn and IPD from 2010 to 2015. Methods Active surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAPSpn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UADPCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UADPCV13. Results Of 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAPSpn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAPSpn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAPSpn and IPD cases, but remained unchanged over the study years. Conclusion Herd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAPSpn, and represent between 5 and 10% of all CAP in this patient population.

BACKGROUND Rising rates of antimicrobial resistance are driven by overuse of antibiotics. Characterizing physician antibiotic prescribing variability can inform interventions to optimize antibiotic use. OBJECTIVES To describe predictors of overall antibiotic prescribing as well as the inter-physician variability in antibiotic prescribing amongst family physicians. METHODS We conducted a 5 year cohort study of antibiotic prescribing rates by family physicians in Ontario, Canada using a repository of electronic medical records. Using multilevel logistic regression models fitted with random intercepts for physicians, we evaluated the association of patient-, physician- and clinic-level characteristics with antibiotic prescribing rates. RESULTS We included 3956921 physician-patient encounters, 322129 unique patients and 313 physicians from 41 family medicine clinics. Physicians prescribed a median of 54 (interdecile range 28-95) antibiotics per 1000 encounters. Female children aged 3-5 years were most likely to receive antibiotics compared with men ≥65 years (OR 4.01, 95% CI 3.89-4.13). The only significant physician-level predictor was median daily patient visits of ≥20 compared with

Background Monitoring and studying community antibiotic use is a critical component in combating rising antimicrobial resistance. Objectives To validate an electronic medical record dataset containing antibiotic prescriptions and to quantify some important differences between prescribing and dispensing databases. Methods We evaluated antibiotics prescribed and dispensed to patients ≥65 years of age during 2011-15. We compared the EMRALD prescribing database with the validated Ontario Drug Benefit (ODB) dispensing database. Using ODB as the gold standard and limiting to EMRALD physicians, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% CIs. We also compared the relative change in antibiotic use prescribed by all physicians to this population over time between the databases using Poisson regression models. Results In this population, 74% of all antibiotics dispensed were from non-EMRALD physicians. Trends in use were discordant over time. When we limited ODB to EMRALD prescribers only to assess the validity of EMRALD data, we observed good sensitivity and excellent specificity for correctly identifying antibiotics at 85% (95% CI 84%-85%) and 98% (95% CI 98%-98%), respectively. The PPV was 78% (95% CI 78%-78%) and the NPV was 99% (95% CI 99%-99%). All performance measures were higher among the highest prescribing physicians. Conclusions We demonstrated EMRALD is well suited for studying antibiotic prescribing by EMRALD physicians. However, due to the frequency with which patients receive antibiotic prescriptions from their non-primary care physicians, we caution against the use of non-population-based prescribing databases to infer antibiotic use rates or trends over time.

The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal.Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations.Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]).Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population.ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov.

Background Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. Methods We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. Results We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2–4) and 6 days (stool; IQR 4.25–6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = − 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). Conclusions The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. Trial registration ClinicalTrials.gov ID NCT01782755. Registered February 4 2013. Electronic supplementary material The online version of this article (10.1186/s12931-018-0950-5) contains supplementary material, which is available to authorized users.

Surveillance data from Southern Ontario show that a majority of Verona Integron-encoded Metallo-β-lactamase (VIM)-producing Enterobacteriaceae are locally acquired. To better understand the local epidemiology, we analysed clinical and environmental blaVIM-positive Enterobacteriaceae from the area. Clinical samples were collected within the Toronto Invasive Bacterial Diseases Network (2010–2016); environmental water samples were collected in 2015. We gathered patient information on place of residence and hospital admissions prior to the diagnosis. Patients with and without plausible source of acquisition were compared regarding risk exposures. Microbiological isolates underwent whole-genome sequencing (WGS); blaVIM carrying plasmids were characterized. We identified 15 patients, thereof 11 with blaVIM-1-positive Enterobacter hormaechei within two genetic clusters based on WGS. Whereas no obvious epidemiologic link was identified among cluster I patients, those in cluster II were connected to a hospital outbreak. Except for patients with probable acquisition abroad, we did not identify any further risk exposures. Two blaVIM-1-positive E. hormaechei from environmental waters matched with the clinical clusters; plasmid sequencing suggested a common ancestor plasmid for the two clusters. These data show that both clonal spread and horizontal gene transfer are drivers of the dissemination of blaVIM-1-carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.

During the first few months of the coronavirus disease 2019 (COVID-19) pandemic, Canadian nursing homes implemented strict no-visitor policies to reduce the risk of introducing COVID-19 in these settings. There are now growing concerns that the risks associated with restricted access to family caregivers and visitors have started to outweigh the potential benefits associated with preventing COVID-19 infections. Many residents have sustained severe and potentially irreversible physical, functional, cognitive, and mental health declines. As Canada emerges from its first wave of the pandemic, nursing homes across the country have cautiously started to reopen these settings, yet there is broad criticism that emerging visitor policies are overly restrictive, inequitable, and potentially harmful. We reviewed the nursing home visitor policies for Canada's 10 provinces and 3 territories as well as international policies and reports on the topic to develop 10 provi-informed, data-driven, and expert-reviewed guidance for the re-opening of Canadian nursing homes to family caregivers and visitors.

Objective Selective reporting of antibiotic susceptibility test results may help guide appropriate antibiotic prescribing, particularly for urinary tract infections. Our objective was to describe laboratory urine culture susceptibility reporting practices and to estimate their impact on antibiotic prescribing in outpatients. Methods We examined all positive urine cultures with Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis associated with an antibiotic prescription among outpatients over 65 years of age in Ontario, Canada from 2014 through 2017. We evaluated antibiotic prescribing in the empirical window (1–3 days before culture result) and in the directed window (0–5 days after culture result). Unadjusted and adjusted odds ratios were reported to estimate the association between reporting and prescribing. Results In total 113 780 eligible urine cultures from 48 laboratories were included in the study cohort. Susceptibility reporting practices were highly variable between laboratories, with a range across antibiotics from norfloxacin (n = 5/48, 10.4% reporting) to nitrofurantoin (n = 40/48, 83.3% reporting). Reporting antibiotic susceptibility was associated with increased odds of prescribing that antibiotic in the directed window (aOR 2.98, 95%CI 2.07–4.28). At the laboratory level, the proportion of urine cultures reporting specific antibiotic susceptibility results was also associated with an increase in prescribing of that antibiotic in the empirical window (adjusted OR 1.23, 95%CI 1.13–1.33, per 25% increase in reporting). Conclusions Laboratory reporting of antibiotic susceptibility results for urine cultures is associated with empirical and directed prescribing of the reported antibiotics. Laboratories can play an important role in guiding appropriate antibiotic selection for urinary indications.

Background Data on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada. Methods We enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations. Results Ninety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case’s spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05–36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92–25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52–27.40). Conclusions Nine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.

Nursing homes have become “ground zero” for the coronavirus disease 2019 (COVID‐19) epidemic in North America, with homes experiencing widespread outbreaks resulting in severe morbidity and mortality among its residents. This manuscript describes a 371‐bed acute care hospital's emergency response to a 126‐bed nursing home experiencing a COVID‐19 outbreak in Toronto, Canada. Like other health care system responses to COVID‐19 outbreaks in nursing homes, this hospital‐nursing home partnership can be characterized in several phases: 1) engagement, relationship and trust‐building; 2) environmental scan, team‐building and immediate response; 3) early phase response; and 4) stabilization and transition period. This article is protected by copyright. All rights reserved.

BackgroundIn Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age.MethodsSurveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16–49, 50–64, ≥65 and ≥50 years).ResultsOf 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively.ConclusionsAdults hospitalised with pCAP in the age cohort of 50–64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

Purpose Alterations in bowel habits are common during critical illness, and bowel protocols are gaining acceptance. Our objective was to characterize bowel protocols in a cross-sectional analysis of ICUs. Materials and methods We engaged 44 adult ICUs and performed content analysis of bowel protocols, addressing initiation criteria, medications incorporated, medication escalation, discontinuation criteria, stool assessment methods, and protocol contraindications. Results Bowel protocols operated in 33/44 ICUs (79.5%). The commonest medications were senna (81.0%) and bisacodyl (75.6%). Less common agents were sodium phosphate (45.9%), glycerin (43.2%), docusate sodium (43.2%), polyethylene glycol 3350 (37.8%), lactulose (29.7%), sodium citrate (16.2%), milk of magnesia (13.5%) and mineral oil (16.2%). Bowel protocols were activated by nurses (62.8%) based on initiation criteria [no bowel movement for 24–96 h (35.1%), opioid use (18.9%), “at risk for constipation” (13.5%), stool on digital rectal exam (10.8%), feeding initiation (10.8%), and ICU admission (8.1%)]. Laxative escalation criteria included time from last bowel movement (59.4%), opioid use (18.9%) and no stool on digital rectal exam (10.8%), while 15 (40.5%) included diarrhea as a discontinuation criterion. Conclusions: Bowel protocols have variable initiation, escalation, and discontinuation criteria incorporating different classes of laxatives, reflecting unclear evidence about optimal bowel management strategies in ICU.

We analyzed population-based surveillance data from the Toronto Invasive Bacterial Diseases Network to describe carbapenemase-producing Enterobacteriaceae (CPE) infections during 2007-2015 in south-central Ontario, Canada. We reviewed patients' medical records and travel histories, analyzed microbiologic and clinical characteristics of CPE infections, and calculated incidence. Among 291 cases identified, New Delhi metallo-β-lactamase was the predominant carbapenemase (51%). The proportion of CPE-positive patients with prior admission to a hospital in Canada who had not received healthcare abroad or traveled to high-risk areas was 13% for patients with oxacillinase-48, 24% for patients with New Delhi metallo-β-lactamase, 55% for patients with Klebsiella pneumoniae carbapenemase, and 67% for patients with Verona integron-encoded metallo-β-lactamase. Incidence of CPE infection increased, reaching 0.33 cases/100,000 population in 2015. For a substantial proportion of patients, no healthcare abroad or high-risk travel could be established, suggesting CPE acquisition in Canada. Policy and practice changes are needed to mitigate nosocomial CPE transmission in hospitals in Canada.

Background All Ontario hospitals are mandated to self-report vancomycin-resistant enterocococi (VRE) bacteremias to Ontario's Ministry of Health and Long-term Care for public reporting purposes. Independent quarterly audits of publicly reported VRE bacteremias between September 2013 and June 2015 were carried out by Public Health Ontario. VRE bacteremia case-reporting errors between January 2009 and August 2013 were identified by a single retrospective audit. Methods Employing a quasiexperimental pre–post study design, the relative risk of VRE bacteremia reporting errors before and after quarterly audits were modeled using Poisson regression adjusting for hospital type, case counts reported to the Ministry of Health and Long-term Care, and autocorrelation via generalized estimating equation. Results Overall, 24.5% (126 out of 514) of VRE bacteremias were reported in error; 114 out of 367 (31%) VRE bacteremias reported before quarterly audits and 12 out of 147 (8.1%) reported after audits were found to be incorrect. In adjusted analysis, quarterly audits of VRE bacteremias were associated with significant reductions in reporting errors when compared with before quarterly auditing (relative risk, 0.17; 95% confidence interval, 0.05-0.63). Risk of reporting errors among community hospitals were greater than acute teaching hospitals of the region (relative risk, 4.39; 95% CI, 3.07-5.70). Conclusions This study found independent quarterly audits of publicly reported VRE bacteremias to be associated with significant reductions in reporting errors. Public reporting systems should consider adopting routine data audits and hospital-targeted training to improve data accuracy.

To describe pre-ICU frailty in critically ill patients using the Clinical Frailty Scale (CFS).We included patients ≥18years admitted to 2 ICUs in Hamilton, Canada. The ICU Research Coordinator (RC) generated 3 CFS scores using: 1) chart review, 2) family interview, 3) patient interview. Subsequently, an overall impression was captured in a final score. Mean differences were calculated to assess the RC intra-rater reliability and inter-rater reliability of chart reviews by the RC, Occupational Therapist (OT), and Geriatrics Resident (GR). Scores were also compared between younger and older patients. We also analyzed the relationship between CFS scores and mortality.We prospectively enrolled 150 patients (mean age 63.8 [SD 15.3] years, APACHE II score 21 [SD 7.3]). CFS were similar between RC, OT, and GR chart reviews (p0.05 for all comparisons). There was no difference between RC chart review and RC final score, or between RC patient interview and RC final score. Scores following the RC family interview and the RC final score were significantly different (-0.24, 95% CI -0.38, -0.09, p0.01). Each 1-point increase in the final CFS scored by the RC was weakly associated with ICU mortality (odds ratio 1.18, 95% CI 0.84-1.66, p=0.33), and hospital mortality (OR 1.19, 95% CI 0.89, -1.59, p=0.24).CFS scores can be generated using medical chart review and can be reliably completed by ICU clinicians and research staff.

Background Consideration of cost determinants is crucial to inform delivery of public vaccination programs. Objectives To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs. Methods Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 - 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions. Results Dataset included 2,943 adult admissions to 17 SOS Network hospitals, 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8) and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14,612 CAD (95% CI: $13,852, $15,372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14,031 (95% CI: $13,295, $14,768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days. Conclusion The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per patient cost of influenza-related hospitalization has been underestimated and prevention programs should be evaluated in this context. This article is protected by copyright. All rights reserved.

A multi-country outbreak of Mycobacterium chimaera infection associated with contaminated heater-cooler devices (HCDs) has been reported, with more than 70 cases in Europe and the United States and two cases in Canada to date. The epidemiological and microbiological characteristics of this outbreak provide evidence for common-source transmission of M. chimaera from the exhaust air of intrinsically contaminated HCDs to patients during cardiac surgery. To date, all reported cases have been associated with Stockert 3T HCDs manufactured at one plant by LivaNova prior to September 2014. Implantation of prosthetic material increases the risk of infection. Infections usually present as prosthetic valve endocarditis, vascular graft infection or disseminated infection. Reported mortality rates have varied, but were often over 40%. Several measures are recommended to facilitate case-finding and mitigate risk of exposure. The feasibility of some risk mitigation measures and their effectiveness in reducing the risk of exposure are yet to be determined. Until HCDs are redesigned in a manner that prevents water contamination and aerosolization, separating the HCD exhaust air from the operating room air during surgery may be the most effective risk mitigation strategy. However, possible unintended consequences of this approach should be considered. This overview summarizes findings from peer-reviewed and other relevant national documents on key features of the outbreak, including the source, identified risk factors for infection, signs and symptoms of infection, burden of disease, risk mitigation measures, management challenges and knowledge gaps.

Objective: Interfacility patient movement plays an important role in the dissemination of antimicrobial-resistant organisms throughout healthcare systems. We evaluated how 3 alternative measures of interfacility patient sharing were associated with C. difficile infection incidence in Ontario acute-care facilities. Design: The cohort included adult acute-care facility stays of ≥3 days between April 2003 and March 2016. We measured 3 facility-level metrics of patient sharing: general patient importation, incidence-weighted patient importation, and C. difficile case importation. Each of the 3 patient-sharing metrics were examined against the incidence of C. difficile infection in the facility per 1,000 stays, using Poisson regression models. Results: The analyzed cohort included 6.70 million stays at risk of C. difficile infection across 120 facilities. Over the 13-year period, we included 62,189 new cases of healthcare-associated CDI (incidence, 9.3 per 1,000 stays). After adjustment for facility characteristics, general importation was not strongly associated with C. difficile infection incidence (risk ratio [RR] per doubling, 1.10; 95% confidence interval [CI], 0.97–1.24; proportional change in variance [PCV], −2.0%). Incidence-weighted (RR per doubling, 1.18; 95% CI, 1.06–1.30; PCV, −8.4%) and C. difficile case importation (RR per doubling, 1.43; 95% CI, 1.29–1.58; PCV, −30.1%) were strongly associated with C. difficile infection incidence. Conclusions: In this 13-year study of acute-care facilities in Ontario, interfacility variation in C. difficile infection incidence was associated with importation of patients from other high-incidence acute-care facilities or specifically of patients with a recent history of C. difficile infection. Regional infection control strategies should consider the potential impact of importation of patients at high risk of C. difficile shedding from outside facilities.

In Ontario, Canada, since 2012, some hospitals discontinued contact precautions for vancomycin-resistant Enterococcus (VRE). Between 2009 and 2018, there was an associated rise in VRE bloodstream infections in hospitals where contact precautions were discontinued but not in hospitals that maintained contact precautions. These data suggest contact precautions are important for hospital VRE control programs.

Antimicrobial overuse contributes to antimicrobial resistance. In the ambulatory setting, where more than 90% of antibiotics are dispensed, there are no Canadian benchmarks for appropriate use. This study aims to define the expected appropriate outpatient antibiotic prescribing rates for three age groups (2, 2-18,18 years) using a modified Delphi method.We developed an online questionnaire to solicit from a multidisciplinary panel (community-academic family physicians, adult-paediatric infectious disease physicians, and antimicrobial stewardship pharmacists) what percentage of 23 common clinical conditions would appropriately be treated with systemic antibiotics followed with in-person meetings to achieve 100% consensus.The panelists reached consensus for one condition online and 22 conditions face-to-face, which took an average of 2.6 rounds of discussion per condition (range, min-max 1-5). The consensus for appropriate systemic antibiotic prescribing rates were, for pneumonia, pyelonephritis, non-purulent skin and soft tissue infections (SSTI), other bacterial infections, and reproductive tract infections, 100%; urinary tract infections, 95%-100%; prostatitis, 95%; epididymo-orchitis, 85%-88%; chronic obstructive pulmonary disease, 50%; purulent SSTI, 35%-50%; otitis media, 30%-40%; pharyngitis, 18%-40%; acute sinusitis, 18%-20%; chronic sinusitis, 14%; bronchitis, 5%-8%; gastroenteritis, 4%-5%; dental infections, 4%; eye infections, 1%; otitis externa, 0%-1%; and asthma, common cold, influenza, and other non-bacterial infections (0%). (Note that some differed by age group.).This study resulted in expert consensus for defined levels of appropriate antibiotic prescribing across a broad set of outpatient conditions. These results can be applied to community antimicrobial stewardship initiatives to investigate the level of inappropriate use and set targets to optimize antibiotic use.La surutilisation d’antimicrobiens contribue à la résistance antimicrobienne. Il n’y a pas de normes canadiennes pour en établir l’utilisation appropriée en milieu ambulatoire, où plus de 90 % des antibiotiques sont prescrits. La présente étude vise à définir le taux de prescription approprié et anticipé d’antibiotiques en milieu ambulatoire dans trois groupes d’âge (moins de 2 ans, de 2 à 18 ans, plus de 18 ans) au moyen de la méthode Delphi modifiée.Les auteurs ont préparé un questionnaire en ligne pour demander à un groupe multidisciplinaire (médecins de famille en milieu communautaire et universitaire, infectiologues pour adultes et pour enfants et pharmaciens en gestion des antimicrobiens) le pourcentage de 23 affections cliniques courantes qui serait traité correctement par des antibiotiques systémiques et l’ont fait suivre de rencontres en salle pour obtenir un consensus à 100 %.Le groupe est parvenu à un consensus en ligne à l’égard d’une affection et à un consensus en salle à l’égard de 22 affections, ce qui a exigé une moyenne de 2,6 séries de discussions par affection (plage minimum-maximum de 1 à 5). Le consensus relatif aux taux de prescription appropriés d’antibiotiques systémiques était de 100 % pour la pneumonie, la pyélonéphrite, les infections non purulentes de la peau et des tissus mous, les autres infections bactériennes et les infections de l’appareil reproducteur; de 95 % à 100 % pour les infections urinaires; de 95 % pour la prostatite; de 85 % à 88 % pour l’épididymo-orchite; de 50 % pour la maladie pulmonaire obstructive chronique; de 35 % à 50 % pour les ITS purulentes; de 30 % à 40 % pour l’otite moyenne; de 18 % à 40 % pour la pharyngite; de 18 % à 20 % pour la sinusite aiguë; de 14 % pour la sinusite chronique; de 5 % à 8 % pour la bronchite; de 4 % à 5 % pour la gastroentérite; de 4 % pour les infections dentaires; de 1 % pour les infections oculaires; de 0 % à 1 % pour l’otite externe et de 0 % pour l’asthme, le rhume banal, la grippe et les autres infections non bactériennes. Il est à souligner que certains pourcentages différaient en fonction des groupes d’âge.La présente étude a suscité un consensus d’experts à l’égard de degrés définis de prescription appropriée d’antibiotiques pour un large éventail d’affections ambulatoires. Ces résultats peuvent être appliqués aux initiatives de gestion des antimicrobiens en milieu communautaire afin d’explorer le degré d’utilisation appropriée et de fixer des objectifs d’optimisation de l’utilisation d’antibiotiques.

Purpose Probiotics may prevent healthcare-associated infections, such as ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and other adverse outcomes. Despite their potential benefits, there are no summative data examining the cost-effectiveness of probiotics in hospitalized patients. This systematic review summarized studies evaluating the economic impact of using probiotics in hospitalized adult patients. Methods We searched MEDLINE, EMBASE, CENTRAL, ACP Journal Club, and other EBM reviews (inception to January 31, 2019) for health economics evaluations examining the use of probiotics in hospitalized adults. Independently and in duplicate, we extracted data study characteristics, risk of bias, effectiveness and total costs (medications, diagnostics/procedures, devices, personnel, hospital) associated with healthcare-associated infections (ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea and antibiotic-associated diarrhea). We used Grading of Recommendations Assessment, Development and Evaluation methods to assess certainty in the overall cost-effectiveness evidence. Results Of 721 citations identified, we included seven studies. For the clinical outcomes of interest, there was one randomized-controlled trial (RCT)-based health economic evaluation, and six model-based health economic evaluations. Probiotics showed favourable cost-effectiveness in six of seven (86%) economic evaluations. Three of the seven studies were manufacturer-supported, all which suggested cost-effectiveness. Certainty of cost-effectiveness evidence was very low because of risk of bias, imprecision, and inconsistency. Conclusion Probiotics may be an economically attractive intervention for preventing ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and antibiotic-associated diarrhea in hospitalized adult patients. Nevertheless, certainty about their cost-effectiveness evidence is very low. Future RCTs examining probiotics should incorporate cost data to inform bedside practice, clinical guidelines, and healthcare policy. Trial registration: PROSPERO CRD42019129929; Registered 25 April, 2019. Electronic supplementary material The online version of this article (10.1007/s12630-019-01525-2) contains supplementary material, which is available to authorized users.

Objective Many jurisdictions lack comprehensive population-based antibiotic use data and rely on third party companies, most commonly IQVIA. Our objective was to validate the accuracy of the IQVIA Xponent antibiotic database in identifying high prescribing physicians compared to the reference standard of a highly accurate population-wide database of outpatient antimicrobial dispensing for patients ≥65 years. Methods We conducted this study between 1 March 2016 and 28 February 2017 in Ontario, Canada. We evaluated the agreement and correlation between the databases using kappa statistics and Bland-Altman plots. We also assessed performance characteristics for Xponent to accurately identify high prescribing physicians with sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Results We included 9,272 physicians. The Xponent database has a specificity of 92.4% (95%CI 92.0%-92.8%) and PPV of 77.2% (95%CI 76.0%-78.4%) for correctly identifying the top 25th percentile of physicians by antibiotic volume. In the sensitivity analysis, 94% of the top 25th percentile physicians in Xponent were within the top 40th percentile in the reference database. The mean number of antibiotic prescriptions per physician were similar with a relative difference of -0.4% and 2.7% for female and male patients, respectively. The error was greater in rural areas with a relative difference of -8.4% and -5.6% per physician for female and male patients, respectively. The weighted kappa for quartile agreement was 0.68 (95%CI 0.67–0.69). Conclusion We validated the IQVIA Xponent antibiotic database to identify high prescribing physicians for patients ≥65 years, and identified some important limitations. Collecting accurate population-based antibiotic use data will remain vital to global antimicrobial stewardship efforts.

IntroductionVentilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysisThe objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and disseminationStudy approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration numberNCT01782755; Pre-results.

BACKGROUND Regional variability in antibiotic use is associated with both antibiotic overuse and antimicrobial resistance. Our objectives were to benchmark outpatient antibiotic use and to evaluate geographic variability among health regions in the province of Ontario, Canada. METHODS This was a cross-sectional study of antibiotics dispensed from outpatient retail pharmacies in Ontario between March 2016 and February 2017. We analyzed variability in the number of antibiotic prescriptions dispensed per 1000 population among Ontario's 14 health regions with crude and adjusted Poisson regression models. Adjusted models controlled for rurality, 4 physician characteristics and 6 population characteristics. RESULTS There were 8 352 578 antibiotics dispensed during the 1-year study period or 621 per 1000 population. The most commonly prescribed antibiotic classes were narrow-spectrum penicillins, macrolides, first-generation cephalosporins and second-generation fluoroquinolones, with adult women receiving the highest rate of prescriptions: 985 antibiotic prescriptions per 1000 population. There was geographic variability in total and class-specific antibiotic use. In the health region with the highest use 778 antibiotics were dispensed per 1000 population whereas in the health region with the lowest use 534 antibiotics were dispensed per 1000 population. The adjusted marginal standardized antibiotic prescription rates for the health regions with the highest and lowest use were 787 (95% confidence interval [CI] 658-934) and 546 (95% CI 494-606) antibiotic prescriptions per 1000 population, respectively. INTERPRETATION We described baseline antibiotic usage in Ontario over a 12-month period, noting variability among some health regions. Our findings highlight the need for interventions to optimize antibiotic use and slow the emergence of antimicrobial resistance.

Background Data are limited on risk factors for vancomycin-resistant Enterococcus (VRE) bacteremia. Methods All patients with a confirmed VRE bacteremia in Ontario, Canada, between January 2009 and December 2013 were linked to provincial healthcare administrative data sources and frequency matched to 3 controls based on age, sex, and aggregated diagnosis group. Associations between predictors and VRE bacteremia were estimated by generalized estimating equations and summarized using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results In total, 217 cases and 651 controls were examined. In adjusted analyses, patient-level predictors included bone marrow transplant (OR 106.99 [95% CI 12.19–939.26]); solid organ transplant (OR 17.17 [95% CI 4.95–59.54]); any cancer (OR 8.64 [95% CI 3.88–19.21]); intensive care unit (ICU) admission (OR 6.81 [95% CI 3.53–13.13]); heart disease (OR 5.27 [95% CI 2.00–13.90]); and longer length of stay (OR 1.07 per day [95% CI 1.06–1.09]). Hospital-level predictors included hospital size (per increase in 100 beds (OR 1.26 [95% CI 1.07–1.48]) and teaching hospitals (OR 3.87 [95% CI 1.85–8.08]). Conclusions Patients with a bone marrow transplant, solid organ transplant, cancer, or who are admitted to the ICU are at highest risk of VRE bacteremia, particularly at large hospitals and teaching hospitals.

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.

The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains. This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16–64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100. Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16–64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: −6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: −28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: −8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7–70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1). These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making. ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

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.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 or65 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.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 adults65 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%).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.

Background Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. Clinical trials registration NCT01517191.

Background To inform public health decision making around influenza prevention and treatment, ongoing surveillance of the influenza burden of disease and assessment of influenza vaccine effectiveness (VE) is critical. The Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network conducts active surveillance each influenza season to characterize the burden of influenza disease and to provide estimates of influenza VE to prevent influenza-related hospitalization in Canadian adults (≥16 years of age). Methods Active surveillance for influenza was conducted at 13 hospitals in four provinces beginning on November 15, 2016 and ending April 30, 2017. Patients admitted with any respiratory diagnosis or symptom were eligible for enrolment. Eligible patients had a nasopharyngeal swab collected and tested for influenza using polymerase chain reaction (PCR). Patients who tested positive for influenza were considered cases; patients who tested negative for influenza were eligible to become matched controls. Detailed demographic and medical information were obtained from the medical record. Influenza VE was estimated as 1 − odds ratio (OR) of influenza in vaccinated vs. unvaccinated patients × 100% using conditional logistic regression, with corresponding 95% confidence intervals (CIs). Results A total of 1,431 influenza cases were enrolled; the majority were influenza A (n = 1,299) and 100% of patients with known influenza A subtype were A/H3N2. Among all influenza cases, 144 (10.1%) patients were admitted to the intensive care unit (ICU) and 91 (6.4%) patients died within 30 days of discharge. Overall adjusted influenza VE for prevention of influenza-related hospitalization in all ages was 23.3% (95% CI: 2.9–39.4%), with slightly lower VE observed in patients ≥65 years (VE: 19.4%; 95% CI: −7.8–39.8%) and higher VE observed in patients Conclusion Overall, influenza VE was low but effective (VE: 23%) for preventing influenza-related hospitalization during the 2016–2017 season in Canada. Given the low influenza VE observed, continued assessment of influenza VE is crucial to inform immunization policy in Canada and to emphasize the importance of the development and utilization of improved influenza vaccines. Disclosures M. K. Andrew, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. sanofi pasteur: Grant Investigator, Research grant. T. F. Hatchette, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. Abbvie: Consultant, Speaker honorarium. J. McElhaney, GSK: Scientific Advisor, Speaker honorarium. sanofi pasteur: Scientific Advisor, Speaker honorarium. A. McGeer, GSK: Grant Investigator, Research grant. Hoffman La Roche: Grant Investigator, Research grant. sanofi pasteur: Grant Investigator, Research grant. A. Poirier, sanofi pasteur: Investigator, Research grant. Actelion: Grant Investigator, Research grant. J. Powis, GSK: Grant Investigator, Research grant. Merck: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Synthetic Biologics: Investigator, Grant recipient. M. Semret, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. S. Trottier, CIHR: Grant Investigator, Research grant. S. A. McNeil, GSK: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. Merck: Collaborator and Consultant, Contract clinical trials and Speaker honorarium. Novartis: Collaborator, Contract clinical trials. sanofi pasteur: Collaborator, Contract clinical trials.

Myeloid-derived suppressor cells are increased with age and elevated in donors with a history of cancer; an age-related effect has never been shown in humans., As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(−) MDSCs across three cohorts: healthy adults (19–59 years old), community-dwelling seniors (61–76 years old), and frail elderly (67–99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.

Influenza vaccination programmes are assumed to have a herd effect and protect contacts of vaccinated persons from influenza virus infection. We searched MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2014 for studies assessing the protective effect of influenza vaccination vs no vaccination on influenza virus infections in contacts. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Of 43,082 screened articles, nine randomised controlled trials (RCTs) and four observational studies were eligible. Among the RCTs, no statistically significant herd effect on the occurrence of influenza in contacts could be found (OR: 0.62; 95% CI: 0.34–1.12). The one RCT conducted in a community setting, however, showed a significant effect (OR: 0.39; 95% CI: 0.26–0.57), as did the observational studies (OR: 0.57; 95% CI: 0.43–0.77). We found only a few studies that quantified the herd effect of vaccination, all studies except one were conducted in children, and the overall evidence was graded as low. The evidence is too limited to conclude in what setting(s) a herd effect may or may not be achieved.

Background Pneumococcal community acquired pneumonia (CAP Spn ) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes. Methods Active surveillance for CAP Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay. Results and conclusions In total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP Spn . Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized Canadian adults in the three years following infant PCV13 immunization programs in Canada.

Background Probiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU). Methods In a randomized blinded trial, patients expected to be mechanically ventilated for ≥72 hours were allocated to receive either 1 × 1010 colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10 %. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality. Results Overall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1 year; (2) protocol adherence was 97 %; (3) no patients received open-label probiotics; and (4) the VAP rate was 19 %. Other infections included: bloodstream infection (19.3 %), urinary tract infections (12.7 %), and skin and soft tissue infections (4.0 %). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7 %) of patients, the median length of stay in ICU was 12 days (quartile 1 to quartile 3, 7–18 days), and in hospital was 26 days (quartile 1 to quartile 3, 14–44 days); 23 patients (15.3 %) died in the ICU. Conclusions The PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients. Trial registration Clinicaltrials.gov NCT01782755. Registered on 29 January 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1495-x) contains supplementary material, which is available to authorized users.

The objective of this study was to determine the impact of selective susceptibility reporting on ciprofloxacin utilization and Gram-negative susceptibility to ciprofloxacin in a hospital setting. Historically at our institution, the microbiology laboratory practice was to report ciprofloxacin susceptibility for all Enterobacteriaceae regardless of susceptibility to other agents. A selective reporting policy was implemented which involved the suppression of ciprofloxacin susceptibility to Enterobacteriaceae when there was lack of resistance to the antibiotics on the Gram-negative panel. Ciprofloxacin utilization (measured in defined daily doses [DDD] per 1,000 patient days) was collected before and after the intervention and compared to moxifloxacin, trimethoprim-sulfamethoxazole, nitrofurantoin, and amoxicillin-clavulanate. Monthly susceptibility of Pseudomonas aeruginosa and Escherichia coli to ciprofloxacin was tabulated. An interrupted time series analysis using segmented regression was performed. The mean monthly ciprofloxacin utilization decreased from 87 (95% CI, 83.7 to 91.2) to 39 (95% CI, 35.0 to 44.0) DDD per 1,000 patient days before and after the implementation of selective reporting, respectively. There was an immediate and sustained reduction in ciprofloxacin usage at 1, 3, 6, 12, and 24 months postintervention ( P < 0.001). A compensatory increase in amoxicillin-clavulanate use was noted starting at 6 months postintervention and persisted for the study period ( P < 0.027). Susceptibility of E. coli , but not that of P. aeruginosa , to ciprofloxacin was higher than predicted starting 12 months after the intervention ( P < 0.05). In conclusion, selective reporting of ciprofloxacin susceptibly may be a useful intervention to reduce targeted antimicrobial utilization and improve Gram-negative susceptibility to ciprofloxacin. This approach should be considered as part of a broader multimodal antimicrobial stewardship program.

Background: Conflicting recommendations exist related to which facial protection should be used by health care workers to prevent transmission of acute respiratory infections, including pandemic influenza. We performed a systematic review of both clinical and surrogate exposure data comparing N95 respirators and surgical masks for the prevention of transmissible acute respiratory infections. Methods: We searched various electronic databases and the grey literature for relevant studies published from January 1990 to December 2014. Randomized controlled trials (RCTs), cohort studies and case–control studies that included data on health care workers wearing N95 respirators and surgical masks to prevent acute respiratory infections were included in the meta-analysis. Surrogate exposure studies comparing N95 respirators and surgical masks using manikins or adult volunteers under simulated conditions were summarized separately. Outcomes from clinical studies were laboratory-confirmed respiratory infection, influenza-like illness and workplace absenteeism. Outcomes from surrogate exposure studies were filter penetration, face-seal leakage and total inward leakage. Results: We identified 6 clinical studies (3 RCTs, 1 cohort study and 2 case–control studies) and 23 surrogate exposure studies. In the meta-analysis of the clinical studies, we found no significant difference between N95 respirators and surgical masks in associated risk of (a) laboratory-confirmed respiratory infection (RCTs: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.64–1.24; cohort study: OR 0.43, 95% CI 0.03–6.41; case–control studies: OR 0.91, 95% CI 0.25–3.36); (b) influenza-like illness (RCTs: OR 0.51, 95% CI 0.19–1.41); or (c) reported workplace absenteeism (RCT: OR 0.92, 95% CI 0.57–1.50). In the surrogate exposure studies, N95 respirators were associated with less filter penetration, less face-seal leakage and less total inward leakage under laboratory experimental conditions, compared with surgical masks. Interpretation: Although N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings, our meta-analysis showed that there were insufficient data to determine definitively whether N95 respirators are superior to surgical masks in protecting health care workers against transmissible acute respiratory infections in clinical settings.

Background Influenza vaccination programs aim to prevent serious outcomes. Given that frailty may impact recovery from influenza, we examined frailty as a predictor of recovery in older adults hospitalized with acute respiratory illness. Methods Data came from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network during the 2011/12, 2012/13, and 2013/14 influenza seasons; all patients were aged 65+. Frailty was measured using a previously validated Frailty Index (FI) of health and functional deficits; baseline frailty was categorized using published cutoffs (0-.1 non-frail, >.1-.21 pre-frail, >.21-.45 frail, >.45 most frail). Recovery was operationalized as being alive 30 days post-discharge with less than two additional health/functional deficits (

Multicenter studies assessing hand hygiene adherence and risk factors for poor performance are scarce. In an observational study involving 13 hospitals across Ontario, Canada, we found a mean adherence rate of 31.2%, and that adherence was positively associated with nurses, single rooms, contact precautions, and the availability of alcohol hand rub dispensers.

Background The spread of CPE is an increasing global threat to patient safety. We describe the introduction and evolution of CPE in south-central Ontario, Canada. Methods The Toronto Invasive Bacterial Diseases Network has performed population based surveillance for CPE in metropolitan Toronto and Peel region from first identified isolates in 2007. All laboratories test/refer all carbapenem non-susceptible Enterobacterial isolates for PCR testing for carbapenemases. Demographic and medical data and travel history are collected from chart review and patient/physician interview. Results Since 2007, 659 patients have been identified as colonized/infected with CPE; 362, 57%) have at least one clinical isolate. Annual incidence has increased from 0 in 2006 to 1.3 per 100,000 in 2016/17 (Figure 1). First bacteremia occurred in 2010, the incidence in 2017 was 0.14 per 100,000 population. 388 (59%) patients were male, median age was 70 years (range 3 months–100 years). Most common genes among first isolates were NDM (306, 46%), OX48 (149, 23%), KPC (122, 19%). Most common species were K. pneumoniae (268, 41%) and E. coli (259, 39%). Over time, second species/same gene were identified in 113 (16%) patients. In addition, 34/xxx patients with isolates with NDM and/or OXA-48 subsequently had a second isolate with a different gene/gene combination. Of 518 patients whose travel and hospitalization history are available, patients with VIM were less likely than other patients to have a foreign hospitalization or travel history (9/28 vs. 341/490, P < 0.0001). Patients with KPC were more likely to have a hospitalization history outside Canada and the Indian subcontinent (25/70, 36%), in Canada (47/164,29%) than to have no hospitalization in the last year (13/93, 14%), or a history of hospitalization in the Indian subcontinent (2/191, 1%) (P < 0.001). The number of incident patients with different hospitalization and travel history over time is shown in Figure 2. Conclusion CPE is increasingly recognized in southern Ontario, both in patients with a history of exposure in healthcare in other countries, and to healthcare in Canada. Intensification of control programs is urgently needed. Disclosures S. Poutanen, MERCK: Scientific Advisor, Speaker honorarium. COPAN: Speaker(but not part of a bureau), Travel reimbursement. Accelerate Diagnostics: Investigator, Research support. Bio-Rad: Investigator, Research support. bioMérieux: Investigator, Research support.

Background The potential role of respiratory viruses in the natural history of community-acquired pneumonia (CAP) in adults has not been well described since the advent of nucleic amplification tests (NATs). Methods From 2004 to 2006, adults with CAP who were admitted to five hospitals were prospectively enrolled in the study, and clinical data, cultures, serology, and nasopharyngeal swabs were obtained. NATs from swabs were tested for influenza, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus 1–4, coronaviruses (OC43, 229E, and NL63), and adenovirus. Results A total of 193 patients were included; the median age was 71 years, 51% of patients were male, and 47% of patients had severe CAP. Overall, 75 patients (39%) had a pathogen identified. Of these pathogens, 29 were viruses (15%), 38 were bacteria (20%), 8 were mixed (4%), and the rest were “unknown.” Influenza (n = 7), hMPV (n = 7), and RSV (n = 5) accounted for most viral infections; other infections included rhinovirus (n = 4), parainfluenza (n = 3), coronavirus (n = 4), and adenovirus (n = 2). Streptococcus pneumoniae was the most common bacterial infection (37%). Compared with bacterial infection, patients with viral infection were older (76 vs 64 years, respectively; p = 0.01), were more likely to have cardiac disease (66% vs 32%, respectively; p = 0.006), and were more frail ( eg , 48% with limited ambulation vs 21% of bacterial infections; p = 0.02). There were few clinically meaningful differences in presentation and no differences in outcomes according to the presence or absence of viral infection. Conclusions Viral infections are common in adults with pneumonia. Easily transmissible viruses such as influenza, hMPV, and RSV were the most common, raising concerns about infection control. Routine testing for respiratory viruses may be warranted for adults who have been hospitalized with pneumonia.