RATIONALE:Identifying patients who could be safely managed at home versus those needing hospitalisation was a particular concern during early COVID-19. Respiratory viruses remain a concern, including new COVID-19 variants, influenza and respiratory syncytial virus. We developed COVIDFree@Home, a mobile application and clinician dashboard for remote monitoring, to determine if remotely collected measures could predict low oxygen saturation in home-isolating patients with COVID-19. METHODS:We conducted a prospective cohort study of patients newly diagnosed with COVID-19 from three Toronto hospitals between 2020 and 2022. Participants used the COVIDFree@Home app daily to enter symptoms, temperature, heart rate and oxygen saturation at home, which clinicians monitored via an online dashboard. We analysed baseline characteristics and remote monitoring variables to identify predictors of oxygen saturation ≤92%. A random forest classifier was trained to predict low oxygen saturation in the following 2 days. A secondary objective was to identify factors predicting hospitalisation. RESULTS:Of 431 participants, 376 (87.2%) entered at least one measure. Of the 376, 49 (13%) experienced low oxygen saturation, and 19 (5.1%) were hospitalised. Baseline factors associated with low oxygen saturation included older age, obesity, pre-existing pulmonary disease and Alpha/Beta variant. The classifier predicted future low oxygen saturation with an area under the curve of 0.68 (sensitivity 57%, specificity 72%, positive predictive value 3%, negative predictive value 99%). Key predictive factors included cough, lower baseline oxygen saturation, severe fatigue, higher temperature and higher heart rate. Factors associated with hospitalisation included dyspnoea, fever, Alpha/Beta variant and comorbidities of hypertension, mental illness and diabetes. Patients with a runny nose or sore throat were less likely to be hospitalised. CONCLUSIONS:During the COVID-19 pandemic, remote monitoring along with knowledge of baseline characteristics could predict low oxygen saturation in the next 2 days in people with COVID-19. This approach may help identify individuals needing medical attention during future pandemics, though further model improvement is necessary. TRIAL REGISTRATION NUMBER:NCT04453774.

Background:During the COVID-19 pandemic, many with acute infection isolated at home, with a small but significant number requiring hospitalization. At the time, since the pathogen was fairly unknown, clinicians were uncertain about which patients would rapidly deteriorate and need hospitalization. We developed the COVIDFree@Home smartphone app and clinician dashboard to monitor and support people managing at home with acute COVID-19 infection. It was uncertain whether such an app would be used by patients and whether it would support patient care. This knowledge would inform telemedicine and digital health tools being used to deliver care to patients remotely at that time. Objective:This study aimed to determine the feasibility of using a smartphone app and clinician dashboard for remote clinical monitoring of people with COVID-19 at home. Methods:A feasibility study set at 3 hospital sites (University Health Network, Sunnybrook Health Sciences Centre, and Trillium Health Partners) between 2020 and 2022 was conducted. Participants newly diagnosed with COVID-19 were asked to enter data into a smartphone app called COVIDFree@Home twice daily for 10 days while isolating at home. Their data, including symptoms, temperature, and oxygen saturation, were monitored on a clinician-facing dashboard. The primary outcome of feasibility was the number of patients who used the app. We also examined patient satisfaction through a survey questionnaire. Results:A total of 431 patients were recruited, out of which 229 (56.5%) were females and the average age was 38.9 (SD 12.8) years. There were 376 (87.2%) participants who used the app to report symptoms or oxygen saturation at least once. Among these participants, 373 (99.2%) reported symptoms and 363 (96.5%) reported oxygen saturation. Participants reported symptoms an average of 1.7 (SD 1.1) times per day for a median of 5 (IQR 3-8) days. Oxygen saturation levels were reported 1.5 times per day for a median of 6 (IQR 4-9) days. There were 19 hospitalizations (4.4%) among study participants. Most patients felt comfortable using the app, felt reassured their data was being monitored and did not have privacy concerns. Conclusions:Patients with acute COVID-19 infection engaged with a remote home monitoring platform, however, not at the recommended frequency or duration. Remote patient monitoring of acute respiratory infection appears viable and can offer patients reassurance. It has the potential to reduce strain on the health care system during future pandemics, but further evidence is required to demonstrate improved health outcomes.

Background:Alterations in smell (anosmia) and taste (dysgeusia) are common with SARS-CoV-2. The study objective was to evaluate for concordance in anosmia and dysgeusia among household members affected by COVID-19. Methods:A retrospective cohort study of individuals followed by the COVIDEO program at Sunnybrook Health Sciences Centre was performed for patients ≥4 years old diagnosed with COVID-19 between April 1, 2020, to December 31, 2020. Households were identified, and index cases were selected based on the first subject assessed by COVIDEO. Controls for each household contact were identified from the COVIDEO database by matching age (within 10 years) and date of diagnosis (closest within 3 months thereafter). Concordance of anosmia and dysgeusia was determined between index cases and household contacts compared to nonhousehold controls. Results:A total of 353 households were identified: 963 subjects (353 index cases, 600 household contacts) and 600 controls. Median age was 30 years (interquartile range [IQR]: 16, 49), and 50% (475/953) were women. Prevalence of anosmia and dysgeusia were 23.6% and 22.7%, respectively. Anosmia concordance was 64.3% between index cases and nonhousehold controls, compared to 65.7% (p = 0.09) between index cases and nongenetically related household members, and 69.4% (p = 0.74) between index cases and genetically related household members. In multivariate analysis, anosmia was more likely to be reported with longer time from symptom onset (OR 1.06 per day [95% CI 1.02 to 1.1]), and with rhinorrhea (OR 2.2 [95% CI 1.6 to 3.0]), or dyspnea (OR 2.4 [95% CI 1.3 to 4.4]). Conclusions:There was no significant difference in anosmia and dysgeusia concordance between genetically related and unrelated household members or non-household controls.

Background:Delays in COVID-19 testing may increase the risk of secondary household and community transmission. Little is known about what patient characteristics and symptom profiles are associated with delays in test seeking.Methods:We conducted a retrospective cohort study of all symptomatic patients diagnosed with COVID-19 and assessed in a COVID Expansion to Outpatients (COVIDEO) virtual care program between March 2020 and June 2021. The primary outcome was later test seeking more than 3 days from symptom onset. Multivariable logistic regression was used to examine predictors of later testing including patient characteristics and symptoms (30 individual symptoms or 7 symptom clusters).Results:Of 5,363 COVIDEO patients, 4,607 were eligible and 2,155/4,607 (46.8%) underwent later testing. Older age was associated with increased odds of late testing (adjusted odds ratio [aOR] 1.007/year; 95% CI 1.00 to 1.01), as was history of recent travel (aOR 1.4; 95% CI 1.01 to 1.95). Health care workers had lower odds of late testing (aOR 0.50; 95% CI 0.39 to 0.62). Late testing was associated with symptoms in the cardiorespiratory (aOR 1.2; 95% CI 1.05, 1.36), gastrointestinal (aOR = 1.2; 95% CI 1.04, 1.4), neurological (aOR 1.1; 95% CI 1.003, 1.3) and psychiatric (aOR 1.3; 95% CI 1.1, 1.5) symptom clusters. Among individual symptoms, dyspnea, anosmia, dysgeusia, sputum, and anorexia were associated with late testing; pharyngitis, myalgia, and headache were associated with early testing.Conclusion:Certain patient characteristics and symptoms are associated with later testing, and warrant further efforts to encourage earlier testing to minimize transmission.

Background Waning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases. Aim We examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time. Methods Using linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days. Results There were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91–1.22) at 42–69 days after vaccination and peaked at 1.27 (95% CI: 1.04–1.55) at 126–153 days when compared with the reference interval (14–41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04–1.15). Individuals aged 18–64 years showed the greatest decline in protection against influenza A(H1N1) (aOR per 28 days = 1.26; 95% CI: 0.97–1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aOR per 28 days = 1.20; 95% CI: 1.08–1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years. Conclusions Influenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Background: Studies have shown an association between workplace safety climate scores and patient outcomes. This study aimed to investigate (1) performance of the hospital safety climate scale that was adapted to assess acute respiratory illness safety climate, (2) factors associated with safety climate scores, and (3) whether the safety scores were associated with following recommended droplet and contact precautions.Methods: A survey of Canadian healthcare personnel participating in a cohort study of influenza during the 2010/2011-2013/2014 winter seasons. Factor analysis and structural equation modeling were used for analyses.Results: Of the 1359 participants eligible for inclusion, 88% were female and 52% were nurses. The adapted items loaded to the same factors as the original scale. Personnel working on higher risk wards, nurses, and younger staff rated their hospital's safety climate lower than other staff. Following guidelines for droplet and contact precautions was positively associated with ratings of management support and absence of job hindrances.Conclusion: The adapted tool can be used to assess hospital safety climates regarding respiratory pathogens. Management support and the absence of job hindrances are associated with hospital staff's propensity and ability to follow precautions against the transmission of respiratory illnesses.

Objectives: To evaluate the impact of virtual care in preventing unnecessary healthcare visits for patients with SARS-CoV-2. Methods: We conducted a retrospective matched cohort study, evaluating the COVID-19 Expansion to Outpatients (COVIDEO) programme involving virtual assessments for all positive patients in the Sun-nybrook assessment centre from January 2020 to June 2021, followed by risk-stratified routine follow-up, couriering of oxygen saturation devices, and 24 hour/day direct-to-physician pager for urgent questions. We linked COVIDEO data to province-wide datasets, matching each eligible COVIDEO patient to <= 10 other Ontario SARS-CoV-2 patients on age, sex, neighbourhood, and date. The primary outcome was emergency department (ED) visit, hospitalization or death within 30 days. Multivariable regression accounted for comorbidities, vaccination, and pre-pandemic healthcare utilization. Results: Among 6508 eligible COVIDEO patients, 4763 (73.1%) were matched to >= 1 non-COVIDEO patient. COVIDEO care was protective against the primary composite outcome (adjusted odds ratio [aOR] 0.91, 95% CI, 0.82-1.02), with a reduction in ED visits (7.8% vs. 9.6%; aOR 0.79, 95% CI, 0.70-0.89), but increase in hospitalizations (3.8% vs. 2.7%, aOR 1.37, 95% CI, 1.14-1.63) reflecting more direct-to-ward admissions (1.3% vs. 0.2%, p < 0.0001). Results were similar when matched comparators were limited to patients who had not received virtual care elsewhere with a decrease in ED visits (7.8 vs. 8.6%, aOR 0.86, 95% CI, 0.75-0.99) and an increase in hospitalizations (3.7 vs. 2.4%, aOR 1.45, 95% CI, 1.17-1.80). Discussion: An intensive remote care programme can prevent unnecessary ED visits and facilitate direct-to-ward hospitalizations and thereby mitigate the impact of COVID-19 on the healthcare system. (c) 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to improve the safety of the environments where we care for older adults in Canada.After providing assistance during the first wave, many Ontario hospitals formally partnered with local congregate care homes in a "hub and spoke" model during second pandemic wave onward.The objective of this article is to describe the implementation and longitudinal outcomes of residents in one hub and spoke model composed of a hospital partnered with 18 congregate care homes including four long-term care and 14 retirement or other congregate care homes.Intervention: Homes were provided continuous seven-day per week access to hospital support, including infection prevention and control (IPAC), testing, vaccine delivery and clinical support as needed.Any COVID-19 exposure or transmission triggered a same-day meeting to implement initial control measures.A minimum of weekly on-site visits occurred for long-term care homes and biweekly for other congregate care homes, with up to daily on-site presence during outbreaks.Outcomes: Case detection among residents increased following implementation in context of increased testing, then decreased post-immunization until the Omicron wave when it peaked.After adjusting for the correlation within homes, COVID-related mortality decreased following implementation (OR=0.51,95% CI, 0.30-0.88;p=0.01).In secondary analysis, homes without pre-existing IPAC programs had higher baseline COVID-related mortality rate (OR=19.19,95% CI, 4.66-79.02;p<0.001) and saw a larger overall decrease during implementation (3.76% to 0.37%-0.98%)as compared to homes with pre-existing IPAC programs (0.21% to 0.57%-0.90%). Conclusion:The outcomes for older adults residing in congregate care homes improved steadily throughout the COVID-19 pandemic.While this finding is multifactorial, integration with a local hospital partner supported key interventions known to protect residents.

Two sodium-dependent vitamin C transporter isoforms (SVCT1 and SVCT2) were identified as ascorbic acid transporters, but their roles in skin have, as yet, not been elucidated. Here we analyze the expression and function of SVCTs in healthy human skin cells and skin tissues, and in UVB-induced cutaneous tissue injury. SVCT1 was primarily found in the epidermis expressed by keratinocytes, whereas SVCT2 expression was in the epidermis and dermis in keratinocytes, fibroblasts, and endothelial cells. Uptake experiments revealed that ascorbic acid affinity of SVCT1 was lower than SVCT2 (K(m)=75 muM and K(m)=44 muM, respectively), but maximal velocity was 9-times higher (36 nmol/min/well). In keratinocytes, SVCT1 was found to be responsible for vitamin C transport, although SVCT2 gene expression was higher. On UVB irradiation, SVCT1 mRNA expression in murine skin declined significantly in a time- and dose-dependent manner, whereas SVCT2 mRNA levels were unchanged. Furthermore, UVB irradiation of keratinocytes in vitro was accompanied by reduced ascorbic acid transport. In summary, these data indicate that the two vitamin C transporter isoforms fulfill specific functions in skin: SVCT1 is responsible for epidermal ascorbic acid supply, whereas SVCT2 mainly facilitates ascorbic acid transport in the dermal compartment. UVB-induced oxidative stress in mice resulted in depletion of SVCT1 mRNA levels and led to significantly decreased ascorbic acid uptake in keratinocytes, providing evidence on why ascorbic acid levels are decreased on UVB irradiation in vivo.

BACKGROUND: The pandemic has affected hundreds of millions of people; early reports suggesting high rates of prolonged symptoms may be prone to selection bias. METHODS: In a program caring for all SARS-CoV-2 positive inpatients and outpatients between March to October 2020, and offering universal 90-day follow-up, we compared those who died prior to 90 days, not responding to follow-up, declining, or accepting follow-up. Among those seen or declining follow-up, we determined the prevalence and predictors of persistent symptoms. RESULTS: Among 993 patients, 21 (2.1%) died prior to 90 days, 506 (50.9%) did not respond, 260 (26.1%) declined follow-up because they were well, and 206 (20.7%) were fully assessed. Of 466 who responded to follow-up inquiry, 133 (28.5%) reported ≥1 persistent symptom, including constitutional (15.5%), psychiatric (14.2%), rheumatologic (13.1%), neurologic (13.1%), cardiorespiratory (12.0%), and gastrointestinal (1.7%). Predictors differed for each symptom type. Any persistent symptom was more common in older patients (adjusted odds ratio [aOR] 1.11, 95% CI 1.04 to 1.18/5 years), those diagnosed in hospital (aOR 2.03, 95% CI 1.24 to 3.33) and those with initial constitutional and rheumatologic symptoms. Patients not responding to follow-up were younger and healthier at baseline. CONCLUSION: Persistent symptoms are common and diverse 3 months post-COVID-19 but are likely over-estimated by most reports.

BACKGROUND:Treatment of infective endocarditis secondary to Pseudomonas aeruginosa can be challenging because of this organism's ability to acquire antimicrobial resistance over time.METHODS:We describe a patient with native aortic valve infective endocarditis due to P. aeruginosa who developed progressive multi-drug resistance while on therapy. The resistance mechanisms were characterized using whole-genome sequencing.RESULTS:We identified two mutations in subsequent isolates (dacB and OprD) that conferred resistance to anti-pseudomonal penicillins, cephalosporins, and carbapenems. The patient was treated with combination high-dose continuous infusion meropenem and ciprofloxacin therapy, in addition to bioprosthetic aortic valve replacement and repair of ventricular septal wall defect. Antibiotics were continued for 6 weeks post-cardiac surgery and the patient remains infection free 18 months post-completion of antibiotic therapy.CONCLUSION:Clinicians should be aware of the ability of P. aeruginosa to acquire resistance mechanisms in response to selective antibiotic pressures in high-inoculum infections such as infective endocarditis. The mutations identified in this case report correlated well with the evolving antimicrobial resistance profile observed.

Background:Most individuals with coronavirus disease 2019 (COVID-19) experience mild symptoms and are managed in the outpatient setting. The aim of this study was to determine whether self-reported symptoms at the time of diagnosis can identify patients at risk of clinical deterioration.Methods:This was a retrospective cohort study of 671 outpatients with laboratory-confirmed COVID-19 diagnosed in Toronto between March 1 and October 16, 2020. We examined the association between patients' baseline characteristics and self-reported symptoms at the time of diagnosis and the risk of subsequent hospitalization.Results:Of 671 participants, 26 (3.9%) required hospitalization. Individuals aged 65 years or older were more likely to require hospitalization (odds ratio [OR] 5.29, 95% CI 2.19 to 12.77), whereas those without medical comorbidities were unlikely to be hospitalized (OR 0.02, 95% CI 0.00 to 0.17). After adjusting for age and presence of comorbidities, sputum production (adjusted OR [aOR] 5.01, 95% CI 1.97 to 12.75), arthralgias (aOR 4.82, 95% CI 1.85 to 12.53), diarrhea (aOR 4.56, 95% CI 1.82 to 11.42), fever (aOR 3.64, 95% CI 1.50 to 8.82), chills (aOR 3.62, 95% CI 1.54 to 8.50), and fatigue (aOR 2.59, 95% CI 1.04 to 6.47) were associated with subsequent hospitalization.Conclusions:Early assessment of symptoms among outpatients with COVID-19 can help identify individuals at risk of clinical deterioration. Additional studies are needed to determine whether more intense follow-up and early intervention among high-risk individuals can alter the clinical trajectory of and outcomes among outpatients with COVID-19.

Objectives The majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnoea is challenging to assess remotely, and the accuracy of subjective dyspnoea measures in capturing hypoxaemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnoea in diagnosing hypoxaemia in COVID-19 patients. Methods This is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from 3 April 2020 to 13 September 2020. Dyspnoea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV) and positive/negative likelihood ratios (+LR/−LR) for detecting hypoxaemia. In the primary analysis, hypoxaemia was defined by oxygen saturation <95%; the diagnostic accuracy of subjective dyspnoea was also assessed across a range of oxygen saturation cutoffs from 92% to 97%. Results During the study period, 89/501 (17.8%) of patients met criteria for home oxygen saturation monitoring, and of these 17/89 (19.1%) were diagnosed with hypoxaemia. The presence/absence of dyspnoea had limited accuracy for diagnosing hypoxaemia, with SN 47% (95% CI 24% to 72%), SP 80% (95% CI 68% to 88%), NPV 86% (95% CI 75% to 93%), PPV 36% (95% CI 18% to 59%), +LR 2.4 (95% CI 1.2 to 4.7) and −LR 0.7 (95% CI 0.4 to 1.1). The SN of dyspnoea was 50% (95% CI 19% to 81%) when a cut-off of <92% was used to define hypoxaemia. A modified Medical Research Council dyspnoea score >1 (SP 98%, 95% CI 88% to 100%), Roth maximal count <12 (SP 100%, 95% CI 75% to 100%) and Roth counting time <8 s (SP 93%, 95% CI 66% to 100%) had high SP that could be used to rule in hypoxaemia, but displayed low SN (≤50%). Conclusions Subjective dyspnoea measures have inadequate accuracy for ruling out hypoxaemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring.

Objectives The majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnea is challenging to assess remotely, and the accuracy of subjective dyspnea measures in capturing hypoxemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnea in diagnosing hypoxemia in COVID-19 patients. Methods This is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from April 3, 2020 to June 8, 2020. Hypoxemia was defined by oxygen saturation <95%. Dyspnea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV), and positive/negative likelihood ratios (+LR/-LR) for detecting hypoxemia. Results During the study period 64/298 (21.5%) of patients met criteria for home oxygen saturation monitoring, and of these 14/64 (21.9%) were diagnosed with hypoxemia. The presence/absence of dyspnea had limited accuracy for diagnosing hypoxemia, with SN 57% (95% CI 30-81%), SP 78% (63%-88%), NPV 86% (72%-94%), PPV 42% (21%-66%), +LR 2.55 (1.3-5.1), -LR 0.55 (0.3-1.0). An mMRC dyspnea score >1 (SP 97%, 95%CI 82%-100%), Roth Maximal Count <12 (SP 100%, 95%CI 75-100%), and Roth Counting time < 8 seconds (SP 93%, 95%CI 66%-100%) had high SP that could be used to rule in hypoxemia, but displayed low SN (≤50%). Conclusions Subjective dyspnea measures have inadequate accuracy for ruling out hypoxemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement N/A ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the institutional review board at Sunnybrook Health Sciences as minimal risk research, using data collected for routine clinical practice, and the requirement for informed consent was waived All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes N/A

Background: The association between antimicrobial use (AMU) and emergence of antimicrobial resistance is well documented. The Canadian Nosocomial Infection Surveillance Program (CNISP) has conducted sentinel surveillance of AMU at participating Canadian hospitals since 2009 resulting in the largest pan-Canadian hospital database of dispensed antimicrobials. Objectives: Describe interhospital variability of AMU across Canada. Methods: Hospitals submit annual AMU data based on patient days (PD). Antimicrobials were measured in defined daily doses (DDD) for adults using the WHO Anatomical Therapeutic Chemical (ATC) system. The AMU data among pediatric patients have been available since 2017 using days of therapy (DOT). Surveillance includes systemic antibacterial agents (J01 ATC codes), oral metronidazole, and oral vancomycin. AMU was assessed using quintiles, interquartile ranges (IQR), and relative IQRs (upper- and lower-quartile values divided by the median). Results: Between 2009 and 2018, 20–26 hospitals participated in adult surveillance each year (35 teaching hospitals and 3 nonteaching hospitals participated in ≥1 year). Over this period, overall AMU decreased by 13% at participating adult hospitals from 645 to 560 DDD per 1,000 PD. AMU varied substantially between hospitals, but this variability decreased over time (Fig. 1). In 2009, the IQRs for overall AMU spanned 309 DDD per 1,000 PD, and in 2018 it spanned only 103 DDD per 1,000 PD. This decrease in variability was due to large decreases in use among hospitals with high use in 2009–2010. Among hospitals in the highest use quintile in 2009–2010, AMU decreased, on average, 44 DDD per 1,000 PD each year. Among hospitals in the lowest use quintile in 2009–2010, AMU increased, on average, 6 DDD per 1,000 PD each year. In 2018, antibiotics with the largest absolute IQR variability were cefazolin (61–113 DDD per 1,000 PD), piperacillin-tazobactam (32–64 DDD per 1,000 PD), and vancomycin (24–49 DDD per 1,000 PD). Among antibiotics with ≥1 DDD per 1,000 PD, antibiotics with the largest relative IQR variability were tobramycin (0.3–6 DDD per 1,000 PD), cefadroxil (0.08–9 DDD per 1,000 PD), and linezolid (0.2–3 DDD per 1,000 PD). In 2018, the IQR for overall pediatric AMU (n = 7 teaching hospitals) was 426–581 DOT per 1,000 PD. Antibiotics with the largest IQRs were vancomycin (0.6–58 DOT per 1,000 PD), cefazolin (33–88 DOT per 1,000 PD), and tobramycin (3–57 DOT per 1,000 PD). Among antibiotics with ≥1 DOT per 1,000 PD in 2018, antibiotics with the largest relative IQRs were tobramycin (3–57 DOT per 1,000 PD), cefuroxime (1–6 DOT per 1,000 PD), and amoxicillin (8–42 DOT per 1,000 PD). Conclusions: There is wide variation in overall antibiotic use across hospitals. Variation between AMU at adult hospitals has decreased between 2009 and 2018; in 2018, antibiotics with the largest IQRs were cefazolin and piperacillin-tazobactam. Benchmarking AMU is crucial for informing antimicrobial stewardship efforts.Funding: CNISP is funded by the Public Health Agency of Canada.Disclosures: Allison McGeer reports funds to her institution from Pfizer and Merck for projects for which she is the principal investigator. She also reports consulting fees from Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.

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 bla VIM -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); bla VIM carrying plasmids were characterized. We identified 15 patients, thereof 11 with bla VIM-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 bla VIM-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 bla VIM-1 -carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.

Background Antimicrobial resistance is a growing threat to the world’s ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada. Methods In this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014–2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd). Results Between 2009 and 2016, 16–18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ≥1 year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p = 0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% ( p = 0.002) and 26% ( p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p < 0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use. Conclusions This study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.