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BackgroundPost-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case.MethodsThis is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power atα = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates ofp0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment.DiscussionHarnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection.Trial registrationThis trial was registered atwww.ClinicalTrials.gov(NCT04321174) on March 25, 2020.

Objective:To determine whether combinations of diagnosis and procedures codes can improve the detection of prosthetic hip and knee joint infections from administrative databases.Design:We performed a validation study of all readmissions from January 1, 2010, until December 31, 2016, following primary arthroplasty comparing the diagnosis and procedure codes obtained from an administrative database based upon the International Classification of Disease, Tenth Revision (ICD-10) to the reference standard of chart review.Setting:Four tertiary-care hospitals in Toronto, Canada, from 2010 to 2016.Participants:Individuals who had a primary arthroplasty were identified using procedure codes.Intervention:Chart review of readmissions identified the presence of a prosthetic joint infection and, if present, the surgical procedure performed.Results:Overall, 27,802 primary arthroplasties were performed. Among 8,844 readmissions over a median follow-up of 669 days (interquartile range, 256–1,249 days), a PJI was responsible for or present in 586 of 8,844 (6.6%). Diagnosis codes alone exhibited a sensitivity of 0.88 (95% CI, 0.85–0.92) and positive predictive value (PPV) of 0.78 (95% CI, 0.74–0.82) for detecting a PJI. Combining a PJI diagnosis code with procedure codes for an arthroplasty and the insertion of a peripherally inserted central catheter improved detection: sensitivity was 0.92 (95% CI, 0.88–0.94) and PPV was 0.78 (95% CI, 0.74–0.82). However, procedure codes were unable to identify the specific surgical approach to PJI treatment.Conclusions:Compared to PJI diagnosis codes, combinations of diagnosis and procedure codes improve the detection of a PJI in administrative databases.

Background Hand hygiene (HH) is an important patient safety measure linked to the prevention of health care-associated infection, yet how outbreaks affect HH performance has not been formally evaluated. Methods A controlled, interrupted time series was performed across 5 acute-care academic hospitals using group electronic monitoring. This system captures 100% of all hand sanitizer and soap dispenser activations via a wireless signal to a wireless hub; the number of activations is divided by a previously validated estimate of the number of daily HH opportunities per patient bed, multiplied by the hourly census of patients on the unit. Daily HH adherence 60 days prior and 90 days following outbreaks on inpatient units was compared to control units not in outbreaks over the same period, using a Poisson regression model adjusting for correlations within hospitals and units. Predictors of HH improvement were assessed in this multivariate model. Results In the 60 days prior to outbreaks, units destined for outbreaks had significantly lower HH adherence compared to control units (incidence rate ratio [IRR], 0.91; 95% confidence interval [CI], .90–.93; P Conclusions Hospital outbreaks tend to occur in units with lower HH adherence and are associated with rapid improvements in HH performance. Group electronic monitoring of HH could be used to develop novel, prospective feedback interventions designed to avert hospital outbreaks.

Background The objective of this review was to examine the current guidelines for infection prevention and control (IPAC) of coronavirus disease-19 (COVID-19) or other coronaviruses in adults 60 years or older living in long-term care facilities (LTCF). Methods EMBASE, MEDLINE, Cochrane library, pre-print servers, clinical trial registries, and relevant grey literature sources were searched until July 31, 2020, using database searching and an automated method called Continuous Active Learning® (CAL®). All search results were processed using CAL® to identify the most likely relevant citations that were then screened by a single human reviewer. Full-text screening, data abstraction, and quality appraisal were completed by a single reviewer and verified by a second. Results Nine clinical practice guidelines (CPGs) were included. The most common recommendation in the CPGs was establishing surveillance and monitoring systems followed by mandating the use of PPE; physically distancing or cohorting residents; environmental cleaning and disinfection; promoting hand and respiratory hygiene among residents, staff, and visitors; and providing sick leave compensation for staff. Conclusions Current evidence suggests robust surveillance and monitoring along with support for IPAC initiatives are key to preventing the spread of COVID-19 in LTCF. However, there are significant gaps in the current recommendations especially with regard to the movement of staff between LTCF and their role as possible transmission vectors. Systematic review registration PROSPERO CRD42020181993

Background The current approach to measuring hand hygiene (HH) relies on human auditors who capture Methods A stepped-wedge cluster randomized quality improvement study was performed on 26 inpatient medical and surgical units across 5 acute care hospitals in Ontario, Canada. The intervention involved daily HH reporting as measured by group electronic monitoring to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (percentage) between baseline and intervention. Secondary outcomes included transmission of antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections. Results After adjusting for the correlation within inpatient units and hospitals, there was a significant overall improvement in HH adherence associated with the intervention (incidence rate ratio [IRR], 1.73 [95% confidence interval {CI}, 1.47–1.99]; P Conclusions The introduction of a system for group electronic monitoring led to rapid, significant improvements in HH performance within a 2-year period. This method offers significant advantages over direct observation for measurement and improvement of HH.

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.

Background: Adults are at risk of being exposed to influenza from many sources. Healthcare personnel (HCP) have the additional risk of being exposed to ill patients.Objective:To determine whether HCP were at higher risk than adults working in nonhealthcare roles (non-HCP).Design:Prospective cohort study.Setting:Acute-care hospitals and other businesses in Toronto, Ontario, Canada.Methods:Adults aged 18–69 years were enrolled for 1 or more of the 2010/2011, 2011/2012, and 2012/2013 influenza seasons. Swabs collected during acute respiratory illnesses were tested for influenza and pre- and postseason blood samples were tested for influenza-specific immune response.Results:The adjusted odds of influenza were similar for HCP and non-HCP (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.63–2.63). Older adults and those vaccinated against influenza had lower odds, and those who shared their workspace and who used corrective eyewear had higher odds of influenza.Conclusions:HCP and other working adults are at similar risk of influenza infection.

Background:Healthcare workers (HCWs) are at risk of acquiring and transmitting respiratory viruses while working in healthcare settings.Objectives:To investigate the incidence of and factors associated with HCWs working during an acute respiratory illness (ARI).Methods:HCWs from 9 Canadian hospitals were prospectively enrolled in active surveillance for ARI during the 2010–2011 to 2013–2014 influenza seasons. Daily illness diaries during ARI episodes collected information on symptoms and work attendance.Results:At least 1 ARI episode was reported by 50.4% of participants each study season. Overall, 94.6% of ill individuals reported working at least 1 day while symptomatic, resulting in an estimated 1.9 days of working while symptomatic and 0.5 days of absence during an ARI per participant season. In multivariable analysis, the adjusted relative risk of working while symptomatic was higher for physicians and lower for nurses relative to other HCWs. Participants were more likely to work if symptoms were less severe and on the illness onset date compared to subsequent days. The most cited reason for working while symptomatic was that symptoms were mild and the HCW felt well enough to work (67%). Participants were more likely to state that they could not afford to stay home if they did not have paid sick leave and were younger.Conclusions:HCWs worked during most episodes of ARI, most often because their symptoms were mild. Further data are needed to understand how best to balance the costs and risks of absenteeism versus those associated with working while ill.

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.

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.

BackgroundA hospital-level pandemic response involves anticipating local surge in healthcare needs.MethodsWe developed a mechanistic transmission model to simulate a range of scenarios of COVID-19 spread in the Greater Toronto Area. We estimated healthcare needs against 2019 daily admissions using healthcare administrative data, and applied outputs to hospital-specific data on catchment, capacity, and baseline non-COVID admissions to estimate potential surge by day 90 at two hospitals (St. Michael’s Hospital [SMH] and St. Joseph’s Health Centre [SJHC]). We examined fast/large, default, and slow/small epidemics, wherein the default scenario (R0 2.4) resembled the early trajectory in the GTA.ResultsWithout further interventions, even a slow/small epidemic exceeded the city’s daily ICU capacity for patients without COVID-19. In a pessimistic default scenario, for SMH and SJHC to remain below their non-ICU bed capacity, they would need to reduce non-COVID inpatient care by 70% and 58% respectively. SMH would need to create 86 new ICU beds, while SJHC would need to reduce its ICU beds for non-COVID care by 72%. Uncertainty in local epidemiological features was more influential than uncertainty in clinical severity. If physical distancing reduces contacts by 20%, maximizing the diagnostic capacity or syndromic diagnoses at the community-level could avoid a surge at each hospital.InterpretationAs distribution of the city’s surge varies across hospitals over time, efforts are needed to plan and redistribute ICU care to where demand is expected. Hospital-level surge is based on community-level transmission, with community-level strategies key to mitigating each hospital’s surge.

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 Antimicrobial stewardship programs (ASPs) using audit and feedback in the intensive care unit (ICU) setting can reduce harms related to inappropriate antibiotic use. However, inappropriate discontinuation or narrowing of antibiotic treatment could increase infection-related mortality in this population. Individual ASP studies are underpowered to detect differences in mortality. Methods We conducted a systematic review and meta-analysis of audit and feedback in the ICU setting, using mortality as our outcome. Results Of 2447 citations, 11 studies met our inclusion criteria. Although a variety of study designs were used to assess reductions in antibiotic use, mortality was analyzed using an uncontrolled before-after study design in all studies. Five studies directed audit and feedback to all or most ICU patients receiving antibiotics and measured overall ICU mortality. In the meta-analysis of these studies, the pooled relative risk of ICU mortality was 1.03 (95% confidence interval, .93-1.14). A second meta-analysis of 3 smaller studies that evaluated mortality only in patients directly assessed by the ASP found a pooled relative risk of ICU mortality of 1.06 (95% confidence interval, .80 to 1.4). Three studies were not appropriate for meta-analysis, but their results were consistent with our overall findings. Conclusions Our systematic review did not identify a change in mortality associated with antimicrobial stewardship using audit and feedback in the ICU setting. These results increase our confidence that audit and feedback can be safely implemented in this setting. Future studies should report standardized estimates of mortality and use more robust study designs to assess mortality, when feasible.

Background Influenza vaccine coverage rates among healthcare workers (HCWs) in acute care facilities in Canada remain below national targets. Objective To determine factors associated with influenza vaccine uptake among HCWs. Methods This secondary analysis of a prospective cohort study included HCWs aged 18-69 years, working ≥20 h/wk in a Canadian acute care hospital. Questionnaires were administered to participants in the fall of the season of participation (2011/12-2013/14) which captured demographic/household characteristics, medical histories, occupational, behavioural and risk factors for influenza. Generalized estimating equation logistic regression was used to determine factors associated with vaccine uptake in the season of participation. Results The adjusted odds ratio for influenza vaccination in the current season was highest for those vaccinated in 3 of 3 previous seasons (OR 156; 95% CI 98, 248) followed by those vaccinated in 2 of 3 and 1 of 3 previous seasons when compared with those not vaccinated. Compared with nurses, physicians (OR 4.2; 95% CI 1.4, 13.2) and support services staff (OR 1.8; 95% CI 1.3, 2.4) had higher odds ratios for vaccine uptake. Conversely, HCWs identifying as Black had lower odds of uptake compared with those with European ancestry (OR 0.44, 95% CI 0.26-0.75) when adjusted for other factors in the model. Conclusion Healthcare workers differ in their annual uptake of influenza vaccine based on their past vaccination history, occupation and ethnicity. These findings indicate a need to determine whether there are other vaccine-hesitant groups within healthcare settings and learn which approaches are successful in increasing their uptake of influenza vaccines.

This report describes transmission of a Burkholderia cenocepacia ET12 strain (ET12-Bc) at the Toronto Adult Cystic Fibrosis (CF) Centre occurring from 2008 to 2017. Epidemiological and genomic data from 11 patients with CF were evaluated. Isolates were analysed using whole genome sequencing (WGS). Epidemiological investigation and WGS analysis suggested nosocomial transmission, despite enhanced infection control precautions. This was associated with subsequent deaths in 10 patients. ET12-Bc positive patients are no longer cared for on the same unit as ET12-Bc negative patients.

Objectives To determine whether a smartphone app, containing local bacterial resistance patterns (antibiogram) and treatment guidelines, improved knowledge of prescribing antimicrobials among medical trainees. Methods We conducted a prospective, controlled, pre-post study of medical trainees with access to a smartphone app (app group) containing our hospital's antibiogram and treatment guidelines compared to those without access (control group). Participants completed a survey which included a knowledge assessment test (score range, 0 [lowest possible score] to 12 [highest possible score]) at the start of the study and four weeks later. The primary outcome was change in mean knowledge assessment test scores between week 0 and week 4. Change in knowledge assessment test scores in the app group were compared to the difference in scores in the control group using multivariable linear regression. Results Sixty-two residents and senior medical students participated in the study. In a multivariable analysis controlling for sex and prior knowledge, app use was associated with a 1.1 point (95% CI: 0.10, 2.1) [β = 1.08, t(1) = 2.08, p = 0.04] higher change in knowledge score compared to the change in knowledge scores in the control group. Among those in the app group, 88% found it easy to navigate, 85% found it useful, and about one- quarter used it daily. Conclusions An antibiogram and treatment algorithm app increased knowledge of prescribing antimicrobials in the context of local antibiotic resistance patterns. These findings reinforce the notion that smartphone apps can be a useful and innovative means of delivering medical education.

Background Prosthetic hip and knee joint infections (PJIs) are challenging to eradicate despite prosthesis removal and antibiotic therapy. There is a need to understand risk factors for PJI treatment failure in the setting of prosthesis removal. Methods A retrospective cohort of individuals who underwent prosthesis removal for a PJI at 5 hospitals in Toronto, Canada, from 2010 to 2014 was created. Treatment failure was defined as recurrent PJI, amputation, death, or chronic antibiotic suppression. Potential risk factors for treatment failure were abstracted by chart review and assessed using a Cox proportional hazards model. Results A total of 533 individuals with prosthesis removal were followed for a median (interquartile range) of 814 (235–1530) days. A 1-stage exchange was performed in 19% (103/533), whereas a 2-stage procedure was completed in 88% (377/430). Treatment failure occurred in 24.8% (132/533) at 2 years; 53% (56/105) of recurrent PJIs were caused by a different bacterial species. At 4 years, treatment failure occurred in 36% of 1-stage and 32% of 2-stage procedures (P = .06). Characteristics associated with treatment failure included liver disease (adjusted hazard ratio [aHR], 3.12; 95% confidence interval [CI], 2.09–4.66), the presence of a sinus tract (aHR, 1.53; 95% CI, 1.12–2.10), preceding debridement with prosthesis retention (aHR, 1.68; 95% CI, 1.13–2.51), a 1-stage procedure (aHR, 1.72; 95% CI, 1.28–2.32), and infection due to Gram-negative bacilli (aHR, 1.35; 95% CI, 1.04–1.76). Conclusions Failure of PJI therapy is common, and risk factors are not easily modified. Improvements in treatment paradigms are needed, along with efforts to reduce orthopedic surgical site infections., Prosthetic joint infections are challenging to eradicate and in this retrospective cohort the characteristics associated with treatment failure included liver disease, presence of a sinus tract, prior debridement with prosthesis retention, a one-stage procedure, and infection with a Gram-negative bacilli.

Background Timely strain typing of group A Streptococci (GAS) is necessary to guide outbreak recognition and investigation. We evaluated the use of (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) combined with cluster analysis software to rapidly distinguish between related and unrelated GAS isolates in real-time. Methods We developed and validated a typing model using 177 GAS isolates with known emm types. The typing model was created using 43 isolates, which included 8 different emm types, and then validated using 134 GAS isolates of known emm types that were not included in model generation. Results Twelve spectra were generated from each isolate during validation. The overall accuracy of the model was 74% at a cutoff value of 80%. The model performed well with emm types 4, 59, and 74 but showed poor accuracy for emm types 1, 3, 12, 28, and 101. To evaluate the ability of this tool to perform typing in an outbreak situation, we evaluated a virtual outbreak model using a “virtual outbreak strain; emm74” compared with a non-outbreak group or an “outgroup “ of other emm types. External validation of this model showed an accuracy of 91.4%. Conclusions This approach has the potential to provide meaningful information that can be used in real time to identify and manage GAS outbreaks. Choosing isolates characterized by whole genome sequencing rather than emm typing for model generation should improve the accuracy of this approach in rapidly identifying related and unrelated GAS strains.

OBJECTIVETo measure transmission frequencies and risk factors for household acquisition of community-associated and healthcare-associated (HA-) methicillin-resistant Staphylococcus aureus (MRSA).DESIGNProspective cohort study from October 4, 2008, through December 3, 2012.SETTINGSeven acute care hospitals in or near Toronto, Canada.PARTICIPANTSTotal of 99 MRSA-colonized or MRSA-infected case patients and 183 household contacts.METHODSBaseline interviews were conducted, and surveillance cultures were collected monthly for 3 months from household members, pets, and 8 prespecified high-use environmental locations. Isolates underwent pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec typing.RESULTSOverall, of 183 household contacts 89 (49%) were MRSA colonized, with 56 (31%) detected at baseline. MRSA transmission from index case to contacts negative at baseline occurred in 27 (40%) of 68 followed-up households. Strains were identical within households. The transmission risk for HA-MRSA was 39% compared with 40% (P=.95) for community-associated MRSA. HA-MRSA index cases were more likely to be older and not practice infection control measures (P=.002–.03). Household acquisition risk factors included requiring assistance and sharing bath towels (P=.001–.03). Environmental contamination was identified in 78 (79%) of 99 households and was more common in HA-MRSA households.CONCLUSIONHousehold transmission of community-associated and HA-MRSA strains was common and the difference in transmission risk was not statistically significant.Infect Control Hosp Epidemiol 2016;1–7

Both hospital admissions and patient isolation increase during influenza season. Influenza testing methodologies that reduce turnaround time (TAT) could reduce time in isolation.We assessed the impact of a new influenza test on TAT and isolation days. TAT and daily mean isolation days were compared at a single hospital over 2 influenza seasons. An automated real-time reverse-transcription polymerase chain reaction assay (rRT-PCR) with random access replaced a conventional rRT-PCR assay for the second influenza season. Automation and random access allowed continuous testing, rather than once daily testing 3-5 d/wk.Confirmed influenza cases (57 vs 68) and total patient days (66,308 vs. 66,366) were similar for the 2012-2013 and 2013-2014 influenza seasons. TAT fell from 35 to 3.6 hours. Daily mean isolation days (32.9 vs 27.7, P .01) fell, as did days in contact precautions (25.0 vs 19.8, P .01) and droplet precautions (6.0 vs 3.5, P .01). Although daily mean droplet precaution days for confirmed influenza rose slightly (0.86 vs 1.1, P = .16), droplet precaution days for suspected influenza fell 85% (2.7 vs 0.41, P .001).Influenza testing technology that reduced TAT from days to hours resulted in a 42% reduction in droplet precaution days and reduced overall isolation days during influenza season.

Background Carbapenemase-producing Enterobacteriaceae (CPE) can colonize hospital drains and spread from drain to patient. The optimal approach to preventing drain colonization is unknown. We present our hospital's experience with a drain decontamination protocol. Methods Our facility is a 450 bed academic hospital in Toronto. Between 2017 and 2019, we identified 32 CPE positive inpatients 24 of whom were known to carry CPE or were CPE screen positive on admission. We implemented a sink drain protocol to prevent plumbing colonization. CPE patients admitted >48 hours have all drains in their room disinfected weekly and when transferred or discharged. Hydrogen peroxide gel (4.5%) is poured into the drain and flushed after 10 minutes. Drain swabs are collected >48 after disinfection; some rooms were also tested pre-disinfection. If post-disinfection swabs were positive, enhanced disinfection methods were used. Results 4.7% (18/387) sink/drain swabs were CPE positive. Eight positive swabs were collected before and ten after disinfection. These 18 positive swabs were from drains in 8 patient rooms and 2 communal showers. Enterobacter species predominated (5/10) and CPE enzymes included KPC(4), NDM(3), OXA-48(2), and mixed NDM&KPC(1). Positive room drains matched the patient's CPE enzyme for 7 of 8 positive rooms. Drain disinfection was successful for 70% (7/10) of positive sinks/drains. Three drains failed disinfection and required the enhanced disinfection protocol. After successful disinfection, all room drains have remained negative on at least one additional swab performed >1 month after successful disinfection but two communal shower drains reverted to positive with the same CPE enzyme on retesting >6 months post-disinfection. Conclusions Sink drains can become contaminated with CPE. Our disinfection protocol was largely successful in eradicating CPE from drains, although two communal shower drains reverted to positive. Disinfection of drains in CPE rooms routinely and at discharge may prevent drain colonization and reduce CPE transmission risk.

The epidemiology of Clostridioides difficile infection (CDI) has drastically changed since the emergence of the epidemic strain BI/NAP1/027, also known as ribotype 027 (R027). However, the relationship between the infecting C. difficile strain and clinical outcomes is still debated. We hypothesized that certain subpopulations of R027 isolates could be associated with unfavorable outcomes. We applied high-resolution multilocus variable-number tandem-repeat analysis (MLVA) to characterize C. difficile R027 isolates collected from confirmed CDI patients recruited across 10 Canadian hospitals from 2005 to 2008. PCR ribotyping was performed first to select R027 isolates that were then analyzed by MLVA (n = 450). Complicated CDI (cCDI) was defined by the occurrence of any of admission to an intensive care unit, colonic perforation, toxic megacolon, colectomy, and if CDI was the cause or contributed to death within 30 days after enrollment. Three major MLVA clusters were identified, MC-1, MC-3, and MC-10. MC-1 and MC-3 were exclusive to Quebec centers, while MC-10 was found only in Ontario. Fewer cases infected with MC-1 developed cCDI (4%) than those infected with MC-3 and MC-10 (15% and 16%, respectively), but a statistically significant difference was not reached. Our data did not identify a clear association between subpopulations of R027 and different clinical outcomes; however, the data confirmed the utility of MLVA’s higher discrimination potential to better characterize CDI populations in an epidemiological analysis. For a patient with CDI, the progression toward an unfavorable outcome is a complex process that probably includes several interrelated strain and host characteristics.

To compare immunogenicity, reactogenicity and acceptability of high- and standard-dose trivalent inactivated influenza vaccine (HDTIV, SDTIV) in 18- to 64-year-olds.We randomized 18- to 64-year-olds to HDTIV or SDTIV in two consecutive years. We collected serum on days 0 and 21, measured haemagglutination inhibition geometric mean titres (GMT) and compared seroconversion, day 21 titres, seroprotection, reactogenicity and acceptability.Immunogenicity was evaluable in 42 of 47 2014 participants, all 33 both-year participants and 87 of 90 2015-only participants. First-dose HDTIV recipients experienced seroconversion more frequently than SDTIV recipients to A(H3N2) in 2014 (13/21, 62% vs. 4/21, 19%, p 0.01) and to all vaccine strains in 2015: (A(H1N1): 24/42, 57% vs. 15/59, 25%; A(H3N2): 42/42, 100% vs. 47/59, 80%; B: 25/42, 60% vs. 13/59, 22%; all p0.01). Day 21 haemagglutination inhibition GMT were higher in first and two sequential-year HDTIV vs. SDTIV recipients: A(H1N1): GMT 749 and 768 vs. 384 (p0.0001, p 0.002); A(H3N2): 1238 and 956 vs. 633 (p 0.0003, p 0.1); and B: 1113 and 1086 vs. 556 (p 0.0005, p 0.02). HDTIV was more reactogenic (local pain score 3 vs. 1 of 10 on day 0/1, p 0.0003), but recipients were equally willing to be revaccinated (HDTIV: 76/83 (92%); SDTIV: 76/80 (95%), p 0.54). The ratios of day 21 GMT in SDTIV recipients vaccinated in 0 to 4 prior years to those in SDTIV and HDTIV recipients vaccinated in 15 or more prior years were A(H1N1): 3.73 and 1.38; A(H3N2) 3.07 and 1.16; and B: 2.01 and 1.21.HDTIV is more immunogenic and reactogenic and as acceptable as SDTIV in 18- to 64-year-olds.

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.

Adenovirus-associated epidemic keratoconjunctivitis (A-EKC) is a cause of large and prolonged outbreaks in ophthalmology clinics and can result in substantial morbidity. A-EKC outbreaks are often the result of contaminated ophthalmologic equipment, surfaces, or hands. Contaminated multidose eye drops are also a likely culprit, but few prior studies provide clear epidemiologic evidence that adenovirus transmission resulted from contamination of eye drops. We describe an A-EKC outbreak at a large, hospital-affiliated eye clinic that affected 44 patients. The unique epidemiology of the outbreak provides strong evidence that contaminated multidose dilating eye drops resulted in adenovirus transmission. Removal of multidose eye medication from the clinic, combined with case finding, enhanced infection control and enhanced environmental cleaning, led to rapid control of the outbreak.

Data on factors associated with the use of antiviral medication to treat influenza in both children and adults are limited.To describe trends in antiviral use, analyze factors associated with antiviral treatment of hospitalized patients with influenza, and to compare use based on guidelines.A retrospective observational cohort of hospitalized patients with laboratory confirmed influenza in southern Ontario hospitals for the 2004/05-2013/14 seasons.Of the 7967 patients, 18% of the 1779 children (15 years) and 66% of the 6188 adults received antiviral therapy. The percentage treated increased from 29% pre-pandemic to 74% during the pandemic, decreased to 55% in 2011/12 and then increased to 65% in 2013/14. Factors significantly associated with antiviral prescription across all age groups during the non-pandemic seasons include influenza type, disease severity, interval between symptom onset and test sample submission, and clinician suspicion of influenza. Rate of treatment of patients meeting guideline criteria was low for children and moderate for adults.Since the pandemic, there has been a sustained increase in the use of antiviral medication for all age groups of hospitalized patients with influenza, but much higher for adults than children. The odds of treatment are higher for patients with more severe disease as well as for those tested within 48 h of symptom onset, both of which are part of the guidelines for treatment with anti-influenza medications.

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.

Progressive immune-associated injury is a hallmark of severe acute respiratory syndrome (SARS). Viral evasion of innate immunity, hypercytokinemia and systemic immunopathology in the SARS coronavirus (SARS CoV) infected host have been suggested as possible mechanisms for the cause of severe pathology and morbidity in SARS patients. The molecular and cellular basis for how SARS CoV impacts the host immune system resulting in severe SARS, however, has not been elucidated. The variable clinical course of SARS may be the result of complex programs of host responses against the infectious agent. Therefore, the systematic analysis of innate and adaptive immune responses to SARS CoV is imperative in building as complete an immunological model as possible of host immunity and inflammatory responses during illness. Here we review recent advances in SARS immunopathogenesis research and present a summary of our findings regarding host responses in SARS patients. We contend that dysregulated type I and II interferon (IFN) responses during SARS may culminate in a failure of the switch from hyper-innate immunity to protective adaptive immune responses in the human host.

Cumulative susceptibility test data (CSTD) are used to guide empirical antimicrobial therapy and to track trends in antibiotic resistance. The Clinical and Laboratory Standards Institute recommends reporting CSTD at least annually and sets the minimum number of isolates per reported organism at 30. To comply, many hospitals combine data from multiple intensive care units (ICUs); however, this may not be appropriate to guide empirical therapy because of variations in patient populations. In this study, susceptibility data for two different ICUs at a tertiary care hospital in Toronto, Canada, were used to create a traditional CSTD report, which combined data from different ICUs, and a rolling-average CSTD report, which pooled 2 years of data for each ICU separately. For simplicity, data for only the most common Gram-negative organisms ( Escherichia coli , Pseudomonas aeruginosa ) and the most relevant antibiotics (ciprofloxacin, piperacillin-tazobactam) were examined. With the rolling-average method, significant differences in susceptibility were seen between the ICUs in 50% of the organism-antimicrobial combinations. Furthermore, the 3% median year-over-year difference in susceptibilities seen for the 16 organism-antibiotic combinations by using the traditional method was lower than the 14% median difference seen for the 20 between-ICU within-year comparisons obtained using the rolling-average method. Changes in our selection of empirical antibiotics resulted from this revised approach, and our results suggest that pooling data from ICUs with different patient populations may not be appropriate. A rolling-average method may be an appropriate strategy for the creation of individual-unit CSTD reports.

Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and may result in severe complications including death. We conducted a prospective study to identify risk factors for complications of CDI (cCDI).Adult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and followed for 90 days. Potential risk factors were measured within 24 hours of diagnosis. Isolates were typed by polymerase chain reaction ribotyping. cCDI was defined as 1 or more of the following: colonic perforation, toxic megacolon, colectomy, admission to an intensive care unit for cCDI, or if CDI contributed to death within 30 days of enrollment. Risk factors for cCDI were investigated by logistic regression.A total of 1380 patients were enrolled. cCDI was observed in 8% of patients. The ribotype was identified in 922 patients, of whom 52% were infected with R027. Age ≥ 80 years, heart rate90/minute, respiratory rate20/minute, white cell count4 × 10(9)/L or ≥ 20 × 10(9)/L, albumin25 g/L, blood urea nitrogen7 mmol/L, and C-reactive protein ≥ 150 mg/L were independently associated with cCDI. A higher frequency of cCDI was observed among R027-infected patients (10.9% vs 7.2%), but the association was not significant in adjusted analysis.CDI complications were associated with older age, abnormal blood tests, and abnormal vital signs. These factors, which are readily available to clinicians at the time of diagnosis, could be used for outcome prediction and risk stratification to select patients who may need closer monitoring or more aggressive therapy.

Background Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea. About one in 5 patients with CDI (median 18%) develop a complication (cCDI), including mortality. Many predictive scores have been published to identify patients at risk of cCDI but none is currently recommended for clinical use and few were validated. We conducted an external validation study of predictive tools for cCDI. Methods Predictive tools were identified through a systematic review. We included those reporting at least an internal validation process. We performed the external validation on a multicenter prospective cohort of 1380 Canadian adults with confirmed CDI. Most cases were elderly (median age 71), had a healthcare facility-associated CDI (90%), and cCDI occurred in 8%. NAP1 strain was found in 52%. The performance of each scoring system was analyzed using individual outcomes. Modifications in predictors were made to match available data in the validation cohort. Results We assessed 3 predictive scores and one predictive model. The performance (95% CI) of higher thresholds are shown in the Table. All scores had a low sensitivity and PPV, and moderate specificity and NPV. The model of Shivashankar 2013 (age, WBC> 15, narcotic use, antacids use, creatinine ratio > 1.5) predicted 25% probability of cCDI. All showed similar AUC (0.63–0.67). Study, outcome (%) Predictors (points) Sen % Spe % PPV % NPV % LR+ Accuracy (%) Na 2015 (2–3 patients) ICU admission, megacolon, colectomy, attributable 30-day death (8%). Age ≥ 65 (1) WBC ≥ 20 (1) Creatinine ≥ 2 mg/dL (1) 46 (36–55) 87 (85–89) 23 (17–29) 95 (94–96) 3.5 (3–4) 84 (82–86) van der Wilden 2013 (≥ 6 patients) ICU, colectomy, attributable 30-day death (7%). Age >70 (2) WBC ≥20 or ≤2 (1) Cardiorespiratory failure (7) Abdominal pain (6)* 61 (51–57) 55 (52–58) 9 (7–11) 95 (93–97) 1.35 (1.3–1.4) 55 (53–58) Hensgens 2013 (≥ 4 patients) ICU, colectomy, all-cause 30-day death (15%). Age (50–84, ≥ 85) (1, 3) Diagnosis in ICU (3) Abdominal surgery (-3) MAP ≤65mmHg (2)* Diarrhea (2) 26 (19–32) 90 88–92) 30 24–37) 87 85–89) 2.5 2–3) 80 (78–82) *Modified Conclusion The predictive tools included in our study showed moderate performance in a validation cohort with a low rate of cCDI and high proportion of NAP1 strains. Further research is needed to develop an accurate predictive tool to guide clinicians in the management of CDI. Disclosures J. Powis, Merck: Grant Investigator, Research grant; GSK: Grant Investigator, Research grant; Roche: Grant Investigator, Research grant; Synthetic Biologicals: Investigator, Research grant

Despite pandemic influenza's long reign atop the list of potential medical catastrophes, the first protocol designed to support critical care triage in a pandemic was published only in 2006. InFACT (the International Forum of Acute Care Trialists) was formed in 2009 and provided a platform for international critical care research collaboration during the 2009-2010 Influenza A(H1N1) pandemic. Over the past 2 years, a number of working groups have emerged from InFACT focused upon improving the investigation and care of patients with severe respiratory illness. Arising from these efforts, in June of 2012, an international group of clinicians convened the first meeting of the PREEDICCT (Providing Resources for Effective and Ethical Decisions In Critical Care Triage) study group. The group's aim is to develop decision support tools appropriate for use in triaging critically ill adult patients during epidemics, mass-casualty scenarios or other resource limited settings. This meeting identified a number of knowledge gaps and research priorities in this area, and suggested a revised framework for the requirements of an adequate triage decision support tool.

Background: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. Methodology/Principal Findings: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. Conclusions/Significance: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Background The demand for inpatient medical services increases during influenza season. A scoring system capable of identifying influenza patients at low risk death or ICU admission could help clinicians make hospital admission decisions. Methods Hospitalized patients with laboratory confirmed influenza were identified over 3 influenza seasons at 25 Ontario hospitals. Each patient was assigned a score for 6 pneumonia severity and 2 sepsis scores using the first data available following their registration in the emergency room. In-hospital mortality and ICU admission were the outcomes. Score performance was assessed using the area under the receiver operating characteristic curve (AUC) and the sensitivity and specificity for identifying low risk patients (risk of outcome

Objective Ribavirin and corticosteroids were used widely as front-line treatments for severe acute respiratory syndrome; however, previous evaluations were inconclusive. We assessed the effectiveness of ribavirin and corticosteroids as the initial treatment for severe acute respiratory syndrome using propensity score analysis. Methods We analyzed data on 1755 patients in Hong Kong and 191 patients in Toronto with severe acute respiratory syndrome using a generalized propensity score approach. Results The adjusted excess case fatality ratios of patients with severe acute respiratory syndrome receiving the combined therapy of ribavirin and corticosteroids within 2 days of admission, compared with those receiving neither treatment within 2 days of admission, were 3.8% (95% confidence interval, −1.5 to 9.2) in Hong Kong and 2.1% (95% confidence interval, −44.3 to 48.5) in Toronto. Conclusions Our results add strength to the hypothesis that the combination of ribavirin and corticosteroids has no therapeutic benefit when given early during severe acute respiratory syndrome infection. Further studies may investigate the effects of these treatments later in disease course.