mRNA COVID-19 vaccine safety among older adults from the Canadian National Vaccine Safety Network.

This study examined short-to-medium term safety of COVID-19 vaccines among adults aged ≥65 years using the Canadian National Vaccine Safety Network active safety surveillance data. Both vaccinated and unvaccinated older adult participants recruited from seven provinces and territories were included in the analysis. Safety was assessed at 7 days after COVID-19 vaccination (dose 1, 2 and 3), and 7 months after dose 1. Multivariable logistic regression was used to examine the association between BNT162b2/mRNA-1273 COVID-19 vaccines and two short-term health events: 1) health event preventing daily activities and/or required medical consultation, 2) serious health events resulting in an emergency department visit and/or hospitalization within 7 days following each dose. We also assessed the rates of serious health events for the period between dose 1 and 2, and 7-months following dose 1. Between December 2020 and February 2022, a total of 173,038, 104,452, and 13,970 older adults completed dose 1, dose 2, and dose 3 surveys, respectively. The control survey was completed by 2,955 unvaccinated older adults. Health events occurred more frequently among recipients after dose 2 homologous mRNA-1273 (adjusted odds ratio [95 % confidence interval]: 2.91 [2.24-3.79]) and dose two heterologous (BNT162b2 followed by mRNA-1273): 1.50 [1.12-2.02] compared to unvaccinated counterparts. There was no difference in event rates after any dose of BNT162b2 and unvaccinated participants. The rates of serious health events following COVID-19 vaccination were very low (≤0.3 %) across all vaccine products and doses, and were not higher compared to unvaccinated controls, and were not associated with an emergency department visit or hospitalization within 7 days following vaccination. Reported symptoms were self-limited and rarely required medical assessment. Our findings further strengthen the current evidence that mRNA COVID-19 vaccines are safe and can be used to inform older adults about expected adverse events following COVID-19 vaccination.

The Strain and the Clinical Outcome of Clostridioides difficile Infection: A Meta-analysis.

Background: The association between bacterial strains and clinical outcomes in Clostridioides difficile infection (CDI) has yielded conflicting results across studies. We conducted a systematic review and meta-analyses to assess the impact of these strains. Methods: Five electronic databases were used to identify studies reporting CDI severity, complications, recurrence, or mortality according to strain type from inception to June 2022. Random effect meta-analyses were conducted to assess outcome proportions and risk ratios (RRs). Results: A total of 93 studies were included: 44 reported recurrences, 50 reported severity or complications, and 55 reported deaths. Pooled proportions of complications were statistically comparable between NAP1/BI/R027 and R001, R078, and R106. Pooled attributable mortality was 4.8% with a gradation in patients infected with R014/20 (1.7%), R001 (3.8%), R078 (5.3%), and R027 (10.2%). Higher 30-day all-cause mortality was observed in patients infected with R001, R002, R027, and R106 (range, 20%-25%).NAP1/BI/R027 was associated with several unfavorable outcomes: recurrence 30 days after the end of treatment (pooled RR, 1.98; 95% CI, 1.02-3.84); admission to intensive care, colectomy, or CDI-associated death (1.88; 1.09-3.25); and 30-day attributable mortality (1.96; 1.23-3.13). The association between harboring the binary toxin gene and 30-day all-cause mortality did not reach significance (RR, 1.6 [0.9-2.9]; 7 studies). Conclusions: Numerous studies were excluded due to discrepancies in the definition of the outcomes and the lack of reporting of important covariates. NAP1/BI/R027, the most frequently reported and assessed strain, was associated with unfavorable outcomes. However, there were not sufficient data to reach significant conclusions on other strains.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN).

BACKGROUND: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. METHODS: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). RESULTS: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. CONCLUSIONS: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

Leveraging Influenza Virus Surveillance From 2012 to 2015 to Characterize the Burden of Respiratory Syncytial Virus Disease in Canadian Adults ≥50 Years of Age Hospitalized With Acute Respiratory Illness.

Background: Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Methods: Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Results: Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. Conclusions: This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza.

Chronic Diarrhea Caused by a Klebsiella oxytoca Toxin Producer Strain Following Antibiotic-Associated Hemorrhagic Colitis: Successful Treatment by Fecal Microbiota Transplant.

Klebsiella oxytoca is a gram-negative bacterium found in fecal microbiota and known to cause several infections in humans, including antibiotic-associated hemorrhagic colitis. We present here a case of colitis caused by K. oxytoca toxin-producing strains that evolved in chronic diarrhea successfully treated by fecal microbiota transplant.

Adverse Events Following Immunization With mRNA and Viral Vector Vaccines in Individuals With Previous Severe Acute Respiratory Syndrome Coronavirus 2 Infection From the Canadian National Vaccine Safety Network.

BACKGROUND: Adults previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop short-term immunity and may have increased reactogenicity to coronavirus disease 2019 (COVID-19) vaccines. This prospective, multicenter, active-surveillance cohort study examined the short-term safety of COVID-19 vaccines in adults with a prior history of SARS-CoV-2. METHODS: Canadian adults vaccinated between 22 December 2020 and 27 November 2021 were sent an electronic questionnaire 7 days post-dose 1, dose 2, and dose 3 vaccination. The main outcome was health events occurring in the first 7 days after each vaccination that prevented daily activities, resulted in work absenteeism, or required a medical consultation, including hospitalization. RESULTS: Among 684 998 vaccinated individuals, 2.6% (18 127/684 998) reported a prior history of SARS-CoV-2 infection a median of 4 (interquartile range: 2-6) months previously. After dose 1, individuals with moderate (bedridden) to severe (hospitalized) COVID-19 who received BNT162b2, mRNA-1273, or ChAdox1-S vaccines had higher odds of a health event preventing daily activities, resulting in work absenteeism or requiring medical consultation (adjusted odds ratio [95% confidence interval]: 3.96 [3.67-4.28] for BNT162b2, 5.01 [4.57-5.50] for mRNA-1273, and 1.84 [1.54-2.20] for ChAdox1-S compared with no infection). Following dose 2 and 3, the greater risk associated with previous infection was also present but was attenuated compared with dose 1. For all doses, the association was lower or absent after mild or asymptomatic infection. CONCLUSIONS: Adults with moderate or severe previous SARS-CoV-2 infection were more likely to have a health event sufficient to impact routine activities or require medical assessment in the week following each vaccine dose.

Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort study.

BACKGROUND: Pregnant individuals have been receiving COVID-19 vaccines following pre-authorisation clinical trials in non-pregnant people. This study aimed to determine the frequency and nature of significant health events among pregnant females after COVID-19 vaccination, compared with unvaccinated pregnant controls and vaccinated non-pregnant individuals. METHODS: We did an observational cohort study, set in seven Canadian provinces and territories including Ontario, Quebec, British Columbia, Alberta, Nova Scotia, Yukon, and Prince Edward Island. Eligibility criteria for vaccinated individuals were a first dose of a COVID-19 vaccine within the previous 7 days; an active email address and telephone number; ability to communicate in English or French; and residence in the aforementioned provinces or territories. Study participants were pregnant and non-pregnant females aged 15-49 years. Individuals were able to participate as controls if they were unvaccinated and fulfilled the other criteria. Data were collected primarily by self-reported survey after both vaccine doses, with telephone follow-up for those reporting any medically attended event. Participants reported significant health events (new or worsening of a health event sufficient to cause work or school absenteeism, medical consultation, or prevent daily activities) occurring within 7 days of vaccination or within the past 7 days for unvaccinated individuals. We employed multivariable logistic regression to examine significant health events associated with mRNA vaccines, adjusting for age group, previous SARS-CoV-2 infection, and trimester, as appropriate. FINDINGS: As of Nov 4, 2021, 191 360 women aged 15-49 years with known pregnancy status had completed the first vaccine dose survey and 94 937 had completed the second dose survey. 180 388 received one dose and 94 262 received a second dose of an mRNA vaccine, with 5597 pregnant participants receiving dose one and 3108 receiving dose two, and 174 765 non-pregnant participants receiving dose one and 91 131 receiving dose two. Of 6179 included unvaccinated control participants, 339 were pregnant and 5840 were not pregnant. Overall, 226 (4·0%) of 5597 vaccinated pregnant females reported a significant health event after dose one of an mRNA vaccine, and 227 (7·3%) of 3108 after dose two, compared with 11 (3·2%) of 339 pregnant unvaccinated females. Pregnant vaccinated females had an increased odds of a significant health event within 7 days of the vaccine after dose two of mRNA-1273 (adjusted odds ratio [aOR] 4·4 [95% CI 2·4-8·3]) compared with pregnant unvaccinated controls within the past 7 days, but not after dose one of mRNA-1273 or any dose of BNT162b2. Pregnant vaccinated females had decreased odds of a significant health event compared with non-pregnant vaccinated females after both dose one (aOR 0·63 [95% CI 0·55-0·72]) and dose two (aOR 0·62 [0·54-0·71]) of any mRNA vaccination. There were no significant differences in any analyses when restricted to events which led to medical attention. INTERPRETATION: COVID-19 mRNA vaccines have a good safety profile in pregnancy. These data can be used to appropriately inform pregnant people regarding reactogenicity of COVID-19 vaccines during pregnancy, and should be considered alongside effectiveness and immunogenicity data to make appropriate recommendations about best use of COVID-19 vaccines in pregnancy. FUNDING: Canadian Institutes of Health Research, Public Health Agency of Canada.

Older Age and Frailty are Associated with Higher Mortality but Lower ICU Admission with COVID-19.

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020. Methods: Patients with laboratory-confirmed COVID-19 admitted to 11 sites in Ontario, Quebec, Alberta, and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Measures included age, sex, demographics, housing, exposures, Clinical Frailty Scale, comorbidities; in addition, length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were assessed. Descriptive analyses and multivariable logistic regressions were conducted. Results: Among 2,011 patients, mean age was 71.0 (range 19-105) years. 29.7% were admitted from assisted living or long-term care facilities. The full spectrum of frailty was represented in both younger and older age groups. 81.8% had at least one underlying comorbidity and 27.2% had obesity. Mortality was 14.3% without ICU admission, and 24.6% for those admitted to ICU. Older age and frailty were independent predictors of lower ICU use and higher mortality; accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened. Conclusions: Frailty is a critical clinical factor in predicting outcomes of COVID-19, which should be considered in research and clinical settings.

Management and clinical outcomes of Lyme disease in acute care facilities in 2 endemic regions of Quebec, Canada: a multicentre retrospective cohort study.

BACKGROUND: Despite increases in cases of Lyme disease, little is known about the management and clinical course of the disease in Canada. We aimed to describe the management and clinical course of Lyme disease in patients treated in acute care facilities in Quebec and to assess adherence to the 2006 Infectious Diseases Society of America (IDSA) guideline. METHODS: This retrospective multicentre cohort study included pediatric and adult patients with serologically confirmed Lyme disease treated in acute care facilities (12 community hospitals and 2 tertiary care centres) of 2 endemic regions of Quebec (Estrie and Montérégie), from 2004 to 2017. We considered drug choice, prescribed dose and treatment duration in assessing adherence of prescriptions to the 2006 IDSA guideline. The main outcome was complete resolution of symptoms at 3 months after the initiation of treatment. RESULTS: We included 272 patients from 14 institutions (age range 3-87 yr). Early disseminated Lyme disease (140 patients [51%]) was predominant. Adherence to the IDSA guideline was observed in 235 (90%) of the 261 cases with complete information, and adherence was stable over time (2004-2013: 57/64 [89%]; 2014-2015: 64/71 [90%]; 2016-2017: 114/126 [90%]; p = 0.8). Non-adherence to the guideline (n = 26) was predominantly due to longer-than-recommended treatment duration (16/26 [62%]). Resolution of objective signs at 3 months after treatment initiation occurred in 265 (99%) of 267 patients, whereas post-treatment Lyme disease syndrome was observed in 27 patients (10%) with increasing incidence over time (2004-2013: 3/65 [5%]; 2014-2015: 4/73 [5%]; 2016-2017: 20/129 [16%]; p = 0.02). INTERPRETATION: We observed clinical resolution of Lyme disease in 99% of the patients, and most treatments (90%) complied with the 2006 IDSA guideline. The incidence of post-treatment Lyme disease syndrome increased over the study period, warranting further prospective studies.

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay.

OBJECTIVE(S): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. METHODS: S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. RESULTS: 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. CONCLUSION(S): Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.

The Canadian National Vaccine Safety Network: surveillance of adverse events following immunisation among individuals immunised with the COVID-19 vaccine, a cohort study in Canada.

INTRODUCTION: COVID-19 vaccines require enhanced safety monitoring after emergency approval. The Canadian National Vaccine Safety Network monitors the safety of COVID-19 vaccines and provides enhanced monitoring for healthy, auto-immune, immunocompromised, pregnant and breastfeeding populations and allows for the detection of safety signals. METHODS AND ANALYSIS: Online participant reporting of health events in vaccinated and unvaccinated individuals 12 years of age and older is captured in three surveys: 1 week after dose 1, 1 week after dose 2 and 7 months after dose 1. Medically attended events are followed up by telephone. The number, percentage, rate per 10 000 and incident rate ratios with 95% CIs are calculated by health event, vaccine type, sex and in 10-year age groups. ETHICS AND DISSEMINATION: Each study site has Research Ethics Board approvals for the project (UBC Children's & Women's, CIUSSS de l'Estrie-CHUS, Health PEI, Conjoint Health Research Ethics Board, University of Calgary and Alberta Health Services, IWK Health, Unity Health Toronto and CHU de Québec-Université Laval Research Ethics Boards). Individuals are invited to participate in this active surveillance and electronic consent is given before proceeding to each survey. Weekly reports are shared with public health and posted on the study website. At least one peer-reviewed manuscript is produced.

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its first variants in fourplex real-time quantitative reverse transcription-PCR assays.

The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is required to identify and isolate contagious patients to prevent further transmission of SARS-CoV-2. In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give the virus a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N) genes. Furthermore, a newly developed primer-probe set targeted human ß2-microglobulin (B2M) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected ≤ 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of nine logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Fourplex assays were evaluated using 160 clinical samples positive for SARS-CoV-2. Results showed that SARS-CoV-2 viral RNA was detected in all samples, including viral strains harboring mutations in the Spike coding sequence that became dominant in the pandemic. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to allow quicker detection of circulating relevant variants in a single reaction.

The 2018 Global Point Prevalence Survey of antimicrobial consumption and resistance in 47 Canadian hospitals: a cross-sectional survey.

BACKGROUND: Patient-level surveillance of antimicrobial use (AMU) in Canadian hospitals empowers the reduction of inappropriate AMU and was piloted in 2017 among 14 hospitals in Canada. We aimed to describe AMU on the basis of patient-level data in Canadian hospitals in 2018 in terms of antimicrobial prescribing prevalence and proportions, antimicrobial indications, and agent selection in medical, surgical and intensive care wards. METHODS: Canadian adult, pediatric and neonatal hospitals were invited to participate in the standardized web-based cross-sectional Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) conducted in 2018. An identified site administrator assigned all wards admitting inpatients to specific surveyors. A physician, pharmacist or nurse with infectious disease training performed the survey. The primary outcomes were point prevalence rates for AMU over the study period regarding prescriptions, indications and agent selection in medical, surgical and intensive care wards. The secondary outcomes were AMU for resistant organisms and practice appropriateness evaluated on the basis of quality indicators. Antimicrobial consumption is presented in terms of prevalence and proportions. RESULTS: Forty-seven of 118 (39.8%) hospitals participated in the survey; 9 hospitals were primary care centres, 15 were secondary care centres and 23 were tertiary or specialized care centres. Of 13 272 patients included, 33.5% (n = 4447) received a total of 6525 antimicrobials. Overall, 74.1% (4832/6525) of antimicrobials were for therapeutic use, 12.6% (n = 825) were for medical prophylaxis, 8.9% (n = 578) were for surgical prophylaxis, 2.2% (n = 143) were for other use and 2.3% (n = 147) were for unidentified reasons. A diagnosis or indication was documented in the patient's file at the initiation for 87.3% (n = 5699) of antimicrobials; 62.9% (n = 4106) of antimicrobials had a stop or review date; and 72.0% (n = 4697) of prescriptions were guided by local guidelines. INTERPRETATION: Overall, three-quarters of AMU was for therapeutic use across participating hospitals. Canadian hospitals should be further incentivized to create and adapt local guidelines on the basis of recent antimicrobial resistance data.

Influenza vaccine during the 2019-2020 season and COVID-19 risk: A case-control study in Québec.

BACKGROUND: We carried out a case-control study that examined whether receipt of the inactivated influenza vaccine during the 2019-2020 season impacted on the risk of coronavirus disease 2019 (COVID-19), as there was a concern that the vaccine could be detrimental through viral interference. METHODS: A total of 920 cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (diagnosed between March and October 2020) and 2,123 uninfected controls were recruited from those who were born in Québec between 1956 and 1976 and who had received diagnostic services at two hospitals (Montréal and Sherbrooke, Québec). After obtaining consent, a questionnaire was administered by phone. Data were analyzed by logistic regression. RESULTS: Among healthcare workers, inactivated influenza vaccine received during the previous influenza season was not associated with increased COVID-19 risk (AOR: 0.99, 95% CI: 0.69-1.41). Among participants who were not healthcare workers, influenza vaccination was associated with lower odds of COVID-19 (AOR: 0.73, 95% CI 0.56-0.96). CONCLUSION: We found no evidence that seasonal influenza vaccine increased the risk of developing COVID-19.

Impact of a hospital-wide computerised approach to optimise the quality of antimicrobial prescriptions in patients with severe obesity: a quasi-experimental study.

BACKGROUND: Rates of adherence to available recommendations for dose adjustments in patients with severe obesity are generally low. Hence, antimicrobials are often underdosed in these patients. Antimicrobial stewardship programmes can improve the use of antimicrobials in hospitalised patients. The aim of the study was to analyse the impact of an antimicrobial stewardship programme based on a computerised clinical decision support system for optimal dosing and antimicrobial use in inpatients with severe obesity. METHODS: This quasi-experimental retrospective study using interrupted time series was conducted in an academic centre in Canada from August 2008 to June 2018. The Antimicrobial Prescription Surveillance System was implemented in August 2010 (intervention 1) and specific rules targeting patients with class III obesity (body mass index ≥ 40 kg/m2) were added in June 2014 (intervention 2). Data were collected from all hospitalised adults receiving antimicrobials which required dose adjustment for severe obesity and were stratified by body mass index. Segmented regression analysis of interrupted time series was used to evaluate the impact of the Antimicrobial Prescription Surveillance System on the proportion of inappropriate days of therapy according to posology and on antimicrobial consumption. RESULTS: Overall, 65 205 antimicrobial prescriptions (68% non-obese, 25% class I-II obesity, and 7% class III obesity) were analysed. In patients with class III obesity, the intervention was associated with a decrease in the proportion of inappropriate days of therapy (trend after the first intervention, -0.8% per 2-month period [95% CI -1.1 to -0.5], p < 0.001; intercept, 11.3% [95% CI 8.2 to 14.5], p < 0.001), which led to a reduction of 35% over an eight-year period (from pre-intervention level of 19.1%). Intervention 1 resulted in a downward trend in antimicrobial consumption, followed by an increasing trend after intervention 2. In these patients, the most frequent interventions made by pharmacists targeted posology (46%). CONCLUSIONS: Antimicrobial Prescription Surveillance System had a positive impact on dosing optimisation and antimicrobial consumption in patients with class III obesity. Improving antimicrobial prescriptions in these patients is important because suboptimal dosing could be associated with unfavourable outcomes.

Increasing incidence and antimicrobial resistance in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. METHODS: We included all incident E. coli BSIs (2014-2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014-2018), region (six areas), age (< 70-years-old and ≥ 70-years-old), and sex (female and male). RESULTS: We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. CONCLUSIONS: Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40-104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.

Does BCG provide long-term protection against SARS-CoV-2 infection? A case-control study in Quebec, Canada.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines became available, it was hypothesized that BCG (Bacillus Calmette-Guérin), which stimulates innate immunity, could provide protection against SARS-CoV-2. Numerous ecological studies, plagued by methodological deficiencies, revealed a country-level association between BCG use and lower COVID-19 incidence and mortality. We aimed to determine whether BCG administered in early life decreased the risk of SARS-CoV-2 infection in adulthood and the severity of COVID-19. METHODS: This case-control study was conducted in Quebec, Canada. Cases were patients with a positive SARS-CoV-2 nucleic acid amplification test performed at two hospitals between March-October 2020. Controls were identified among patients with non-COVID-19 samples processed by the same microbiology laboratories during the same period. Enrolment was limited to individuals born in Quebec between 1956 and 1976, whose vaccine status was accessible in a computerized registry of 4.2 million BCG vaccinations. RESULTS: We recruited 920 cases and 2123 controls. Fifty-four percent of cases (n = 424) and 53% of controls (n = 1127) had received BCG during childhood (OR: 1.03; 95% CI: 0.89-1.21), while 12% of cases (n = 114) and 11% of controls (n = 235) had received two or more BCG doses (OR: 1.14; 95% CI: 0.88-1.46). After adjusting for age, sex, material deprivation, recruiting hospital and occupation there was no evidence of protection conferred by BCG against SARS-CoV-2 (AOR: 1.01; 95% CI: 0.84-1.21). Among cases, 77 (8.4%) needed hospitalization and 18 (2.0%) died. The vaccinated were as likely as the unvaccinated to require hospitalization (AOR: 1.01, 95% CI: 0.62-1.67) or to die (AOR: 0.85, 95% CI: 0.32-2.39). CONCLUSIONS: BCG does not provide long-term protection against symptomatic COVID-19 or severe forms of the disease.

Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. METHODS: During 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. RESULTS: From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. CONCLUSIONS: In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.

Clinical impact of accepting or rejecting a recommendation from a clinical decision support system-assisted antibiotic stewardship program.

Background: Outcomes associated with physician responses to recommendations from an antimicrobial stewardship program (ASP) at an individual patient level have not yet been assessed. We aimed to compare clinical characteristics and mortality risk among patients for whom recommendations from an ASP were accepted or refused. Methods: A prospective cohort study was performed with hospitalized adults who received intravenous or oral antimicrobials at a 677-bed academic centre in Canada in 2014-2017. We included patients with an alert produced by a clinical decision support system (CDSS) for whom a recommendation was made by the pharmacist to the attending physician. The outcome was 90-day in-hospital all-cause mortality. Results: We identified 3,197 recommendations throughout the study period, of which 2,885 (90.2%) were accepted. The median length of antimicrobial treatment was significantly shorter when a recommendation was accepted (0.26 versus 1.78 d; p < 0.001). Refusal of a recommendation was not associated with mortality (odds ratio 1.32; 95% confidence interval, 0.93 to 1.89; p = 0.12). The independent risk factors associated with in-hospital mortality were age, Charlson Comorbidity Index score, admission to a critical care unit, duration between admission and recommendation, and issuance of a recommendation on a carbapenem. Conclusions: The duration of antimicrobial treatment was significantly shorter when a recommendation originating from a CDSS-assisted ASP program was accepted. Future prospective studies including potential residual confounding variables, such as the source of infection or physiological derangement, might help in understanding whether CDSS-assisted ASP will have a direct impact on patient mortality.

Historique: Les résultats liés aux réponses des médecins aux recommandations du programme de gestion antimicrobienne (PGA) n'ont pas encore été évalués à l'égard de chaque patient. Les chercheurs ont visé à comparer les caractéristiques cliniques et le risque de mortalité chez les patients dont les recommandations provenant d'une PGA ont été acceptées ou refusées. Méthodologie: Les chercheurs ont procédé à une étude de cohorte prospective auprès d'adultes hospitalisés qui avaient reçu des antimicrobiens par voie intraveineuse ou orale à un centre universitaire de 667 lits composé de deux établissements du Canada entre 2014 et 2017. Ils ont inclus les patients pour qui s'était déclenchée une alerte produite par un système d'aide à la décision clinique (SADC) et pour qui le pharmacien avait fait une recommandation au médecin traitant. Le résultat était la mortalité toutes causes confondues après un séjour hospitalier de 90 jours. Résultats: Les chercheurs ont extrait 3 197 recommandations tout au long de l'étude, dont 2 885 (90,2 %) ont été acceptées. La durée médiane du traitement antimicrobien était considérablement plus courte lorsqu'une recommandation était acceptée (0,26 par rapport à 1,78 jour; p < 0,001). Le refus d'une recommandation n'était pas associé à la mortalité (rapport de cotes de 1,32; IC de 95 %, 0,93 à 1,89; p = 0,12). Les facteurs de risque indépendants associés à la mortalité en milieu hospitalier étaient l'âge, l'indice de Charlson, l'admission dans une unité de soins intensifs, la période entre l'admission et la recommandation, et la formulation d'une recommandation sur un carbapénem. Conclusion: La durée du traitement antimicrobien était beaucoup plus courte lorsque la recommandation d'un PGA assisté par un SADC était acceptée. De futures études prospectives incluant de potentielles variables confusionnelles résiduelles, telles que la source de l'infection ou le dérangement physiologique, pourraient contribuer à établir si un PGA assisté par un SADC aura des conséquences directes sur la mortalité des patients.

Anosmie et dysgueusie associées à l'infection au SRAS-CoV-2: étude cas­témoins appariée selon l'âge.

CONTEXTE: On a signalé l'anosmie et la dysgueusie comme symptômes potentiels de la maladie à coronavirus 2019. Cette étude visait à confirmer si ces symptômes sont caractéristiques chez les personnes ayant eu un résultat positif au dépistage du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2). MÉTHODES: Nous avons réalisé une étude cas­témoins appariée selon l'âge dans la région des Cantons-de-l'Est, au Québec, entre le 10 et le 23 mars 2020. Nous avons inclus les adultes (18 ans et plus) ayant obtenu un résultat positif au dépistage du SRAS-CoV-2 par test d'amplification en chaîne par polymérase couplée à une transcription inverse. Les cas ont été appariés (1:1) par tranche d'âge de 5 ans avec des témoins sélectionnés aléatoirement parmi tous les patients ayant eu un résultat négatif au dépistage pendant la même période. Les données démographiques et de laboratoire ont été récupérées dans les dossiers médicaux. Les symptômes cliniques et les comorbidités associés à l'anosmie et à la dysgueusie ont été notés lors d'entrevues téléphoniques faites au moyen d'un questionnaire standardisé. RÉSULTATS: Parmi les 2883 personnes soumises au dépistage du SRAS-CoV-2, nous avons recensé 134 cas positifs (70 femmes [52,2 %] et 64 hommes [47,8 %]; âge médian 57,1 ans [intervalle interquartile 41,2­64,5 ans]). Les symptômes indépendamment associés à l'infection confirmée au SRAS-CoV-2 dans une analyse de régression logistique conditionnelle étaient les suivants : anosmie et/ou dysgueusie (rapport de cotes [RC] ajusté 62,9; intervalle de confiance [IC] de 95 % 11,0­359,7), myalgie (RC ajusté 7,6; IC de 95 % 1,9­29,9), vision trouble (RC ajusté 0,1; IC de 95 % 0,0­0,8) et douleur thoracique (RC ajusté 0,1; IC de 95 % 0,0­0,6). INTERPRÉTATION: Nous avons observé un lien étroit entre les symptômes olfactifs et gustatifs et la positivité au SRAS-CoV-2. Ces symptômes devraient être considérés comme une caractéristique fréquente et distinctive de l'infection au SRAS-CoV-2 et devraient servir d'indication de dépistage, et même de répétition du dépistage chez les personnes dont le résultat initial est négatif.