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Background Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction–confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses. Results We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4–1) and 0.3 (0.3–0.4), respectively. Conclusions Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19–vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

Empirical antibiotics are not recommended for coronavirus disease 2019 (COVID-19).In this retrospective study, patients admitted to Toronto General Hospital's general internal medicine from the emergency department for COVID-19 between March 1 and August 31, 2020 were compared with those admitted for community-acquired pneumonia (CAP) in 2020 and 2019 in the same months. The primary outcome was antibiotics use pattern: prevalence and concordance with COVID-19 or CAP guidelines. The secondary outcome was antibiotic consumption in days of therapy (DOT)/100 patient-days. We extracted data from electronic medical records. We used logistic regression to model the association between disease and receipt of antibiotics, linear regression to compare DOT.The COVID-19, CAP 2020, and CAP 2019 groups had 67, 73, and 120 patients, respectively. Median age was 71 years; 58.5% were male. Prevalence of antibiotic use was 70.2%, 97.3%, and 90.8% for COVID-19, CAP 2020, and CAP 2019, respectively. Compared with CAP 2019, the adjusted odds ratio (aOR) for receiving antibiotics was 0.23 (95% CI 0.10 to 0.53,There are opportunities for antimicrobial stewardship to address unnecessary antibiotic use.L’antibiothérapie empirique n’est pas recommandée pour le traitement de la maladie à coronavirus 2019 (COVID-19).Dans cette étude rétrospective, les chercheurs ont comparé les patients atteints de COVID-19 hospitalisés au département de médecine interne générale duLe groupe COVID-19, le groupe POC-20 et le groupe POC-19 étaient composés de 67, 73 et 120 patients, respectivement. Ils avaient un âge médian de 71 ans, et 58,5 % étaient de sexe masculin. La prévalence d’utilisation d’antibiotiques s’élevait à 70,2 %, 97,3 % et 90,8 % dans les groupes COVID-19, POC-20 et POC-19, respectivement. Par rapport au groupe POC-19, le rapport de cotes rajusté (RCr) relatif à la réception d’antibiotiques s’élevait à 0,23 (IC à 95 %, 0,10 à 0,53,L’utilisation inutile d’antibiotiques pourrait très bien être prise en charge par la gérance des antimicrobiens.

Background: Febrile neutropenia (FN) is a medical emergency with significant morbidity and mortality for oncology patients, requiring comprehensive workup and timely antibiotic administration. We evaluated concordance with locally developed FN guidelines and outcomes of cancer patients admitted to general internal medicine at an academic teaching hospital. Methods: We conducted a retrospective observational cohort study of patients admitted between July 1, 2016, and June 30, 2017, for FN. Patients were classified as having low-risk or high-risk FN according to their malignancy and chemotherapy. Primary outcome was the proportion of patients receiving guideline-concordant antibiotics within 48 hours of admission to general internal medicine. Secondary outcomes were the proportion of patients in whom empirical antibiotics were active against pathogens isolated, rate of antibiotic-associated adverse events, and in-hospital mortality. We used logistic regression to model relationship between FN risk and guideline-concordant antibiotics. Results: Among 100 patients included, 34 (34%) were low-risk FN and 66 (66%) were high-risk. Proportion of guideline-concordant empirical antibiotics was significantly lower among low-risk FN patients than high-risk patients: 12 (35%) of 34 versus 47 (71%) of 66 (P = .001). Empirical antibiotics were active against 17 (94%) of 18 isolated pathogens. The mortality rate was 3%, and 16% of patients experienced antibiotic-associated adverse events. Hematological malignancy and infectious diseases–trained physician involvement were associated with guideline-concordant prescribing, with adjusted odds ratios of 3.76 (95% CI, 1.46–9.70; P = .006) and 3.71 (95% CI, 1.49–9.23; P = .005), respectively. Conclusions: Guideline concordance was low compared to published reports. Factors influencing appropriate antimicrobial prescribing in patients with FN warrant further exploration.

Importance Recent changes in guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as a first-line treatment. Objective To estimate the net cost of first-line fidaxomicin compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving for the prevention of recurrence. Data sources and study selection We identified randomized, placebo-controlled trials directly comparing fidaxomicin with vancomycin that reported on recurrence. Medication costs were obtained from the Veterans Affairs Federal Supply Schedule (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through a systematic review for each country. Data extraction, synthesis and outcome measures For efficacy, data on CDI recurrence at day 40 were pooled using a restricted maximal likelihood random effects model. For the cost review, the mean cost across identified studies was adjusted to reflect May 2022 dollars. These were used to estimate the net cost per recurrence prevented with fidaxomicin and the price point below which fidaxomicin would be cost saving. Results The estimated mean system costs of a CDI recurrence were $15 147USD and $8806CAD, respectively. Preventing one recurrence by using first-line fidaxomicin over vancomycin would cost $38 222USD (95%CI $30 577–$57 332) and $13 760CAD (95%CI $11 008–$20 640), respectively. The probability that fidaxomicin was cost saving exceeded 95% if priced below $1140USD or $860CAD, respectively. Conclusions and Relevance An increased drug expenditure on fidaxomicin may not be offset through recurrence prevention unless the fidaxomicin price is negotiated.

The World Health Organization (WHO) has recognized antimicrobial resistance (AMR) as a top threat to global health. However, the public has an incomplete understanding of AMR and its consequences.The aim of this study was to explore patients' understanding, perspective and health outcome expectations for antibiotic therapy within an inpatient internal medicine population.A mixed methods study, combining a cross-sectional survey with qualitative methods. Fourteen questions (10 paper survey and four open ended interview questions) were used, and were completed by the participant in one sitting. Participants were recruited from General Internal Medicine units at two academic hospitals in Canada (convenience sample).Thirty participants were included. Out of a scale of 1-100%, participants indicated moderate concern (mean of 40%) about getting an infection that could not be cured by antibiotics. The majority agreed that they trusted their healthcare team to decide on appropriate antibiotic therapy (mean of 81%). The participants strongly agreed (mean of 90%) that it was important to understand the rationale for their antibiotic therapyThe study results showed varying levels of patients' antibiotic knowledge and large gaps in awareness related to AMR. Exploring the role and workflow of interdisciplinary healthcare professionals may be a potential strategy to minimize patients' knowledge gap related to antimicrobial therapy and AMR.

The COVID-19 pandemic affected access to care, and the associated public health measures influenced the transmission of other infectious diseases. The pandemic has dramatically changed antibiotic prescribing in the community. We aimed to determine the impact of the COVID-19 pandemic and the resulting control measures on oral antibiotic prescribing in long-term care facilities (LTCFs) in Alberta and Ontario, Canada using linked administrative data. Antibiotic prescription data were collected for LTCF residents 65 years and older in Alberta and Ontario from 1 January 2017 until 31 December 2020. Weekly prescription rates per 1000 residents, stratified by age, sex, antibiotic class, and selected individual agents, were calculated. Interrupted time series analyses using SARIMA models were performed to test for changes in antibiotic prescription rates after the start of the pandemic (1 March 2020). The average annual cohort size was 18,489 for Alberta and 96,614 for Ontario. A significant decrease in overall weekly prescription rates after the start of the pandemic compared to pre-pandemic was found in Alberta, but not in Ontario. Furthermore, a significant decrease in prescription rates was observed for antibiotics mainly used to treat respiratory tract infections: amoxicillin in both provinces (Alberta: −0.6 per 1000 LTCF residents decrease in weekly prescription rate, p = 0.006; Ontario: −0.8, p < 0.001); and doxycycline (−0.2, p = 0.005) and penicillin (−0.04, p = 0.014) in Ontario. In Ontario, azithromycin was prescribed at a significantly higher rate after the start of the pandemic (0.7 per 1000 LTCF residents increase in weekly prescription rate, p = 0.011). A decrease in prescription rates for antibiotics that are largely used to treat respiratory tract infections is in keeping with the lower observed rates for respiratory infections resulting from pandemic control measures. The results should be considered in the contexts of different LTCF systems and provincial public health responses to the pandemic.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence.Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools.Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available.Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy.Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Background Deaths following Staphylococcus aureus bacteremia (SAB) may be related or unrelated to the infection. In SAB therapeutics research, the length of follow-up should be optimized to capture most attributable deaths and minimize nonattributable deaths. We performed a secondary analysis of a systematic review to describe attributable mortality in SAB over time. Methods We systematically searched Medline, Embase, and Cochrane Database of Systematic Reviews from 1 January 1991 to 7 May 2021 for human observational studies of SAB. To be included in this secondary analysis, the study must have reported attributable mortality. Two reviewers extracted study data and assessed risk of bias independently. Pooling of study estimates was not performed due to heterogeneity in the definition of attributable deaths. Results Twenty-four observational cohort studies were included. The median proportion of all-cause deaths that were attributable to SAB was 77% (interquartile range [IQR], 72%–89%) at 1 month and 62% (IQR, 58%–75%) at 3 months. At 1 year, this proportion was 57% in 1 study. In 2 studies that described the rate of increase in mortality over time, 2-week follow-up captured 68 of 79 (86%) and 48 of 57 (84%) attributable deaths that occurred by 3 months. By comparison, 1-month follow-up captured 54 of 57 (95%) and 56 of 60 (93%) attributable deaths that occurred by 3 months in 2 studies. Conclusions The proportion of deaths that are attributable to SAB decreases as follow-up lengthens. Follow-up duration between 1 and 3 months seems optimal if evaluating processes of care that impact SAB mortality. Clinical Trials Registration PROSPERO CRD42021253891.

Background Peer comparison audit and feedback has demonstrated effectiveness in improving antibiotic prescribing practices, but only a minority of prescribers view their reports. We rigorously tested 3 behavioral nudging techniques delivered by email to improve report opening. Methods We conducted a pragmatic randomized controlled trial among Ontario long-term care prescribers enrolled in an ongoing peer comparison audit and feedback program which includes data on their antibiotic prescribing patterns. Physicians were randomized to 1 of 8 possible sequences of intervention/control allocation to 3 different behavioral email nudges: a social peer comparison nudge (January 2020), a maintenance of professional certification incentive nudge (October 2020), and a prior participation nudge (January 2021). The primary outcome was feedback report opening; the primary analysis pooled the effects of all 3 nudging interventions. Results The trial included 421 physicians caring for >28 000 residents at 450 facilities. In the pooled analysis, physicians opened only 29.6% of intervention and 23.9% of control reports (odds ratio [OR], 1.51 [95% confidence interval {CI}, 1.10–2.07], P = .011); this difference remained significant after accounting for physician characteristics and clustering (adjusted OR [aOR], 1.74 [95% CI, 1.24–2.45], P = .0014). Of individual nudging techniques, the prior participation nudge was associated with a significant increase in report opening (OR, 1.62 [95% CI, 1.06–2.47], P = .026; aOR, 2.16 [95% CI, 1.33–3.50], P = .0018). In the pooled analysis, nudges were also associated with accessing more report pages (aOR, 1.28 [95% CI, 1.14–1.43], P Conclusions Enhanced nudging strategies modestly improved report opening, but more work is needed to optimize physician engagement with audit and feedback. Clinical Trials Registration NCT04187742.

Precise estimates of mortality in Staphylococcus aureus bacteraemia (SAB) are important to convey prognosis and guide the design of interventional studies.We performed a systematic review and meta-analysis to estimate all-cause mortality in SAB and explore mortality change over time.The MEDLINE and Embase databases, as well as the Cochrane Database of Systematic Reviews, were searched from January 1, 1991 to May 7, 2021.Human observational studies on patients with S. aureus bloodstream infection were included.The study analyzed data of patients with a positive blood culture for S. aureus.Two independent reviewers extracted study data and assessed risk of bias using the Newcastle-Ottawa Scale. A generalized, linear, mixed random effects model was used to pool estimates.A total of 341 studies were included, describing a total of 536,791 patients. From 2011 onward, the estimated mortality was 10.4% (95% CI, 9.0%-12.1%) at 7 days, 13.3% (95% CI, 11.1%-15.8%) at 2 weeks, 18.1% (95% CI, 16.3%-20.0%) at 1 month, 27.0% (95% CI, 21.5%-33.3%) at 3 months, and 30.2% (95% CI, 22.4%-39.3%) at 1 year. In a meta-regression model of 1-month mortality, methicillin-resistant S. aureus had a higher mortality rate (adjusted OR (aOR): 1.04; 95% CI, 1.02-1.06 per 10% increase in methicillin-resistant S. aureus proportion). Compared with prior to 2001, more recent time periods had a lower mortality rate (aOR: 0.88; 95% CI, 0.75-1.03 for 2001-2010; aOR: 0.82; 95% CI, 0.69-0.97 for 2011 onward).SAB mortality has decreased over the last 3 decades. However, more than one in four patients will die within 3 months, and continuous improvement in care remains necessary.

Background Several outpatient coronavirus disease 2019 (COVID-19) therapies have reduced hospitalization in randomized controlled trials. The choice of therapy may depend on drug efficacy, toxicity, pricing, availability, and available infrastructure. To facilitate comparative decision-making, we evaluated the efficacy of each treatment in clinical trials and estimated the cost per hospitalization prevented. Methods Wherever possible, we obtained relative risk for hospitalization from published randomized controlled trials. Otherwise, we extracted data from press releases, conference abstracts, government submissions, or preprints. If there was >1 study, the results were meta-analyzed. Using relative risk, we estimated the number needed to treat (NNT), assuming a baseline hospitalization risk of 5%, and compared the cost per hospitalization prevented with the estimate for an average Medicare COVID-19 hospitalization ($21 752). Drug pricing was estimated from GoodRx, from government purchases, or manufacturer estimates. Administrative and societal costs were not included. Results will be updated online as new studies emerge and/or final numbers become available. Results At a 5% risk of hospitalization, the estimated NNT was 80 for fluvoxamine, 91 for colchicine, 72 for inhaled corticosteroids, 24 for nirmatrelvir/ritonavir, 50 for molnupiravir, 28 for remdesivir, 25 for sotrovimab, 29 for casirivimab/imdevimab, and 29 for bamlanivimab/etesevimab. For drug cost per hospitalization prevented, colchicine, fluvoxamine, inhaled corticosteroids, and nirmatrelvir/ritonavir were below the Medicare estimated hospitalization cost. Conclusions Many countries are fortunate to have access to several effective outpatient therapies to prevent COVID-19 hospitalization. Given differences in efficacy, toxicity, cost, and administration complexity, this assessment serves as one means to frame treatment selection.

Antimicrobials are among the most prescribed medications in Canada, with over 90% of antibiotics prescribed in outpatient settings. Seniors prescribed antimicrobials are particularly vulnerable to adverse drug events and antimicrobial resistance. The extent of inappropriate antibiotic prescribing in outpatient Canadian medical practice, and the potential long-term trends in this practice, are unknown. This study is the first in Canada to examine prescribing quality across two large-scale provincial healthcare systems to compare both quantity and quality of outpatient antibiotic use in seniors. Population-based analyses using administrative health databases were conducted in British Columbia (BC) and Ontario (ON), and all outpatient, oral antimicrobials dispensed to seniors (≥65 years) from 1 January 2000 to 31 December 2018 were identified. Antimicrobials were linked to an indication using a 3-tiered hierarchy. Tier 1 indications, which always require antibiotics, were given priority, followed by Tier 2 indications that sometimes require antibiotics, then Tier 3, which never require antibiotics. Prescription rates were calculated per 1000 population, and trends were examined overall, by drug class, and by patient demographics. Prescribing remained steady in both provinces, with 11,166,401 prescriptions dispensed overall in BC, and 27,656,014 overall in ON. BC prescribed at slightly elevated rates (range: 790 to 930 per 1000 residents), in comparison to ON (range: 745 to 785 per 1000 residents), throughout the study period. For both provinces, a Tier 3 diagnosis was the most common reason for antibiotic use, accounting for 50% of all indication-associated antibiotic prescribing. Although Tier 3 indications remained the most prescribed-for diagnoses throughout the study period, a declining trend over time is encouraging, with much room for improvement remaining. Elevated prescribing to seniors continues across Canadian outpatient settings, and prescribing quality is of high concern, with 50% of all antimicrobials prescribed inappropriately for common infections that do not require antimicrobials.

Deaths followingWe systematically searched Medline, Embase, and Cochrane Database of Systematic Reviews from 1 January 1991 to 7 May 2021 for human observational studies of SAB. To be included in this secondary analysis, the study must have reported attributable mortality. Two reviewers extracted study data and assessed risk of bias independently. Pooling of study estimates was not performed due to heterogeneity in the definition of attributable deaths.Twenty-four observational cohort studies were included. The median proportion of all-cause deaths that were attributable to SAB was 77% (interquartile range [IQR], 72%-89%) at 1 month and 62% (IQR, 58%-75%) at 3 months. At 1 year, this proportion was 57% in 1 study. In 2 studies that described the rate of increase in mortality over time, 2-week follow-up captured 68 of 79 (86%) and 48 of 57 (84%) attributable deaths that occurred by 3 months. By comparison, 1-month follow-up captured 54 of 57 (95%) and 56 of 60 (93%) attributable deaths that occurred by 3 months in 2 studies.The proportion of deaths that are attributable to SAB decreases as follow-up lengthens. Follow-up duration between 1 and 3 months seems optimal if evaluating processes of care that impact SAB mortality.PROSPERO CRD42021253891.

Antimicrobial Resistance (AMR) causes more than a million deaths globally per year due to infections incurable with currently available antibiotics. Failing to effectively address AMR will have significant negative consequences for Canadians and the Canadian economy. Canada is behind on allocation of required funding and nationally coordinated AMR mitigation strategies relative to other high-income countries. A Pan-Canadian AMR action plan and development of a new governance model is pending. Recent AMR-specific funding commitments are significant but fall short while distribution of funds indicate a siloed approach. Canada could initiate progress towards AMR mitigation through incorporation within the scope of budget allocations intended for COVID-19 recovery and mitigation efforts. We discuss the following components for inclusion: development of infectious disease diagnostics and therapeutics; antimicrobial stewardship interventions in long-term care and Indigenous communities; environmental monitoring of AMR; comprehensive antimicrobial use, and AMR surveillance; and support for capacity-building in low and middle-income countries.