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Staphylococcus aureus bacteremia (SAB) is a common infection worldwide. We compared SAB mortality in low- and middle-income countries (LMIC) versus high-income countries (HIC) in a meta-analysis.We searched MEDLINE, Embase, and Cochrane Database of Systematic Reviews from 1991-2021 and included observational, single-country studies on patients with positive blood cultures for S. aureus. The main outcome was the proportion of patients with SAB who died in the hospital. A generalized linear mixed random-effects model was used to pool estimates, and a meta-regression was used to adjust for study-level characteristics.A total of 332 studies involving 517,671 patients in 39 countries were included. No study was conducted in a low-income country. Only 33 (10%) studies were performed in middle-income countries (MIC), which described 6,216 patients. The pooled in-hospital mortality was 32.4% (95% confidence interval [CI] 27.2%-38.2%, TIn SAB studies, LMIC are poorly represented. In-hospital mortality was significantly higher in MIC than in HIC. Research should be conducted in LMIC to characterize differences in care processes driving the mortality gap.

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 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.

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.

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.

Background Antibiotic use (AU) and antibiotic resistance (AR; AUR) reporting to National Healthcare Safety Network (NHSN) is suboptimal by US hospitals. The Society of Infectious Diseases Pharmacists (SIDP) and the Society for Healthcare Epidemiology of America (SHEA) conducted a survey of their membership to 1) Identify characteristics of US health systems that report AUR data 2) Determine how NHSN AUR data are used by health systems and 3) Identify barriers to AUR reporting. Methods An anonymous survey was posted on SurveyMonkey from 1/21- 2/21/2020 and links were emailed to SIDP and SHEA Research Network members. Data were analyzed in Excel and RStudio. Respondent and hospital data were reported as frequencies and percentages. Fisher’s Exact test was used to compare survey responses from NHSN AUR reporters to non-reporters. Results A total of 238 individuals from 43 states responded to our survey. Respondents were primarily pharmacists (84%), from urban (45%), non-profit medical centers (80%) with >250 beds (65%). 62% of respondents reported to the AU option while 19% reported to the AR option. Respondents not using software for local AU or AR tracking were less likely than those using any software for local tracking to report to AU (19% vs 64%) and AR (2% vs 30%) options (P< 0.0001). Among AU and AR reporters 41% and 54% used clinical decision support software to aggregate compile data for upload while 54% and 38% used their electronic health record, and 5% and 8% used another method. Over half of AU (56%) and AR (51%) reporters upload data manually. Regular use of the NHSN data analysis tools was reported by 36% and 9% of those reporting AU and AR data respectively. The most common barriers to reporting were related to technical issues (software, IT support, data formatting) and time/salary support. Among non-reporters, increased expectations to report and better software solutions were most commonly identified as the best ways to increase reporting. Conclusion Efforts to improve AUR reporting should focus on software solutions and increasing the utility of AUR analytical tools. Increasing expectations to report may also help to improve reporting rates. The lower rate of AR vs AU reporting suggests that interventions should also target the AR option. Disclosures Brian J. Werth, PharmD, Shionogi Inc. (Grant/Research Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

Objectives We compared the effectiveness of cefazolin versus cloxacillin in the treatment of MSSA bacteraemia in terms of mortality and relapse. Methods A retrospective cohort study examined consecutive patients with Staphylococcus aureus bacteraemia from six academic and community hospitals between 2007 and 2010. Patients with MSSA bacteraemia who received cefazolin or cloxacillin as the predominant definitive antibiotic therapy were included in the study. Ninety-day mortality was compared between the two groups matched by propensity scores. Results Of 354 patients included in the study, 105 (30%) received cefazolin and 249 (70%) received cloxacillin as the definitive antibiotic therapy. In 90 days, 96 (27%) patients died: 21/105 (20%) in the cefazolin group and 75/249 (30%) in the cloxacillin group. Within 90 days, 10 patients (3%) had a relapse of S. aureus infection: 6/105 (6%) in the cefazolin group and 4/249 (2%) in the cloxacillin group. All relapses in the cefazolin group were related to a deep-seated infection. Based on the estimated propensity score, 90 patients in the cefazolin group were matched with 90 patients in the cloxacillin group. In the propensity score-matched groups, cefazolin had an HR of 0.58 (95% CI 0.31–1.08, P = 0.0846) for 90 day mortality. Conclusions There was no significant clinical difference between cefazolin and cloxacillin in the treatment of MSSA bacteraemia with respect to mortality. Cefazolin was associated with non-significantly more relapses compared with cloxacillin, especially in deep-seated S. aureus infections.

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.