Documenting the indication for antimicrobial prescribing: A retrospective observational study of long-term care homes.

BACKGROUND: Overuse of antimicrobials in residents of long-term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long-term care (LTC) homes setting to improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility-level variability of antibiotic indication documentation in this setting. METHODS: This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1 2021 and December 31 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level. RESULTS: Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range [IQR]: 10.8%-31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%-42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits. CONCLUSIONS: There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications.

Variability in changes in physician outpatient antibiotic prescribing from 2019 to 2021 during the COVID-19 pandemic in Ontario, Canada.

Objective: To evaluate inter-physician variability and predictors of changes in antibiotic prescribing before (2019) and during (2020/2021) the coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted a retrospective cohort analysis of physicians in Ontario, Canada prescribing oral antibiotics in the outpatient setting between January 1, 2019 and December 31, 2021 using the IQVIA Xponent data set. The primary outcome was the change in the number of antibiotic prescriptions between the prepandemic and pandemic period. Secondary outcomes were changes in the selection of broad-spectrum agents and long-duration (>7 d) antibiotic use. We used multivariable linear regression models to evaluate predictors of change. Results: There were 17,288 physicians included in the study with substantial inter-physician variability in changes in antibiotic prescribing (median change of -43.5 antibiotics per physician, interquartile range -136.5 to -5.0). In the multivariable model, later career stage (adjusted mean difference [aMD] -45.3, 95% confidence interval [CI] -52.9 to -37.8, p < .001), family medicine (aMD -46.0, 95% CI -62.5 to -29.4, p < .001), male patient sex (aMD -52.4, 95% CI -71.1 to -33.7, p < .001), low patient comorbidity (aMD -42.5, 95% CI -50.3 to -34.8, p < .001), and high prescribing to new patients (aMD -216.5, 95% CI -223.5 to -209.5, p < .001) were associated with decreases in antibiotic initiation. Family medicine and high prescribing to new patients were associated with a decrease in selection of broad-spectrum agents and prolonged antibiotic use. Conclusions: Antibiotic prescribing changed throughout the COVID-19 pandemic with overall decreases in antibiotic initiation, broad-spectrum agents, and prolonged antibiotic courses with inter-physician variability. These findings present opportunities for community antibiotic stewardship interventions.

A retrospective cohort study of prescribing outcomes in outpatients treated with nirmatrelvir-Ritonavir for COVID-19 in an interdisciplinary community clinic.

BACKGROUND: Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting. METHODS: We conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir. RESULTS: There were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths. INTERPRETATION: Nirmatrelvir-ritonavir was associated with a high prevalence of clinically significant DDIs, which required mitigation strategies and a high frequency of mild ADEs. Collaborative assessment to address medication alterations resulted in high treatment adherence.

Antibiotic prescribing guideline recommendations in COVID-19: a systematic survey.

Background: COVID-19 and antimicrobial resistance (AMR) are two intersecting public health crises. Antimicrobial overuse in patients with COVID-19 threatens to worsen AMR. Guidelines are fundamental in encouraging antimicrobial stewardship. We sought to assess the quality of antibiotic prescribing guidelines and recommendations in the context of COVID-19, and whether they incorporate principles of antimicrobial stewardship. Methods: We performed a systematic survey which included a search using the concepts "antibiotic/antimicrobial" up to November 15, 2022 of the eCOVID-19 living map of recommendations (RecMap) which aggregates guidelines across a range of international sources and all languages. Guidelines providing explicit recommendations regarding antibacterial use in COVID-19 were eligible for inclusion. Guideline and recommendation quality were assessed using the AGREE II and AGREE-REX instruments, respectively. We extracted guideline characteristics including panel representation and the presence or absence of explicit statements related to antimicrobial stewardship (i.e., judicious antibiotic use, antimicrobial resistance or adverse effects as a consequence of antibiotic use). We used logistic regression to evaluate the relationship between guideline characteristics including quality and incorporation of antimicrobial stewardship principles. Protocol registration (OSF): https://osf.io/4pgtc. Findings: Twenty-eight guidelines with 63 antibiotic prescribing recommendations were included. Recommendations focused on antibiotic initiation (n = 52, 83%) and less commonly antibiotic selection (n = 13, 21%), and duration of therapy (n = 15, 24%). Guideline and recommendation quality varied widely. Twenty (71%) guidelines incorporated at least one concept relating to antimicrobial stewardship. Including infectious diseases expertise on the guideline panel (OR 9.44, 97.5% CI: 1.09-81.59) and AGREE-REX score (OR 3.26, 97.5% CI: 1.14-9.31 per 10% increase in overall score) were associated with a higher odds of guidelines addressing antimicrobial stewardship. Interpretation: There is an opportunity to improve antibiotic prescribing guidelines in terms of both quality and incorporation of antimicrobial stewardship principles. These findings can help guideline developers better address antibiotic stewardship in future recommendations beyond COVID-19. Funding: This project was funded by Michael G. DeGroote Cochrane Canada and McMaster GRADE centres.

Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study.

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.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Population-based evaluation of the effectiveness of nirmatrelvir-ritonavir for reducing hospital admissions and mortality from COVID-19.

BACKGROUND: A randomized controlled trial involving a high-risk, unvaccinated population that was conducted before the Omicron variant emerged found that nirmatrelvir-ritonavir was effective in preventing progression to severe COVID-19. Our objective was to evaluate the effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 while Omicron and its subvariants predominate. METHODS: We conducted a population-based cohort study in Ontario that included all residents who were older than 17 years of age and had a positive polymerase chain reaction test for SARS-CoV-2 between Apr. 4 and Aug. 31, 2022. We compared patients treated with nirmatrelvir-ritonavir with patients who were not treated and measured the primary outcome of hospital admission from COVID-19 or all-cause death at 1-30 days, and a secondary outcome of all-cause death. We used weighted logistic regression to calculate weighted odds ratios (ORs) with confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. RESULTS: The final cohort included 177 545 patients, 8876 (5.0%) who were treated with nirmatrelvir-ritonavir and 168 669 (95.0%) who were not treated. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. We found that the occurrence of hospital admission or death was lower in the group given nirmatrelvir-ritonavir than in those who were not (2.1% v. 3.7%; weighted OR 0.56, 95% CI 0.47-0.67). For death alone, the weighted OR was 0.49 (95% CI 0.39-0.62). Our findings were similar across strata of age, drug-drug interactions, vaccination status and comorbidities. The number needed to treat to prevent 1 case of severe COVID-19 was 62 (95% CI 43-80), which varied across strata. INTERPRETATION: Nirmatrelvir-ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports use to treat patients with mild COVID-19 who are at risk for severe disease.

A cross-sectional study of hospital antimicrobial stewardship programmes in the COVID-19 era.

Background: Antimicrobial resistance (AMR) continues to be a global public health issue amid the COVID-19 pandemic; however, unprecedented demands on hospital antimicrobial stewardship programmes (ASPs) potentially altered their core activities. Objective: We sought to understand how ASPs have been involved in and impacted by the pandemic. Methods: The 2021 Ontario ASP Landscape Survey was developed based on previous provincial questionnaires and emerging literature on the impact of COVID-19 on hospital ASPs. After pre-testing and piloting, the online questionnaire was distributed to hospital antimicrobial stewardship practitioners in the fall of 2021. Descriptive statistics and inductive thematic analysis were performed. Results: The response rate was 78% (98/125 organizations); 96% (94/98) of organizations had or were in the process of formalizing an ASP and 53% (50/94) reported designated funding/resources. Despite 82% reporting no change in dedicated full-time equivalents during the pandemic, ASPs were frequently involved in developing treatment guidelines/clinical pathways (51%), anticipating/managing drug shortages (46%) and obtaining investigational use drugs (32%). While many core ASP activities continued, prospective audit and feedback and prescriber education were modified or suspended by 43% and 40% of programmes, respectively. Decreased frequency, adaptation of activities (i.e. virtual or other technology) and challenges with staffing/resources were commonly reported themes. Knowledge translation (KT) activities and 'collaboration and coordination' also emerged as salient themes. Conclusions: Hospital antimicrobial stewardship practitioners in Ontario have made significant contributions to the pandemic response while continuing to deliver adapted ASP services, despite resource constraints. Moving forward, ASPs will need to continue building capacity while leveraging broader networks to advance the antimicrobial stewardship agenda.

Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings. DATA SOURCE: A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022. STUDY ELIGIBILITY: Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted. METHODS: Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed. RESULTS: Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40). CONCLUSION: The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.

Documenting the indication for antimicrobial prescribing: a scoping review.

BACKGROUND: Documenting an indication when prescribing antimicrobials is considered best practice; however, a better understanding of the evidence is needed to support broader implementation of this practice. OBJECTIVES: We performed a scoping review to evaluate antimicrobial indication documentation as it pertains to its implementation, prevalence, accuracy and impact on clinical and utilisation outcomes in all patient populations. ELIGIBILITY CRITERIA: Published and unpublished literature evaluating the documentation of an indication for antimicrobial prescribing. SOURCES OF EVIDENCE: A search was conducted in MEDLINE, Embase, CINAHL and International Pharmaceutical Abstracts in addition to a review of the grey literature. CHARTING AND ANALYSIS: Screening and extraction was performed by two independent reviewers. Studies were categorised inductively and results were presented descriptively. RESULTS: We identified 123 peer-reviewed articles and grey literature documents for inclusion. Most studies took place in a hospital setting (109, 89%). The median prevalence of antimicrobial indication documentation was 75% (range 4%-100%). Studies evaluating the impact of indication documentation on prescribing and patient outcomes most commonly examined appropriateness and identified a benefit to prescribing or patient outcomes in 17 of 19 studies. Qualitative studies evaluating healthcare worker perspectives (n=10) noted the common barriers and facilitators to this practice. CONCLUSION: There is growing interest in the importance of documenting an indication when prescribing antimicrobials. While antimicrobial indication documentation is not uniformly implemented, several studies have shown that multipronged approaches can be used to improve this practice. Emerging evidence demonstrates that antimicrobial indication documentation is associated with improved prescribing and patient outcomes both in community and hospital settings. But setting-specific and larger trials are needed to provide a more robust evidence base for this practice.

Estimating daily antibiotic harms: an umbrella review with individual study meta-analysis.

BACKGROUND: There is growing evidence supporting the efficacy of shorter courses of antibiotic therapy for common infections. However, the risks of prolonged antibiotic duration are underappreciated. OBJECTIVES: To estimate the incremental daily risk of antibiotic-associated harms. METHODS: We searched three major databases to retrieve systematic reviews from 2000 to 30 July 2020 in any language. ELIGIBILITY: Systematic reviews were required to evaluate shorter versus longer antibiotic therapy with fixed durations between 3 and 14 days. Randomized controlled trials included for meta-analysis were identified from the systematic reviews. PARTICIPANTS: Adult and paediatric patients from any setting. INTERVENTIONS: Primary outcomes were the proportion of patients experiencing adverse drug events, superinfections and antimicrobial resistance. RISK OF BIAS ASSESSMENT: Each randomized controlled trial was evaluated for quality by extracting the assessment reported by each systematic review. DATA SYNTHESIS: The daily odds ratio (OR) of antibiotic harm was estimated and pooled using random effects meta-analysis. RESULTS: Thirty-five systematic reviews encompassing 71 eligible randomized controlled trials were included. Studies most commonly evaluated duration of therapy for respiratory tract (n = 36, 51%) and urinary tract (n = 29, 41%) infections. Overall, 23 174 patients were evaluated for antibiotic-associated harms. Adverse events (n = 20 345), superinfections (n = 5776) and antimicrobial resistance (n = 2330) were identified in 19.9% (n = 4039), 4.8% (n = 280) and 10.6% (n = 246) of patients, respectively. Each day of antibiotic therapy was associated with 4% increased odds of experiencing an adverse event (OR 1.04, 95% CI 1.02-1.07). Daily odds of severe adverse effects also increased (OR 1.09, 95% CI 1.00-1.19). The daily incremental odds of superinfection and antimicrobial resistance were OR 0.98 (0.92-1.06) and OR 1.03 (0.98-1.07), respectively. CONCLUSION: Each additional day of antibiotic therapy is associated with measurable antibiotic harm, particularly adverse events. These data may provide additional context for clinicians when weighing benefits versus risks of prolonged antibiotic therapy.

Predictors and microbiology of respiratory and bloodstream bacterial infection in patients with COVID-19: living rapid review update and meta-regression.

BACKGROUND: The prevalence of bacterial infection in patients with COVID-19 is low, however, empiric antibiotic use is high. Risk stratification may be needed to minimize unnecessary empiric antibiotic use. OBJECTIVE: To identify risk factors and microbiology associated with respiratory and bloodstream bacterial infection in patients with COVID-19. DATA SOURCES: We searched MEDLINE, OVID Epub and EMBASE for published literature up to 5 February 2021. STUDY ELIGIBILITY CRITERIA: Studies including at least 50 patients with COVID-19 in any healthcare setting. METHODS: We used a validated ten-item risk of bias tool for disease prevalence. The main outcome of interest was the proportion of COVID-19 patients with bloodstream and/or respiratory bacterial co-infection and secondary infection. We performed meta-regression to identify study population factors associated with bacterial infection including healthcare setting, age, comorbidities and COVID-19 medication. RESULTS: Out of 33 345 studies screened, 171 were included in the final analysis. Bacterial infection data were available from 171 262 patients. The prevalence of co-infection was 5.1% (95% CI 3.6-7.1%) and secondary infection was 13.1% (95% CI 9.8-17.2%). There was a higher odds of bacterial infection in studies with a higher proportion of patients in the intensive care unit (ICU) (adjusted OR 18.8, 95% CI 6.5-54.8). Female sex was associated with a lower odds of secondary infection (adjusted OR 0.73, 95% CI 0.55-0.97) but not co-infection (adjusted OR 1.05, 95% CI 0.80-1.37). The most common organisms isolated included Staphylococcus aureus, coagulase-negative staphylococci and Klebsiella species. CONCLUSIONS: While the odds of respiratory and bloodstream bacterial infection are low in patients with COVID-19, meta-regression revealed potential risk factors for infection, including ICU setting and mechanical ventilation. The risk for secondary infection is substantially greater than the risk for co-infection in patients with COVID-19. Understanding predictors of co-infection and secondary infection may help to support improved antibiotic stewardship in patients with COVID-19.

Virtual learning collaboratives to improve urine culturing and antibiotic prescribing in long-term care: controlled before-and-after study.

BACKGROUND: Urine culturing practices are highly variable in long-term care and contribute to overprescribing of antibiotics for presumed urinary tract infections. The purpose of this study was to evaluate the use of virtual learning collaboratives to support long-term care homes in implementing a quality improvement programme focused on reducing unnecessary urine culturing and antibiotic overprescribing. METHODS: Over a 4-month period (May 2018-August 2018), 45 long-term care homes were self-selected from five regions to participate in virtual learning collaborative sessions, which provided an orientation to a quality improvement programme and guidance for implementation. A process evaluation complemented the use of a controlled before-and-after study with a propensity score matched control group (n=127) and a difference-in-difference analysis. Primary outcomes included rates of urine cultures performed and urinary antibiotic prescriptions. Secondary outcomes included rates of emergency department visits, hospital admission and mortality. An 18-month baseline period was compared with a 16-month postimplementation period with the use of administrative data sources. RESULTS: Rates of urine culturing and urinary antibiotic prescriptions per 1000 resident days decreased significantly more among long-term care homes that participated in learning collaboratives compared with matched controls (differential reductions of 19% and 13%, respectively, p<0.0001). There was no statistically significant changes to rates of emergency department visits, hospital admissions or mortality. These outcomes were observed with moderate adherence to the programme model. CONCLUSIONS: Rates of urine culturing and urinary antibiotic prescriptions declined among long-term care homes that participated in a virtual learning collaborative to support implementation of a quality improvement programme. The results of this study have refined a model to scale this programme in long-term care.

The Impact of COVID-19 on Outpatient Antibiotic Prescriptions in Ontario, Canada; An Interrupted Time Series Analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has potentially impacted outpatient antibiotic prescribing. Investigating this impact may identify stewardship opportunities in the ongoing COVID-19 period and beyond. METHODS: We conducted an interrupted time series analysis on outpatient antibiotic prescriptions and antibiotic prescriptions/patient visits in Ontario, Canada, between January 2017 and December 2020 to evaluate the impact of the COVID-19 pandemic on population-level antibiotic prescribing by prescriber specialty, patient demographics, and conditions. RESULTS: In the evaluated COVID-19 period (March-December 2020), there was a 31.2% (95% CI, 27.0% to 35.1%) relative reduction in total antibiotic prescriptions. Total outpatient antibiotic prescriptions decreased during the COVID-19 period by 37.1% (95% CI, 32.5% to 41.3%) among family physicians, 30.7% (95% CI, 25.8% to 35.2%) among subspecialist physicians, 12.1% (95% CI, 4.4% to 19.2%) among dentists, and 25.7% (95% CI, 21.4% to 29.8%) among other prescribers. Antibiotics indicated for respiratory infections decreased by 43.7% (95% CI, 38.4% to 48.6%). Total patient visits and visits for respiratory infections decreased by 10.7% (95% CI, 5.4% to 15.6%) and 49.9% (95% CI, 43.1% to 55.9%). Total antibiotic prescriptions/1000 visits decreased by 27.5% (95% CI, 21.5% to 33.0%), while antibiotics indicated for respiratory infections/1000 visits with respiratory infections only decreased by 6.8% (95% CI, 2.7% to 10.8%). CONCLUSIONS: The reduction in outpatient antibiotic prescribing during the COVID-19 pandemic was driven by less antibiotic prescribing for respiratory indications and largely explained by decreased visits for respiratory infections.

Effect of Antibiotic-Prescribing Feedback to High-Volume Primary Care Physicians on Number of Antibiotic Prescriptions: A Randomized Clinical Trial.

Importance: Antibiotic overuse contributes to adverse drug effects, increased costs, and antimicrobial resistance. Objective: To evaluate peer-comparison audit and feedback to high-prescribing primary care physicians (PCPs) and assess the effect of targeted messaging on avoiding unnecessary antibiotic prescriptions and avoiding long-duration prescribing. Design, Setting, and Participants: In this 3-arm randomized clinical trial, administrative data collected from IQVIA's Xponent database were used to recruit the highest quartile of antibiotic-prescribing PCPs (n = 3500) in Ontario, Canada. Interventions: Physicians were randomized 3:3:1 to receive a mailed letter sent in December 2018 addressing antibiotic treatment initiation (n = 1500), a letter addressing prescribing duration (n = 1500), or no letter (control; n = 500). Outliers at the 99th percentile at baseline for each arm were excluded from analysis. Main Outcomes and Measures: The primary outcome was total number of antibiotic prescriptions over 12 months postintervention. Secondary outcomes were number of prolonged-duration prescriptions (>7 days) and antibiotic drug costs (in Canadian dollars). Robust Poisson regression controlling for baseline prescriptions was used for analysis. Results: Of the 3465 PCPs included in analysis, 2405 (69.4%) were male, and 2116 (61.1%) were 25 or more years from their medical graduation. At baseline, PCPs receiving the antibiotic initiation letter and duration letter prescribed an average of 988 and 1000 antibiotic prescriptions, respectively; at 12 months postintervention, these PCPs prescribed an average of 849 and 851 antibiotic prescriptions, respectively. For the primary outcome of total antibiotic prescriptions 12 months postintervention, there was no statistically significant difference in total antibiotic use between PCPs who received the initiation letter compared with controls (relative risk [RR], 0.96; 97.5% CI, 0.92-1.01; P = .06) and a small statistically significant difference for the duration letter compared with controls (RR, 0.95; 97.5% CI, 0.91-1.00; P = .01). For PCPs receiving the duration letter, this corresponds to an average of 42 fewer antibiotic prescriptions over 12 months. There was no statistically significant difference between the letter arms. For the initiation letter, compared with controls there was an RR of 0.98 (97.5% CI, 0.93-1.03; P = .42) and 0.97 (97.5% CI, 0.92-1.02; P = .19) for the outcomes of prolonged-duration prescriptions and antibiotic drug costs, respectively. At baseline, PCPs who received the duration letter prescribed an average of 332 prolonged-duration prescriptions with $14 470 in drug costs. There was an 8.1% relative reduction (RR, 0.92; 97.5% CI, 0.87-0.97; P < .001) in prolonged-duration prescriptions, and a 6.1% relative reduction in antibiotic drug costs (RR, 0.94; 97.5% CI, 0.89-0.99; P = .01). This corresponds to an average of 24 fewer prolonged-duration prescriptions and $771 in drug cost savings per PCP over 12 months. Conclusions and Relevance: In this randomized clinical trial, a single mailed letter to the highest-prescribing PCPs in Ontario, Canada providing peer-comparison feedback, including messaging on limiting antibiotic-prescribing durations, led to statistically significant reductions in total and prolonged-duration antibiotic prescriptions, as well as drug costs. Trial Registration: ClinicalTrials.gov Identifier: NCT03776383.

Metrics for evaluating antibiotic use and prescribing in outpatient settings.

Antimicrobial stewardship interventions in outpatient settings are diverse and a variety of outcomes have been used to evaluate these efforts. This narrative review describes, compares and provides specific examples of antibiotic use and other prescribing measures to help antimicrobial stewards better understand, interpret and implement metrics for this setting. A variety of data have been used including those generated from drug sales, prescribing and dispensing activities, however data generated closest to when an individual patient consumes an antibiotic is usually more accurate for estimating antibiotic use. Availability of data is often dependent on context such as information technology infrastructure and the healthcare system under consideration. While there is no ideal antibiotic use or prescribing metric for evaluating antimicrobial stewardship activities in the outpatient setting, the intervention of interest and available data sources are important factors. Common metrics for estimating antimicrobial use include DDD per 1000 inhabitants per day (DID) and days of therapy per 1000 inhabitants/day (DOTID). Other prescribing metrics such as antibiotic prescribing rate (APR), proportion of prescriptions containing an antibiotic, proportion of prolonged antibiotic courses prescribed, estimated appropriate APR and quality indicators are used to assess specific aspects of antimicrobial prescribing behaviour such as initiation, selection, duration and appropriateness. Understanding the context of prescribing practices helps to ensure feasibility and relevance when implementing metrics and targets for improvement in the outpatient setting.

Community pharmacist prescribing of antimicrobials: A systematic review from an antimicrobial stewardship perspective.

BACKGROUND: Pharmacist prescribing authority is expanding, while antimicrobial resistance is an increasing global concern. We sought to synthesize the evidence for antimicrobial prescribing by community pharmacists to identify opportunities to advance antimicrobial stewardship in this setting. METHODS: We conducted a systematic review to characterize the existing literature on community pharmacist prescribing of systemic antimicrobials. We searched MEDLINE, EMBASE and International Pharmaceutical Abstracts for English-language articles published between 1999 and June 20, 2019, as well as hand-searched reference lists of included articles and incorporated expert suggestions. RESULTS: Of 3793 articles identified, 14 met inclusion criteria. Pharmacists are most often prescribing for uncomplicated urinary tract infection (UTI), acute pharyngitis and cold sores using independent and supplementary prescribing models. This was associated with high rates of clinical improvement (4 studies), low rates of retreatment and adverse effects (3 studies) and decreased health care utilization (7 studies). Patients were highly satisfied (8 studies) and accessed care sooner or more easily (7 studies). Seven studies incorporated antimicrobial stewardship into study design, and there was overlap between study outcomes and those relevant to outpatient antimicrobial stewardship. Pharmacist intervention reduced unnecessary prescribing for acute pharyngitis (2 studies) and increased the appropriateness of prescribing for UTI (3 studies). CONCLUSION: There is growing evidence to support the role of community pharmacists in antimicrobial prescribing. Future research should explore additional opportunities for pharmacist antimicrobial prescribing and ways to further integrate advanced antimicrobial stewardship strategies in the community setting. Can Pharm J (Ott) 2021;154:xx-xx.

Concordance between high antibiotic prescribing and high opioid prescribing among primary care physicians: a cross-sectional study.

BACKGROUND: Antimicrobial resistance and opioid misuse both present major public health challenges, and identifying high prescribers of both of these agents can help provide a common target for intervention. We sought to determine the association between being a high prescriber of antibiotics and being a high prescriber of opioids in the primary care setting. METHODS: We performed a cross-sectional study of the antibiotic- and opioid-prescribing habits of primary care physicians in Ontario, Canada between Mar. 1, 2017, and Feb. 28, 2018, using administrative databases. We defined high prescribers as the top quartile of antibiotic or opioid prescribers using 3 antibiotic-prescribing metrics (prescriptions per patient visit, proportion of prescriptions that were broad spectrum and proportion of prescriptions > 8 d) and 3 opioid-prescribing metrics (prescriptions per patients seen, proportion of prescriptions > 90 mg of morphine equivalents and proportion of prescriptions > 28 d). We tabulated agreement between prescribing metrics using the κ statistic. RESULTS: We included 9994 physicians. We observed minimal overlap between high antibiotic initiation and high opioid initiation (618 physicians [6.2%]) (κ = 0.00, 95% confidence interval -0.02 to 0.02). There was slight agreement between the antibiotic-prescribing indices and between the opioid-prescribing indices (within-class, range of κ 0.05 to 0.18). There was slight disagreement to slight agreement across antibiotic- and opioid-prescribing metrics (between-class, range of κ -0.09 to 0.16). INTERPRETATION: Among primary care physicians, there was a lack of association between high antibiotic prescribing and high opioid prescribing. Our findings suggest that separate tailored approaches to antibiotic and opioid stewardship strategies are needed.

Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis.

BACKGROUND: The proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance. OBJECTIVE: The aim was to estimate the prevalence and associated factors of antibiotic prescribing in patients with COVID-19. DATA SOURCES: We searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9 2020. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials; cohort studies; case series with ≥10 patients; and experimental or observational design that evaluated antibiotic prescribing. PARTICIPANTS: The study participants were patients with laboratory-confirmed SARS-CoV-2 infection, across all healthcare settings (hospital and community) and age groups (paediatric and adult). METHODS: The main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness and age. We pooled proportion data using random effects meta-analysis. RESULTS: We screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30 623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3-80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95% CI 0.03-0.33) compared with adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95% CI 1.18-1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95% CI 1.15-1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7-15.2%) from 31 studies. CONCLUSIONS: Three-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely to be high in patients with COVID-19.