COVID-19 Vaccination is Associated with Reduced Outpatient Antibiotic Prescribing In Older Adults with Confirmed SARS-CoV-2: A Population Wide Cohort Study.

BACKGROUND: Antibiotics are frequently prescribed unnecessarily in outpatients with COVID-19. We sought to evaluate factors associated with antibiotic prescribing in those with SARS-CoV-2 infection. METHODS: We performed a population-wide cohort study of outpatients 66 years or older with PCR-confirmed SARS-CoV-2 from January 1st 2020 to December 31st 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1-week before (pre-diagnosis) and 1-week after (post-diagnosis) 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, 3,020 (22%) and 6,372 (13%) received at least one antibiotic prescription within 1 week of a SARS-CoV-2 positive result, respectively. Antibiotic prescribing in nursing home and community residents occurred at 15.0 and 10.5 prescriptions per 1000 person-days pre-diagnosis and 20.9 and 9.8 per 1000 person-days post-diagnosis, 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 post-diagnosis IRRs of 0.7 (95%CI 0.4-1) and 0.3 (95%CI 0.3-0.4) respectively. CONCLUSIONS: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis, though 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.

Trends in hospital antibiotic utilization during the coronavirus disease 2019 (COVID-19) pandemic: A multicenter interrupted time-series analysis

Objective: To describe the evolution of respiratory antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic across 3 large hospitals that maintained antimicrobial stewardship services throughout the pandemic. Design: Retrospective interrupted time-series analysis. Setting: A multicenter study was conducted including medical and intensive care units (ICUs) from 3 hospitals within a Canadian epicenter for COVID-19. Methods: Interrupted time-series analysis was used to analyze rates of respiratory antibiotic utilization measured in days of therapy per 1,000 patient days (DOT/1,000 PD) in medical units and ICUs. Each of the first 3 waves of the pandemic were compared to the baseline. Results: Within the medical units, use of respiratory antibiotics increased during the first wave of the pandemic (rate ratio [RR], 1.76;95% CI, 1.38–2.25) but returned to the baseline in waves 2 and 3 despite more COVID-19 admissions. In ICU, the use of respiratory antibiotics increased in wave 1 (RR, 1.30;95% CI, 1.16–1.46) and wave 2 of the pandemic (RR, 1.21;95% CI, 1.11–1.33) and returned to the baseline in the third wave, which had the most COVID-19 admissions. Conclusions: After an initial surge in respiratory antibiotic prescribing, we observed the normalization of prescribing trends at 3 large hospitals throughout the COVID-19 pandemic. This trend may have been due to the timely generation of new research and guidelines developed with frontline clinicians, allowing for the active application of new research to clinical practice.

Trends in hospital antibiotic utilization during the coronavirus disease 2019 (COVID-19) pandemic: A multicenter interrupted time-series analysis.

Objective: To describe the evolution of respiratory antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic across 3 large hospitals that maintained antimicrobial stewardship services throughout the pandemic. Design: Retrospective interrupted time-series analysis. Setting: A multicenter study was conducted including medical and intensive care units (ICUs) from 3 hospitals within a Canadian epicenter for COVID-19. Methods: Interrupted time-series analysis was used to analyze rates of respiratory antibiotic utilization measured in days of therapy per 1,000 patient days (DOT/1,000 PD) in medical units and ICUs. Each of the first 3 waves of the pandemic were compared to the baseline. Results: Within the medical units, use of respiratory antibiotics increased during the first wave of the pandemic (rate ratio [RR], 1.76; 95% CI, 1.38-2.25) but returned to the baseline in waves 2 and 3 despite more COVID-19 admissions. In ICU, the use of respiratory antibiotics increased in wave 1 (RR, 1.30; 95% CI, 1.16-1.46) and wave 2 of the pandemic (RR, 1.21; 95% CI, 1.11-1.33) and returned to the baseline in the third wave, which had the most COVID-19 admissions. Conclusions: After an initial surge in respiratory antibiotic prescribing, we observed the normalization of prescribing trends at 3 large hospitals throughout the COVID-19 pandemic. This trend may have been due to the timely generation of new research and guidelines developed with frontline clinicians, allowing for the active application of new research to clinical practice.

Survey of physical activity in persons with limb loss during the COVID-19 pandemic in the United States.

BACKGROUND: Physical activity has been shown to be fundamental in the prevention of numerous diseases and disorders. Achieving and maintaining physical activity levels can be particularly challenging in those with impairments, such as those experiencing a lower limb amputation. To slow the spread of the virus, COVID-19 lockdown mandates imposed by the US state governments may have inadvertent consequences on physical activity levels of those dependent on specific forms of exercise. Understanding how physical activity levels may have affected persons with limb loss can inform intervention strategies for this vulnerable population. OBJECTIVES: Examine the effects of the COVID-19 pandemic on physical activity levels in persons with limb loss. STUDY DESIGN: Mixed-method design. METHODS: A 20-item logic web-based survey and semistructured interviews were administered to individuals who were 18 years or older, spoke English, and had a history of lower limb loss. Quantitative data were analyzed using SPSS v25, whereas qualitative data were analyzed using constant comparison to formulate themes. RESULTS: There were a significant effect on the amount of physical activity minutes performed per day, a negative effect on the ability to exercise and participate in societal engagements, and a series of barriers to performing physical activity because of the pandemic. CONCLUSION: Physical activity was reduced significantly in persons with limb loss during the COVID-19 pandemic. A combination of health concerns, fitness center closures, and social distancing mandates were the primary drivers behind the decrease in activity.

Pharmacokinetic/Pharmacodynamic Considerations of Alternate Dosing Strategies of Tocilizumab in COVID-19.

Tocilizumab is one of few treatments that have been shown to improve mortality in patients with coronavirus disease 2019 (COVID-19), but increased demand has led to relative global shortages. Recently, it has been suggested that lower doses, or fixed doses, of tocilizumab could be a potential solution to conserve the limited global supply while conferring equivalent therapeutic benefit to the dosing regimens studied in major trials. The relationship between tocilizumab dose, exposure, and response in COVID-19 has not been adequately characterized. There are a number of pharmacokinetic (PK) parameters that likely differ between patients with severe COVID-19 and patients in whom tocilizumab was studied during the US FDA approval process. Likewise, it is unclear whether a threshold exposure is necessary for tocilizumab efficacy. The safety and efficacy of fixed versus weight-based dosing of tocilizumab has been evaluated outside of COVID-19, but it is uncertain if these observations are generalizable to severe or critical COVID-19. In the current review, we consider the potential advantages and limitations of alternative tocilizumab dosing strategies. Leveraging PK models and simulation analyses, we demonstrate that a fixed single dose of tocilizumab 400 mg is unlikely to produce PK exposures equivalent to those achieved in the REMAP-CAP trial, although weight-stratified dosing appears to produce more uniform exposure distribution. Data from current and future trials could provide PK/pharmacodynamic insight to better inform dosing strategies at the bedside. Ultimately, rational dosing strategies that balance available limited supply with patient needs are required.

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.