Publications

Insulin prices have been a hot topic in the United States, where there is a lack of price regulation on drugs, and there have been reports of Americans crossing the border to purchase insulin in Canada at much lower prices. We conducted a cross-sectional time-series analysis comparing insulin spending using IQVIA (Durham, North Carolina, USA) data on aggregate insulin prescription volumes dispensed in the United States and Canada from January 2016 to April 2019 to quantify insulin spending and pricing differences between the countries. We obtained data on diabetes rates from the US Centers for Disease Control and Prevention and Statistics Canada. The primary outcome of this study was the difference in total annual insulin spending and spending per insulin user between the United States and Canada. We also examined spending on the top 5 most used insulins per year in the United States and the percentage change of spending on insulin products from January 2016 to April 2019. In 2018, the US spent $28 billion (USD) on insulin compared with $484 million in Canada. The average American insulin user spent $3490 on insulin in 2018 compared with $725 among Canadians. Over the study period, the average cost per unit of insulin in the United States increased by 10.3% compared with only 0.01% in Canada. These findings demonstrate that the United States spent considerably more on insulin than Canada, and prices continue to increase. Implementing national legislation for drug pricing regulations using reference pricing could stabilize and potentially decrease insulin prices in the United States.

BACKGROUND: Although automated urine cultures (UCs) following urinalysis (UA) are often used in emergency departments (EDs) to identify urinary tract infections (UTIs), results are often reported as no organism growth or the growth of clinically insignificant organisms, leading to the overdetection and overtreatment of asymptomatic bacteriuria (ASB).

METHODS: A process change was implemented at a US Department of Veterans Affairs medical center ED that automatically cancelled UCs if UAs had < 5 white blood cells per high-power field (WBC/HPF). An option for do not cancel (DNC) UC was available. Data were prospectively collected for 3 months postimplementation and included UA/UC results, presence of UTI symptoms, antibiotics prescribed, and health care utilization.

RESULTS: Postintervention, 684 UAs (37.2%) were evaluated from ED visits. Postintervention, of 255 UAs, 95 (37.3%) were negative with UC cancelled, 95 (37.3%) were positive with UC processed, 43 (16.9%) were ordered as DNC, and 22 (8.6%) were ordered without a UC. UC processing despite a negative UA significantly decreased from 100% preintervention to 38.6% postintervention (P < .001). Inappropriate prescribing of antibiotics for ASB was reduced from 10.2% preintervention to 1.9% postintervention (odds ratio = 0.17; P = .01). In patients with negative UA specimens, antibiotic prescribing decreased by 25.3% postintervention. No reports of outpatient, ED, or hospital visits for symptomatic UTI were found within 7 days of the initial UA postintervention.

CONCLUSIONS: The UA to reflex culture process change resulted in a significant reduction in processing of inappropriate UCs and unnecessary antibiotic use for ASB. There were no missed UTIs or other adverse patient outcomes.

OBJECTIVE: Our objective was to compare patterns of dental antibiotic prescribing in Australia, England, and North America (United States and British Columbia, Canada).

DESIGN: Population-level analysis of antibiotic prescription.

SETTING: Outpatient prescribing by dentists in 2017.

PARTICIPANTS: Patients receiving an antibiotic dispensed by an outpatient pharmacy.

METHODS: Prescription-based rates adjusted by population were compared overall and by antibiotic class. Contingency tables assessed differences in the proportion of antibiotic class by country.

RESULTS: In 2017, dentists in the United States had the highest antibiotic prescribing rate per 1,000 population and Australia had the lowest rate. The penicillin class, particularly amoxicillin, was the most frequently prescribed for all countries. The second most common agents prescribed were clindamycin in the United States and British Columbia (Canada) and metronidazole in Australia and England. Broad-spectrum agents, amoxicillin-clavulanic acid, and azithromycin were the highest in Australia and the United States, respectively.

CONCLUSION: Extreme differences exist in antibiotics prescribed by dentists in Australia, England, the United States, and British Columbia. The United States had twice the antibiotic prescription rate of Australia and the most frequently prescribed antibiotic in the US was clindamycin. Significant opportunities exist for the global dental community to update their prescribing behavior relating to second-line agents for penicillin allergic patients and to contribute to international efforts addressing antibiotic resistance. Patient safety improvements will result from optimizing dental antibiotic prescribing, especially for antibiotics associated with resistance (broad-spectrum agents) or C. difficile (clindamycin). Dental antibiotic stewardship programs are urgently needed worldwide.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture.

METHODS: This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures.

RESULTS: CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55-13.73) and CRPA (OR 2.82, 95% CI 2.04-3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures.

CONCLUSIONS: Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.

BACKGROUND: The drug supply chain is global and at risk of disruption and subsequent drug shortages, especially during unanticipated events.

OBJECTIVE: Our objective was to determine the impact of coronavirus disease 2019 (COVID-19) on drug purchases overall, by class, and for specific countries.

METHODS: A cross-sectional time series analysis of country-level drug purchase data from August 2014 to August 2020 from IQVIA MIDAS was conducted. Standardized units per 100 population and percentage increase in units purchased were assessed from 68 countries and jurisdictions in March 2020 (when the World Health Organization declared COVID-19 a pandemic). Analyses were compared by United Nations development status and drug class. Autoregressive integrated moving average models tested the significance of changes in purchasing trends.

RESULTS: Before COVID-19, standardized medication units per 100 population ranged from 3990 to 4760 monthly. In March 2020, there was a global 15% increase in units of drugs purchased to 5309.3 units per 100 population compared with the previous year; the increase was greater in developed countries (18.5%; P < 0.001) than in developing countries (12.8%; P < 0.0001). After the increase in March 2020, there was a correction in the global purchase rate decreasing by 4.7% (April to August 2020 rate, 21,334.6/100 population; P < 0.001). Globally, we observed high purchasing rates and large changes for respiratory medicines such as inhalers and systemic adrenergic drugs (March 2020 rate, 892.7/100 population; change from 2019, 28.5%; P < 0.001). Purchases for topical dermatologic products also increased substantially (42.2%), although at lower absolute rates (610.0/100 population in March 2020; P < 0.0001). Interestingly, purchases for systemic anti-infective agents (including antiviral drugs) increased in developing countries (11.3%; P < 0.001), but decreased in developed countries (1.0%; P = 0.06).

CONCLUSION: We observed evidence of global drug stockpiling in the early months of the COVID-19 pandemic, especially among developed countries. Actions toward equitable distribution of medicines through a resilient drug supply chain should be taken to increase global response to future unanticipated events, such as pandemics.

BACKGROUND: Little is known about the effect of the COVID-19 pandemic on antimicrobial consumption worldwide.

OBJECTIVES: To describe the impact of the WHO Global Action Plan on Antimicrobial Resistance (GAP-AMR) on antimicrobial consumption pre-pandemic and to evaluate the impact of the COVID-19 pandemic on antimicrobial consumption worldwide.

METHODS: A cross-sectional time-series analysis using a dataset of monthly purchases of antimicrobials (antibiotics, antivirals and antifungals) from August 2014 to August 2020. Antimicrobial consumption per 1000 population was assessed pre-pandemic by economic development status using linear regression models. Interventional autoregressive integrated moving average (ARIMA) models tested for significant changes with pandemic declaration (March 2020) and during its first stage from April to August 2020, worldwide and by country development status.

RESULTS: Prior to the pandemic, antimicrobial consumption decreased worldwide, with a greater apparent decrease in developed versus developing countries (-8.4%, P = 0.020 versus -1.2%, P = 0.660). Relative to 2019, antimicrobial consumption increased by 11.2%, P < 0.001 in March 2020. The greatest increase was for antivirals in both developed and developing countries (48.2%, P < 0.001; 110.0%, P < 0.001) followed by antibiotics (6.9%, P < 0.001; 5.9%, P = 0.003). From April to August 2020, antimicrobial consumption decreased worldwide by 18.7% (P < 0.001) compared with the previous year. Specifically, antibiotic consumption significantly decreased in both developed and developing countries (-28.0%, P < 0.001; -16.8%, P < 0.001).

CONCLUSIONS: The global decrease in antimicrobial consumption pre-pandemic suggests a positive impact of the WHO GAP-AMR. During the pandemic, an initial increase in antimicrobial consumption was followed by a decrease worldwide. AMR plans should specify measures to ensure full implementation of AMR efforts during health crises such as the COVID-19 pandemic.

OBJECTIVE: To evaluate opportunities for assessing penicillin allergies among patients presenting to dental clinics.

DESIGN: Retrospective cross-sectional study.

SETTING: VA dental clinics.

PATIENTS: Adult patients with a documented penicillin allergy who received an antibiotic from a dentist between January 1, 2015, and December 31, 2018, were included.

METHODS: Chart reviews were completed on random samples of 100 patients who received a noncephalosporin antibiotic and 200 patients who received a cephalosporin. Each allergy was categorized by severity. These categories were used to determine patient eligibility for 3 testing groups based on peer-reviewed algorithms: (1) no testing, (2) skin testing, and (3) oral test-dose challenge. Descriptive and bivariate statistics were used to compare facility and patient demographics first between true penicillin allergy, pseudo penicillin allergy, and missing allergy documentation, and between those who received a cephalosporin and those who did not at the dental visit.

RESULTS: Overall, 19% lacked documentation of the nature of allergic reaction, 53% were eligible for skin testing, 27% were eligible for an oral test-dose challenge, and 1% were contraindicated from testing. Male patients and African American patients were less likely to receive a cephalosporin.

CONCLUSIONS: Most penicillin-allergic patients in the VA receiving an antibiotic from a dentist are eligible for penicillin skin testing or an oral penicillin challenge. Further research is needed to understand the role of dentists and dental clinics in assessing penicillin allergies.

To investigate factors that influence antibiotic prescribing decisions, we interviewed 49 antibiotic stewardship champions and stakeholders across 15 hospitals. We conducted thematic analysis and subcoding of decisional factors. We identified 31 factors that influence antibiotic prescribing decisions. These factors may help stewardship programs identify educational targets and design more effective interventions.

OBJECTIVE: To describe national trends in testing and detection of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE) and associate testing with culture and facility characteristics.

DESIGN: Retrospective cohort study.

SETTING: Department of Veterans' Affairs medical centers (VAMCs).

PARTICIPANTS: Patients seen at VAMCs between 2013 and 2018 with cultures positive for CRE, defined by national VA guidelines.

INTERVENTIONS: Microbiology and clinical data were extracted from national VA data sets. Carbapenemase testing was summarized using descriptive statistics. Characteristics associated with carbapenemase testing were assessed with bivariate analyses.

RESULTS: Of 5,778 standard cultures that grew CRE, 1,905 (33.0%) had evidence of molecular or phenotypic carbapenemase testing and 1,603 (84.1%) of these had carbapenemases detected. Among these cultures confirmed as carbapenemase-producing CRE, 1,053 (65.7%) had molecular testing for ≥1 gene. Almost all testing included KPC (n = 1,047, 99.4%), with KPC detected in 914 of 1,047 (87.3%) cultures. Testing and detection of other enzymes was less frequent. Carbapenemase testing increased over the study period from 23.5% of CRE cultures in 2013 to 58.9% in 2018. The South US Census region (38.6%) and the Northeast (37.2%) region had the highest proportion of CRE cultures with carbapenemase testing. High complexity (vs low) and urban (vs rural) facilities were significantly associated with carbapenemase testing (P < .0001).

CONCLUSIONS: Between 2013 and 2018, carbapenemase testing and detection increased in the VA, largely reflecting increased testing and detection of KPC. Surveillance of other carbapenemases is important due to global spread and increasing antibiotic resistance. Efforts supporting the expansion of carbapenemase testing to low-complexity, rural healthcare facilities and standardization of reporting of carbapenemase testing are needed.