key: cord-0815993-oqbcqz5a
authors: Knight, Braden D.; Shurgold, Jayson; Smith, Glenys; MacFadden, Derek R.; Schwartz, Kevin L.; Daneman, Nick; Tropper, Denise Gravel; Brooks, James
title: The impact of COVID-19 on community antibiotic use in Canada: an ecological study
date: 2021-10-30
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.10.013
sha: d5e22fbea63c4aec5a2e1a8c0731794dbc8cb8dc
doc_id: 815993
cord_uid: oqbcqz5a

OBJECTIVES: The COVID-19 pandemic has impacted the incidence of infectious diseases and medical care. This study aimed to describe the impact of the COVID-19 pandemic on community-level antibiotic use. METHODS: Using national antibiotic dispensing data from IQVIA’s CompuScript database, this ecological study investigated antibiotic dispensing through community retail pharmacies in Canada from November 2014 to October 2020. Analyses were stratified by age, sex, prescription origin, and approximate indication. RESULTS: Adjusting for seasonality, the national rate of antibiotic dispensing in Canada decreased by 26.5% (50.4 to 37.0 average prescriptions per 1,000 inhabitants) during the first eight months of the Canadian COVID-19 period (March to October 2020), compared to the pre-COVID-19 period. Prescribing rates in children ≤18 years decreased from 43.7 to 12.2 prescriptions per 1,000 inhabitants in males (-72%) and from 46.8 to 14.9 prescriptions per 1,000 inhabitants in females (-68%) in April 2020. Rates in adults ≥65 decreased from 74.9 to 48.8 prescriptions per 1,000 inhabitants in males (-35%) and from 91.7 to 61.3 prescriptions per 1,000 inhabitants in females (-33%) in May 2020. Antibiotic prescriptions from family physicians experienced a greater decrease compared to surgeons and infectious disease physicians. Prescribing rates for antibiotics for respiratory indications decreased by 56% in May 2020 (29.2 to 12.8 prescriptions per 1,000 inhabitants), compared to prescribing rates for urinary tract infections (9.4 to 7.8 prescriptions per 1,000 inhabitants; -17%) and skin and soft tissue infections (6.4 to 5.2 prescriptions per 1,000 inhabitants; -19%). CONCLUSIONS: The first eight months of the COVID-19 pandemic reduced community antibiotic dispensing by 26.5% in Canada, compared to the marginal decrease of 3% in antibiotic consumption between 2015 and 2019. Further research is needed to understand the implications and long-term effects of the observed reductions on antibiotic use on antibiotic resistance in Canada.

The COVID-19 pandemic has had an unparalleled impact on the Canadian health care system. 29

While much of the focus of clinical care and research of COVID-19 has been in the inpatient 30 setting, the access and delivery of primary care services in Canada has dramatically changed, 31 including a notable shift toward virtual care 1, 2 . Additionally, physical distancing policies enacted 32 during the pandemic period may have reduced the transmission of communicable pathogens, 33 such as influenza and respiratory syncytial virus and obviated the need for some assessments and 34 antibiotic prescribing (both appropriate and inappropriate) 3 . Whether directly related to changes 35 to primary care accessibility and delivery or from fewer patients seeking medical care, there has 36 been an overall decrease to the number of physician interactions in Canada 1,2 , which can have 37 downstream impacts on prescribing. For these reasons, we examined whether COVID-19 38 resulted in significant national changes in community antibiotic prescribing patterns in Canada 4,5 , 39 as has been reported in other regions 6, 7 . 40 41 In Canada, access to antibiotics for use in humans is restricted to prescription by medical and 42 allied health professionals, including physicians, dentists and pharmacists. Between 2015 and 43 2019, the national rate of antibiotic dispensing in the community had remained stable in Canada, 44 decreasing by only three percent 8 . In recent years, approximately 90% of all antibiotics 45 consumed by humans in Canada were dispensed through community retail pharmacies, with 46 roughly two-thirds of these prescriptions originating from family doctors or general 47 practitioners 8 . Recent literature has suggested that the COVID-19 pandemic has had a disruptive 48 effect on prescribing practices 6, 7 . The inappropriate use of antibiotics can have manifold 49 J o u r n a l P r e -p r o o f projection methods have been previously used in similar studies [16] [17] [18] [19] . The data were stratified by 74 patient age, sex, prescription origin, and approximate indication. Age groupings were defined as 75 follows: children aged 0 to 18 years, adults aged 19 to 64 years, and adults aged 65 years and 76 older. Prescription origins (predominantly corresponding to the prescribing physician's specialty) 77

were defined as follows: family physicians (FP) had specialties of family physician or general 78 practitioner; non-family physicians (non-FP) were all other physician specialties; and non-79 physician prescribers were all other licensed prescribers (e.g. allied professionals, dentists, and 80 nurse practitioners). Some physician specialties of interest were identified, specifically 81 paediatricians, infectious disease physicians, and surgeons (i.e. general surgeons, orthopedic 82 surgeons, plastic surgeons and cardiothoracic surgeons). Physician specialty was used as a 83 possible surrogate to explore whether the indication for necessary prescribing changed (e.g. 84 infectious diseases physician antibiotic prescribing) and to examine how volume of prescriptions 85 was reduced due to effects of decreased healthcare access (e.g. prescribing by surgeons). 86

Approximate antibiotic indications were defined based on typical clinical use, and were 87 categorized as infections related to: respiratory, urinary tract, skin and soft tissue, or other 88 infections 20 (Table S1) Rates of antibiotic dispensing were calculated as the number of prescriptions dispensed per 1,000 99 inhabitants per month. The number of defined daily doses (DDDs) per 1,000 inhabitants was also 100 investigated and showed similar trends to prescription counts ( Figure S1 ). Due to an interest in 101 analyzing antibiotic consumption in children, we pursued all primary analyses using prescription 102 counts to allow for comparability, as DDDs cannot be reliably used for paediatric populations 22 . 103 104 Analysis 105

Descriptive statistics were used to compare the rates of antibiotic prescription counts each month 106 between January and October 2020 to the corresponding month in 2019. An interrupted time 107 series analysis was used to determine whether the overall monthly trend in antibiotic dispensing 108 was significantly different during the Canadian COVID-19 period compared to the year prior. 109

Although there was no harmonized start date to the implementation of public health measures in 110 Canada, March 2020 was chosen as the first month of the COVID-19 pandemic period to 111 correspond with many initial provincial public health interventions and the closure of the 112 Canadian and United States land boarder to non-essential travel. Monthly antibiotic dispensing 113 rates were stratified by age, sex, prescription origin, and approximate indication. For each strata, 114 seasonality adjustment was performed using a twelfth order autoregressive model with 115 backwards stepwise selection for autoregressive terms. As data were at the monthly level, a 116 twelfth order model was chosen to account for annual (twelve time point) correlation between 117 7 the data, while allowing for the flexibility to explore finer correlation patterns (one to eleven 118 time points). A backwards stepwise process was used to determine which autoregressive 119 parameters should be in the model for each strata. Each model incorporated terms for a step and 120 slope change; due to the noticeable abrupt change in the data, we interpreted a significant step 121 change beginning in March 2020 as the effect of the pandemic on antibiotic dispensing and the 122 significance (p-value) of this coefficient is reported. This interrupted time series with a 123 seasonality adjustment was used to confirm that any variation observed in percent change was 124 due to the COVID-19 pandemic and not natural seasonal change, especially due to the fact that 125 the COVID-19 period overlapped with months of historically lower antibiotic use. All analyses 126 were conducted in SAS version 9.4. 127

128

This study was conducted using aggregated administrative health data. No data on individuals 130 were available, therefore informed patient consent was not required. 131

The national rate of antibiotic dispensing in Canada decreased by an average of 26.5% in the first 135 eight months of the COVID-19 pandemic. National dispensing decreased by up to 40% in May 136 2020 when compared to the corresponding month in 2019 (52.7 to 31.9 prescriptions per 1,000 137 inhabitants) ( Table 1 ). The disparity narrowed to a decrease of 21% in August 2020 (45.2 to 35.6 138 prescriptions per 1,000 inhabitants), then broadened to a decrease of 30% in October 2020 (54. in May 2020. In seniors aged 65 years or more, dispensing decreased by 35% in males (74.9 to 154 48.8 prescriptions per 1,000 inhabitants) and by 33% in females (91.7 to 61.3 prescriptions per 155 1,000 inhabitants) in May 2020. Adjusting for seasonality, the national rate of antibiotic 156 dispensing during the COVID-19 period was significantly different (p <0.01) from the pre-157 COVID-19 period for each age and sex strata. 158

The rates of antibiotic prescriptions originating from all prescriber groups (i.e. family physicians, 160 non-family physicians, and non-physicians) during the COVID-19 period were significantly 161 different from the rates pre-pandemic after adjusting for seasonality (FP 31.0 to 20.8 average 162 prescriptions per 1,000 inhabitants, p=0.020; non-FP 7.1 to 5.6 average prescriptions per 1,000 163 9 inhabitants, p<0.001; non-physicians 12.3 to 10.6 average prescriptions per 1,000 inhabitants, 164 p<0.001) (Figure 3 ). While the greatest number of prescriptions originated from family 165 physicians before and during the pandemic (accounting for approximately 62% of prescriptions 166 in 2019 and 56% of prescriptions during the first eight months of the pandemic), the rate of 167 prescriptions originating from family physicians decreased by a maximum of 44% in May 2020 168 (32.8 to 18.5 prescriptions per 1,000 inhabitants), compared to a maximum decrease of 39% for 169 non-family physicians in April 2020 (7.6 to 4.6 prescriptions per 1,000 inhabitants) and by 32% 170 for non-physicians in May 2020 (12.3 to 8.4 prescriptions per 1,000 inhabitants) (Figure 3a) . 171

While the rate of antibiotic dispensing nearly returned to pre-COVID-19 rates for non-family 172 physicians and non-physicians during the summer of 2020, rates remained well below baseline 173 for family physicians until the end of the study. We were unable to examine the reasons for the reduction in dispensing. Although the CS 231 database is nationally representative, it does not include information from the three Canadian 232 12 territories, nor from inpatient populations. The database is administrative in nature and therefore 233 is not maintained for research purposes. The CS database does not link antibiotic prescriptions to 234 diagnoses, limiting assessment or interpretation of prescription appropriateness. Indications were 235 approximated based on typical clinical usage. Information on morbidity and mortality was not 236 available, limiting analysis or interpretation pertaining to the potential underuse of antibiotics. 237

We were unable to assess if the observed reduction in antibiotic dispensing during the COVID-238 19 pandemic in Canada led to increased infectious complications. We were also unable to 239 account for antibiotic recommendations that were not received by retail pharmacies. While effort 240 has been made to adjust for seasonality, the COVID-19 pandemic has introduced novel 241 simultaneous factors that are difficult to identify, define and fully account for. 

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Feb Skin and Soft Tissue 5.3655 Mar Skin and Soft Tissue 5

Skin and Soft Tissue % Change

Sep Skin and Soft Tissue