Outpatient Antibiotic Use in Canadian Provinces: Comparison
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Please note this is a comparison between Version 2 by Camila Xu and Version 1 by Ariana Saatchi.

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.

  • antibiotics
  • antimicrobial drug resistance
  • outpatient care

1. Introduction

The World Health Organization formally acknowledged the crisis of antimicrobial resistance (AMR) in 2014, and released a global action plan the next year [1]. In response, the United States, the United Kingdom (UK) and Australia have not only established jurisdiction-specific plans for the reduction of antibiotic use, but have also gone one step further and pledged to decrease inappropriate antibiotic use [2,3,4,5][2][3][4][5]. Despite the urgency, Canada has yet to disseminate a national action plan that focuses on the quality of antibiotic prescribing [6]. The continued knowledge gap on suboptimal prescribing quality precludes the scope of tangible targets for intervention, and research to parse inappropriate antibiotic use in Canada is vital [7,8][7][8].
Outpatient prescribing accounts for the majority of human antibiotic use in Canada, with 90% of all antibiotics dispensed in the community setting [8]. Evaluating appropriate antibiotic use is especially relevant for older Canadians (≥65 years), who are prescribed antimicrobials at elevated rates compared to other cohorts, particularly for respiratory tract infections (RTI) and urinary tract infections (UTI), with incidence of hospitalizations and “superbug” infections greater than in younger populations [9,10,11,12,13,14][9][10][11][12][13][14]. Historically, antibiotic use in seniors has been framed as a catch-22 situation, wherein both the prescription and/or reservation of antibiotics confer increased patient risk for adverse outcomes; however, recent studies counter this myth and report no association between reductions in antibiotic use and increased bacterial complications [15]. In the absence of documented patient harms, the stagnant rates of prescribing in Canadian seniors are especially alarming and require prompt attention to reduce antibiotic use within this population. In Canada, antibiotic receipt is the single most important risk factor for Clostridioides difficile infection and the acquisition of resistant infections, and it is the second most common cause of emergency department visits for adverse drug events [16,17][16][17]. Despite moderate declines in incidence across Canada since 2009, C. difficile remains one of the most burdensome pathogens, particularly in the elderly, causing more deaths than influenza each year [16].
On a global scale, the quantities of antibiotic use in humans, animals and agriculture have been surveilled for decades [18,19,20,21][18][19][20][21]. However, studies examining prescription quality have been hindered by the absence of encompassing guidelines, varying clinical factors and a high-level of expert subjectivity in defining inappropriate use. Moreover, the defining features of inappropriate use—antibiotic prescription in the absence of a bacterial etiology, the overuse of broad-spectrum agents, suboptimal dosing and/or duration of therapy—are diverse and difficult to aggregate [22]. Spivak et al. characterized early attempts to measure prescribing quality as trying to open a black box [22]. Since the publication of Spivak’s paper, several countries, including the United States and the UK have published criteria that define appropriateness; however, in Canada, inappropriate antibiotic use has remained largely unexamined and unknown.

2. Discussion

This is the first studyone in Canada to evaluate primary care antibiotic appropriateness across two large provinces. Across Ontario and BC, indications for which antibiotics are not required were the most heavily prescribed for seniors—In any study year, followed by antibiotic prescribing for Tier 1 where antibiotics are always required. Both provinces were similar in the agents prescribed for indications apart from tetracyclines—wherein BC prescribing eclipsed Ontario and overall prescribing for doxycycline in BC was six times more than in Ontario. With respect to prescribing quality, Canadian seniors continue to be overprescribed antibiotics for conditions that do not warrant their use [14,23][14][23]. Despite the fact that antibiotic use is unnecessary, Tier 3 indications were prescribed at rates 2–4 times higher than other tiers. In both provinces, bronchitis received high levels of antibiotic prescription; however, while BC prescribing remained stable for this indication, Ontario saw a 30% reduction in antibiotic use. 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. Robust and ongoing elevated prescribing for Tier 3 indications has been corroborated across multiple studies and geographic regions [11,24,25,26,27][11][24][25][26][27]. Despite the inefficacy of antibiotics for non-bacterial conditions, prescriptions issued for these diagnoses continue to dominate. In the US, 30% of outpatient prescribing is inappropriate; moreover, these rates have not significantly improved for adult populations since their initial reporting in 2016 [24,25][24][25]. In the United Kingdom, at least 20% of all antibiotics are used inappropriately in the outpatient setting [28,29][28][29]. Our study identified 49% of all indication-associated prescriptions in Ontario, and 53% in BC were dispensed inappropriately to Canadian seniors. A previous study examining a relatively small and select group of Canadian practitioners reported only 13% of prescriptions issued to seniors in Ontario were inappropriate [14]. The population wide sampling of our study provides a more accurate view of overall practices, and our methodology (i.e., diagnostic classification into Tiers 1, 2 and 3) aligns with previous published data from the United States and offers a more direct comparison with reported results, dissuading the notion that Canadian seniors receive less inappropriate or unnecessary prescriptions. In comparing the most common agents used, Ontario has adopted increased use of penicillins over time, driven by the use of amoxicillin. This shift to the use of beta-lactams is accompanied by the decreased use of macrolides, erythromycin in the early days and, more recently, clarithromycin, quinolones, mostly related to ciprofloxacin, and sulfonamides/trimethoprim classes. Despite the aggregate stability in prescribing, the shifting landscape of common agents highlight trends of optimization, in the absence of reduced quantity. A decline in use for the same three classes is also reflected in BC; however, a complimentary increase has been observed in tetracycline antibiotics—prescribed at rates four times that of ON. One reason for this difference in magnitude may be doxycycline first entering the BC formulary in 2002, but only covered by the Ontario Drug Benefit Program (ODB) as of 2009 [30,31][30][31]. Additionally, we speculate that the suspected switch to the use of doxycycline for respiratory infections in BC may explain the interprovincial gap, where beta-lactams are the preferred agents in Ontario. Another reason for the disparity in tetracycline use might be the varying population demographics across provinces—with BC’s population older, on average [32]. Trends in antibiotic use for both provinces, across various patient demographics were comparable—with females aged 65–79 years, in urban settings and lower income quintiles being more likely to be prescribed (Supplement, Table S3). However, a difference in prescribing culture may also be culpable as Bugs and Drugs, the leading clinical practice guideline in BC, emphasizes tetracycline use more so than other comparable resources [33]. By contrast, Health Quality Ontario promotes the use of beta-lactam monotherapy, especially for cases of community-acquired pneumonia. The divergence in clinical guidelines and prescribing practice highlight a stark difference across two otherwise comparable healthcare systems. Provincial antibiograms and/or patient demographics might account for this difference in antibiotic use; however, this provincial variability is likely multifactorial, and not clearly elucidated. Although optimization of drug choice, with narrowest spectrum and shortest duration being a central tenant of antimicrobial stewardship, this study highlights the reduction of unnecessary prescribing as an ongoing, high priority issue for Canadian seniors. Elevated antimicrobial use in Canadian seniors is especially concerning in the wake of prolonged antimicrobial stewardship (AMS) efforts. Formal evaluation of AMS impact was beyond the scope of this study; however, both provinces have endeavored to curb the unnecessary use of antibiotics. In BC, the Do Bugs Need Drugs campaign has been operating since 2005, offering accredited courses on appropriate antibiotic use, disseminating guidelines and physician resources [34]. By contrast, Public Health Ontario promotes the principles of AMS, put forth through federal initiatives and further adopted by the Choosing Wisely initiative in 2016 [35,36][35][36]. These initiatives promote conversations between clinicians and patients regarding unnecessary antibiotic use. Although some improvements in the trends of antibiotic classes used were identified in this study, there remains a high level of inappropriate prescribing in both provinces. In BC, AMS efforts have been attributed to an overall decline in antibiotic use; however, this trend is driven by younger populations with much work to be done in seniors [23]. This study has limitations inherent to all retrospective studies using administrative health data. Physician billing records were used to extract indication data to characterize antibiotic prescriptions. In BC, 89% of all prescriptions were linked to a physician record for a common infection, with only 50% of Ontario prescriptions linked. These rates were expected cross-provincially and demonstrate an improvement in linkage, in comparison to previous studies of Canadian outpatient care [37]. The unlinked prescriptions in Ontario could be evenly attributed to diagnoses beyond the scope of this study or no record. The latter are likely attributable to hospital and/or emergency department visits, with subsequent prescriptions dispensed in the community, not included within study scope. Although it is notable that Canadian primary-care physician claims data has a high positive-predictive value for diagnosis of common infections, including acute non-bacterial upper-respiratory infections (0.84, 95% CI: 0.81 to 0.88), differences in coding practices across provinces are not unknown [38]. In BC, the inflated use of certain Tier 3 codes (e.g., other-genitourinary-conditions) may signify an underlying systematic difference in provincial coding practices. Often utilized by prescribers for patient presentations that do not fulfill more specific diagnosis criterium (e.g., cystitis), elevated use of these codes raises alarms regarding prescribing or coding quality. These “other” diagnoses also exist for skin/soft tissue and respiratory tract infections. By 2018, prescribing for “other respiratory tract” infections halved in BC, although it was still twice the Ontario rate. The difference in scale for these indications, across otherwise comparable landscapes of primary care, compels further investigation into BC administrative data. Despite its routine utilization for research purposes, no previous studies validating BC administrative health data, for relevant ICD−9 codes, were identified by the authors. Furthermore, as the nature of our data prevents nested analyses, multiple prescriptions were permitted per individual, and our standard error may be biased. Rates do not account for unfilled prescriptions, and levels of compliance to medications are unknown. In the absence of lab data to confirm bacterial infection, or patient comorbidity data, our use of billing codes may be subject to misclassification bias. Finally, ourthis study focused exclusively on patients aged >65. Substantial improvements in antibiotic prescribing in paediatrics have occurred, but assessments in other age groups are needed.

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