Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study.

BACKGROUND: 13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13 programmes on invasive pneumococcal disease (IPD) and all-cause pneumonia hospitalisation in older adults (aged ≥65 years) using a retrospective observational study. METHODS: We extracted monthly IPD and all-cause pneumonia cases from laboratory and health administrative databases between January 2005 and December 2018. Using a quasi-experimental difference-in-differences design, we calculated the ratio of risk ratios (RRRs) using incidence rates of IPD or all-cause pneumonia cases before (pre-PCV13 period) and after (PCV13 period) 2010 with rates of fractures as controls. RESULTS: The rates of all IPD or PCV serotype-specific IPD for older adults in both Ontario and BC did not change in 8 years after childhood PCV13 programme implementation. All-cause pneumonia increased in Ontario (RRR 1.38, 95% CI 1.11 to 1.71) but remained unchanged in BC. CONCLUSIONS: Indirect community protection of older adults from hospitalisation with pneumococcal disease stalled despite maturation of childhood PCV13 vaccination programmes in two Canadian provinces.

Retrospective cohort analysis of outpatient antibiotic prescribing for community-acquired pneumonia in Canadian older adults.

BACKGROUND: This retrospective cohort study is the first in North America to examine population-level appropriate antibiotic use for community-acquired pneumonia (CAP) in older adults, by agent, dose and duration. With the highest rates of CAP reported in the elderly populations, appropriate antibiotic use is essential to improve clinical outcomes. Given the ongoing crisis of antimicrobial resistance, understanding inappropriate antibiotic prescribing is integral to direct community stewardship efforts. METHODS: All outpatient primary care visits for CAP (aged ≥65 years) were identified using physician billing codes between January 1 2014 to December 31 2018 in British Columbia (BC) and Ontario (ON). Categories of prescribing were derived from existing literature, and constructed for clinical relevance using Canadian and international guidelines available during the study period. Categories were mutually exclusive and included: guideline adherent (first-line agent, adherent dose/duration), clinically appropriate (non-first line agent, presence of comorbidities), effective but unnecessary (first-line agent, excess dose/duration), undertreatment (first-line agent, subtherapeutic dose/duration), and not recommended (non-first line agent, absence of comorbidities). Proportions of prescribing were examined by category. Temporal trends in prescribing were examined using Poisson regression. RESULTS: A total of 436,441 episodes of CAP were identified, with 46% prescribed an antibiotic in BC, and 52% in Ontario. Guideline adherent prescribing was minimal for both provinces (BC: 2%; ON: 1%) however the largest magnitude of increase was reported in this category by the final study year (BC-Rate Ratio [RR]: 3.4, 95% Confidence Interval [CI]: 2.7-4.3; ON-RR: 4.62, 95% CI: 3.4-6.5). Clinically appropriate prescribing accounted for the most antibiotics issued, across all study years (BC: 61%; ON: 74%) (BC-RR: 0.8, 95% CI: 0.8-0.8; ON-RR: 0.9, 95% CI: 0.8-0.9). Excess duration of therapy was the hallmark characteristic for effective but unnecessary prescribing (BC: 92%; ON: 99%). The most common duration prescribed was 7 days, followed by 10. Not recommended prescribing was minimal in both provinces (BC: 4%; ON: 7%) and remained stable by the final study year (BC-RR: 1.1, 95% CI: 0.9-1.2; ON-RR: 0.9, 95% CI: 0.9-1.1). CONCLUSION: Three quarters of antibiotic prescribing for CAP was appropriate in Ontario, but only two thirds in BC. Shortening durations-in line with evidence for 3 to 5-day treatment presents a focused target for stewardship efforts.

Quality of antibiotic prescribing for pediatric community-acquired Pneumonia in outpatient care.

BACKGROUND: Antibiotics remain the primary treatment for community acquired pneumonia (CAP), however rising rates of antimicrobial resistance may jeopardize their future efficacy. With higher rates of disease reported in the youngest populations, effective treatment courses for pediatric pneumonia are of paramount importance. This study is the first to examine the quality of pediatric antibiotic use by agent, dose and duration. METHODS: A retrospective cohort study included all outpatient/primary care physician visits for pediatric CAP (aged < 19 years) between January 1 2014 to December 31 2018. Relevant practice guidelines were identified, and treatment recommendations extracted. Amoxicillin was the primary first-line agent for pediatric CAP. Categories of prescribing included: guideline adherent, effective but unnecessary (excess dose and/or duration), under treatment (insufficient dose and/or duration), and not recommended. Proportions of attributable-antibiotic use were examined by prescribing category, and then stratified by age and sex. RESULT(S): A total of 42,452 episodes of pediatric CAP were identified. Of those, 31,347 (76%) resulted in an antibiotic prescription. Amoxicillin accounted for 51% of all prescriptions. Overall, 27% of prescribing was fully guideline adherent, 19% effective but unnecessary, 10% under treatment, and 44% not recommended by agent. Excessive duration was the hallmark of effective but unnecessary prescribing (97%) Macrolides accounted for the majority on non-first line agent use, with only 32% of not recommended prescribing preceded by a previous course of antibiotics. CONCLUSION(S): This study is the first in Canada to examine prescribing quality for pediatric CAP by agent, dose and duration. Utilizing first-line agents, and shorter-course treatments are targets for stewardship.

Retrospective Cohort Analysis of Outpatient Antibiotic Use for Clostridioides difficile-Indicated Agents in British Columbia, from 2000 to 2018.

Background: Clostridioides difficile (CDI) is the most common cause of nosocomial diarrheal infections. Historically, metronidazole was the first-line treatment, but guidelines now indicate oral vancomycin and fidaxomicin as primary antibiotics for initial episodes. A provincial stewardship program has operated in British Columbia (BC), since 2005. Since the program's inception, surveillance of antibiotic use has been ongoing. However, this is the first study to review community-acquired CDI-indicated antibiotic use. Moreover, this study offers the first interpretation of fidaxomicin use in BC since its addition to the provincial formulary. Methods: A retrospective cohort analysis included all outpatient dispensations for CDI-related antibiotics from January 1, 2000, to December 31, 2018. Antibiotic dispensations were extracted for metronidazole, vancomycin, and fidaxomicin. Consumption rates were calculated as prescriptions per 1000 population. Rates were examined overall and then stratified by medication, age, and sex. Secondary outcomes of interest included an examination of adherence to provincial special authority criteria; and proportions of outpatient antibiotic use attributable to administrative health records for CDI. Results: The average annual rate of prescribing was 18.5 per 1000 population for all CDI-indicated antibiotics. The rate of prescribing increased (15%) over the 19-year study period, from 17.2 to 19.8 dispensations per 1000 population. Metronidazole accounted for the most antibiotics dispensed in every study year; however, by 2018 it demonstrated the most modest increase in use (15%). In comparison, fidaxomicin increased by 226% by 2018. Vancomycin had the highest percentage increase (621%), with the greatest change occurring from 2014 to 2015, correlating to the dissemination of new clinical practice guidelines. Conclusion: This is the first study to evaluate outpatient prescribing for CDI-indicated antibiotics, and one of the few studies to examine fidaxomicin since its introduction to Canadian formularies. Although causation cannot be inferred from study results, oral vancomycin, and fidaxomicin use has increased in line with, or in advance-of guidelines.

A Time Series Analysis Evaluating Antibiotic Prescription Rates in Long-Term Care during the COVID-19 Pandemic in Alberta and Ontario, Canada.

The COVID-19 pandemic affected access to care, and the associated public health measures influenced the transmission of other infectious diseases. The pandemic has dramatically changed antibiotic prescribing in the community. We aimed to determine the impact of the COVID-19 pandemic and the resulting control measures on oral antibiotic prescribing in long-term care facilities (LTCFs) in Alberta and Ontario, Canada using linked administrative data. Antibiotic prescription data were collected for LTCF residents 65 years and older in Alberta and Ontario from 1 January 2017 until 31 December 2020. Weekly prescription rates per 1000 residents, stratified by age, sex, antibiotic class, and selected individual agents, were calculated. Interrupted time series analyses using SARIMA models were performed to test for changes in antibiotic prescription rates after the start of the pandemic (1 March 2020). The average annual cohort size was 18,489 for Alberta and 96,614 for Ontario. A significant decrease in overall weekly prescription rates after the start of the pandemic compared to pre-pandemic was found in Alberta, but not in Ontario. Furthermore, a significant decrease in prescription rates was observed for antibiotics mainly used to treat respiratory tract infections: amoxicillin in both provinces (Alberta: −0.6 per 1000 LTCF residents decrease in weekly prescription rate, p = 0.006; Ontario: −0.8, p < 0.001); and doxycycline (−0.2, p = 0.005) and penicillin (−0.04, p = 0.014) in Ontario. In Ontario, azithromycin was prescribed at a significantly higher rate after the start of the pandemic (0.7 per 1000 LTCF residents increase in weekly prescription rate, p = 0.011). A decrease in prescription rates for antibiotics that are largely used to treat respiratory tract infections is in keeping with the lower observed rates for respiratory infections resulting from pandemic control measures. The results should be considered in the contexts of different LTCF systems and provincial public health responses to the pandemic.

Estimating population-based incidence of community-acquired pneumonia and acute otitis media in children and adults in Ontario and British Columbia using health administrative data, 2005-2018: a Canadian Immunisation Research Network (CIRN) study.

BACKGROUND: There is a paucity of data on the burden of the full spectrum of community-acquired pneumonia (CAP) and acute otitis media (AOM) from outpatient and inpatient settings across the age spectrum. METHODS: We conducted a population-based retrospective study in Ontario and British Columbia (BC), Canada, to estimate the incidence rate of CAP and AOM in children and adults over a 14-year period using health administrative databases. CAP and AOM cases were identified from outpatient physician consultation and hospitalisation data in both provinces, and from emergency department visit data in Ontario. RESULTS: During 2005-2018, Ontario had 3 607 124 CAP, 172 290 bacterial CAP, 7814 pneumococcal pneumonia, and 8 026 971 AOM cases. The incidence rate of CAP declined from 3077/100 000 in 2005 to 2604/100 000 in 2010 before increasing to 2843/100 000 in 2018; bacterial CAP incidence rate also declined from 178/100 000 in 2005 to 112/100 000 in 2010 before increasing to 149/100 000 in 2018. The incidence rate of AOM decreased from 4192/100 000 in 2005 to 3178/100 000 in 2018. BC had 970 455 CAP, 317 913 bacterial CAP, 35 287 pneumococcal pneumonia and 2 022 871 AOM cases. The incidence rate of CAP in BC decreased from 2214/100 000 in 2005 to 1964/100 000 in 2010 before increasing to 2176/100 000 in 2018; bacterial CAP incidence rate increased from 442/100 000 in 2005 to 981/100 000 in 2018. The incidence rate of AOM decreased from 3684/100 000 in 2005 to 2398/100 000 in 2018. The incidence rate of bacterial CAP increased with age in older adults (≥65 years) with the highest burden in the oldest cohort aged ≥85 years both before and after 13-valent pneumococcal conjugate vaccine (PCV13) programme in both provinces. Hospitalised pneumococcal pneumonia decreased slightly but non-hospitalised pneumococcal pneumonia increased in BC during PCV13 period. No consistent direct benefit of PCV13 on CAP was observed in the paediatric population. CONCLUSIONS: There is a substantial burden of CAP and AOM in Ontario and BC. Indirect benefits from childhood PCV vaccination and polysaccharide vaccination of older adults have not substantially decreased the burden of pneumococcal pneumonia in older adults.

Healthcare Costs for Pneumococcal Disease in the Era of Infant Immunization With 13-Valent Pneumococcal Conjugate Vaccine: A Population-Based Study.

OBJECTIVES: Invasive pneumococcal disease (IPD) and a variety of clinical syndromes caused by pneumococci, such as acute otitis media (AOM), acute sinusitis (AS), and community-acquired pneumonia (CAP), cause a substantial burden on healthcare systems. Few studies have explored the short-term financial burden of pneumococcal disease after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the infant immunization programs. This population-based study evaluated changes in costs associated with healthcare utilization for pneumococcal disease after the PCV13 introduction in the infant immunization program in British Columbia, Canada. METHODS: Individuals with pneumococcal disease were identified using provincial administrative data for the 2000 to 2018 period. Total direct healthcare costs were determined using case-mix methodology for hospitalization and fee-for-service codes for outpatient visits and medications dispensed. Costs were adjusted to 2018 Canadian dollars. Changes in the annual healthcare costs were evaluated across vaccine eras (pre-PCV13, 2000-2010; PCV13, 2011-2018) using generalized linear models, adjusting for the 7-valent pneumococcal conjugate vaccine program (2004-2010). RESULTS: During the 19-year study period, pneumococcal disease resulted in 6.3 million cases among 85 million total patient-years, resulting in total healthcare costs of $7.9 billion. More than 6.2 million cases were treated in outpatient setting, costing $0.65 billion (8% of total costs associated with pneumococcal disease treatment), whereas 370 000 hospitalized cases were 3% of all cases, which accrued $7.25 billion (92% of total costs) in costs. Healthcare costs for all studied infections nearly doubled over the study period from $248 million in 2000 to $476 million in 2018 (P = .003). In contrast, there were large declines in total annual costs in the PCV13 era for IPD (adjusted relative rate (aRR) 0.73; 95% confidence interval [CI] 0.56-0.95; P = .032), AOM (aRR 0.70; 95% CI 0.59-0.83; P = .001), and AS (aRR 0.68; 95% CI 0.54-0.85; P = .004) compared with the pre-PCV13 era. Total costs increased marginally in the PCV13 era for all-cause CAP (aRR 1.04; 95% CI 0.94-1.15; P = .484). CONCLUSIONS: This study confirms a temporal association in declining economic burden for IPD, AOM, and AS after the PCV13 introduction. Nevertheless, the total economic burden continues to be high in the PCV13 era, mainly driven by increasing CAP costs.

A population-based analysis to determine the impact of the 13-valent pneumococcal conjugate vaccine on community-acquired pneumonia in British Columbia, Canada.

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality globally. We determined the impact of 13-valent pneumococcal conjugate vaccine (PCV13) use on community-acquired pneumonia (CAP) rates eight years after the vaccine was introduced in the infant immunization program. METHODS: Using diagnostic codes from administrative databases, we calculated the overall and age-specific CAP incidence per month (2000-2018). Changes in the CAP incidence before and after the PCV13 vaccine program introduction were evaluated using negative binomial regression model adjusting for 7-valent pneumococcal conjugate vaccine program. RESULTS: The PCV13 vaccine infant immunization program was associated with declining CAP incidence among children aged 0-2 years (adjusted Incidence Rate Ratio (aIRR): 0.91; 95% CI: 0.87-0.96). Overall CAP incidence did not decrease in those aged 3-5 years (0.98; 95% CI: 0.93-1.04), 6-17 years (1.02; 95% CI: 0.97-1.08), 18-49 years (1.02; 95% CI:0.98-1.05), 50-64 years (1.07; 95% CI: 1.04-1.11), ≥65 years (1.05; 95% CI:1.02-1.08). CONCLUSIONS: The PCV13 infant immunization program is temporally associated with a reduction in CAP incidence in vaccine target age group. However, no significant decrease in CAP incidence in other age groups warrants further study of the etiology of CAP to develop and implement effective prevention programs.

Patterns of dental antibiotic prescribing in 2017: Australia, England, United States, and British Columbia (Canada).

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.

Appropriateness of Outpatient Antibiotic Use in Seniors across Two Canadian Provinces.

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. This study is the first in Canada to examine prescribing quality across two large-scale provincial healthcare systems to compare both quantity and quality of outpatient antibiotic use in seniors. Population-based analyses using administrative health databases were conducted in British Columbia (BC) and Ontario (ON), and all outpatient, oral antimicrobials dispensed to seniors (≥65 years) from 1 January 2000 to 31 December 2018 were identified. Antimicrobials were linked to an indication using a 3-tiered hierarchy. Tier 1 indications, which always require antibiotics, were given priority, followed by Tier 2 indications that sometimes require antibiotics, then Tier 3, which never require antibiotics. Prescription rates were calculated per 1000 population, and trends were examined overall, by drug class, and by patient demographics. Prescribing remained steady in both provinces, with 11,166,401 prescriptions dispensed overall in BC, and 27,656,014 overall in ON. BC prescribed at slightly elevated rates (range: 790 to 930 per 1000 residents), in comparison to ON (range: 745 to 785 per 1000 residents), throughout the study period. For both provinces, a Tier 3 diagnosis was the most common reason for antibiotic use, accounting for 50% of all indication-associated antibiotic prescribing. 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. Elevated prescribing to seniors continues across Canadian outpatient settings, and prescribing quality is of high concern, with 50% of all antimicrobials prescribed inappropriately for common infections that do not require antimicrobials.

Quantifying the Gap between Expected and Actual Rates of Antibiotic Prescribing in British Columbia, Canada.

Despite decades of stewardship efforts to combat antimicrobial resistance and quantify changes in use, the quality of antibiotic use in British Columbia (BC) remains unknown. As the overuse and misuse of antibiotics drives antibiotic resistance, it is imperative to expand surveillance efforts to examine the quality of antibiotic prescriptions. In late 2019, Canadian expected rates of antibiotic prescribing were developed for common infections. These rates were utilized to quantify the gap between the observed rates of prescribing and Canadian expected rates for antibiotic use for the province of BC. The prescribing data were extracted and matched to physician billing systems using anonymized patient identifiers from 1 January 2000 to 31 December 2018. Outpatient prescribing was further subdivided into community and emergency department settings and stratified by the following age groups: <2 years, 2-18 years, and ≥19 years. The proportions of physician visits that received antibiotic prescription were compared against the Canadian expected rates to quantify the unnecessary use for 18 common indications. Respiratory tract infections (RTI), including acute bronchitis, acute sinusitis, and acute pharyngitis, reported significant levels of overprescribing. Across all ages and health care settings, prescribing for RTI indications occurred at rates 2-8 times higher than the expected rates recommended by a group of expert Canadian physicians. Understanding the magnitude of unnecessary prescribing is a first step in delineating the provincial prescribing quality. The quantification of antibiotic overuse offers concrete targets for provincial stewardship efforts to reduce unnecessary prescribing by an average of 30% across both outpatient and emergency care settings.

Population-based incidence of invasive pneumococcal disease in children and adults in Ontario and British Columbia, 2002-2018: A Canadian Immunization Research Network (CIRN) study.

BACKGROUND: Invasive pneumococcal disease (IPD) burden, evaluated in Canada using reported confirmed cases in surveillance systems, is likely underestimated due to underreporting. We estimated the burden of IPD in Ontario and British Columbia (BC) by combining surveillance data with health administrative databases. METHODS: We established a cohort of 27,525 individuals in Ontario and BC. Laboratory-confirmed IPD cases were identified from Ontario's integrated Public Health Information System and the BC Centre for Disease Control Public Health Laboratory. Possible IPD cases were identified from hospitalization data in both provinces, and from emergency department visit data in Ontario. We estimated the age and sex adjusted annual incidence of IPD and pneumococcal conjugate/polysaccharide vaccine (PCV/PPV) serotype-specific IPD using Poisson regression models. RESULTS: In Ontario, 20,205 overall IPD cases, including 15,299 laboratory-confirmed cases, were identified with relatively stable age- and sex-adjusted annual incidence rates ranging from 13.7/100,000 (2005) to 13.6/100,000 (2018). In BC, 7,320 overall IPD cases, including 5,932 laboratory-confirmed cases were identified; annual incidence rates increased from 10.9/100,000 (2002) to 13.2/100,000 (2018). Older adults aged ≥ 85 years had the highest incidence rates. During 2007-2018 the incidence of PCV7 serotypes and additional PCV13 serotypes decreased while the incidence of unique PPV23 and non-vaccine serotypes increased in both provinces. CONCLUSIONS: IPD continues to cause a substantial public health burden in Canada despite publicly funded pneumococcal vaccination programs, resulting in part from an increase in unique PPV23 and non-vaccine serotypes.

Regional variation in the potentially inappropriate first-line use of fluoroquinolones in Canada as a key to antibiotic stewardship? A drug utilization review study.

BACKGROUND: Serious adverse effects of fluoroquinolone antibiotics have been described for more than decade. Recently, several drug regulatory agencies have advised restricting their use in milder infections for which other treatments are available, given the potential for disabling and possibly persistent side effects. We aimed to describe variations in fluoroquinolone use for initial treatment of urinary tract infection (UTI), acute bacterial sinusitis (ABS), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the outpatient setting across Canada. METHODS: Using administrative health data from six provinces, we identified ambulatory visits with a diagnosis of uncomplicated UTI, uncomplicated AECOPD or ABS. Antibiotic exposure was determined by the first antibiotic dispensed within 5 days of the visit. RESULTS: We identified 4,303,144 uncomplicated UTI events among 2,170,027 women; the proportion of events treated with fluoroquinolones, mostly ciprofloxacin, varied across provinces, ranging from 18.6% (Saskatchewan) to 51.6% (Alberta). Among 3,467,678 ABS events (2,087,934 patients), between 2.2% (Nova Scotia) and 11.2% (Ontario) were dispensed a fluoroquinolone. For 1,319,128 AECOPD events among 598,347 patients, fluoroquinolones, mostly levofloxacin and moxifloxacin, ranged from 5.8% (Nova Scotia) to 35.6% (Ontario). The proportion of uncomplicated UTI and ABS events treated with fluoroquinolones declined over time, whereas it remained relatively stable for AECOPD. CONCLUSIONS: Fluoroquinolones were commonly used as first-line therapies for uncomplicated UTI and AECOPD. However, their use varied widely across provinces. Drug insurance formulary criteria and enforcement may be a key to facilitating better antibiotic stewardship and limiting potentially inappropriate first-line use of fluoroquinolones.

Outpatient antibiotic use in British Columbia, Canada: reviewing major trends since 2000.

BACKGROUND: With 90% of all antibiotics in Canada being used in the community setting, tracking outpatient prescribing is integral to mitigate the issue of antimicrobial resistance. In 2005, a provincial programme was launched in British Columbia (BC) to disseminate information regarding the judicious use of antibiotics. These efforts include educational campaigns, updated practitioner guidelines and academic detailing. The impact of provincial stewardship on community prescribing requires ongoing evaluation. OBJECTIVES: This study examines outpatient prescribing to quantify rates of antibiotic use, evaluate major trends over time and identify new targets for stewardship. METHODS: A retrospective cohort design using population-level data. RESULTS: This study included over 3.5 million unique individuals with a total of 51 367 938 oral antibiotic prescriptions dispensed over a 19 year period (2000-18). Overall antibiotic utilization decreased by 23% over the course of the study period. This trend in the reduction of antibiotic prescription was observed across all major antibiotic classes, apart from the class of other antibacterials, which was mostly related to use of nitrofurantoin. The largest magnitudes of decreased prescribing were observed in the paediatric population. Prescribing across two distinct eras of provincial stewardship reaffirmed preliminary findings of programme efficacy, when compared with pre-stewardship levels of antibiotic use. CONCLUSIONS: Outpatient prescribing in BC is decreasing overall, and this study confirms an association between provincial stewardship interventions and improvements in antibiotic use. Pronounced declines in paediatric populations are promising, and further research is underway to examine prescribing quality.

Community Antibiotic Use at the Population Level During the SARS-CoV-2 Pandemic in British Columbia, Canada.

BACKGROUND: The objective of this study was to examine the aggregate rates of antibiotic use at the population level and compare these rates over time against historical averages to identify the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting control measures on community prescribing. METHODS: We collected antibiotic prescriptions and physician office visits from January 1, 2016, to July 21, 2020. We calculated monthly prescription rates stratified by sex, age group, profession, diagnosis type, and antibiotic class. We looked at monthly prescription rate as a moving average over time. Using the interrupted time series analysis method, we estimated the changes in prescription rates after March 2020. RESULTS: The moving average of overall monthly prescription rates during January-June 2020 was below the minimum of the historical years' moving averages (2016-2019). We observed a >30% reduction in overall monthly prescription rates in April, May, and July of 2020 compared with the same months of 2019. We observed that overall monthly prescription rates experienced a significant level change of -12.79 (P < .001) during the coronavirus disease 2019 pandemic after March 2020, with the greatest level change being -18.02 among children 1-4 years of age (P < .001). We estimated an average -5.94 (P < .001) change in respiratory tract infection (RTI)-associated monthly prescription rates after March 2020. Overall prescription rates comparing January-July 2019 and their 2020 counterparts showed a decrease in monthly prescribing ranging from -1 to -5 for amoxicillin, amoxicillin and enzyme inhibitors, azithromycin, clarithromycin, and sulfamethoxazole. CONCLUSIONS: In British Columbia, Canada, overall and RTI-specific monthly antibiotic prescription rates declined significantly during April-July 2020 compared with the same months in prepandemic years.

Outpatient prescribing and prophylactic antibiotic use for recurrent urinary tract infections in British Columbia, Canada.

INTRODUCTION: Urinary tract infection (UTI) is one of the most common infections, has frequent recurrences, and may debilitate quality of life. UTI is considered recurrent if there are three individual cases of UTI within 12 months. The objective of this study was to set a baseline for recurrent urinary tract infections (rUTI) in women, and rUTI-associated antibiotic prescribing in the presence of antimicrobial stewardship efforts. METHODS: Data for rUTI in women were organized through a provincial prescription database, physician billing system, and a consolidation file to combine antibiotic prescribing, diagnoses, and patient demographics. Rates of rUTI cases and prescriptions were examined, and trends of antibiotics were separated by major anatomical therapeutic chemical classes. RESULTS: A total of 2 234 903 rUTI-associated prescriptions were dispensed for 674 785 rUTI cases from 2008-2018; 2 205 703 prescriptions were for treatment and 29 310 prescriptions were for prophylaxis of rUTI. The prevalence of rUTI cases declined by 59%, while overall rUTI-associated antibiotic prescribing decreased by 73%. The greatest decrease was seen in quinolones (87%), while nitrofurantoin became the most common rUTI antibiotic dispensed, accounting for 42% of prescriptions overall. CONCLUSIONS: Implementation of numerous antimicrobial stewardship efforts may have contributed to the decrease in antibiotic prescribing, particularly for quinolones. In line with local antibiograms and guidelines, nitrofurantoin is the most used antibiotic for rUTI by far, distinctly preferred over other antibiotics secondary to the lack of E. coli resistance.

Impact of the 13-valent pneumococcal conjugate vaccine on acute otitis media and acute sinusitis epidemiology in British Columbia, Canada.

BACKGROUND: Numerous studies have characterized the 13-valent pneumococcal conjugate vaccine (PCV13) programme's beneficial effects on acute otitis media (AOM) and acute sinusitis (AS) rates in children; however, few studies have examined the impact on adults. OBJECTIVES: This retrospective cohort study evaluates the overall effect of the PCV13 immunization programme on the incidence of AOM and AS at the population level. METHODS: Health administrative databases were linked to assess outpatient visits, hospitalizations and antibiotic utilization from 2000 to 2018. Multivariable Poisson regression was used to evaluate the impact of the PCV13 vaccine programme (2011-18) compared with the pre-PCV13 era (2000-10), overall and by age. RESULTS: From 2000 to 2018, the incidence of AOM decreased by 50% (62 to 31 per 1000 population) while sinusitis decreased by 18% (33 to 27 per 1000 population). In the PCV13 era, the incidence of AOM declined [incidence rate ratio (IRR): 0.70; 95% CI: 0.70-0.70], in parallel with decreased incidence of antibiotic utilization (IRR: 0.65; 95% CI: 0.64-0.65). A reduction was also observed in the incidence of AS during the PCV13 era compared with the pre-PCV13 era (IRR: 0.88; 95% CI: 0.88-0.88), mainly driven by declines among those younger than 65 years of age. In contrast, an increase in AS incidence was noted in individuals aged ≥65 years (IRR: 1.03; 95% CI: 1.02-1.03). A decrease in antibiotic prescription rates for sinusitis was observed for those under 65 years of age. CONCLUSIONS: The PCV13 immunization programme is associated with a reduction in the incidence of AOM and AS. Moreover, the associated use of antibiotics for these diagnoses has comparably decreased across paediatric, as well as adult populations.

Incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate pneumococcal vaccine in British Columbia: A retrospective cohort study.

BACKGROUND: A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period. METHODS: Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras. RESULTS: Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era. CONCLUSIONS: A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.

The protective effect of pneumococcal vaccination on cardiovascular disease in adults: A systematic review and meta-analysis.

BACKGROUND: Epidemiological studies suggest that there is a link between pneumococcal infection and adverse cardiovascular outcomes such as myocardial infarction. Multiple studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. Therefore, a meta-analysis was conducted to summarize available evidence on the impact of PPV23 on cardiovascular disease. METHODS: A literature search from January 1946 to September 2019 was conducted across Embase, Medline and Cochrane. All studies were included that evaluated PPV23 compared with a control (placebo, no vaccine or another vaccine) for any cardiovascular events, including: myocardial infarction (MI), heart failure and cerebrovascular events. Risk ratios (RRs) were pooled using random effects models. RESULTS: Eighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91; 95% CI: 0.84-0.99), and MI (RR: 0.88; 95% CI: 0.79-0.98) in all age groups, with a significant effect in those aged ≥65 years, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95% CI: 0.68-0.88), specifically in those aged ≥65 years (RR: 0.71; 95% CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination. CONCLUSIONS: Polysaccharide pneumococcal vaccination decreased the risk for some adverse cardiovascular events, specifically acute MI in the vaccinated population, particularly for those individuals aged ≥65 years. It would be highly beneficial to vaccinate the population who is at greater risk of cardiovascular diseases.

Impacts of Human Papillomavirus Immunization Programs on Rates of Anogenital Warts in British Columbia, Canada, 2000 to 2017.

BACKGROUND: In 2008, British Columbia (BC) implemented a school-based quadrivalent human papillomavirus (HPV-4) immunization program for girls born in 1994 or later. In 2015, an expanded clinic-based program included men who report sex with men (MSM) born in 1989 or later. To evaluate the impacts of HPV-4 programs on anogenital warts (AGWs), diagnosis rates were measured among women who report sex with men (WSM), men who report sex with women (MSW), and MSM. METHODS: Diagnoses of AGW were ascertained from 16 sexually transmitted infection clinics. Rates were calculated as new AGW diagnoses over person-years (py) at risk and stratified by age group, calendar period, and birth cohort. Adjusted relative rates (aRR) were estimated using multivariable Poisson regression. RESULTS: There were 204,832 clinic visits by 85,158 individuals: 28,366 (33%) WSM, 35,688 (42%) MSW, and 14,534 (17%) MSM. After adjusting for age and period, AGW rates in the 1994-1996 birth cohort decreased by 56% overall (1.21 vs. 2.72 cases/100 py; aRR, 0.44; 95% confidence interval [CI], 0.34-0.59), 65% among WSM (0.97 vs. 2.77 cases/100 py; aRR, 0.35; 95% CI, 0.22-0.57), 58% among MSW (1.60 vs. 3.78 cases/100 py; aRR, 0.42; 95% CI, 0.28-0.65), and 41% among MSM (1.14 vs. 1.19 cases/100 py; aRR, 0.59; 95% CI, 0.38-0.91) versus the 1991-1993 birth cohort. CONCLUSIONS: The HPV-4 programs had significant impacts on lowering AGW rates in BC. The greatest decrease was among WSM eligible for the school-based program, followed by birth cohorts of men who likely have sex with HPV-4 eligible women. The smallest decrease among MSM may reflect the later introduction of the clinic-based program.