Canadian Antimicrobial Resistance Surveillance System Report 2021

Table of contents

• Glossary
• Introduction
• Executive summary
• Key findings
• Technical annex
  • Methicillin-resistant Staphylococcus aureus bloodstream infections
  • Vancomycin-resistant Enterococcus (VRE) bloodstream infections
  • Carbapenemase-producing Enterobacterales (CPE) infections and colonization
  • Clostridioides difficile infections (CDI)
  • Neisseria gonorhoeae (GC) infections
  • Mycobacterium tuberculosis (TB) infections
  • Invasive Streptococcus pneumonia diseases (IPD)
  • Invasive Streptococcus pyogenes (group A Streptococcus) infections
• Antimicrobial consumption by humans, Canada 2015-2019
  • Key findings
  • Overall antimicrobial consumption by humans: National perspective
  • Overall antimicrobial consumption by humans: Canadian jurisdiction
  • Overall antimicrobial consumption by humans: Top 5 antimicrobial classes
  • Overall antimicrobial consumption by humans: AWaRe categorization
  • Overall antimicrobial consumption by humans: International perspective
  • Antimicrobial consumption by humans in the community sector: Defined daily doses
  • Antimicrobial consumption by humans in the community sector: Prescriptions filled
  • Antimicrobial consumption by humans in the community sector: Prescription origin
  • Antimicrobial consumption by humans in the community sector: Carbapenems dispensed
  • Antimicrobials purchased by the hospital sector: Defined daily doses
• Antimicrobial prescribing in the community sector, before and during the COVID-19 pandemic
  • Key findings
• Antimicrobials intended for use in animals in Canada
  • Key findings
  • Antimicrobials sold for use in animals
  • Antimicrobials sold for use in animals: International perspective
  • Indication for antimicrobial use in animals (farm-level surveillance)
  • Integrating information on antimicrobials intended for use across sectors (humans, animals and crops)
• Authors
• Appendices
• Footnotes
• References

Glossary

AMR

Antimicrobial resistance

AMU

Antimicrobial use

ARO

Antimicrobial-resistant organism

AST

Antimicrobial susceptibility testing

ATC

Anatomical therapeutic chemical

BSI

Bloodstream infection

CA

Community-associated

CAHI

Canadian Animal Health Institute

CARSS

Canadian Antimicrobial Resistance Surveillance System

CDI

Clostridioides difficile infection

CIPARS

Canadian Integrated Program for Antimicrobial Resistance Surveillance

CNDSS

Canadian Notifiable Disease Surveillance System

CNISP

Canadian Nosocomial Infection Surveillance Program

CPE

Carbapenemase-producing Enterobacteriaceae

CTBLSS

Canadian Tuberculosis Laboratory Surveillance System

DDD

Defined Daily Dose

DDDvetCA

Veterinarian-Defined Daily Dose Canadian standard

ESAC-Net

European Surveillance of Antimicrobial Consumption Network

eSTREP

National Laboratory Surveillance of Invasive Streptococcal Disease

ESVAC

European Surveillance of Veterinary Antimicrobial Consumption

GAS

Group A Streptococcus pyogenes

GASP–Canada

Gonococcal Antimicrobial Surveillance Program – Canada

HA

Healthcare-associated

Kg

Kilogram

KPC

Klebsiella pneumoniae carbapenemase

MDR

Multidrug-resistant

mg/PCU

Milligrams per population correction unit

MIC

Minimum inhibitory concentration

MLST

Multi-locus sequence typing

MRSA

Methicillin-resistant Staphylococcus aureus

NAP

North American pulse type

NDM

New Delhi metallo-β-lactamase

NIHB

Non-Insured Health Benefits

NML

National Microbiology Laboratory

OXA

Oxacillinase

PCU

Population corrected unit

PHAC

Public Health Agency of Canada

PMRA

Pest Management Regulatory Agency

SME

Serratia marcescens enzyme

ST

Sequence type

TB

Tuberculosis (Mycobacterium tuberculosis)

VRE

Vancomycin-resistant Enterococcus

WHO

World Health Organization

XDR

Extensively drug-resistant

Introduction

Antimicrobial resistance (AMR) is an increasing threat to global heath and is recognized by the World Health Organization and the United Nations as one of the top ten global health threats facing humanity. Globally, an estimated 4.95 million deaths in 2019 were associated with antimicrobial-resistant bacterial infections, of which 1.27 million deaths were directly attributable to AMR (Murray et al., 2022). In Canada, it was estimated that in 2018, over one-quarter of bacterial infections were resistant to at least one antibiotic and that 14,000 Canadian deaths were associated with AMR, of which AMR was directly responsible for 5,400 (Canadian Council of Academies, 2019). As increasing levels of AMR threaten the continued effectiveness of antimicrobial therapies, efforts must be made to develop and access new antimicrobials, as well as preserve the effectiveness of existing antimicrobials through improvements to their judicious use; otherwise, the delivery of common procedures, including chemotherapy, caesarian sections and invasive surgery, will be jeopardized.

The 2021 Canadian Antimicrobial Resistance Surveillance System (CARSS) report presents an integrated view of available national-level data on antimicrobial resistance (AMR) and antimicrobial use (AMU) generated by the Public Health Agency of Canada (PHAC) and its partners from human populations and animal populations. While it must be acknowledged that there is always opportunity to further strengthen the AMR and AMU data included in this report, data from these contributing surveillance systems can be used to detect changes in epidemiological trends over time associated with AMR in priority organisms and AMU in humans and animals.

Addressing AMR in Canada requires a coordinated multi-sectoral response from partners in government, human health, animal health, agri-food, industry, academia, professional associations and the general public. While there are many areas that warrant further attention in Canada, PHAC is committed to improving the surveillance of AMR and AMU in priority areas. This includes:

• Capturing AMR and AMU trends in key under-represented rural and remote regions by recruiting additional hospitals and expanding surveillance into regions that are currently not represented by PHAC data.
• Assessing the burden of AMR and the appropriateness of AMU in older Canadians, the highest prescribed age group by far, by gathering data from long-term care to further determine the risk posed for to this specific at-risk population group.
• Detecting and monitoring the spread of AMR in Canada by integrating diagnostic laboratory data generated by provincial, territorial and private public health partners to identify new AMR threats.
• Monitoring trends of AMU in populations through wastewater-based epidemiology to allow for more targeted trends analysis and interventions.
• Improving our knowledge of populations impacted by antimicrobial-resistant gonorrhea to better inform interventions and prevent further spread.
• Initiating the surveillance of AMR and AMU in the community setting through the use of de-identified electronic medical records to investigate the burden of AMR in the primary care setting and identity inappropriate prescribing practices.
• Improving the detection of AMR threats in the food chain by expanding agri-food surveillance to include beef and dairy cow farms, and increasing the number of retail meat-products tested for AMR.

The surveillance findings presented in this report largely reflect the pre-pandemic period. The effects of the COVID-19 pandemic on AMR and AMU in Canada are only now beginning to emerge, and are likely to be complex. For example, while outpatient AMU appears to have decreased in the early stages of the pandemic, the inappropriate use of antimicrobials (a primary driver of AMR) in acute-care settings may have increased as a result of real or perceived risks of COVID-19 bacterial co-infection. Additionally, risks associated with healthcare resource constraints (e.g. reallocated or insufficient staffing) may have limited AMR surveillance activities, preventing a timely response to potential AMR threats. Conversely, heightened infection prevention and control measures enacted to prevent the spread of COVID-19 may have the collateral benefit of preventing the spread of AMR, and the overall decrease in the number of Canadians admitted to hospitals may consequently reduce the frequency of healthcare-acquired infections. To date, the net effect of pandemic-related factors on the burden of AMR in Canada remains unknown.

Through the response to COVID-19, Canada has strengthened multi-sectoral collaboration and public health capacity, and is better positioned to address emerging and future public health threats, including AMR. The additional surveillance actions being undertaken will serve to further strengthen the gathering and analysis of AMR and AMU trends to inform the development of additional targeted interventions to address the growing threat posed by AMR.

Executive summary

This 2021 Canadian Antimicrobial Resistance Surveillance System (CARSS) report builds on previously published data and methodologies, prioritizing data acquired by the Public Health Agency of Canada and its partners on antimicrobial resistance and antimicrobial use in humans, animals and crops.

While most of the information in this report predates the COVID-19 pandemic, these data will contribute to the pre-COVID-19 trends of AMR and AMU in Canada and will come to serve as an important reference for future analyses.

Summary of results between 2015 and 2019 (unless otherwise stated)

Antimicrobial resistance in humans:

Resistance rates increased for 3 of the 4 priority organisms monitored in hospitalized inpatients: methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), vancomycin-resistant Enterococcus (VRE)-BSI and carbapenemase-producing Enterobacterales (CPE); but decreased for Clostridioides difficile infection.
Other trends of specific concern include:

• While MRSA-BSIs have traditionally been associated with hospitalizations, the rate of community-associated MRSA-BSIs more than doubled.
• The number of patients testing positive for CPE (with or without signs of infection) increased by 250%.

For infections typically acquired in the community sector, the main concern is a 44% increase in the rate of multidrug-resistant gonorrhoea.
Other trends include:

• The proportion of vaccine-preventable (PCV-13) multidrug-resistant invasive Streptococcus pneumoniae infections increased by 25% (2014 to 2018), but remained universally susceptible to penicillin.
• Rates of AMR in culture-positive Mycobacterium tuberculosis remained stable.

Antimicrobial use in humans:

Overall, antimicrobial use (AMU) decreased by 5%, however there are some areas of concern:

• Antimicrobial prescribing in seniors aged 80 years or more increased by 13%.
• The community use of carbapenems, the broadest spectrum antimicrobials available, increased by 68%.
• The per capita consumption of "Reserve" category antimicrobials^{Footnote 1} increased by 2%.

Antimicrobial prescribing in the community sector during the first 8 months of the COVID-19 pandemic was lower compared to previous years. This trend appears to be related to a decrease in the number of physician visits during this time.

• The overall rate of antimicrobial prescribing decreased by up to 40%.
• The largest decrease in the rate of antimicrobial prescribing was observed in the pediatric populations (by 70%); however, the rate of antimicrobial prescribing in seniors (aged 80 years or more) only decreased by 28%.

Antimicrobial use in animals^{Footnote 2}:

In 2019, approximately 1 million kilograms of antimicrobials were sold for use in animals, which represents 78% of all antimicrobials distributed in Canada (compared to 79% in 2018). Other trends include:

• Overall, the tonnage of active antimicrobial ingredients sold for use in production animals decreased by 11% between 2018 and 2019.
• Adjusted for animal populations and weights, animals in Canada consumed nearly 3-times as many antibiotics in 2019 compared to the median value reported by 31 European countries in 2018.

Key findings

This trend summary provides a high-level interpretation drawn from clinical, epidemiological and/or resistance information available at the time of publication. More information can be found in the Technical annex.

Trend summary

Trend summary provides a high-level interpretation drawn from clinical, epidemiological and/or resistance information

Topic	Reporting years	Trend
Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections	2015-2019	Getting Worse
Vancomycin-resistant Enterococcus (VRE) bloodstream infections	2015-2019	Getting Worse
Carbapenemase-producing Enterobacterales (CPE) infection and colonization	2015-2019	Getting Worse
Clostridioides difficile infections (CDI)	2015-2019	Getting Better
Neisseria Gonorrhoeae (GC) infections	2015-2019	Getting Worse
Drug-resistant Mycobacterium tuberculosis (TB) infections	2015-2019	Stable
Invasive Streptococcus pneumoniae diseases (IPD)	2014-2018	Getting Worse
Invasive Streptococcus pyogenes infections (Group A Streptococcus)	2014-2018	Stable
Antimicrobial use in humans	2015-2019	Caution
Antimicrobials intended for use in animals	2015-2019	Caution
Impact of COVID-19 on antimicrobial use in humans	2019-2020	Trending down

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI): 2015-2019

• The rate of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) increased by 57%, driven by a 125% increase in community-associated (CA)-MRSA.
• 18% of MRSA-BSI cases died within 30 days of diagnosis (all-cause mortality).
• All MRSA blood isolates remained susceptible to linezolid and vancomycin. Resistance remained high for clindamycin, erythromycin and resistance to tetracycline doubled.

In total:

• 61 to 69 reporting hospitals
• 3,333 MRSA-BSI cases
• 589 deaths

Source:

• The Canadian Nosocomial Infection Surveillance Program (CNISP)

Figure a: Text description

Year	2015	2016	2017	2018	2019
HA-MRSA-BSI (10,000 patient-days)	0.39	0.43	0.44	0.51	0.45
CA-MRSA-BSI (1,000 patient-admissions)	0.19	0.26	0.25	0.37	0.43

Vancomycin-resistant Enterococcus (VRE) bloodstream infections (BSI): 2015-2019

• The rate of healthcare-associated (HA) VRE-BSI doubled.
• Daptomycin resistance increased from 0.0% in 2015 to 4.3% in 2019
• 34% of HA-VRE-BSI cases died within 30 days of diagnosis (all-cause mortality).

In total:

• 57 to 68 reporting hospitals
• 773 HA-VRE-BSI cases
• 275 deaths

Source:

• The Canadian Nosocomial Infection Surveillance Program (CNISP)

Figure b: Text description

Year	2015	2016	2017	2018	2019
HA-VRE-BSI	0.13	0.17	0.22	0.31	0.26

Carbapenemase-producing Enterobacterales (CPE) infections and colonization: 2015-2019

• The rate of healthcare-associated (HA) CPE colonization tripled.
• While the number of HA-CPE infections remained low, the rate of HA-CPE infection more than doubled.
• 21% of patients with HA-CPE infection died within 30 days of diagnosis (all-cause mortality).
• CPE remains highly resistant to most antimicrobials.

In total:

• 58 to 72 reporting hospitals
• 110 HA-CPE infections
• 23 deaths

Source:

• The Canadian Nosocomial Infection Surveillance Program (CNISP)

Figure c: Text description

Year	2015	2016	2017	2018	2019
HA-CPE infection	0.02	0.02	0.02	0.04	0.05
HA-CPE colonization	0.04	0.10	0.12	0.18	0.16

Clostridioides difficile infections (CDI): 2015-2019

• The rate of healthcare-associated (HA) Clostridioides difficile infections (CDI decreased by 22%.
• 2.4% of HA-CDI cases died within 30 days of diagnosis (attributable mortality).
• The rate of community-associated (CA) CDI decreased by 22%.

In total:

• 66 to 73 reporting hospitals
• 19,579 CDI cases (HA + CA)
• 1,684 deaths (estimated)
• 450 attributable to CDI (estimated)

Source:

• The Canadian Nosocomial Infection Surveillance Program (CNISP)

Figure d: Text description

Year	2015	2016	2017	2018	2019
HA-CDI (10,000 patient-days)	4.63	4.39	4.19	3.94	3.62
CA-CDI (1,000 patient-admissions)	1.50	1.34	1.37	1.36	1.17

Neisseria Gonorrhoeae infections: 2015-2019

• The rate of gonorrhea infection increased by 70%.
• The proportion of cultured multidrug-resistant (MDR) Neisseria gonorrhoeae (GC) isolates increased by 44%
• Eleven cases of extensively drug-resistant (XDR) gonococci were identified in Canada

In total:

• 142,633 reported cases
• 24,484 tested for AMR
• 2,489 MDR cases

Source: The Gonococcal Antimicrobial Surveillance Program (GASP-Canada) and the Canadian Notifiable Disease Surveillance System

Figure e: Text description

Year	2015	2016	2017	2018	2019
Total isolates tested (n)	(n = 4,190)	(n = 4,538)	(n = 5,290)	(n = 5,607)	(n = 4,859)
Number of MDR isolates	361	406	645	446	601
Percentage of MDR isolates	9%	9%	12%	8%	12%

Drug-resistant Mycobacterium tuberculosis (TB) infections: 2015-2019

• The rate of TB infection in Canada remained stable at approximately 4.8 cases per 100,000 population.
• The proportion of culture-positive TB isolates resistant to one or more anti-TB drug was 10% in 2019.
• The proportion of multidrug-resistant (MDR) culture-positive TB isolates^{Footnote 3} was 1.3% in 2019.
• Only one case of extensively drug-resistant (XDR) TB has been reported since 2015.

In total:

• 7,361 TB cases
• 701 resistant culture-positive TB cases
• 95 multidrug-resistant (MDR-TB) cases

Source:

• The Canadian Tuberculosis Laboratory Surveillance Program (CTBLSS)

Figure f: Text description

Year	2015	2016	2017	2018	2019
Mono-resistant TB	8.5%	7.4%	6.8%	8.3%	8.9%
Poly-resistant TB	0.2%	0.3%	0.4%	0.3%	0.3%
Multidrug-resistant TB	1.6%	1.2%	0.9%	1.4%	1.2%
Extensively drug-resistant TB	0.0%	0.0%	0.0%	0.1%	0.0%

Streptococcus pneumoniae - invasive pneumococcal diseases (IPD): 2014-2018

• The rate of invasive pneumococcal disease (IPD) increased from 9.0 to 10.9 cases per 100,000 population.
• The proportion of multidrug resistance (i.e. Streptococcus pneumoniae isolates resistant to three or more classes of antimicrobials) identified in vaccine preventable (PCV13) IPD cases increased by 25%, from 9.2% to 11.5%.
• The proportion of multidrug resistant (MDR) isolates identified in non-vaccine preventable (non-PCV13) IPD cases increased by 74%.

In total:

• 17,182 cases of IPD
• 1,220 cases of MDR-IPD (estimated)

Source:

• The National Surveillance of Invasive Streptococcal Disease (eSTREP) and the Canadian Notifiable Disease Surveillance System (CNDSS)

Figure g: Text description

Year	2014	2015	2016	2017	2018
MDR (PCV13 serotypes)	9.2%	12.3%	10.2%	14.6%	11.5%
MDR (Non-PCV13 serotypes)	3.5%	4.8%	4.8%	7.8%	6.1%

Invasive Streptococcus pyogenes – Group A Streptococcus (iGAS) infections: 2014-2018

• The rate of invasive Group A Streptococcus (iGAS) infections increased by 65%.
• All Streptococcus pyogenes isolatestested were susceptible to penicillin.

In total:

• 11,310 cases of GAS
• 0 cases resistant to penicillin

Source:

• The National Surveillance of Invasive Streptococcal Disease (eSTREP) and the Canadian Notifiable Disease Surveillance System (CNDSS)

Figure h: Text description

Year	2014	2015	2016	2017	2018
Penicillin (resistance)	0.0%	0.0%	0.0%	0.0%	0.0%
Erythromycin (resistance)	7.1%	8.3%	8.8%	9.9%	9.6%
Clindamycin (resistance)	2.6%	3.2%	3.9%	6.8%	3.5%

Antimicrobial use in humans: 2015-2019

• The consumption of antimicrobials by humans decreased by 5%.
• Seniors aged 80 years or more continued to have the highest rates of antimicrobial prescribing in the community sector, increasing by 13%.
• The rate of community prescribing for carbapenem-class antimicrobials increased by 68%.

In total:

• 207.6 million defined daily doses were filled by community retail pharmacies in 2019
• 16.4 million defined daily doses purchased by hospitals in 2019

Source:

• IQVIA, Indigenous Services Canada, Statistics Canada and the World Health Organization

Figure i: Text description

Year	2015	2016	2017	2018	2019
0 to 18	539.9	556.1	530.6	526.7	490.9
19 to 44	582.5	570.0	554.1	547.7	528.4
45 to 64	611.9	626.3	645.5	649.6	628.6
65 to 79	903.6	873.7	875.7	883.1	859.3
80+	1090.4	1161.3	1246.1	1266.3	1230.7

Antimicrobials intended for use in animals

• The number of kilograms of active antimicrobial ingredients sold for use in production animals decreased by 11% between 2018 and 2019.
• Between 2018 and 2019:
  • antimicrobial sales for use in pigs, poultry, and fish decreased;
  • antimicrobial sales for use in cattle, horses, companion animals and small ruminants increased.
• In 2019, Canada distributed the eighth highest quantity of antimicrobials intended for use in animals compared to the latest data from 31 European countries.

In total:

• 975,000 kilograms of antimicrobials distributed

Sources:

• The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), the Canadian Animal Health Institute (CAHI), Health Canada (HC) and the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC), Fisheries and Oceans Canada, Statistics Canada, Agriculture and Agri-Food Canada, Equestrian Canada, Chicken Farmers of Canada, Egg Farmers of Canada, Canadian Hatching Egg Producers, and Canfax.

Notes:

• As of December 1st, 2018, HC regulations require manufacturers, importers and compounders to report annual sales of medically important antimicrobials intended for use in animals. This data replaces the data historically provided on a voluntary basis by CAHI. Trends across these data sources should be interpreted with caution.
• The use of antimicrobial growth promoters have transitioned to medically important antimicrobials.
• The PCU (Population correction unit) accounts for the size of the animal population, including the number and average weight at treatment. Mg/PCU (milligrams per PCU) is the mg of antimicrobials sold or used in animals divided by the population correction unit. This excludes ionophores and chemical coccidiostats.

Figure j: Text description

Data for figure	Total (kg)	Total (mg/PCUEU—European weights)	Total (mg/PCUCA—Canadian weights)
2015 (CAHI)	1187135.8	183.0	175.2
2016 (CAHI)	1051010.0	160.0	154.2
2017 (CAHI)	934872.7	141.2	136.8
2018 (VASR)	1082768.0	162.9	150.3
2019 (VASR)	968985.0	143.0	131.7

Special analysis: Antimicrobial prescribing in humans during the COVID-19 pandemic

To describe the impact of the COVID-19 pandemic on human antimicrobial consumption in Canada, the monthly rate of prescriptions in 2020 was compared against the same month in 2019. March was selected as the beginning of the Canadian COVID-19 pandemic, corresponding with the closure of the Canada-United States land boarder.

• Between March and October 2020, the overall rate of antimicrobial prescribing in the community sector decreased by 26%.
• The overall rate of antimicrobial prescribing in the community decreased by a maximum of 40% in May 2020.

The rate of antimicrobial prescribing to pediatrics decreased by a maximum of 70%, compared to a maximum of 29% in seniors aged 80 years or more.

Figure k: Text description

Month	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct	Nov	Dec
Year 2019	60.0	49.7	54.7	54.0	52.7	46.7	47.5	45.2	47.9	54.2	51.7	57.6
Year 2020	61.3	50.6	48.4	33.4	31.9	35.2	36.9	35.6	36.8	38.1	n/a	n/a

Technical annex

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI): 2015-2019

Key findings

• The rate of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) more than doubled between 2015 and 2019.
• 18% of MRSA-BSI cases identified between 2015 and 2019 died within 30 days of diagnosis (all-cause mortality).
• All MRSA blood isolates were susceptible to vancomycin and linezolid.

Figure 1: Text description

Year	2015	2016	2017	2018	2019
HA-MRSA-BSI (10,000 patient-days)	0.39	0.43	0.44	0.51	0.45
CA-MRSA-BSI (1,000 patient-admissions)	0.19	0.26	0.25	0.37	0.43

Healthcare-associated (HA) MRSA-BSI results

Between 2015 and 2019, the rate of HA-MRSA-BSI increased by 15.4%, from 0.39 to 0.45 cases per 10,000 patient-days. For all cases of HA-MRSA-BSI identified between 2015 and 2019, all-cause mortality within 30 days of diagnosis was 22.1%.

In 2019, laboratory results were available for 79.3% of reported HA-MRSA-BSI cases. Between 2015 and 2019, the proportion of strain type CMRSA 2 decreased from 56.3% to 36.1%, CMRSA 7 increased from 5.0% to 6.1% and CMRSA 10 increased from 26.6% to 37.5%.

Canadian standard, American standard and sector

Canadian standard	American standard	Sector
CMRSA2	USA100/USA800	Historically healthcare-associated
CMRSA7	USA400	Historically community-associated
CMRSA10	USA300

Between 2015 and 2019, all HA-MRSA blood isolates were susceptible to vancomycin (the most used antimicrobial in this setting) and less than 1% were non-susceptible to daptomycin. The overall MRSA susceptibility pattern for 2019, including those antimicrobials that are not used for bloodstream MRSA infections was as follows: no resistance to linezolid was detected and the prevalence of resistance to tetracycline (6.9%), rifampin (2.3%) and trimethoprim-sulfamethoxazole (1.1%) was low. Resistance to tetracycline increased by 115.6%, from 3.2% to 6.9% between 2015 and 2019.

Table 1: Antimicrobial resistance patterns from healthcare-associated methicillin-resistant Staphylococcus aureus blood isolates, Canada, 2015-2019

Proportion (%) of resistant isolates per year
Year	2015	2016	2017	2018	2019
Isolates tested (n)	219	273	296	334	261
Ciprofloxacin	80.4	78.4	77.0	74.6	72.0
Clindamycin	66.7	48.0	47.6	50.3	49.2
Daptomycin	0.0	1.1	0.7	0.0	0.0
Erythromycin	84.0	79.9	80.7	76.9	75.1
Linezolid	0.0	0.0	0.0	0.0	0.0
Rifampin	0.5	2.6	1.0	0.9	2.3
Tetracycline	3.2	4.8	5.4	4.5	6.9
Tigecycline	0.9	0.0	0.0	0.0	0.0
Trimethoprim-sulfamethoxazole	1.8	1.5	1.4	0.9	1.1
vancomycin	0.0	0.0	0.0	0.0	0.0

A subset of isolates were tested against ciprofloxacin in 2015 and clindamycin in 2019. Some antimicrobials are presented for epidemiological purposes only. Daptomycin and tigecycline are reported as non-susceptible.

Community-associated MRSA-BSI results

Between 2015 and 2019, the rate of CA-MRSA-BSI increased by 126.3%, from 0.19 to 0.43 cases per 1,000 patient-admissions. For all cases of CA-MRSA-BSI identified between 2015 and 2019, all-cause mortality within 30 days of diagnosis was 13.3%.

In 2019, laboratory results were available for 71.4% of reported CA-MRSA-BSI cases identified in hospital inpatients. Between 2015 and 2019, the proportion of strain type CMRSA 2 increased from 13.0% to 15.2%, CMRSA 7 increased from 11.0% to 14.4% and CMRSA 10 decreased from 62.3% to 59.2%.

Between 2015 and 2019, all CA-MRSA blood isolates were susceptible to vancomycin (the most used antimicrobial in this setting) and less than 1% were non-susceptible to daptomycin. The overall MRSA susceptibility pattern for 2019, including those antimicrobials that are not used for bloodstream infections was as follows: no resistance to linezolid and rifampin was detected and the prevalence of resistance to tetracycline (6.6%) and trimethoprim-sulfamethoxazole (1.6%) was low.

Table 2: Antimicrobial resistance patterns from community-associated methicillin-resistant Staphylococcus aureus blood isolates, Canada, 2015-2019

Proportion (%) of resistant isolates per year
Year	2015	2016	2017	2018	2019
Isolates tested (n)	154	228	232	334	320
Ciprofloxacin	81.1	75.4	76.3	69.2	68.1
Clindamycin	36.4	39.5	36.6	33.2	29.4
Daptomycin	0.6	0.9	1.3	0.0	0.0
Erythromycin	77.9	75.9	81.0	73.4	76.3
Linezolid	0.0	0.0	0.0	0.0	0.0
Rifampin	0.6	1.3	2.6	0.9	0.0
Tetracycline	3.9	7.5	7.8	9.9	6.6
Tigecycline	0.6	0.0	0.0	0.0	0.0
Trimethoprim-sufamethoxazole	1.3	2.6	1.3	3.3	1.6
Vancomycin	0.0	0.0	0.0	0.0	0.0

A subset of isolates were tested against ciprofloxacin in 2015 and daptomycin in 2019. Some antimicrobials are presented for epidemiological purposes only. Daptomycin and tigecycline reported as non-susceptible.

Data source: Canadian Nosocomial Infection Surveillance Program (61 to 69 reporting hospitals).

Methodology has been previously published in the 2020 CARSS Report.

Vancomycin-resistant Enterococcus bloodstream infections: 2015-2019

Key findings

• The rate of healthcare-associated (HA) vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) doubled between 2015 and 2019, decreasing 16% between 2018 and 2019.
• 34% of HA-VRE-BSI cases identified between 2015 and 2019 died within 30 days of diagnosis (all-cause mortality).

Healthcare-associated VRE-BSI results

Between 2015 and 2019, the rate of HA-VRE-BSI doubled (0.13 to 0.26 per 10,000 patient-days), despite a decrease of 16.1% between 2018 and 2019 (0.31 to 0.26 per 10,000 patient-days). For all cases of HA-VRE-BSI identified between 2015 and 2019, all-cause mortality within 30 days of diagnosis was 33.6%. In 2019, 86.6% of all reported VRE-BSI were healthcare-associated, down from 96.3% in 2015.

Figure 2: Text description

Year	2015	2016	2017	2018	2019
HA-VRE-BSI	0.13	0.17	0.22	0.31	0.26

Healthcare-associated VRE-BSI in adult and pediatric populations

While the number of HA-VRE-BSI identified in pediatric hospitals between 2015 and 2019 was low (n=19), the rate increased by over 700% (0.03 to 0.25 cases per 10,000 patient-days). During the same time-period, the rate of HA-VRE-BSI identified in adult hospitals more than doubled (from 0.16 to 0.35 cases per 10,000 patient-days), noting a decrease of 22.2% between 2018 and 2019 (0.45 to 0.35 per 10,000 patient-days). The increases reported in pediatric hospitals in 2019 was limited to two hospitals and preliminary 2020 rates indicate a significant decrease.

Multi-locus sequence typing (MLST) and antimicrobial susceptibility testing

In 2019, the organisms identified as causing HA-VRE-BSI were 98.8% E. faecium and 1.2% E. faecalis; MLST and antimicrobial susceptibility testing results were available for 98.2% of E. faecium isolates. ST1478 remained the predominant strain type (32.7%), followed by ST734 (11.5%) and ST117 (9.7%).

In 2019, daptomycin non-susceptibility remained detectable (4.3%), resistance to high-level gentamicin remained high (30.4%) and resistance to linezolid increased (0.0% in 2015 to 2.2% in 2019).

Table 3: Antimicrobial resistance patterns from vancomycin-resistant Enterococcus faecium blood isolates, Canada, 2015-2019

Proportion (%) of resistant isolates per year
Year	2015	2016	2017	2018	2019
Isolates tested (n)	73	83	108	159	138
Ampicillin	100.0	100.0	100.0	100.0	100.0
Chloramphenicol	0.0	2.4	9.3	2.5	17.4
Ciprofloxacin	100.0	100.0	100.0	100.0	100.0
Daptomycin	0.0	8.4	8.3	6.9	4.3
Erythromycin	95.9	90.4	94.4	95.6	94.9
Gentamycin (high-level)	8.2	14.5	38.0	43.4	30.4
Levofloxacin	100.0	100.0	100.0	98.7	100.0
Linezolid	0.0	1.2	0.0	1.3	2.2
Nitrofurantoin	31.5	36.1	44.4	29.6	38.4
Penicillin	100.0	100.0	100.0	100.0	100.0
Synergicid	2.7	9.6	7.4	10.1	9.4
Rifampin	94.5	94.0	94.4	89.3	89.9
Streptomycin (high-level)	35.6	34.9	35.2	32.1	26.1
Tetracycline	60.3	51.8	57.4	64.2	71.0
Tigecycline	0.0	0.0	0.0	0.6	0.0

Some antimicrobials are presented for epidemiological purposes only. Daptomycin is reported as non-susceptible.

Data source: Canadian Nosocomial Infection Surveillance Program (CNISP) (57 to 68 reporting hospitals).

Methodology has been previously published in the 2020 CARSS report.

Carbapenemase-producing Enterobacterales (CPE) infections and colonization: 2015-2019

Key findings

• Between 2015 and 2019, the rate of healthcare-associated (HA) carbapenemase-producing Enterobacterales (CPE) colonization tripled.
• While the rate of HA-CPE infections more than doubles, the overall number infections remained low.
• 21% of patients with HA-CPE infection died within 30 days of diagnosis (all-cause mortality).

CPE colonization and infection results

Between 2015 and 2019, the rate of HA-CPE colonization in hospital inpatients still tripled (0.04 to 0.17 per 10,000 patient-days), despite a decrease of 5.6% between 2018 and 2019. Similarly, between 2015 and 2019, the rate of HA-CPE infection in hospital inpatients increased by 150% (0.02 to 0.05 cases per 10,000 patient-days). For all HA-CPE infections identified between 2015 and 2019, all-cause mortality was 20.9% (n=23/110). While the relationship between the increased detection of CPE and hospital screening practices was not assessed, CPE remains an important emerging public health threat.

Figure 3: Text description

Year	2015	2016	2017	2018	2019
HA-CPE infection	0.02	0.02	0.02	0.04	0.05
HA-CPE colonization	0.04	0.10	0.12	0.18	0.16

In total, 918 CPE isolates were submitted to PHAC for analysis between 2015 and 2019 (i.e. clinical, screening and reference testing isolates from inpatient and outpatient settings). The most predominant carbapenemases were klebsiella pneumoniae (KPC) (48.7%), New Delhi metallo-β-lactamase (NDM) (28.2%) and oxacillinase-48 (OXA-48) (14.8%). The proportion of resistance remained high for the majority of antimicrobials tested.

Table 4: Antimicrobial resistance patterns from carbapenemase-producing Enterobacterales isolates, Canada, 2015-2019

Proportion (%) of resistant isolates per year
Year	2015	2016	2017	2018	2019
Isolates tested (n)	81	161	187	228	261
Amikacin	27.2	26.1	17.1	19.3	8.8
Cefotaxime	90.1	92.5	92.5	93.0	95.8
ceftazidime	85.2	86.3	85.6	84.2	89.3
Ciprofloxacin	79.0	82.6	73.8	69.3	70.1
Gentamicin	49.4	38.5	34.2	35.1	33.0
Meropenem	84.0	87.0	80.0	86.8	72.8
Piperacillin-tazobactam	92.6	72.0	85.0	92.1	90.8
Tigecycline	16.0	19.9	9.6	13.2	13.8
Tobramycin	49.4	46.6	38.0	44.3	46.4
Trimethoprim-sulfamethoxazole	72.8	63.4	60.4	62.7	73.9

Source: Canadian Nosocomial Infection Surveillance Program (CNISP) (58 to 72 reporting hospitals).

Methodology has been previously published in the 2020 CARSS report.

“The global emergence of carbapenemase producing bacteria capable of hydrolyzing the once effective carbapenem antibiotics is considered a contemporary public health concern” (Hansen, 2021)

All isolates harboured known carbapenemase genes (some demonstrated in vitro susceptibility to meropenem). Some antimicrobials are presented for epidemiological purposes only.

Clostridioides difficile infections: 2015-2019

Key findings

• The rate of healthcare-associated (HA) Clostridioides difficile infection (CDI) decreased by 22% between 2015 and 2019.
• 2% of HA-CDI cases identified between 2015 and 2019 died within 30 days of diagnosis (attributable mortality).

Healthcare-associated CDI results

Between 2015 and 2019, the rate of HA-CDI decreased by 21.7% (4.6 to 3.6 cases per 10,000 patient- days). For all cases of HA-CDI identified between 2015 and 2019, all-cause mortality within 30 days of diagnosis was 9.4% and attributable mortality was 2.4%.

Figure 4: Text description

Year	2015	2016	2017	2018	2019
HA-CDI (10,000 patient-days)	4.63	4.39	4.19	3.94	3.62
CA-CDI (1,000 patient-admissions)	1.50	1.34	1.37	1.36	1.17

In 2019, laboratory results were available for 74.6% (n= 425/570) of eligible HA-CDI (i.e. cases identified in March and April). North American pulsed field (NAP) type 4 and NAP-11 associated ribotype strains were predominant (20.5% and 20.2%, respectively), followed by NAP-1 associated ribotype strains (9.4%).

Table 5: Antimicrobial resistance patterns from healthcare-associated Clostridioides difficile isolates, Canada, 2015-2019

Proportion (%) of resistant isolates per year
Year	2015	2016	2017	2018	2019
Isolates tested (n)	540	494	526	475	425
Clindamycin	25.0	22.1	21.9	47.4	40.2
Metronidazole	0.0	0.0	0.0	0.0	0.0
Moxifloxacin	28.1	17.2	18.6	12.4	11.8
Rifampin	2.0	1.6	2.5	1.7	0.7
Vancomycin	0.0	0.0	0.0	0.0	0.0

One metronidazole resistant isolate was identified in 2018. The increase in clindamycin resistance in 2018 represents a reclassification (an increase in samples with MIC values of 6–8 mg/L; high-level clindamycin resistance remained stable). Some antimicrobials are presented for epidemiological purposes only.

Community-associated CDI results

Between 2015 and 2019, the rate of CA-CDI decreased by 22.0% (1.5 to 1.2 cases per 1,000 patient-admissions). For all cases of CA-CDI identified between 2015 and 2019, all-cause mortality within 30 days of diagnosis was 5.8% and attributable mortality was 1.9%.

In 2019, laboratory results were available for 74.4% (n=122/164) of eligible CA-CDI (i.e. cases identified in March and April). North American pulsed field (NAP) type 4 and NAP-11 associated ribotype strains were predominant (19.7% and 18.0%, respectively), followed by NAP-1 associated ribotype strains (6.6%).

Table 6: Antimicrobial resistance patterns from community-associated Clostridioides difficile isolates, Canada, 2015-2019

Proportion (%) of resistant isolates per year
Year	2015	2016	2017	2018	2019
Isolates tested (n)	205	163	150	156	122
Clindamycin	28.8	22.1	22.7	52.6	39.3
Metronidazole	0.0	0.0	0.0	0.0	0.0
Moxifloxacin	16.1	11.0	10.7	7.1	11.5
Rifampin	1.5	0.6	0.7	1.3	1.6
Vancomycin	0.0	0.0	0.0	0.0	0.0

The increase in clindamycin resistance in 2018 represents a reclassification (an increase in samples with MIC values of 6–8 mg/L; high-level clindamycin resistance remained stable). Some antimicrobials are presented for epidemiological purposes only.

North American Pulsed field type (NAP) and ribotype associations

NAP type	Ribotypes
NAP-1	027, 176, 075, 385, 080, 036, 019
NAP-4	020, 014, 076, 629, 207, 077, 511, 221, 011, ns70, 006, 154, 354, 325, 296
NAP-11	106, 103, 024, 072, 016

Data source: Canadian Nosocomial Infection Surveillance Program (66 to 73 reporting hospitals).

Methodology has been previously published in the 2020 CARSS Report.

Neisseria gonorrhoeae infections: 2015-2019

Key findings

• The rate of gonorrhea infection increased by 70%, from 55.5 to 94.3 cases per 100,000 inhabitants
• The proportion of cultured multidrug-resistant (MDR) Neisseria gonorrhoeae (GC) isolates increased by 44%, from 8.6% to 12.4%; mainly driven by macrolide (i.e. azithromycin) resistance.
• Eleven cases of extensively drug-resistant (XDR) gonococci were identified in Canada, threatening the success of current treatment recommendations.

Results

Between 2015 and 2019, the number of cases of gonorrhea diagnosed in Canada increased from 55.5 to 94.3 cases per 100,000 inhabitants. In total, 142,633 cases were reported during the five-year period, of which 24,484 (17.2%) were tested for antimicrobial resistance. Resistance to at least one antibiotic was identified in 67.7% (n=16,570/24,484) of tested isolates, 10% (2,459/24,484) were MDR and <0.1% (11/24,484) were XDR.

Figure 5: Text description

Year	2015	2016	2017	2018	2019
Total isolates tested (n)	(n = 4,190)	(n = 4,538)	(n = 5,290)	(n = 5,607)	(n = 4,859)
Number of MDR isolates	361	406	645	446	601
Percentage of MDR isolates	9%	9%	12%	8%	12%

Notes:

• Data source: Gonococcal Antimicrobial Surveillance Program – Canada and the Canadian Notifiable Disease Surveillance System
• Methodology has been previously published in the 2020 CARSS Report
• With acknowledgement to the participating provincial public health laboratories

Neisseria gonorrhoeae drug resistance definitions

• Multidrug-resistance (MDR) Neisseria gonorrhoeae (GC) is defined as decreased susceptibility to cephalosporin or resistance to azithromycin as well as to at least two other antimicrobials.
• Extensively drug-resistant (XDR) gonococci is defined as decreased susceptibility to a cephalosporin plus resistance to azithromycin as well as resistance to at least two other antimicrobials.

Mycobacterium tuberculosis infections: 2015-2019

Key findings

• The rate of Mycobacterium tuberculosis (TB) infection in Canada remained stable at approximately 4.8 cases per 100,000 population between 2015 and 2019.
• In 2019, 11% of TB isolates were resistant to any first-line anti-TB drug:
  • 8.9% were mono-resistant.
  • 0.3% were poly-resistant.
  • 1.3% were multi-drug resistant.
• Only one case of extensively drug-resistant (XDR) TB has been reported since 2015.

Results

In 2019, 1,627 incident cases of TB were reported in Canada. Mycobacterium Tuberculosis (MTB) complex was isolated in 98.7% (n=1,607) of cases and Mycobacterium bovis (BCG) was isolated in the remaining 1.7% (n=20). Resistance to at least one anti-TB drug was detected in 10.4% (n=168) of culture-positive MTB complex isolates (Figure 6). Of these isolates, 81.5% (n=137) were resistant to isoniazid, 25.6% (n=43) were resistant to pyrazinamide, 13.7% (n=33) were resistant to rifampin. In 2019, 11.9% (n=20) of resistant MTB complex isolates were multi-drug resistant (Figure 6) and no MTB complex isolates were XDR-TB (Table 7).

While there was minimal difference between age groups, MTB complex isolated in older individuals (>74 years) was relatively less resistant to anti-TB drugs than MTB complex isolated from the younger age-groups (Figure 7). Stratified by sex, the proportion of resistant MTB complex isolated in males has historically been lower than the proportion of resistant MTB complex isolated in females; however, the proportion was approximately equal in 2019.

Figure 6: Text description

Pie charts for tuberculosis isolates tested for anti-tuberculosis drug resistance in Canada, in 2019. A total of 1,627 isolates were tested. 20 of those were M. Bovis Bacillus Calmette-Guérin (BCG) isolates; the remaining 1,607 were Mycobacterium tuberculosis (MTB) complex isolates. Of the 1,607 Mycobacterium tuberculosis complex isolates, 1,439 of them were susceptible, while the remaining 168 were resistant to first-line anti-tuberculosis drugs. Of the 168 resistant isolates, 143 were mono-resistant, 5 were poly-resistant, and 20 were multidrug-resistant. Of the 143 mono-resistant isolates, 112 were resistant to isoniazid (INH), 3 were resistant to rifampin (RMP), 27 were resistant to pyrazinamide (PZA), and 1 was resistant to ethambutol (EMB). Of the 20 multidrug-resistant isolates, 8 were resistant to isoniazid and rifampin; 1 was resistant to isoniazid, rifampin and ethambutol; 4 were resistant to isoniazid, rifampin, ethambutol, and pyrazinamide; and 7 were resistant to isoniazid, rifampin, and pyrazinamide. Of the 5 poly-resistant isolates, all 5 were resistant to isoniazid and pyrazinamide. No isolates were extensively drug-resistant.

Abbreviations:

• MTB: Mycobacterium Tuberculosis
• BCG: Mycobacterium bovis
• MDR: Multidrug-resistant
• XDR: Extensively drug-resistant
• INH: Isoniazid
• RMP: Rifampin
• PZA: Pyrazinamide
• EMB: Ethambutol

Table 7: Antimicrobial resistance patterns from Tuberculosis (TB) isolates by resistance classification, Canada, 2015-2019

Proportion (%) of resistant isolates per year
Year	2015	2016	2017	2018	2019
Isolates tested (n)	1331	1450	1522	1458	1607
Any resistance	10.4	9	8.1	10.1	10.5
Mono-resistant	8.5	7.4	6.8	8.3	8.9
Poly-resistant	0.2	0.3	0.4	0.3	0.3
Multidrug-resistant	1.6	1.2	0.9	1.4	1.2
Extensively drug-resistant	0.0	0.0	0.0	0.1	0.0

Figure 7: Text description

Age Group	Any Resistance	Multidrug-resistant TB
<15	8.9%	2.2%
15-24	10.2%	1.6%
25-34	11.9%	2.4%
35-44	10.4%	0.9%
45-54	11.0%	1.0%
55-64	12.2%	1.1%
65-74	11.0%	0.0%
75+	7.3%	0.8%

Source: Canadian Tuberculosis Laboratory Surveillance System (CBTLSS) and the Canadian Notifiable Disease Surveillance System (CNDSS)

Methods

MTB resistance data on first-line and second-line anti-TB drugs was submitted by all Canadian jurisdictions to the Canadian Tuberculosis Laboratory Surveillance System (CBTLSS). Isolates from culture-positive TB cases were tested for antimicrobial susceptibility. Any TB isolates demonstrating positive cultures of M. tuberculosis complex (M. tuberculosis, M. africanum, M. canetti, M. caprae, M. microti, M. pinnipedii or M. bovis) were included in the analyses. M. bovis Bacillus Calmette-Guérin (BCG) isolates were excluded since they represent a complication of TB vaccination often found in immune-compromised patients, where the strain is not infectious. Types of drug resistance were tabulated and a five-year trend assessed:

• Mono-resistance (i.e. resistance to only one first-line anti-TB drug);
• Poly-resistance (i.e. resistance to more than one first-line anti-TB drug, other than both isoniazid and rifampin);
• Multi-drug resistance (i.e. resistance to at least both isoniazid and rifampin);
• Extensive drug resistance (i.e. resistance to any fluoroquinolone, such as ciprofloxacin and moxifloxacin), and at least one of three second-line injectable drugs (capreomycin, kanamycin and amikacin), in addition to multi-drug resistance.

Invasive Streptococcus pneumoniae infections (IPD): 2014-2018

Key findings

• The rate of invasive pneumococcal disease (IPD) increased by 21% from 9.0 to 10.9 cases per 100,000 people between 2014 and 2018.
• The proportion of multidrug resistance (i.e. Streptococcus pneumoniae isolates resistant to three or more classes of antimicrobials) identified in vaccine preventable (PCV13) IPD cases increased by 25%, from 9% to 12% between 2014 and 2018.
• The proportion of multidrug resistant (MDR) isolates identified in non-vaccine preventable (non-PCV13) IPD cases increased by 74%, from 4% to 6% between 2014 and 2018.

Results

Between 2014 and 2018, the rate of invasive disease due to S. pneumoniae increased by 21.1%, from 9.0 to 10.9 per 100,000 inhabitants. In 2018, laboratory results were available from 44.5% (n=1,792/4,026) of all IPD cases. The proportion of S. pneumonia isolates resistant to clarithromycin was 25.8%, followed by penicillin (11.1%) and non-susceptibility to doxycycline was 8.4%. All S. pneumoniae isolates were susceptible to daptomycin, linezolid, tigecycline and vancomycin.

Between 2014 and 2018, the proportion of S. pneumoniae isolates identified as MDR (i.e. isolates resistant to three or more classes of antimicrobials) increased by 52.0%, from 5.0% (n=56) to 7.6% (n=137). The proportion MDR was highest in serotypes 15A (non-PCV13) and 19A (PCV13), with 58.0% (n=23) and 29.0% (n=27) demonstrating this pattern of resistance, respectively.

Vaccine preventable drug-resistance in IPD cases

IPD (including some MDR-associated IPD serotypes) can be prevented through the use of the pneumococcal conjugate 13-valent (PCV-13) vaccine and the pneumococcal polysaccharide 23-valent (PNEUMOVAX®23) vaccine. In 2018, the highest proportion of resistance in PCV13-vaccine preventable IPD serotypes was clarithromycin (22.5%), followed by doxycycline (13.8%), clindamycin (11.0%) and penicillin (10.6%). Between 2014 and 2018, no resistance was observed to ertapenem and <1% of isolates were resistant to moxifloxacin. Between 2014 and 2018, the proportion of MDR in PCV13-vaccine preventable IPD serotypes increased by 25.0%, from 9.1% to 11.6%.

Table 8: Antimicrobial resistance patterns from Streptococcus pneumoniae isolates (PCV13 serotypes) by resistance classification, Canada, 2014-2018

Proportion (%) of resistant isolates per year
Year	2014	2015	2016	2017	2018
Isolates (n) tested	294	292	284	295	520
Susceptible	66.7	69.5	70.4	65.8	70.6
Resistant to one antimicrobial class	15.3	12.3	12.3	10.2	10.8
Resistant to two antimicrobial classes	8.8	5.8	7.0	9.5	7.1
Multidrug-resistant	9.2	12.3	10.2	14.6	11.5

Multidrug-resistance is defined as resistance to three or more antimicrobial classes.

Non-vaccine preventable drug-resistant IPD cases

In 2018, the highest proportion of resistance in non-vaccine preventable IPD serotypes (non-PCV13) was clarithromycin (27.1%) and penicillin (11.3%). Between 2014 and 2018, <1% of isolates were resistant to ertapenem, imipenem and moxifloxacin. Between 2014 and 2018, the proportion of MDR in non-vaccine preventable IPD serotypes (non-PCV13) increased by 74.3%, from 3.5% to 6.1%.

Table 9: Antimicrobial resistance patterns from Streptococcus pneumoniae isolates (non-PCV13 serotypes) by resistance classification, Canada, 2014-2018

Proportion (%) of resistant isolates per year
Year	2014	2015	2016	2017	2018
Isolates (n) tested	822	836	830	834	1,272
Susceptible	69.0	69.6	68.8	64.5	61.5
Resistant to one antimicrobial class	19.3	20.6	20.2	22.8	26.7
Resistant to two antimicrobial classes	8.2	5.0	6.1	4.9	5.7
Multidrug-resistant	3.5	4.8	4.8	7.8	6.1

Multidrug-resistance is defined as resistance to three or more antimicrobial classes.

Notes:

• Sources: The National Surveillance of Invasive Streptococcal Disease (eSTREP) and the Canadian Notifiable Disease Surveillance System (CNDSS)
• Methodology has been previously published in the 2020 CARSS Report
• With acknowledgement of contributions from the University of Manitoba, Toronto Bacterial Disease network, Alberta Provincial Laboratory, Laboratoire de santé publique du Quebec and all provincial/territorial public health laboratories who submit isolates to the eSTREP program.

Invasive Streptococcus pyogenes (group A Streptococcus) infections: 2014-2018

Key findings

• The rate of invasive Group A Streptococcal (iGAS) disease increased by 65% from 5.2 to 8.6 cases per 100,000 inhabitants between 2014 and 2018.
• All Streptococcus pyogenes isolates were susceptible to penicillin and vancomycin.
• Erythromycin resistance remained stable with rates at 7.1% - 9.6% between 2014 and 2018

Results

Between 2014 and 2018, the rate of iGAS increased by 65.4%, from 5.2 to 8.6 cases per 100,000 inhabitants. In 2018, laboratory results were available for 94.5% (n=2,760/2,922) of iGAS cases (noting variations in the definition of sterile sites by province). All Streptococcus pyogenes isolates were susceptible to penicillin and vancomycin.

Table 10: Antimicrobial resistance patterns from Streptococcus pyogenes isolates, Canada, 2014-2018

Proportion (%) of resistant isolates per year
Year	2014	2015	2016	2017	2018
Isolates tested (n)	1460	1453	1768	2052	2760
Clindamycin (Resistance)	2.6	3.2	3.9	6.8	3.5
Erythromycin (Resistance)	7.1	8.3	8.8	9.9	9.6
Penicillin (Resistance)	0.0	0.0	0.0	0.0	0.0
Vancomycin (Resistance)	0.0	0.0	0.0	0.0	0.0

Notes:

• Sources: The National Surveillance of Invasive Streptococcal Disease (eSTREP) and the Canadian Notifiable Disease Surveillance System (CNDSS)
• Methodology has been previously published in the 2020 CARSS Report
• With acknowledgement of contributions from the University of Manitoba, Toronto Bacterial Disease network, Alberta Provincial Laboratory, Laboratoire de santé publique du Quebec and all provincial/territorial public health laboratories who submit isolates to the eSTREP program.

Antimicrobial consumption by humans, Canada, 2015-2019

Key findings

• Between 2015 and 2019, overall human consumption of antimicrobials decreased by 5%, noting an increase of 2% in the use of antimicrobials that should be reserved for suspected or confirmed multidrug-resistant infections.
• The rate of antimicrobial prescribing in the community sector was highest in seniors aged 80 years or more and increased by 13% between 2015 and 2019.
• Between 2015 and 2019, the rate of prescriptions originating from nurses and pharmacists increased by 68% and 210%, respectively.

Overall antimicrobial consumption by humans: National perspective

Between 2015 and 2019, human antimicrobial consumption (including antimicrobials dispensed by community retail pharmacies and antimicrobials purchased by hospitals) decreased by 5.4%, from 17.3 to 16.3 defined daily doses (DDDs) per 1,000 inhabitant-days, driven by a decrease of 19.7% in doses purchased by hospitals.

In 2019, 92.7% of DDDs were dispensed in the community sector through community retail pharmacies and the remaining 7.3% were purchased for use by hospitals. Between 2015 and 2019, the estimated cost (adjusted to 2019 Canadian dollars) of all antimicrobials consumed decreased by 9.2%, from $836.3 million to $759.6 million.

Figure 8: Text description

Year	2015	2016	2017	2018	2019
Hospital sector (purchased)	544.2	526.0	509.9	611.7	437.1
Community sector (dispensed)	5755.1	5741.5	5710.4	5713.1	5523.4

Overall antimicrobial consumption by humans: Canadian jurisdictions

In 2019, Prince Edward Island and Newfoundland and Labrador (data combined) consumed the largest quantity of antimicrobials per capita, decreasing by 9.2% since 2015 (10,010.2 to 9,087.1 DDDs per 1,000 inhabitants). British Columbia and the territories (data combined) consumed the smallest quantity of antimicrobials per capita.

Between 2015 and 2019, antimicrobial consumption decreased in all Canadian jurisdictions; Saskatchewan had the largest change in consumption, with a decrease of 10.7% (7,889.4 to 7,045.3 DDDs per 1,000 inhabitants), followed by Prince Edward Island and Newfoundland and Labrador at 9.2% (9,827.9 to 9,087.1 DDDs per 1,000 inhabitants).

Figure 9: Text description

Year	2015	2016	2017	2018	2019
BC & TE	6008.3	5776.0	5745.1	5729.8	5475.9
AB	6768.5	6708.0	6547.2	6414.1	6442.1
SK	7889.4	7843.2	7260.7	7189.8	7045.3
MB	6811.7	6863.1	6747.5	6697.0	6322.1
ON	6182.8	6164.8	6129.2	6500.1	5860.3
QC	5603.3	5724.8	5713.6	5676.7	5479.6
NB	7140.0	6946.5	7171.9	7125.2	7034.6
NS	7564.7	7316.1	7607.1	7582.5	7245.0
PE & NL	10010.2	9827.9	9986.7	9682.8	9087.1
Abbreviations: BC & TE = British Columbia combined with Yukon, Northwest Territories and Nunavut; AB = Alberta; SK = Saskatchewan; MB = Manitoba; ON = Ontario; QC = Quebec; NB = New Brunswick; NS = Nova Scotia; PE & NL = Prince Edward Island combined with Newfoundland and Labrador.

Overall antimicrobial consumption by humans: Top 5 antimicrobial classes

In 2019, the most consumed classes of antimicrobials by humans were tetracyclines (1,186.2 DDDs per 1,000 inhabitants), penicillins with extended spectrum (1,178.7 DDDs per 1,000 inhabitants), macrolides (781.9 DDDs per 1,000 inhabitants), penicillin combinations (489.4 DDDs per 1,000 inhabitants) and first generation cephalosporins (474.3 DDDs per 1,000 inhabitants). Between 2018 and 2019, fluoroquinolones dropped from the fourth to the sixth most consumed antimicrobial class (551.8 to 469.3 DDDs per 1,000 inhabitants).

Figure 10: Text description

Year	2015	2016	2017	2018	2019
Tetracyclines	997.0	1008.1	1058.6	1234.0	1186.2
Penicillins (extended spectrum)	1228.2	1255.1	1257.3	1247.5	1178.7
Macrolides	1047.8	987.5	937.6	872.3	781.9
Penicillins (combination)	355.0	396.6	446.6	471.2	489.4
First-generation cephalosporins	467.4	498.9	481.2	481.7	474.3
Fluoroquinolones	754.5	679.9	581.9	551.8	469.3

Overall antimicrobial consumption by humans: AWaRe categorization

The World Health Organization’s AWaRe program has published a list of antibiotics that should be reserved for the treatment of suspected or confirmed multidrug-resistant organisms, referred to as “Reserve” antibiotics. Between 2015 and 2019, the consumption of these antibiotics in Canada increased by 2.3%. This increase was largely driven by an increase of 83.1% in the consumption of daptomycin (2.7 to 5.0 DDDs per 1,000 inhabitants).

Between 2015 and 2019, the consumption of WHO AWaRe “Watch” antibiotics (i.e. antibiotics that have high resistance potential) decreased by 25.2% (2,471.4 to 1,848.4 to DDDs per 1,000 inhabitants) and the consumption of WHO AWaRe “Access” (i.e. antibiotics that are active against many common susceptible pathogens and have lower resistance potential) increased by 7.5% (3,817.0 to 4,102.7 DDDs per 1,000 inhabitants).

Figure 11: Text description

Year	Access	Watch	Reserve
2015	3817.0	2471.4	9.1
2016	3934.3	2325.3	7.3
2017	4036.6	2175.9	7.7
2018	4252.2	2064.1	8.3
2019	4102.6	1848.4	9.3

Overall antimicrobial consumption by humans: International perspective

In 2019, Canada consumed the 13th lowest quantity of antimicrobials when compared to 30 countries reporting to the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) – one of the largest internationally standardized antimicrobial consumption surveillance systems. The metric for comparison is J01 antimicrobials (antibiotics for systemic use) measured by DDDs consumed per capita by humans in the community and hospital sectors.

In general, the rate of human antimicrobial consumption in the Netherlands (the country with the lowest reported consumption, 9.5 DDDs per 1,000 inhabitant-days) is nearly half the rate in Canada (16.3 DDDs per 1,000 inhabitant-days). The rate of human antimicrobial consumption in Canada is approximately half that of the rate in Greece (the country with the highest reported consumption, 34.1 DDDs per 1,000 inhabitant-days).

Figure 12: Text description

Country	Community sector	Hospital sector	Total (as reported by EU)
Greece	32.4	1.68	34.1
Cyprus	n/a	n/a	30.1
Romania	24	1.73	25.8
France	23.3	1.74	25.1
Spain	23.1	1.63	24.7
Poland	22.2	1.42	23.6
Ireland	21	1.77	22.8
Italy	19.8	1.89	21.7
Belgium	19.8	1.54	21.3
Luxembourg	19.8	1.38	21.1
Bulgaria	19.1	1.63	20.7
Malta	18.7	1.99	20.7
Iceland	19.5	n/a	19.5
Slovakia	18	1.38	19.3
Portugal	17.9	1.4	19.3
Croatia	16.9	1.85	18.8
United Kingdom	15.6	2.53	18.2
Czechia	n/a	n/a	16.9
Canada	15.12	1.19	16.3
Lithuania	13.4	2.12	15.6
Denmark	13.4	1.86	15.3
Norway	13.6	1.3	14.9
Finland	12.6	2.1	14.7
Hungary	13.3	1.16	14.4
Latvia	12	1.88	13.9
Slovenia	11.5	1.5	13
Sweden	10.3	1.48	11.8
Estonia	10.2	1.54	11.8
Germany	11.4	n/a	11.4
Austria	9.9	n/a	9.9
Netherlands	8.7	0.8	9.5

Notes: Austria, Germany and Iceland report consumption in the community sector only. Czechia and Cyprus report overall consumption (community and hospital sectors combined). Data from the United Kingdom represents England, Northern Ireland and Scotland. Consumption reported by Canada includes vancomycin, metronidazole, colistin and fidaxomicin.

Source: The European Centre for Disease Prevention and Control and the Public Health Agency of Canada.

Antimicrobial consumption by humans in the community sector: Defined daily doses

Between 2015 and 2019, human antimicrobial consumption in the community sector decreased by 4.0% (15.8 to 15.1 DDDs per 1,000 inhabitant-days) and the proportion of total DDDs dispensed in Canada attributed to the community sector increased from 91.4% to 92.7%.

Antimicrobial consumption by humans in the community sector: Prescriptions filled

Between 2015 and 2019, the rate of antimicrobial prescriptions dispensed by retail pharmacies decreased by 3.0% (641.6 to 622.5 prescriptions per 1,000 inhabitants) and the number of DDDs decreased by 4.0% (5,755.1 to 5,523.4 DDDs per 1,000 inhabitants).

In 2019, the rate of antimicrobial prescriptions dispensed by retail pharmacies was highest in females aged 80 years or more (1,310.0 prescriptions per 1,000 inhabitants), followed by males aged 80 years or more (1,112.7 prescriptions per 1,000 inhabitants). The lowest rate was males aged 19 to 44 years (364.9 prescriptions per 1,000 inhabitants), followed by males aged 0 to 18 years (471.1 prescriptions per 1,000 inhabitants) and females aged 0 to 18 (511.7 prescriptions per 1,000 inhabitants).

The rate of antimicrobial prescriptions filled by retail pharmacies decreased for all age categories between 2018 and 2019.

Figure 13: Text description

Sex	Female					Male
Year	2015	2016	2017	2018	2019	2015	2016	2017	2018	2019
0 to 18	561.9	576.6	551.8	546.8	511.7	519.0	536.5	510.3	507.5	471.1
19 to 44	760.9	745.1	724.4	720.0	697.3	407.5	398.9	387.9	380.3	364.9
45 to 64	725.1	738.8	760.4	764.8	739.2	497.5	512.3	528.9	532.7	516.1
65 to 79	996.2	958.9	958.5	965.0	938.1	802.4	780.8	785.5	793.8	773.5
80+	1153.9	1228.6	1316.4	1347.7	1310.0	989.9	1056.9	1138.4	1143.5	1112.7

Antimicrobial consumption by humans in the community sector: Prescription origin

Between 2015 and 2019, an 8.4% decrease (420.3 to 384.8 prescriptions per 1,000 inhabitants) was observed in the rates of prescriptions originating from general practitioners (GP) and family physicians (FP) and the rate of prescriptions originating from all other physician specialities increased by 3.4% (83.9 to 86.8 prescriptions per 1,000 inhabitants).

Of non-physician sources, the rate of prescribing increased by 9.8% (137.0 to 150.4 prescriptions per 1,000 inhabitants) between 2015 and 2019. While overall prescribing by dentists increased by 1.2% (46.9 to 47.4 prescriptions per 1,000 inhabitants), prescribing by nurse practitioners and pharmacists increased by 67.6% (10.0 to 16.8 prescriptions per 1,000 inhabitants) and 210.3% (3.3 to 10.1 prescriptions per 1,000 inhabitants), respectively.

In 2019, family physicians and general practitioners were responsible for 62% of prescriptions, compared to dentists (8%), nurses (3%) and pharmacists (2%).

Figure 14: Text description

Year	General practitioners and family physicians	All other physician specialties
2015	420.3	83.9
2016	418.1	85.2
2017	415.9	86.2
2018	412.0	88.4
2019	384.8	86.8

Figure 15: Text description

Year	Dentists	Nurse practitioners	Optometrists	Pharmacists	Veterinarians
2015	46.9	10.0	0.4	3.3	0.9
2016	49.8	11.3	0.6	5.6	0.9
2017	49.7	13.0	0.8	6.8	0.9
2018	48.4	14.8	0.9	8.3	0.8
2019	47.4	16.8	0.9	10.1	0.8

Antimicrobial consumption by humans in the community sector: Carbapenems dispensed

Between 2015 and 2019, carbapenem consumption in the community increased by 68.3% (3.8 to 6.4 DDDs per 1,000 inhabitants), largely driven by an increase of 156.4% in the use of meropenem (0.6 to 1.6 DDDs per 1,000) and an increase of 49.8% in the use of ertapenem (3.1 to 4.6 DDDs per 1,000 inhabitants).

Figure 16: Text description

Year	All carbapenems	Ertapenem	Meropenem
2015	3.8	3.1	0.6
2016	4.8	3.8	1.0
2017	5.6	4.2	1.3
2018	6.8	4.7	2.0
2019	6.4	4.6	1.6

Antimicrobials purchased by the hospital sector: Defined daily doses

Between 2015 and 2019, the quantity of antimicrobials purchased by hospitals decreased by 19.7% (from 544.2 to 437.1 DDDs per 1,000 inhabitants), largely driven by a decrease of 28.5% between 2018 and 2019 (611.7 to 437.1 DDDs per 1,000 inhabitants, subject to returns adjustment). The proportion of total DDDs consumed by humans in Canada attributed to hospital purchasing decreased from 8.6% in 2015 to 7.3% in 2019.

Antimicrobial prescribing in the community sector before and during the COVID-19 pandemic: preliminary results, January to October 2020

Key findings

• Between March and October 2020, the overall rate of antimicrobial prescribing decreased by 27% when compared to the same eight-month period in 2019.
• Overall prescribing decreased by a maximum of 40% in May 2020.
• Prescribing to children (aged 0 to 18 years) decreased by a maximum of 70% in April 2020.
• Prescribing to seniors (aged 80 years or more) decreased by a maximum of 28% in May 2020.

Methods

To assess the impact of the COVID-19 pandemic on prescribing practices in Canada, the rate of prescribing by month in 2020 was compared against the corresponding month in 2019. The start of the Canadian pandemic period was defined as March 2020, corresponding with the closure of the Canada-United States land boarder. Final statistics on the entire pandemic period will be published in a future report.

The analysis dataset was comprised of 20 months of community antibiotic prescribing dispensing data from IQVIA’s Canadian CompuScript (CS) database, covering all ten Canadian provinces from March 2019 to October 2020. Information on prescription drug strengths and dosages was obtained from Health Canada’s Drug Product Database (DPD) using drug identification numbers (DIN). Population estimates were obtained from mid-year census population estimates from Statistics Canada.

During the start of the COVID-19 pandemic (March to October 2020), the average rate of antimicrobial prescribing decreased by 26.5% when compared to the same months in 2019 (50.4 to 37.0 prescriptions per 1,000 inhabitants). The largest decreases were observed in the early months of the pandemic; the rate of antimicrobial prescribing decreased by 38% (54.0 to 33.4 prescriptions per 1,000 inhabitants) in April 2020 and by 40% (52.7 to 31.9 prescriptions per 1,000 inhabitants) in May 2020. While the disparity narrowed during the summer months, the rate of antimicrobial prescribing decreased again by 30% (54.2 to 38.1 prescriptions per 1,000 inhabitants) in October 2020.

Figure 17: Text description

Year	2019
Month	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct	Nov	Dec
Before COVID-19	60.0	49.7	54.7	54.0	52.7	46.7	47.5	45.2	47.9	54.2	51.7	57.6
During COVID-19	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a
Year	2020
Month	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct	Nov	Dec
Before COVID-19	61.3	50.6	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a
During COVID-19	n/a	n/a	48.4	33.4	31.9	35.2	36.9	35.6	36.8	38.1	n/a	n/a

The start of the Canadian pandemic period was defined as March 2020, corresponding with the closure of the Canada-United States land boarder.

Between the months of March to October 2019 compared to the same months in 2020, the rate of antimicrobial prescribing was higher in females compared to males.

Figure 18: Text description

Year	2019
Month	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct	Nov	Dec
Male: Before COVID-19	49.2	40.7	44.7	44.1	43.0	38.2	38.4	36.2	38.4	43.7	42.0	47.6
Male: During COVID-19	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a
Female: Before COVID-19	70.7	58.5	64.6	63.7	62.3	55.2	56.5	54.2	57.4	64.6	61.2	67.5
Female: During COVID-19	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a
Year	2020
Month	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct	Nov	Dec
Male: Before COVID-19	50.9	41.7	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a
Male: During COVID-19	n/a	n/a	38.5	25.7	25.2	28.1	29.3	27.8	28.6	29.6	n/a	n/a
Female: Before COVID-19	71.7	59.4	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a
Female: During COVID-19	n/a	n/a	58.2	41.0	38.5	42.1	44.4	43.2	45.0	46.4	n/a	n/a

The average rate of antimicrobial prescribing decreased for all age categories during the first eight months of the COVID-19 pandemic (March to October). The smallest reduction during this period was in those aged 80 years or more, decreasing by 18.8% (102.8 to 83.5 prescriptions per 1,000 inhabitants); the largest reduction during this period was in those aged 0 to 18 years, decreasing by 50.7% (37.2 to 18.3 prescriptions per 1,000 inhabitants).

Figure 19: Text description

Month	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct
0 to 18	21.12%	11.50%	-28.12%	-70.07%	-67.60%	-55.16%	-44.03%	-38.68%	-45.31%	-52.03%
19 to 44	0.64%	0.39%	-9.49%	-33.08%	-35.75%	-21.94%	-20.37%	-19.10%	-20.51%	-24.90%
45 to 64	-2.87%	-1.29%	-7.48%	-30.29%	-34.32%	-20.42%	-19.64%	-19.00%	-20.58%	-27.22%
65 to 79	-2.60%	-0.19%	-8.43%	-33.53%	-35.87%	-18.30%	-18.69%	-19.80%	-20.08%	-28.13%
80+	-3.16%	0.10%	-7.32%	-27.74%	-29.47%	-12.94%	-15.19%	-17.54%	-14.75%	-23.33%

Antimicrobial intended for use in animals in Canada

Key findings

• Between 2018 and 2019, the tonnage of antimicrobial active ingredient distributed for use in production animals decreased by 11%^{Footnote 2}.
• Between 2018 and 2019:
  • antimicrobial sales for use in pigs, poultry and fish decreased;
  • antimicrobial sales for use in cattle, horses, companion animals and small ruminants increased.
• In 2019, Canada distributed the eighth highest quantity of antimicrobials intended for use in animals compared to the latest data (2018) from 31 European countries.

Methodology update

Changes to the Food and Drug Regulations (published May of 2017) aim to increase the oversight of antimicrobials available for use in animals. Since 2018, manufacturers, importers, and compounders must provide annual sales reports of medically important antimicrobials intended for use in animals (Health Canada (HC), 2020). These reports will replace the data historically provided on a voluntary basis by the Canadian Animal Health Institute (CAHI).

To help with these reporting requirements, Health Canada’s Veterinary Drugs Directorate and the Public Health Agency of Canada’s Centre for Foodborne, Environment and Zoonotic Infectious Diseases and the Canadian Network for Public Health Intelligence (CNPHI) developed an online sales data collection system, called the Veterinary Antimicrobial Sales Reporting (VASR) system.

This report categorizes antimicrobials according to their importance to human medicine as per a categorization system developed by Health Canada’s Veterinary Drugs Directorate. In this system, Category I antimicrobials are considered of very high importance to human medicine (e.g. fluoroquinolones). Category II are of high importance to human medicine (e.g. macrolides), and Category III antimicrobials are of medium importance to human medicine (e.g. tetracyclines). Category IV antimicrobials (i.e. low importance to human medicine, such as ionophores) are not included in this document. In Canada, antimicrobials that are considered medically important can be found in Health Canada’s List A: List of certain antimicrobial active pharmaceutical ingredients.

Antimicrobials sold for use in animals

Between 2018 and 2019, the kilograms of antimicrobials sold for use in animals decreased by 10.5% (1.1 million to 1.0 million kilograms). Similarly, for production animals, the quantity of antimicrobials measured in milligrams (mg) per population correction unit (PCU) decreased by 12% (150 to 132 mg/PCU) using the Canadian standard weights of animals and by 12% (163 to 143 mg/PCU) using the European standard weights of animals.

Figure 20: Text description

Metrics	Total (kg)	Total (mg/PCUEU—European weights)	Total (mg/PCUCA—Canadian weights)
2015 (CAHI)	1187135.8	183.0	175.2
2016 (CAHI)	1051010.0	160.0	154.2
2017 (CAHI)	934872.7	141.2	136.8
2018 (VASR)	1082768.0	162.9	150.3
2019 (VASR)	968985.0	143.0	131.7

Notes:

• Population data used for live horses was from 2010. VASR data excludes antifungals, antiparasitics, antivirals, Category IV antimicrobials, and uncategorized not medically important antimicrobials. CAHI data excludes ionophores and chemical coccidiostats.
• Sources: The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), the Canadian Animal Health Institute (CAHI), the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC), Fisheries and Oceans Canada, Statistics Canada, Agriculture and AgriFood Canada, Equestrian Canada, Chicken Farmers of Canada, Egg Farmers of Canada, Canadian Hatching Egg Producers, and Canfax.
• The figure indicates a break in the lines between the data as provided by CAHI (2015, 2016, and 2017) and the data provided in the VASR system. These two data sources have different data providers; trends should be interpreted with caution.

In 2019, the top five classes of antimicrobial active ingredients sold for use in animals by weight (excluding quantities of antimicrobial classes which cannot be independently reported) were tetracyclines (495,116 kilograms), macrolides (115,822 kilograms), penicillins (91,095 kilograms), sulfonamides (53,226 kilograms) and lincosamides (46,390 kilograms). Overall, one percent of antimicrobial active ingredients sold for use in animals were Category I (i.e. of very high importance to human medicine); however, sales of category I antimicrobials increased by 10% between 2018 and 2019.

Figure 21: Text description

Year	2018	2019
Nitrofurans	49	23
Polymyxins	16	8
Fluoroquinolones	716	937
Aminocyclitols	1,241	744
Cephalosporins (3rd gen)	1,946	1,676
Penicillin-beta-lactamase inhibitor combinations	2636	2748
Cephalosporins (1st or 2nd gen)	2,820	3,147
Aminoglycosides	14,467	6,487
Amphenicols	11,318	13,030
Diamino-sulfa combos	22,051	25,519
Lincosamides	46,583	46,390
Sulfonamides	88,274	53,226
Penicillins	117,222	91,095
NIR	106,121	120,455
Macrolides	129,579	115,822
Tetracyclines	544,102	495,116

Notes: Not independently reported (NIR) antimicrobials include aminocoumarins, bacitracins, diaminopyrimidines, fusidic acid, glycopeptides, nitroimidazoles, orthosomycins, phosphonic acid derivatives, pleuromutilins, pseudomonic acids, streptogramins, and therapeutic agents for tuberculosis. Data exclude antifungals, antiparasitics, antivirals, category IV antimicrobials, and uncategorized not medically important antimicrobials.

Between 2018 and 2019, sales of antimicrobials for use in pigs, poultry and fish decreased; sales for use in cattle, horses, companion animals and small ruminants increased. For additional information on antimicrobials intended for use in veal calves, horses, small ruminants and other animals, please see the most recent CIPARS Report.

Aquaculture

• Kilograms of antimicrobials sold for use in aquaculture decreased by 29% between 2018 and 2019.
• In 2019, the only antimicrobial classes sold for use in aquaculture were tetracyclines and amphenicols.

Beef cattle

• Kilograms of antimicrobials sold for use in beef cattle increased by 14% between 2018 and 2019, noting an increase of 6% in the sales of Category I antimicrobials.
• In 2019, the top three antimicrobial classes sold for use in beef cattle were tetracyclines, macrolides, and amphenicols.

Dairy cattle

• Kilograms of antimicrobials sold for use in dairy cattle increased by 15% between 2018 and 2019 noting a decrease of 25% in the sales of Category I antimicrobials.
• In 2019, the top three antimicrobial classes sold for use in dairy cattle were tetracyclines, diaminopyrimidine-sulfonamide combinations, and penicillins.

Poultry (chickens and turkeys)

• Kilograms of antimicrobials sold for use in poultry decreased by 9% between 2018 and 2019.
• In 2019, the highest quantity of antimicrobials sold for use in poultry was not independently reported;
• Small quantities (less than one kilogram) of fluoroquinolones and third generation cephalosporins (antimicrobials of very high importance to human medicine) were sold or compounded for use in poultry in 2018 and 2019.

Pigs

• Kilograms of antimicrobials sold for use in pigs decreased by 21% between 2018 and 2019, noting a decrease of 24% in the sales of Category I antimicrobials.
• In 2019, the top three antimicrobial classes sold for use in pigs were tetracyclines, macrolides, and penicillins.

Companion animals

• Kilograms of antimicrobials sold for use in companion animals increased by 17% between 2018 and 2019, noting an increase of 24% in the sales of Category I antimicrobials.
• In 2019, the top three antimicrobial classes sold for use in companion animals were first or second generation cephalosporins, penicillins and β-lactamase inhibitors combinations, and antimicrobials grouped in the “not independently reported’’ category.

Figure 22: Text description

Year	2018	2019
Animal species	Average	Average
Pigs	620355	491640
Cattle	266343	297810
Poultry	147853	134351
Aquaculture	17596	12507
Other Animals	10274	10093
Companion Animals	6373	7440
Horses	1236	1504
Small Ruminants	43	68

Notes: VASR data excludes antifungals, antiparasitics, antivirals, Category IV antimicrobials, and uncategorized not medically important antimicrobials.

Figure 23: Text description

Year	2018	2019
Animal species	Average	Average
Pigs	353.8	277.5
Poultry	196.7	175.2
Cattle	67.1	72.7
Aquaculture	92.5	66.9
Companion Animals	40.8	47.6
Horses	2.6	3.1
Small Ruminants	0.8	1.2

Notes: VASR data excludes antifungals, antiparasitics, antivirals, Category IV antimicrobials, and uncategorized not medically important antimicrobials. “Other Animal” species could not be ascribed to any of the current species; hence no denominator could be determined for these species and these data were excluded. Note the denominator for aquaculture was calculated differently than for the terrestrial animal species (modified ESVAC approach). Additional information can be found in the most recent CIPARS Report

Antimicrobials sold for use in animals: International perspective

The European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) Network collects and reports data on the quantity of antimicrobials intended for use in animals in 31 European countries. This information is reported in milligrams per population correction unit (mg/PCU) and was the best publically available source for country-specific international comparisons.

When compared to the latest data provided by ESVAC and making the assumption that the data are comparable, Canada ranked eighth highest in terms of quantities of antimicrobials sold for use in production animals compared to European countries.

It is important to note that the structure and detail in the data for animal production classes available in the European datasets differ from the Canadian datasets; hence this figure should be interpreted with caution. The Canadian denominator data included the numbers of live beef cows, which are not included as a separate category in the European data.

Figure 24: Text description

European Countries (2018)	European Countries (2018)	Canada (2019) - European weights	Canada (2019) - Canadian weights	Median (of EU countries)
Austria	50	143	132	57
Belgium	113	143	132	57
Bulgaria	120	143	132	57
Croatia	67	143	132	57
Cyprus	466	143	132	57
Czechia	57	143	132	57
Denmark	38	143	132	57
Estonia	53	143	132	57
Finland	19	143	132	57
France	64	143	132	57
Germany	88	143	132	57
Greece	91	143	132	57
Hungary	181	143	132	57
Iceland	5	143	132	57
Ireland	46	143	132	57
Italy	244	143	132	57
Latvia	36	143	132	57
Lithuania	33	143	132	57
Luxembourg	34	143	132	57
Malta	151	143	132	57
Netherlands	58	143	132	57
Norway	3	143	132	57
Poland	167	143	132	57
Portugal	187	143	132	57
Romania	83	143	132	57
Slovakia	49	143	132	57
Slovenia	43	143	132	57
Spain	219	143	132	57
Sweden	13	143	132	57
Switzerland	40	143	132	57
United Kingdom	30	143	132	57

Notes: VASR data (manufacturer and importer data) excludes antifungals, antiparasitics, antivirals, Category IV antimicrobials, and uncategorized not medically important antimicrobials. The PCU denominator was harmonized to the greatest extent possible with the ESVAC network (the ESVAC denominator does not include beef cows, whereas in Canada beef cows are a significant population and are included; ESVAC excludes companion animal data from the numerator). The Canadian data used for live horses was from 2010.

Sources: European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption, 2020. Sales of veterinary antimicrobial agents in 31 European countries in 2018. (EMA/24309/2020). Available at: https://www.ema.europa.eu/en/documents/report/sales-veterinary-antimicrobial-agents-31-european-countries-2018-trends-2010-2018-tenth-esvac-report_en.pdf. Accessed January 23, 2021.

It is important to note that the structure and detail in the data for animal production classes available in the European datasets differ from the Canadian datasets; hence this figure should be interpreted with caution.

Indication for antimicrobial use in animals (farm-level surveillance)

Information on the indication for AMU in broiler chickens, grower finisher pigs and turkeys was available through sentinel farm surveillance conducted in 2019. The majority of AMU was for disease prevention (primarily for the prevention of enteric diseases)

Figure 25: Text description

Broiler chicken
Year	2015	2016	2017	2018	2019
Number of flocks/herds	135	136	137	141	147
Disease treatment	32.3	14.5	26.0	22.2	32.8
Disease prevention	115.5	115.4	108.0	102.1	109.7
Growth promotion	0.7	0.3	0.5	0.1	0.0
Grower-finisher pigs
Year	2015Footnote *	2016Footnote *	2017	2018	2019
Number of flocks/herds	85	91	82	97	107
Disease treatment	16.0	3.7	15.1	8.9	20.2
Disease prevention	90.0	76.8	58.2	83.5	102.1
Growth promotion	70.3	35.0	46.1	27.6	7.9
Turkeys
Year	2015	2016	2017	2018	2019
Number of flocks/herds	Not available	72	74	95	98
Disease treatment	Not available	2.0	6.0	6.2	16.3
Disease prevention	Not available	58.1	51.9	47.0	67.2
Growth promotion	Not available	0.1	0.7	0.1	0.0
Footnotes Footnote 1 Feed AMU data only. Return to footnote * referrer

For broiler chicken flocks

In 2019, there was continued use of medically important antimicrobials for growth promotion purposes on three of the 107 sentinel farms.

Excluding the use of Category IV antimicrobials (including ionophores and flavophospholipols) in feed, the reported quantity of antimicrobials used for growth promotion declined to 21 DDD/1000 PDAR, or 13% (21/162) of overall use in feed for 2019. Comparatively, it was 42 DDD/1000 PDAR, or 24% (42/178) in 2018. Antimicrobials administered by water and injection were used for disease prevention or treatment only, not growth promotion.

For broiler chicken flocks

There were no broiler chicken sentinel farms reporting the use of antimicrobials for growth promotion in 2019.

For turkey flocks

There were no turkey sentinel farms reporting antimicrobials for growth promotion in 2019.

Integrating information on antimicrobials intended for use across sectors (human, animals and crops)

Overall

The total kilograms of antimicrobials sold for use among the human and animal as well as plant sectors was calculated through the integration of data sourced from IQVIA, VASR and the Health Canada’s Pest Management Regulatory Agency.

In 2019, a total of 1.2 million kg of medically important antimicrobials were sold in Canada. Sales for use in production animals represented 78% of the total, humans represented 22%, companion animals represented <1% and antimicrobials for use as pesticides on food crops represented <1%.

However, in 2019, there were approximately 23 animals for every human in Canada (an underestimate, as the numbers of fish are not included in the numbers of animals). When the biomass of people and animals was taken into account, this revealed that approximately 1.4 times more antimicrobials were intended for use in production animals than in people using European standard weights of animals. It would be 1.3 times using Canadian standard weights of animals.

While similar antimicrobial groups were distributed or purchased for use in both sectors, the types of antimicrobials sold varied (Figure 26). Sales for antimicrobials in the animal sector reflected relatively more tetracyclines and macrolides than the human sector. Conversely, there were relatively more sales of third generation (and higher generation) cephalosporins and fluoroquinolones in the human sector than the animal sector. In Canada, the carbapenem class antimicrobials have never been licensed for use in animals.

Figure 26: Text description

Antimicrobial class	Human Data	Animal Sales Data
Carbapenems	1095.7	0.0
Fluoroquinolones and quinolones	16577.0	937.0
Cephalosporins (1st and 2nd gen)	44893.7	3234.0
Cephalosporins (3rd gen and higher)	5863.5	1676.0
Aminoglycosides	167.9	6487.0
Lincosamides	6514.4	46390.0
Trimethoprim and sulfas	19827.0	78962.0
Macrolides	14073.9	115822.0
Penicillins	138390.6	93843.0
Others*	14108.3	134044.0
Tetracyclines	8328.4	495116.0

Data sources: IQVIA and VASR.

Others for humans includes: bacitracin, ceftobiprole medocaril, ceftolozane:tazobactam, chloramphenicol, colistin, daptomycin, fidaxomicin, fosfomycin, fusidic acid, linezolid, metronidazole, nitrofurantoin, and vancomycin.

Others for animals includes: aminocoumarins, aminocyclitols, amphenicols, cyclic polypeptides, fusidic acid, glycopeptides, nitrofurantoins, nitroimidazoles, orthosomycins, phosphonic acid derivatives, pleuromutilins, polymyxins, pseudomonic acids, streptogramins, and therapeutic agents for tuberculosis.

Methods: Antimicrobial use information (i.e., farm-level data)

In 2019, antimicrobial use information was voluntarily provided by 352 sentinel farms participating in the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS; 147 broiler chicken flocks, 98 turkey flocks, and 107 grower-finisher pig herds). More details can be found in the CIPARS 2019 Design and Methods (Public health Agency of Canada (PHAC), 2020).

Authors

Table 11: Primary authors, contributing authors and acknowledgements

Primary authors	Program	Contributing authors	Program	Acknowledgements	Program
Dr. Oscar Niragira Jayson Shurgold Linda Pelude Dr. Carolee Carson Dr. James Brooks	CARSS CARSS CNISP CIPARS PHAC	Dr. Aboubakar Mounchili Dr. Agnes Agunos Dr. Anne Deckert Dr. Donald Sheppard Tanya Lary Averil Griffith Braden D Knight Dr. David Leger Delvin Rao Drew Greydanus George Golding Glenys Smith Irene Martin Kelly Baekyung Choi Laura F. Mataseje Melissa McCracken Michael R. Mulvey Reshele Senoli Perera Robyn Mitchell Dr. Sheryl Gow Tim Du Walter Demczuk	CTBLSS CIPARS CIPARS AMRTF AMRTF NML CARSS CIPARS CARSS CARSS CNISP CARSS NML CNISP CNISP CNISP NML CTBLSS CNISP CIPARS CNISP NML	Caroline M Desjardins Anada Silva Cecilla Mcclellan Denise Gravel-Tropper Jami Mackenzie Jennifer Campbell Joëlle Cayen Marianna Ofner Romeo Hizon Vivienne Steele Wallis Rudnick CNISP participating hospitals Contributors to CIPARS Health Canada VASR IQVIA Statistics Canada	CARSS CNISP CNISP CARSS CARSS CNISP CNISP IPC CNISP CNISP CNISP

Appendices

Appendix A: Antibiotics included in each antimicrobial class (i.s. ATC grouping), Human sector

Table 12: Antibiotics included in each antimicrobial class (i.s. ATC grouping), Human sector

Atc4	Atc4 description	Atc5	Atc5 description	Molecule
A07a	Intestinal anti-infectives	A07aa	Antibiotics	Fidaxomicin
				Vancomycin
J01a	Tetracyclines	J01aa	Tetracyclines	Doxycycline
				Minocycline
				Tetracycline
				Tigecycline
J01b	Amphenicols	J01ba	Amphenicols	Chloramphenicol
J01c	Beta-lactam antibacterials, penicillins	J01ca	Penicillins with extended spectrum	Amoxicillin
				Ampicillin
				Piperacillin
		J01ce	Beta-lactamase sensitive penicillins	Penicillin g
				Penicillin v
		J01cf	Beta-lactamase resistant penicillins	Cloxacillin
				Dicloxacillin
				Flucloxacillin
				Oxacillin
		J01cr	Combinations of penicillins, incl. Beta-lactamase inhibitors	Amoxicillin: clavulanic acid
				Clavulanic acid: ticarcillin
				Piperacillin
				Piperacillin: tazobactam
J01d	Other beta-lactam antibacterials	J01db	First-generation cephalosporins	Cefadroxil
				Cefazolin
				Cephalexin
		J01dc	Second-generation cephalosporins	Cefaclor
				Cefoxitin
				Cefprozil
				Cefuroxime
		J01dd	Third-generation cephalosporins	Cefixime
				Cefotaxime
				Ceftazidime
				Ceftriaxone
		J01de	Fourth-generation cephalosporins	Cefepime
		J01df	Monobactams	Aztreonam
		J01dh	Carbapenems	Cilastatin: imipenem
				Ertapenem
				Meropenem
		J01di	Other cephalosporins and penems	Ceftobiprole medocaril
				Ceftolozane: tazobactam
J01e	Sulfonamides and trimethoprim	J01ea	Trimethoprim and derivatives	Trimethoprim
		J01ec	Intermediate-acting sulfonamides	Sulfadiazine
				Sulfamethoxazole
		J01ee	Combinations of sulfonamides and trimethoprim, incl. Derivatives	Sulfamethoxazole: trimethoprim
J01f	Macrolides, lincosamides and streptogramins	J01fa	Macrolides	Azithromycin
				Clarithromycin
				Erythromycin
				Erythromycin ethylsuccinate
				Spiramycin
		J01ff	Lincosamides	Clindamycin
				Lincomycin
J01g	Aminoglycoside antibacterials	J01ga	Streptomycins	Streptomycin
		J01gb	Other aminoglycosides	Amikacin
				Gentamicin
				Tobramycin
J01m	Quinolone antibacterials	J01ma	Fluoroquinolones	Ciprofloxacin
				Gatifloxacin
				Levofloxacin
				Moxifloxacin
				Norfloxacin
				Ofloxacin
J01x	Other antibacterials	J01xa	Glycopeptide antibacterials	Telavancin
				Vancomycin
		J01xb	Polymyxins	Colistin
				Polymyxin b
		J01xc	Steroid antibacterials	Fusidic acid
		J01xd	Imidazole derivatives	Metronidazole
		J01xe	Nitrofuran derivatives	Nitrofurantoin
		J01xx	Other antibacterials	Bacitracin
				Daptomycin
				Fosfomycin
				Linezolid
				Methenamine
P01a	Agents against amoebiasis and other protozoal diseases	P01ab	Nitroimidazole derivatives	Metronidazole

Appendix B: Supplementary figures

Figure 27: Text description

Year	2015	2016	2017	2018	2019
Adult hospitals	0.78	0.91	0.95	1.25	1.20
Mixed hospitals	0.57	0.76	0.71	0.81	0.96
Pediatric hospitals	0.70	0.78	0.68	0.83	0.98

Figure 28: Text description

Year	2015	2016	2017	2018	2019
Overall	20.5	19.1	16.4	18.8	16.2
HA-MRSA	25.3	21.7	20.6	25.7	19.8
CA-MRSA	12.1	16.0	13.1	12.3	13.7

Figure 29: Text description

Year	2015	2016	2017	2018	2019
All-cause mortality (n)	34	36	7	66	74
All-cause mortality (per 100 cases)	41.5	31.9	32.2	29.9	36.5

Figure 30: Text description

Year	2015	2016	2017	2018	2019
Overall Overall (all-cause)	9.8	8.4	7.9	8.0	8.6
Overall Overall (attributable)	3.0	2.4	2.3	1.3	2.3
HA-CDI HA-CDI (all-cause)	11.4	9.1	9.0	9.2	8.2
HA-CDI HA-CDI (attributable)	3.4	2.5	2.8	1.1	2.1
CA-CDI CA-CDI (all-cause)	5.1	6.3	4.0	4.1	9.8
CA-CDI CA-CDI (attributable)	1.9	2.1	0.6	1.8	3.0

Appendix C: Participating CNISP hospitals

Table 13: Participating CNISP hospitals

Hospital name	City	Province
Alberta Children’s Hospital	Calgary	AB
BC Children’s Hospital	Vancouver	BC
BC Women’s Hospital	Vancouver	BC
Bridgepoint Active Healthcare	Toronto	ON
Burin Peninsula Health Care Centre	Burin	NL
Carbonear General Hospital	Carbonear	NL
Centre hospitalier de l'Université de Montréal (CHUM)	Montreal	QC
Children’s Hospital of Eastern Ontario (CHEO)	Ottawa	ON
Children’s Hospital of Western Ontario	London	ON
Centre hospitalier universitaire Sainte-Justine	Montreal	QC
Civic Campus, Ottawa Hospital	Ottawa	ON
Dartmouth General Hospital	Halifax	NS
Dr. G.B. Cross Memorial Hospital	Clarenville	NL
Foothills Medical Centre	Calgary	AB
General Campus, Ottawa Hospital	Ottawa	ON
General Hospital & Miller Centre	St. John’s	NL
General Hospital, Hamilton Health Sciences Centre	Hamilton	ON
Halifax Infirmary	Halifax	NS
Health Sciences Centre-Winnipeg	Winnipeg	MB
Hôpital Maisonneuve-Rosemont	Montréal	QC
Hospital for Sick Children	Toronto	ON
Hôtel-Dieu de Québec	Québec	QC
IWK Health Centre	Halifax	NS
Janeway Children’s Hospital and Rehabilitation Centre	St. John’s	NL
Jurvinski Hospital and Cancer Center, Hamilton Health Sciences Centre	Hamilton	ON
Kelowna General Hospital	Kelowna	BC
Kingston General Hospital	Kingston	ON
Lion’s Gate	North Vancouver	BC
McMaster Children’s Hospital, Hamilton Health Sciences Centre	Hamilton	ON
Montreal Children’s Hospital, McGill University Health Centre	Montréal	QC
Montreal General Hospital, McGill University Health Centre	Montréal	QC
Montreal Neurological Institute, McGill University Health Centre	Montréal	QC
Moose Jaw hospital	Moose Jaw	SK
Mount Sinai Hospital	Toronto	ON
Nanaimo Regional General Hospital	Nanaimo	BC
North York General Hospital	Toronto	ON
Pasqua Hospital	Regina	SK
Peter Lougheed Centre	Calgary	AB
Powell River General Hospital	Powell River	BC
Prince County Hospital	Summerside	PE
Princess Margaret	Toronto	ON
Qikiqtani General Hospital	Iqaluit	NU
Queen Elizabeth Hospital	Charlottetown	PE
Regina General Hospital	Regina	SK
Rehabilitation Centre	Halifax	NS
Richmond General Hospital	Richmond	BC
Rockyview General Hospital	Calgary	AB
Royal Jubilee	Victoria	BC
Royal University Hospital	Saskatoon	SK
Royal Victoria Hospital, McGill University Health Centre	Montréal	QC
Sechelt Hospital (formerly St. Mary’s)	Sechelt	BC
SMBD - Jewish General Hospital	Montréal	QC
South Health Campus	Calgary	AB
Squamish General Hospital	Squamish	BC
St Joseph’s Healthcare	Hamilton	ON
St. Clare’s Mercy Hospital	St. John’s	NL
St. Michael's Hospital	Toronto	ON
St. Paul’s Hospital	Saskatoon	SK
Stollery Children’s Hospital	Edmonton	AB
Sudbury Regional Hospital	Sudbury	ON
Sunnybrook Hospital	Toronto	ON
The Moncton Hospital	Moncton	NB
Toronto General Hospital	Toronto	ON
Toronto Western Hospital	Toronto	ON
UBC Hospital	Vancouver	BC
University Hospital	London	ON
University Hospital of Northern BC	Prince George	BC
University of Alberta Hospital	Edmonton	AB
University of Manitoba Children’s Hospital	Winnipeg	MB
University of Ottawa Heart Institute, Ottawa Hospital	Ottawa	ON
Vancouver General Hospital (VGH)	Vancouver	BC
Veterans Memorial Building	Halifax	NS
Victoria General	Halifax	NS
Victoria General Hospital	Victoria	BC
Victoria Hospital	London	ON
Western Memorial Regional Hospital	Corner Brook	NL

Footnotes

References

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