Canadian Antimicrobial Resistance Surveillance System Report 2015

Alternate Formats

Table of Contents

Glossary

AMR
Antimicrobial resistance
AMU
Antimicrobial use
BSI
Bloodstream infection
CAHI
Canadian Animal Health Institute
CA-MRSA
Community-associated Methicillin-resistant Staphylococcus aureus
CARSS
Canadian Antimicrobial Resistance Surveillance System
CDI
Clostridium difficile infection
CIPARS
Canadian Integrated Program for Antimicrobial Resistance Surveillance
CNISP
Canadian Nosocomial Infection Surveillance Program
CPO
Carbapenamase-producing organisms
CRE
Carbapenem-resistant Enterobacteriaceae
CTBLSS
Canadian Tuberculosis Laboratory Surveillance System
CTLTN
Canadian Tuberculosis Laboratory Technical Network
ESAC-Net
European Surveillance of Antimicrobial Consumption Network
ESBL
Extended-spectrum β-lactamase
ESVAC
European Surveillance of Veterinary Antimicrobial Consumption
GAS
Group A Streptococcus
GBS
Group B Streptococcus
GNB
Gram-negative Bacilli
HA-CDI
Health care-associated Clostridium difficile infection
HA-MRSA
Health care-associated Methicillin-resistant Staphylococcus aureus
HIV
Human Immunodeficiency Virus
IPD
Invasive pneumococcal disease
IV
Intravenous
LFZ
Laboratory for Foodborne Zoonoses
MDR
Multi-drug-resistant
MDR-TB
Multi-drug-resistant Tuberculosis
MRSA
Methicillin-resistant Staphylococcus aureus
NML
National Microbiology Laboratory
NNRTI
Non-nucleoside reverse transcriptase inhibitor
NRTI
Nucleoside reverse transcriptase inhibitor
OIE
World Organisation for Animal Health
PCU
Population Correction Unit
PCV7
7-valent pneumococcal conjugate vaccine
PCV13
13-valent pneumococcal conjugate vaccine
SSTI
Skin and soft tissue infection
TB
Tuberculosis
TMP-SMX
Trimethoprim-sulfamethoxazole
UTI
Urinary tract infection
VDD
Veterinary Drug Directorate
VRE
Vancomycin-resistant Enterococci
VRSA
Vancomycin-resistant Staphylococcus aureus
WHO
World Health Organization
XDR-TB
Extensively drug-resistant Tuberculosis

Message from the Chief Public Health Officer of Canada

Antimicrobial resistance is a serious and growing issue. It threatens the world's ability to prevent and treat an ever-increasing range of infections. In Canada alone, total medical care costs associated with antimicrobial resistant infections have been estimated at one billion dollars.

To better understand the problem, surveillance systems, like those stewarded by the Public Health Agency of Canada, provide timely collection and analysis of reliable data on antimicrobial use and resistance. In turn, that data supports health professionals and policy makers in making informed decisions, and in taking concrete action on the prudent use of antimicrobials to mitigate diseases.

That is why strengthening our surveillance platform is critical to informing our understanding of the problem. Better integration of surveillance, as outlined in Antimicrobial Resistance and Use in Canada: A Federal Framework for Action, is key. The creation of the Canadian Antimicrobial Resistance Surveillance System (CARSS) which aims to provide an integrated and national picture on antimicrobial use and resistance will help us do just that.

This report is the first step in the creation of CARSS. It represents the first-ever integrated antimicrobial use and resistance surveillance report. It will help integrate existing systems, enhance our surveillance and analysis, and better inform provinces, territories and stakeholders. It highlights analysis informed by the data we receive from our many partners across Canada. It also provides us with important new information: for example, how Canada's use of medically-important antibiotics in animals and humans compares with other countries.

We commend and thank all contributors for their efforts. This report is made possible by the many jurisdictions, organizations and individuals who provide the data that makes CARSS such an important tool in addressing the impacts of antimicrobial resistance. We look forward to consulting with stakeholders over the next year, to help us shape future reports, and to continue building a strong, effective and responsive antimicrobial surveillance system in Canada.

Dr. Gregory Taylor
Chief Public Health Officer of Canada

Krista Outhwaite
President, Public Health Agency of Canada

At a glance

The Government of Canada is committed to leading activities that will prevent, limit and control the emergence and spread of AMR as described in Antimicrobial Resistance and Use in Canada: A Federal Framework for Action. The Canadian Antimicrobial Resistance Surveillance System (CARSS) is an essential component of this work and has been established by the Public Health Agency of Canada (the Agency) to strengthen the coordination and integration of antimicrobial resistance (AMR) and antimicrobial use (AMU) activities and information in Canada. One of CARSS' key responsibilities is to produce an annual report on the status of AMR/AMU in Canada.

This is the first CARSS report. It provides an integrated summary of current and available AMR/AMU information from seven Agency surveillance systems and laboratory reference services. This initial analysis points the way forward for AMR/AMU surveillance in the Agency and provides a benchmark for progress on AMR/AMU moving forward. Future CARSS activities and reports will consider stakeholder feedback, surveillance information needs and gaps, and will include information from other Agency surveillance systems with AMR/AMU components and new surveillance initiatives.

In Canada, AMR and AMU remain a concern due to increased resistance levels detected in pathogenic microbes and antimicrobial use levels that are not declining as needed to preserve the effectiveness of remaining antimicrobials. The threat of AMR is not just a Canadian problem, it is a global problem.  Increasing the integration of surveillance will position Canada to continue and improve its contribution to the global AMR mitigation efforts.

Canadian Antimicrobial Resistance Surveillance System (CARSS)

CARSS was created as the national focal point for AMR/AMU surveillance in Canada. It represents an important step in the evolution of the Agency's surveillance programs to act against AMR. CARSS will oversee and champion federal surveillance transformation activities, beginning within the Agency. Through CARSS, the Agency will address the requirements and data needs identified by internal and external stakeholders from a comprehensive integrated perspective.  CARSS will work with the Agency's existing surveillance programs to identify new opportunities to collect, share and analyse AMR/AMU data in Canada.

As the overarching AMR/AMU surveillance system for the Agency, CARSS will work nationally and internationally with experts, programs and stakeholders to inform evidence-based actions. Using accurate, relevant and timely data, CARSS will provide an annual, comprehensive, integrated AMR/AMU surveillance report to inform AMR/AMU research and policy on stewardship, innovation and disease prevention.

The AMR/AMU landscape is dynamic and rapidly changing and will require CARSS to adapt to the information needs of stakeholders and decision-makers. As a result, the continued evolution of CARSS will be underpinned by dialogue and consultation with experts and stakeholders across Canada and internationally, ensuring that integration is maximized and that information meets stakeholder needs.

Antimicrobial Use

  • Since 2001, AMU (in defined daily doses per 1,000 person-days) has declined in communities and hospitals.
  • Since 2006, the total antimicrobials distributed for sale in animals (adjusted for animal population and weight) has remained stable.
  • The purchasing of antimicrobials considered "restricted" in the hospital setting has substantially increased over time, particularly in treating Gram-positive infections.
  • In 2013, approximately 1.4 times more antimicrobials were distributed for use in animals than humans in Canada (adjusting for population and weight).
  • The total antimicrobials distributed for animal use in Canada was 42 times higher than in Norway (the country with the lowest use, ranked number 1). Overall, Canada ranked 21 out of 27 countries based on levels of antimicrobial sales.
  • Canada's use of human outpatient antimicrobials was 1.6 times higher than in the Netherlands (the country with lowest use, ranked number 1). Overall, Canada was 11th of 29 countries based on total use of antimicrobials.

Antimicrobial Resistance

  • In 2013, resistance to antimicrobials (cephalosporins) used for treating gonorrhoea was present in 3.9% of infections, raising concerns that treatment with these antimicrobials may not be effective.
  • Since 2009, methicillin-resistant Staphylococcus aureus (MRSA) infection rates have been decreasing, especially in hospital settings. However, current MRSA infection rates continue to exceed those observed in the early 2000s, and MRSA remains a significant cause of infection.
  • Clostridium difficile infection rates in hospital settings have remained stable since 2007.
  • Carbapenems are broad-spectrum antimicrobials usually reserved for use in more severe infections. The annual overall rate of infection resistant to carbapenems (specifically Carbapenem-Resistant Enterobacteriaceae) has approximately remained the same.
  • Vaccination programs against Streptococcus pneumoniae have helped reduce the rate of infection caused by an important multidrug-resistant strain of the bacteria.
  • In 2013, resistant Salmonella bacteria caused 759 reported human cases of disease (out of a total of 2,987 human Salmonella cases).

Introduction

Since the early twentieth century dramatic improvements to human health have been made as a result of  better public health systems, hygiene and infection control, the development of vaccines and, in addition, the extensive use of antimicrobials. As new classes of antimicrobialsReference a have been introduced over time, health professionals have more tools in their arsenal to manage and treat infectious diseases, including preventative use in surgeries, chemotherapy and the treatment of immunocompromised patients. Veterinarians have also benefited from the use of antimicrobials in the prevention and treatment of diseases in animals. Since similar classes of antimicrobials are used in both populations antimicrobial selection pressure has been levied in multiple settings leading to the emergence and spread of antimicrobial-resistant organisms.

"We are in a constant struggle to protect ourselves from the potentially harmful, complex and unseen world of microbes. Canada has made advancements in combating the more harmful micro-organisms. But despite all our progress, our ability to overcome infectious diseases remains, at best, limitedFootnote 1."

Dr. David Butler Jones
Chief Public Health Officer of Canada
(2005-2013)

The broader and increased use of antimicrobials in humans and animals has accelerated the development of resistance and made some infections harder to treat with commonly-used antimicrobials. Even more concerning is the ability of some microbes to become resistant to more than one group of antimicrobials which further limits treatment options. As very few new antimicrobials are in development and rates of AMR are increasing, we are now threatened with a return to similar levels of disease and death observed in the early twentieth century.

The Government of Canada has been addressing aspects of AMR for some time. The Agency operates surveillance programs that monitor AMR and AMU in a variety of settings including hospitals, communities, veterinary and agricultural settings; however, existing national surveillance does not provide a complete picture of the state of AMR and AMU in Canada. This limits the ability to effectively monitor the emergence and spread of resistant infections, or to measure the impact of interventions aimed at counteracting loss in antimicrobial effectiveness.

In October 2014, the Government of Canada published Antimicrobial Resistance and Use in Canada: A Federal Framework for Action which represented an important step towards meeting the challenge posed by AMR. The Framework describes the Government of Canada's commitment to lead activities to prevent, limit and control the emergence and spread of AMR.

The Agency's existing AMR surveillance systems generate a significant amount of information. When established these systems were designed as standalone systems and integration between systems was not prioritized. To better understand the magnitude and impact of AMR in Canada and to address the threat it poses, the Agency must adapt its surveillance approach so that more comprehensive information is available to inform public health decision-making and implementation of interventions to combat AMR.

The first step towards necessary change is the establishment of CARSS, which will strengthen the coordination and integration of Agency AMR/AMU activities and information. CARSS will also provide leadership on AMR/AMU surveillance, inform and direct the expansion of surveillance activities to areas of greatest need and provide useful and relevant information to stakeholders and the public in support of antimicrobial stewardship interventions to protect the health of Canadians.

Scope of the Report

This first CARSS report integrates currently available Agency AMR/AMU data into a more integrated summary of surveillance information. The data analysis will be used to identify gaps and inform surveillance enhancements.   This report is intended to provide Agency AMR/AMU surveillance stakeholders and public health partners with information on current Canadian AMR/AMU surveillance activities and findings.  This is also a starting place for future discussions about the way forward for integrated AMR/AMU surveillance in Canada.

Background

AMR simply means that the antimicrobial drugs that were once effective against a particular microbe no longer work because the microbe's biological makeup has changed and it has become resistant to treatment. This resistance can occur naturally, or can be acquired when an infection is treated with an antimicrobial that kills only some of the microbes. Those that resist the treatment survive and multiply. Over time, more and more of the resistant microbes remain in our environment, eventually leading to the emergence of new strains of disease-causing microbes that are partially or fully resistant to antimicrobial treatment.

AMR microbes move and spread in the same way as all infectious disease-causing microbes do. Resistant microbes are generally found where AMU is higher and disease conditions are more common (e.g., hospitals). Modern medical and veterinary practice depends on the widespread availability of effective antimicrobials to prevent and treat infections in humans and animals. Without them, our ability to fight infectious disease would be significantly impeded. Actions to mitigate AMR and improve AMU stewardship must be built on a foundation of high-quality and timely surveillance information.

Surveillance

The Agency's Infectious Diseases Prevention and Control Branch is responsible for managing the systems that currently perform AMR/AMU surveillance. This report includes information from seven Agency surveillance systems (listed below). Moving forward, future reports will respond to stakeholder feedback and surveillance information needs and will include information from other Agency AMR/AMU systems as well as new Agency surveillance initiatives.

  1. The Canadian Nosocomial Infection Surveillance Program (CNISP), established in 1994, is a collaborative effort between the Agency and sentinel hospitals participating as members of the Canadian Hospital Epidemiology Committee (CHEC), a subcommittee of the Association of Medical Microbiology and Infectious Disease (AMMI) Canada.  This program collects data on select antimicrobial-resistant organisms in over 60 largely university-affiliated hospitals in all provinces. The data collected provides clinicians and decision-makers with evidence-based benchmarks, identifies trends and supports the development of national guidance documents to help reduce the transmission of AMR.
  2. The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), established in 2002, monitors AMU in animals and humans, as well as AMR in Salmonella in humans, animals and retail food. Antimicrobial resistance in Campylobacter and Escherichia coli (E. coli) are monitored in animals and food of animal origin. The data collected supports antimicrobial stewardship in human and animal health and identifies potential measures to slow the spread of AMR along the food chain. The focus of CIPARS is on bacteria and antimicrobials of public health importance; veterinary pathogens other than Salmonella are not covered.
  3. FluWatch is Canada's national surveillance system that monitors the spread of influenza and influenza-like illnesses on an ongoing basis. FluWatch reports contain specific information for health professionals on influenza viruses and antiviral resistance in Canada.
  4. The Canadian Tuberculosis Laboratory Surveillance System (CTBLSS) monitors drug resistance patterns in Mycobacterium tuberculosis. The Agency collaborates with the Canadian Tuberculosis Laboratory Technical Network and participating laboratories (representing all provinces and territories) to monitor this resistance in Canada.
  5. The Antimicrobial-resistant Neisseria gonorrhoeae Surveillance System has monitored antimicrobial susceptibilities of N. gonorrhoeae since 1985. The National Microbiology Laboratory (NML) works in collaboration with provincial laboratories.
  6. The national surveillance of Invasive Streptococcal Disease is a passive surveillance system that monitors antimicrobial susceptibilities in Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus agalactiae isolated from sterile sites such as blood and spinal fluid. NML collaborates with provincial laboratories, the University of Manitoba and the Canadian Antimicrobial Resistance Alliance to monitor antimicrobial susceptibilities.
  7. The Canadian HIV Strain and Drug Resistance Surveillance Program monitors drug resistance in HIV isolates obtained from treatment-naïve individuals with newly diagnosed HIV infection. Five provinces currently participate in this surveillance initiative.

In addition to the systems above, NML and the Laboratory for Foodborne Zoonoses (LFZ) support all Agency AMR surveillance programs and detect new and emerging AMR organisms through laboratory reference services to all provinces and territories.

Human AMU data is purchased by the Agency from IMS Health Canada IncFootnote 2. These data include information on prescriptions dispensed by retail pharmacies in Canada, antimicrobials purchased by Canadian hospitals, and diagnoses for which physicians have recommended an antimicrobial in the community. This data is received at the provincial level; information for the Yukon, Northwest Territories and Nunavut is not currently included.

The Canadian Antimicrobial Resistance Surveillance System (CARSS)

The threat posed by AMR simply does not allow the Agency to maintain the status quo. A comprehensive national understanding of AMR/AMU in Canada is required to mitigate the effects of AMR and to increase prudent AMU practices. This report provides the first integration of AMR/AMU surveillance information collected through existing Agency surveillance activities. Before CARSS, reporting was carried out by individual surveillance systems, often with limited explanation or interpretation for key audiences. As a result, the Canadian picture of AMR/AMU is incomplete and our understanding of the success of interventions aimed at counteracting loss in antimicrobial effectiveness due to rising AMR is limited. Integrated and comprehensively translated information will allow the Agency to determine and understand the full AMR/AMU picture, monitor the effectiveness of stewardship interventions, and better position Canada internationally.

The creation of CARSS is a key commitment within the Government of Canada's Federal Framework for Action on AMR. CARSS will be a national focal point for AMR/AMU surveillance and its creation is an important step in the evolution of surveillance leading to concrete action on AMR. CARSS will address gaps by working with existing surveillance programs to integrate current surveillance activities, enhance knowledge through additional work on AMR/AMU within the Agency and set strategic priorities. CARSS will begin its work within the Agency with a view to a longer term inclusion of other Federal, Provincial, Territorial, and external partners.

The following are objectives for CARSS:

  1. Integrate AMR/AMU surveillance information from within and outside the Agency.
  2. Provide an annual integrated report of AMR/AMU in Canada.
  3. Provide leadership on AMR/AMU surveillance.
  4. Inform and direct strategic AMR/AMU surveillance transformation activities.
  5. Create and track performance indicators for AMR/AMU surveillance.

CARSS will be positioned as the overarching AMR surveillance system for the Agency.  Because CARSS is being built on the foundation of the current Agency AMR/AMU systems it will be in an excellent position to achieve these objectives. It will work with and support AMR/AMU experts, programs and stakeholders to develop its governance structure.  Its surveillance data will inform evidence-based actions and the assessment of AMR mitigation and stewardship interventions. Ultimately the information generated by CARSS will intersect with and inform AMR/AMU research and policy on stewardship, innovation and disease prevention, both domestic and globally.

CARSS will provide information in a timely integrated manner that meets stakeholder needs, working towards including information from beyond the Agency (other Government departments and Provinces and Territories) to complete the AMR/AMU picture. This will require an incremental approach to CARSS and its broader transformation activities. The AMR/AMU landscape is dynamic and rapidly changing with many players. As a result CARSS will be evergreen and adaptable to the AMR/AMU information needs of stakeholders and decision-makers. The adaptation and formation of CARSS will be underpinned by dialogue and consultation with experts and stakeholders across Canada and internationally.

CARSS will oversee and champion federal surveillance transformation activities laid out in the body of this report, and others as they are identified, including actions outlined in the surveillance pillar of the Federal Framework. CARSS will work with stakeholders and Agency programs to identify data gaps. The linkages CARSS establishes with partners and stakeholders will maximize integration and seek to ensure that information meets stakeholder needs. Because CNISP, CIPARS, and other Agency AMR/AMU surveillance programs are components of CARSS, the Agency will address the requirements of stakeholders and data requirements from a comprehensive, rather than an individual program viewpoint.

Future annual AMR and AMU surveillance reports will build on the structure of this initial report. New sections will be added as data from new surveillance initiatives are gathered. The provision of accurate, relevant and timely data on AMR and AMU will serve as an important foundation for the development of best practices and priority setting for decision-makers. Discussion of progress in mitigating AMR and increasing prudent AMU will be a part of the annual CARSS report.

Antimicrobial Use in Canada

Antimicrobial Use in Humans

In 2013, Canadian community doctors with offices outside of the hospital setting made more than 293 million diagnoses, with 8% of these involved recommending an antimicrobialFootnote 2. Antimicrobials were most commonly recommended for pneumonia, acute bronchitis and acute sinusitis (Figure 1). Although it is not known if there were other comorbidities that guided the physician recommendations (due to data collection methodology), this finding signals possible misuse of antimicrobials since acute bronchitis and sinusitis are often viral rather than bacterial in originFootnote 3Footnote 4.

Compared to 2007 (the first year data was available), in 2013, physician recommendationsReference b for antimicrobial treatments decreased from 97% to 84% for upper urinary tract infections, from 58% to 52% for chronic sinusitis, and from 26% to 20% for acne, while recommendations for treating pneumonia increased from 75% to 85%. In 2013, a higher rate of children aged zero to two were recommended antimicrobials than adults aged 20 and older and a higher proportion of female patients were recommended an antimicrobials compared to male patientsFootnote 2 across all diagnoses.

Figure 1. Number of infections diagnosed by doctors in the community per 10,000 individuals and the percentage of these diagnoses with a recommendation for an antimicrobial, 2013Reference c

   Number of infections diagnosed by doctors in the community per 10,000 individuals and the percentage of these diagnoses with a recommendation for an antimicrobial, 2013 - Text Description
Figure 1. Number of infections diagnosed by doctors in the community per 10,000 individuals and the percentage of these diagnoses with a recommendation for an antimicrobial, 2013.
Diagnostic class Number of diagnoses per 10,000 individuals Percentage of diagnoses with antimicrobial recommendations
Acute bronchitis 803 77.85
Acute sinusitis 464 83.52
Diseases of the ear 2733 25.78
Lower urinary tract infections or cystitis 1342 68.87
Pneumonia 355 84.46
Skin and soft tissue infections 794 64.53
Upper respiratory tract infections 3255 32.59

A bar graph showing the total number of diagnoses for each diagnostic class per 10,000 individuals and boxes showing the percentage of each diagnosis that resulted with an antimicrobial recommendation in Canada during 2013. The horizontal axis represents the diagnostic class. The left vertical axis represents the number of diagnoses per 10,000 individuals while the right vertical axis represents the percentage of diagnoses with an antimicrobial recommendation.

Pharmacy dispensations

Between 2001 and 2013, AMU declined  from 208,016 to a total of 200,400 kg dispensed by Canadian community pharmacies (Figure 2Footnote 2). Community pharmacy dispensations represent 70% of all antimicrobials used in Canada. Both the prescription rates (per 1,000 population-days) and mass of active ingredients for antimicrobials dispensed by community pharmacies were at their lowest since the beginning of AMU surveillance in 2000. When examining individual drugs over time, erythromycin and penicillin V had reductions in use while nitrofurantoin, moxifloxacin and azithromycin had increases. Although the reductions far outweighed the increases observed between 2000 to 2013, these changes should continue to be monitored in the event that increases outweigh reductions (e.g., prescriptions for nitrofurantoin increased 139% between 2000 and 2013).

Among all antimicrobials dispensed in 2013, the highest number of prescriptions were provided to the youngest (zero to five years) and oldest (65 years and older) age groups. Yet between 2011 and 2013, the greatest overall reduction was in children in the zero to five year age group, from 1,003 to 872 prescriptions per 1,000 children. The antimicrobials most commonly dispensed in 2013 were amoxicillin, clarithromycin and doxycyclineFootnote 2. The decrease in prescriptions to children aligns with suggested guidelines for antimicrobial prescribing in this population.

There is also variation in AMU between provinces and territories. In 2013, Newfoundland and Labrador had the highest amounts of use measured by prescription rates, mass of active ingredients, and defined daily dosage rates. Prescription rates for parenteral (injections and intravenous) products in Québec, New Brunswick and Nova Scotia were more than twice the rate of any other province and were more than 15 times the rates in British Columbia, Manitoba and Ontario. These differences may be due to the fact that patients who were treated at hospital outpatient clinics filled their antimicrobial prescriptions at community pharmacies, rather than at the hospital.

Hospital purchases

Hospital purchases represent 30% of all antimicrobials used in people in CanadaFootnote 2. When measured by defined daily doses per 1,000 inhabitant-days there was a slight decrease from 2.97 to 2.69 defined daily doses per 1,000 population-days in antimicrobials purchased in 2001 compared to 2013. These were the lowest levels observed since 2001, the first year with available data on hospital AMU (Figure 2).

In 2013, rates of parenteral (injections and intravenous) antimicrobials purchased by hospitals were nine times higher than oral antimicrobials. The most commonly purchased antimicrobials in 2013 were ceftriaxone, penicillin G and piperacillin with enzyme inhibitor (tazobactam) productsFootnote 2. Between 2010 and 2013, there were large increases in hospital purchases of ceftriaxone, piperacillin and tazobactam products, while use of penicillin G decreased by over 60% between 2009 and 2013. These increases are likely due to greater resistance to those antimicrobials that would have otherwise been the first choice for treatment, leading to an increased use of these antimicrobialsFootnote 5.

Hospital purchasing of antimicrobials in 2013 varied across provinces and territories. Manitoba had the highest purchase levels while Ontario had the lowest. Ceftriaxone was the highest purchased in the majority of hospitals with the exception of Ontario, Québec and New Brunswick, where penicillin G was the most purchased. Saskatchewan had the lowest proportion of parenteral products purchased (85%) while New Brunswick had the highest (94%), with the remaining products consisting of oral antimicrobials.

Figure 2. Defined daily doses per 1,000 population-days dispensed through community pharmacies or purchased by hospitals in Canada, 2001-2013

   Defined daily doses per 1,000 population-days dispensed through community pharmacies or purchased by hospitals in Canada, 2001-2013 - Text Description
Figure 2. Defined daily doses per 1,000 population-days dispensed through community pharmacies or purchased by hospitals in Canada, 2001-2013
Year 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Pharmacy dispensation 18.6 17.8 17.9 17.3 17.7 17.8 17.7 17.8 17.7 17.7 18.7 18.1 17.6
Hospital purchases 3.0 2.7 2.8 3.0 30 2.8 2.8 2.8 2.9 2.7 2.8 2.8 2.7

Stacked column graph showing the number of defined daily doses per 1,000 population-days dispensed either through pharmacies or purchased by hospitals in Canada from 2001 to 2013. The horizontal axis represents the year and the vertical axis represents the total defined daily doses per 1,000 population-days.

Antimicrobials of critical importance to human medicine in the hospital

Treatment of severe infectious diseases usually occurs in the hospital setting, often with drugs administered via injection (intravenous or intramuscular). The Agency seeks the expertise of infectious disease physicians, family physicians and pharmacists through the Antimicrobial Use Working Group to assist in the interpretation and development of the Human Antimicrobial Use ReportFootnote 2. This group was consulted on how they would cluster antimicrobials to treat Gram-negative and Gram-positive infections in the hospital setting (Table 1). Members categorized critical ("last-recourse") antimicrobials into two groups, "restricted" or "non-restricted" based on their availability and whether they are considered "last recourse" in the treatment of certain infections. The restricted group includes drugs that are available for use but are restricted within the hospital formulariesReference d while the non-restricted group includes those that are easily availableReference e and widely used in the hospital but still considered to be "last recourse". Other widely-used antimicrobials in hospitals are considered first-line drugs so do not meet the definition of "last recourse" and are not included in either group.

Table 1. Identification of critical antimicrobials for treating bacterial infections in the hospital setting by group and type of infection
Type of infection Restricted Non-Restricted
Gram-negative bacterial infections Amikacin
Colistin
Fosfomycin
Imipenem
Meropenem
Tobramycin
Tigecycline
Ertapenem
Gentamicin
Moxifloxacin
Piperacillin-tazobactam
Gram-positive bacterial infections Daptomycin
Linezolid
Vancomycin

The Agency analyses information on antimicrobials purchased by hospitals in Canada. The above grouping was assigned to drugs present in hospital purchasing data and was used to identify purchasing changes over time. Among Gram-negative infections, non-restricted drugs are the main group of antimicrobials used for treatment. Between 2001 and 2003, drugs in the restricted group were used more frequently for treating Gram-negative infections than non-restricted drugs (Figure 3).  However since 2003, the use of non-restricted antimicrobials began to increase, with levels in 2013 representing 19 times those of 2001, mainly driven by increases in the purchasing of piperacillin-tazobactam products. Since resistance to these particular antimicrobials in Gram-negative bacterial infections is currently low, non-restricted antimicrobials continue to be effective in combatting infections and should remain the primary choice by physicians for treating these infections in the hospital.

Vancomycin is a non-restricted drug, used primarily for the treatment of Gram-positive infections, with use remaining relatively stable over time. The use of restricted antimicrobials for treating Gram-positive infections has been increasing since 2002 with 2013 use levels 14 times higher than those observed in 2001. Increases in restricted drugs could be due to their increased effectiveness against certain infections, resistance to non-restricted and first-line drugs in Gram-positive infections and changes in clinical practice guidelines or formularies.

Figure 3. Proportion change in the total kilograms of restricted and non-restricted antimicrobials per 1,000 patient-discharges purchased by hospitals for the treatment of Gram-positive and Gram-negative infections in Canadian hospitals, 2001-2013

   Proportion change in the total kilograms of restricted and non-restricted antimicrobials per 1,000 patient-discharges purchased by hospitals for the treatment of Gram-positive and Gram-negative infections in Canadian hospitals, 2001-2013 - Text Description
Figure 3. Proportion change in the total kilograms of restricted and non-restricted antimicrobials per 1,000 patient-discharges purchased by hospitals for the treatment of Gram-positive and Gram-negative infections in Canadian hospitals, 2001-2013
  Gram Negative Bacteria Gram Positive Bacteria
  2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Restricted antimicrobials 0.0 1.48 1.62 -0.02 0.10 0.37 0.49 0.55 0.74 0.66 1.71 2.74 2.45 0.0 1.75 2.37 2.90 5.20 5.90 7.57 9.19 10.89 10.05 11.15 13.97 14.05
Non-restricted antimicrobials 0.0 -0.31 0.23 0.64 1.18 1.57 2.16 2.45 3.73 3.85 5.85 12.68 19.37 0.00 0.66 -0.56 -0.87 -0.85 -0.89 -0.90 -0.90 -0.87 -0.88 -0.84 -0.87 -0.90

Line graph showing the proportion change in the total kilograms of antimicrobials per 1,000 patient discharges by type of bacteria treated and year that were purchased by hospitals in Canada from 2001 to 2013 with each line representing the group of antimicrobials. The horizontal axis represents the year and type of bacteria treated (Gram Negative and Gram Positive) and the vertical axis represents the proportion change in the total kilograms per 1,000 patient discharges compared to 2001 which is the first year of data.

Antimicrobial Use in Animals

It is well recognized that the "...use of an antimicrobial anywhere can increase resistance to any antimicrobial anywhere elseFootnote 6". Hence, mitigation of the emergence, spread and impact of AMR requires an understanding of all the settings in which antimicrobial exposure occurs. The World Health Organization (WHO) Advisory Group on Integrated Surveillance of Antimicrobial Resistance, the World Organisation for Animal Health (OIE) and Codex Alimentarius all recommend that countries perform surveillance of antimicrobials used in animals. Some organizations also recommend surveillance in other non-human sectors, such as antimicrobials used on crops. Use of antimicrobials in animals can select for resistance in veterinary pathogens (i.e., those pathogens that cause disease in animals), but can also cause resistance in pathogens that can be transmitted to humans through the food chain (e.g., foodborne Escherichia coli and Enterococcus) which can exchange resistance genes with other pathogens causing human disease.

Total antimicrobials distributed for animal use

Antimicrobials used in food-production animals represent a large pressure in promoting the development or spread of AMR. Information on antimicrobials distributed for sale for use in animals has been voluntarily provided to CIPARS since 2006 by the Canadian Animal Health Institute (CAHI)Footnote 6. In 2013, 1.6 million kg of antimicrobial active ingredients were distributed for use in animals in Canada; 2% lower than in 2012 and 10% lower than reported in 2006.  This does not account for different potencies of antimicrobial drugs which can affect interpretation of the data (metric currently under development for Canada).

In 2013, 99.4% of the total antimicrobials distributed for veterinary use in Canada were used in food-production animals, versus 0.6% in companion animals. The majority (68%) of antimicrobials distributed for use in animals were in the same classes as those used in human medicine. The remaining 32% are not found in classes used in human medicine and include the ionophores and chemical coccidiostats.

As in previous years, the predominant classes of antimicrobials distributed for sale in 2013 in descending order were the tetracyclines, ionophores, "other antimicrobialsReference f", β-lactams and the macrolides. Nova Scotia and New Brunswick had a greater than 10% decline in the reported quantity of antimicrobials distributed between 2012 and 2013, while Manitoba and Prince Edward Island showed a more than 10% increase in the same time period. However, it should be noted that subsequent interprovincial distribution of antimicrobials can occur after surveillance data are captured.

Fluoroquinolones have been classified as of critical importance by the WHO and as "very high importance to human medicine" by Health Canada's Veterinary Drugs Directorate (VDD). Fluoroquinolones are licensed only for certain animal species in Canada and have warnings on their labels recommending against extra-label use due to AMR concerns. The overall quantity of fluoroquinolones distributed for use in animals in 2013 increased by 11% over 2012. Third-generation cephalosporins are also of critical importance and are licensed for use in some animal species in Canada.  CAHI data provided to CIPARS shows a decline of 15% in the quantity of cephalosporins used in animals (5,454 kg) from 2012 to 2013, however the data cannot be stratified into specific types of cephalosporins (such as third-generation cephalosporins) due to CAHI accounting rulesReference g.

To better understand trends over time, adjustments for animal population numbers and weights were made to the total amounts distributed for animal use. A standard animal weight at treatment (European) was used for each animal production class to determine the "biomass" of the animal populationFootnote 8. Using this biomass adjustment, the overall quantity of antimicrobials distributed remained relatively stable over time, with a 1% decrease since 2006 and a 2% decline since 2012 (Figure 4).  This stability in quantity of antimicrobials distributed comes at a time when other nations are taking significant measures to decrease the quantities of antimicrobials intended for use in animals, or to restrict certain mass medication use practices, such as use for antimicrobial growth promotion. For example, 18 of 20 countries providing data to the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) between 2010 and 2012 showed a decrease in salesFootnote 8.

Figure 4. Medically-important antimicrobials distributed for use in animals over time; measured as kg active ingredient and mg active ingredient, adjusted for population and weightReference h

   Medically-important antimicrobials distributed for use in animals over time; measured as kg active ingredient and mg active ingredient, adjusted for population and weight - Text Description
Figure 4. Medically-important antimicrobials distributed for use in animals over time; measured as kg active ingredient and mg active ingredient, adjusted for population and weight
Year Total kilograms Total milligrams adjusted for population and European weights
2006 1,310,373 159.42
2007 1,171,796 143.26
2008 1,143,187 140.17
2009 1,141,213 151.02
2010 1,037,313 141.28
2011 1,121,831 160.14
2012 1,127,191 161.89
2013 1,086,528 158.10

Line graph showing two lines with one representing the total milligrams of antimicrobials distributed for use in animals adjusted for population and European weights and total kilograms of antimicrobials distributed for use in animals in Canada from 2006 to 2013. The horizontal axis represents the year. The left vertical axis represents the total kilograms of active ingredient while the right vertical axis represents the milligrams of active ingredient adjusted for population and weights.

Indication for AMU in animals

There are three reasons for AMU in animals in Canada: treatment of disease, prevention of disease and to improve feed efficiency or promote growth (production claims). The use of antimicrobials as growth promoters is not permitted in the European Union. The United States and Canada are currently taking measures to remove production claims from approved labels for medically-important antimicrobials. Information on reasons for AMU in production animals is collected by CIPARS through surveillance of volunteer sentinel grower-finisher pig and broiler chicken farmsFootnote 6.

In 2013, 12% of the sampled pig herds and 8% of the sampled chicken flocks reported no use of antimicrobials. This highlights the heterogeneity of use practices by farmers/veterinarians. In farms reporting use of antimicrobials, the majority were administered through feed, rather than by injection or via water. There are also important differences in the types and relative quantities of antimicrobials used in different food animal sectors in the CIPARS farm surveillance program.

Overall, the greatest use of antimicrobials on sampled grower-finisher pig and broiler chicken farms was for disease prevention. For broiler chickens in 2013, 93% of antimicrobials were used in feed, primarily for the prevention of necrotic enteritis (Clostridium perfringens - macrolides, penicillins, streptogramins, bacitracin) and coccidiosis (ionophores and chemical coccidiostats). Only 12% of broiler chicken flocks reported using antimicrobials for production claims (bacitracin, virginiamycin, bambermycin and penicillin).

Antimicrobials were administered by participating grower-finisher pig farms via feed for disease treatment (11%), prevention (47%) and production claims (36%). For disease prevention, lincomycin and tylosin were reported mainly for use in the prevention of enteric disease and chlortetracycline for prevention of respiratory disease. Tylosin, ionophores, lincomycin and chlortetracycline were reported as being used for production claims.

Integration of Human and Non-Human Antimicrobial Use Data

Canada is a major producer of food animals for domestic and international markets, with approximately 18 times more animals than humans; the majority of which are poultry (approximately 600 million). In 2013, approximately 1.4 million kg of medically-important antimicrobials were distributed and/or sold for use in humans, animals and crops in Canada. Of the medically-important antimicrobials (all classes used in human medicine), 78% were used in production animals; approximately four times more antimicrobials distributed for animals than sold for human use. Of the remaining total medically-important antimicrobials distributed and/or sold for use in Canada, 21% were for use in humans, 1% for companion animals and less than 1% in cropsReference i.

Adjusting for underlying population and average weight, in 2013, there were approximately 1.4 times more antimicrobials distributed for use in animals than humans (based on kg active ingredient adjusted by biomassFootnote 6). Since 2006, the quantity of antimicrobials distributed (adjusted by population and weight) for humans increased slightly with few variations year over year to 2013 (Figure 5). Part of this increase is because information for parenteral products provided through community pharmacies was not available prior to 2010. In contrast, the quantity of antimicrobials adjusted by population and weight for animals has a greater degree of variation.

Figure 5. Quantity of antimicrobials distributed and/or sold for use in animals and humans, accounting for population and weight (2006-2013)Reference j

Quantity of antimicrobials distributed and/or sold for use in animals and humans, accounting for population and weight (2006-2013) - Text Description
Figure 5. Quantity of antimicrobials distributed and/or sold for use in animals and humans, accounting for population and weight (2006-2013)
Year Humans Animals
2006 106.21 139.22
2008 104.81 123.05
2008 104.33 120.22
2009 105.33 129.91
2010 102.23 121.99
2011 108.06 138.34
2012 112.29 139.85
2013 116.33 135.95

Line graph showing the total milligrams of antimicrobials adjusted for populations and weights distributed and/or sold with each line representing either humans or animals in Canada from 2006 to 2013. The horizontal axis represents the year with the vertical axis representing the total milligrams of antimicrobials adjusted for populations and weights. Parenteral products included in human data as of 2010. For animals, these data do not include quantities of antimicrobials imported under "own-use" provisions (own use importation - OUI) or imported as active pharmaceutical ingredients (API).


Because the same or similar antimicrobials are used in humans and animals, AMU in both sectors contributes to the emergence and spread of resistance in bacteria causing human infections. Understanding the overall contribution of each sector's AMU to resistance will help to preserve the effectiveness of antimicrobials for treating and preventing infections in both animals and humans. Some antimicrobial classes are sold or distributed more often for use in humans than animals and vice-versa. In humans, the predominant classes of antimicrobials sold (by kg active ingredient in descending order) are β-lactams, cephalosporins, fluoroquinolones and macrolides (Figure 6). In animals, they are tetracyclines, "other" antimicrobialsReference k, β-lactams and macrolides.

Figure 6. Percentage of total kilograms of antimicrobials distributed and/or sold for use in animals and humans by antimicrobial class in Canada, 2013Reference l

Percentage of total kilograms of antimicrobials distributed and/or sold for use in animals and humans by antimicrobial class in Canada, 2013 - Text Description
Figure 6. Percentage of total kilograms of antimicrobials distributed and/or sold for use in animals and humans by antimicrobial class in Canada, 2013
Antimicrobial Class Human Animal
Aminoglycosides 1.3 98.7
Beta-lactams 53.7 46.3
Cephalosporins 91.9 8.1
Fluoroquinolones 97.9 2.1
Lincosamides 12.1 87.9
Macrolides 17.7 82.3
Other antimicrobials 9.1 90.9
Tetracyclines 1.3 98.7
Trimethoprim and sulfonamides 24.3 75.7

Stacked column graph showing the percentage of total kilograms of active ingredient for antimicrobials sold or distributed for use in humans or animals in Canada for 2013. The horizontal axis represents the antimicrobial class and the vertical axis represents the percentage of total kilograms. These data do not include quantities of antimicrobials for animals imported under the "own-use" provisions (own use importation - OUI) or imported as active pharmaceutical ingredients (API).

International Comparisons

Human antimicrobial use

The European Surveillance of Antimicrobial Consumption Network (ESAC-Net) collects information from the European Union Member Countries to estimate the total amount of outpatient antimicrobials usedFootnote 10. A total of 28 countries provided information for 2013. When outpatient AMU in Europe was compared with Canadian community pharmacy dispensation (Figure 7) it was found that Canada has similar levels of AMU as Finland, but slightly higher than Denmark. Canada's overall outpatient use represented 1.6 times the level of use reported by the Netherlands (country with lowest use) and half the level estimated in Greece (country with the highest level of use). Overall, Canada ranked 11th out of the 29 countries classified by increasing levels of total AMU.

Figure 7. Outpatient antimicrobial use (DDD per 1,000 inhabitant-days) reported in 28 European countries and Canada, 2013

Outpatient antimicrobial use (DDD per 1,000 inhabitant-days) reported in 28 European countries and Canada, 2013 - Text Description
Figure 7. Outpatient antimicrobial use (DDD per 1,000 inhabitant-days) reported in 28 European countries and Canada, 2013
Country Total
Greece 32.0
France 30.10
Romania 29.80
Belgium 29.60
Italy 28.60
Luxembourg 27.70
Spain 24.20
Ireland 23.80
Malta 23.80
Slovakia 23.60
Poland 23.30
Iceland 21.90
United Kingdom 21.50
Croatia 21.10
Bulgaria 19.90
Czec Republic 19.00
Lithuania 18.50
Finland 18.30
Canada 17.60
Denmark 16.40
Austria 16.30
Norway 16.20
Germany 15.80
Slovenia 14.50
Hungary 13.80
Latvia 13.50
Sweden 13.00
Estonia 11.70
Netherlands 10.80

Bar graph showing the quantity of antimicrobials measured in defined daily doses per 1,000 inhabitant per day used in 28 European countries and Canada in 2013. The horizontal axis lists the name of the country while the vertical axis represents the total defined daily doses per 1,000 inhabitant per day.

Distribution of antimicrobials for animal use

The European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) collects and reports information from member countries on antimicrobial agents intended for use in animalsFootnote 8. The data available through their reports is focused on food-producing animals. In 2012, a total of 26 member countries provided information on levels of antimicrobial salesFootnote 8. When compared to the countries participating in the ESVAC network, Canada ranked 21 out of 27 countries by increasing levels of antimicrobial sales adjusted by population and weight (Figure 8). Canada's total milligrams distributed adjusted by population was  42 times that used in Norway (country with lowest use) and less than half of that reported by Cyprus (country with highest use). Canada's ranking would increase if we could account for the currently unrecorded imports of antimicrobials which fall under own-use importation (OUI) and imports of Active Pharmaceutical Ingredients (API) for animal use. The latest information from an Ipsos/Impact Vet study prepared for CAHI estimated that the lost opportunity value due to OUI and API was 13% of total animal health product sales, not just antimicrobials.

One reason for Canada's higher position is that unlike EU countries, Canada still uses antimicrobials for production claims . The Netherlands have significantly reduced AMU by over 50%, from 165 mg per population correction unit (PCU) in 2009Footnote 11 to 74.9 mg per PCU in 2012Footnote 8. Canada's total use mirrors that reported by the Netherlands in 2009 prior to their reductions. This suggests that while our commodity sectors are different, a significant reduction of AMU in Canada is possible.

Figure 8. Antimicrobial sales for 2012 for animals (quantity adjusted by population and weight) for Canada and countries participating in the European Surveillance of Veterinary Antimicrobial Consumption networkReference m

Antimicrobial sales for 2012 for animals (quantity adjusted by population and weight) for Canada and countries participating in the European Surveillance of Veterinary Antimicrobial Consumption network - Text Description
Figure 8. Antimicrobial sales for 2012 for animals (quantity adjusted by population and weight) for Canada and countries participating in the European Surveillance of Veterinary Antimicrobial Consumption network
Country Milligrams adjusted by population and weight
Cypres 396.5
Italy 341.0
Hungary 245.5
Spain 242.0
Germany 204.8
Belgium 161.1
Canada 160.5
Portugal 157.1
Poland 132.2
France 102.6
Bulgaria 98.9
Czec Republic 79.8
Netherlands 74.9
United Kingdom 66.3
Ireland 58.0
Estonia 56.0
Austria 54.9
Denmark 44.1
Luxembourg 43.6
Slovakia 43.2
Latvia 41.1
Lithuania 39.4
Slovenia 37.0
Finland 23.8
Sweden 13.5
Iceland 5.9
Norway 3.8

Bar graph showing the quantity of antimicrobials sold for animals measured in milligrams adjusted for populations and weights as reported by European countries participating in the European Surveillance of Veterinary Antimicrobial Consumption Network and in Canada for 2012. The horizontal axis lists the name of the country while the vertical axis represents the total milligrams adjusted by populations and weights.

AMU Conclusion

Antimicrobial use is one of the main contributors to the emergence and spread of antimicrobial-resistant organisms. Limiting the selective pressure posed by inappropriate and over use of antimicrobials must be achieved through stewardship-informed reductions in the levels of antimicrobials used in human and animal sectors. It is encouraging to note that Canadian levels of antimicrobials (defined daily doses per 1,000 population-days) dispensed through community pharmacies intended for use in humans were lower in 2013 compared to previous years. Even more encouraging is the fact that the biggest decreases in use were in prescriptions dispensed to children younger than five years of age, which implies that prescribers may be following suggested guidelines for this age group. In contrast, the total antimicrobials distributed for animal use remained relatively stable in animals (as measured by the quantity distributed corrected for biomass). This is of concern because similar classes of antimicrobials used to treat and prevent infections in animals are also used in humans.

Food-production animals are, by quantity, the primary sector where antimicrobials are used and represent a large selection pressure for AMR. Based on surveillance of both human and animal AMU, educational campaigns and stewardship programs should continue to stress the need to reduce the proportion of antimicrobials that are provided unnecessarily or in the presence of other available treatments. Although reductions over time have been observed for overall human AMU, it should be determined if this could be the result of using more potent antimicrobials. This has been identified to be the case in the hospital setting, where physicians tend to care for patients with more severe and life-threatening diseases. These potent antimicrobials are considered to be of "last recourse" as other antimicrobials might not have been effective in treating the infection. From hospital purchasing data, large increases in the use of antimicrobials considered of "restricted use" were observed over time, particularly in those used for treating Gram-positive bacteria. The level of use of these antimicrobials should be monitored closely to ensure that these antimicrobials are used properly, preserving their efficacy for treating drug-resistant infections.

Next Steps

The Agency currently reports on antimicrobials dispensed in the community through pharmacies, purchased by hospitals, distributed for animal use, and used in the farm setting (grower-finisher pigs and chickens) and for the first time, antimicrobials sold for use in cropsReference n.

Additional human AMU surveillance will be carried out through the collection of AMU data in the hospital setting through a subset of CNISP hospitals and by including data on on-reserve populations through Health Canada's First Nations and Inuit Health Branch. Animal use information will be enhanced through a partnership between CIPARS and FoodNet Canada to collect some regional AMU information from beef cattle, dairy cattle, layer chicken and turkey farms located within the FoodNet sentinel sites. In addition, the Agency will work with international partners such as the United States Food and Drug Administration (FDA), ESVAC and the OIE to identify and utilize the best metrics for regional, national and international reporting of AMU in animals.

The Agency will monitor the effects of regulatory and policy changes, such as Health Canada's work with CAHI to implement the removal of production claims of medically-important antimicrobials, through AMU/AMR surveillance of antimicrobials distributed for use for all animals and on sentinel broiler chicken and grower-finisher pig farms.

Together, these activities will provide a broader understanding of human and animal AMU, including reasons for use and outcomes. This will help to inform the development of stewardship programs and treatment guidelines ensuring appropriate AMU to help protect their effectiveness in treating Canadians.

Antimicrobial Resistance in Canada

The following section provides information on antimicrobial-resistant microbes currently under surveillance by the Agency. Information identified by the WHOFootnote 12 is denoted for each microbe under "Antimicrobials of Importance".

Organisms Transmitted in Health Care Settings

Organisms of importance in health care settings include those that cause infections acquired during hospitalization or as the result of health care provided in hospitals or alternate settings such as outpatient clinics, physician/dental offices and long-term care facilities. These organisms can cause severe, life-threatening infections, especially in the elderly, young infants and patients who have weakened immune systems due to other diseases, such as cancers and heart or kidney disease. AMR is particularly significant in these settings as the organisms spread easily from person-to-person within or between health care facilities and have been linked to large hospital outbreaks. In addition, patients are prescribed antimicrobial agents for other infections or for prevention of infection, which may lead to the emergence of novel AMR. Many of these organisms are now emerging in community settings as well as in individuals with no recent exposure to health care settings.

Clostridium difficile (C. difficile)

Antimicrobials of Importance: metronidazole, vancomycin, fidaxomicin

C. difficile is the most common cause of infectious diarrhea in hospitals and long-term care facilities in Canada. Symptoms of C. difficile infection (CDI) range from diarrhea and abdominal cramps to more serious intestinal inflammation that can cause death. While resistance in C. difficile is not a concern at present, the extensive use of antimicrobials in hospitals to treat patients often creates a competitive advantage for C. difficile (which is frequently carried in human intestines). The competing bacteria are reduced by the administered antimicrobials, resulting in the overgrowth of C. difficile. The disease is caused by the bacterium-releasing toxins that destroy the lining of the bowel that, in turn, causes bloating and frequent watery diarrhea. Most cases of CDI occur in patients who are elderly and who have other underlying medical conditions. C. difficile spreads rapidly in health care settings by direct contact because it is naturally resistant to many antimicrobials used to treat other infections and C. difficile spores in the environment tend to be  resistant to more commonly used disinfectants. It is estimated that 1.5% of all hospitalized patients will develop CDI during the course of their hospitalization. Approximately 15% of these will develop severe disease and 6% will die from the infectionFootnote 13Footnote 14.

A more virulent strain of C. difficile emerged in 2000. This strain, characterized as the North American pulsed-field Type 1 (NAP1) was found to be resistant to fluoroquinolones, a class of antimicrobials commonly used to treat other infections in both the hospital and community setting. NAP1 has spread throughout North America and Europe and is responsible for increasing CDI rates, hospital outbreaks and more severe disease especially in the elderly.

Resistance to the first-line antimicrobials used for treatment of CDI is rare; however the rate of response to metronidazole, the first-line treatment regimen for mild-to-moderate CDI, has been decreasing. Recurrence of the disease occurs in approximately 30% of patients who initially responded to antimicrobial therapyFootnote 15.

For initial episodes consisting of mild-to-moderate CDI, treatment with oral metronidazole is recommended, while oral vancomycin is used for treating initial episodes of severe CDI or in patients who have failed metronidazole on more than two occasions. If the infection is severe and has complications, oral vancomycin is administered with or without intravenous metronidazole. In 2012, Health Canada approved the use of fidaxomicin, a new antimicrobial used specifically for treating CDI. Fidaxomicin is currently recommended for use in patients with recurrent or non-responsive CDI that has failed both metronidazole and vancomycin. Fidaxomicin is generally considered equal to oral vancomycin in terms of cure rates.

The Agency has collected information on health care-associated (HA) CDI through CNISP since 2005. A total of 22,032 cases of HA-CDI have been reported to the Agency between 2007 and 2013 of which 3.1% (679 cases) were in children. In 2013, the overall rate of HA-CDI was 3.99 cases per 1,000 patient admissions, which is lower than the rate of 4.61 reported in 2007 (Figure 9 ). In 2013, 3.1% of deaths in CNISP hospitals could be attributed to CDI compared to 4.8% in 2007. In 2013, 29.6% of C.difficile strains submitted to the Agency were the NAP1 strain compared to 41.1% in 2007. Over the entire surveillance period, two C.difficile strains were resistant to metronidazole. In 2012, one C.difficile strain from Western Canada showed diminished susceptibility to vancomycin.

Figure 9. Incidence of health care-associated Clostridium difficile infections per 1,000 patients admissions and per 10,000 patient-days, 1997, 2005, 2007-2013

Incidence of health care-associated Clostridium difficile infections per 1,000 patients admissions and per 10,000 patient-days, 1997, 2005, 2007-2013 - Text Description
Figure 9. Incidence of health care-associated Clostridium difficile infections per 1,000 patients admissions and per 10,000 patient-days, 1997, 2005, 2007-2013
Year Per 1,000 patient admissions Per 10,000 patient-days
1997 5.90 6.63
2005 4.50 6.40
2007 4.51 6.77
2008 5.84 7.47
2009 4.65 5.81
2010 4.54 6.12
2011 5.09 6.65
2012 4.08 6.04
2013 4.25 5.36

Clustered bar graph showing the rate of Clostridium difficile infections per 1,000 patient-admissions and per 10,000 patient days (each rate represented by its own bar) reported in Canada during 1997, 2005 and from 2007-2013. The horizontal axis represents the year and the vertical axis the rate.

Multi-Drug-Resistant Enterobacteriaceae

Antimicroibals of Importance: Carbapenems (ertapenem, imipenem, meropenem, doripenem), extended-spectrum cephalosporins (ceftazidime, ceftriaxone, cefotaxime), fluoroquinolones

Enterobacteriaceae are Gram-negative bacilli (GNB) commonly encountered in health care settings and include species such as Escherichia coli, Klebsiella spp. and Enterobacter spp. These organisms are normal flora in the gastrointestinal tract in healthy humans, but they are a cause of infections, including urinary tract infections, bloodstream infections, and wound infections. Enterobacteriaceae have mixed susceptibility to commonly-prescribed antimicrobials. One form of resistance occurs when GNB acquire the ability to produce extended spectrum β-lactamases (ESBL), an enzyme class that renders it resistant to commonly-used extended-spectrum (third-generation) cephalosporins (i.e., ceftazidime, cefotaxime and ceftriaxone) as well as beta-lactam-lactamase inhibitor combinations (i.e., piperacillin tazobacatam, etc.).

The carbapenem group of antimicrobials is a relatively safe and generally effective treatment for ESBL as well as other highly resistant Gram-negative organisms, and there are few alternative treatments available when resistance to carbapenems occurs. Enterobacteriaceae that have acquired resistance to carbapenems are called carbapenem-resistant Enterobacteriaceae (CRE). Some CRE are also carbapenamase-producing organisms (CPO) by virtue of their ability to produce enzymes, called carbapenamases, which break down carbapenems. There are other GNB outside of the Enterobacteriaceae family that have also shown to be resistant to carbapenems. These include Acinetobacter spp. and Pseudomonas spp. Both of these bacteria can be found in the hospital environment and can cause infection in vulnerable patients.

All of these bacteria cause a variety of diseases ranging from pneumonia to UTIs, as well as serious BSIs or wound infections with symptoms varying depending on the disease. Individuals can also harbour ESBL-producing bacteria and CRE without causing disease (referred to as colonization). ESBL and CRE infections and colonization typically occur in ill patients with exposure to acute and long-term care settings.

CNISP has been collecting information on CRE and CPO in patients hospitalized in sentinel CNISP hospitals since 2010Footnote 16. Participation in surveillance has increased from 33 CNISP hospitals in 2010 to 38 CNISP hospitals in 2013. Between 2010 and 2013, CNISP hospitals have reported a total of 390 cases of CRE and 219 cases of CPO (Figure 10). Among the 219 CPO cases, 74 (33.8%) were infections, 106 (48.4%) were in patients who harboured the bacteria without showing signs of infection (colonization) and the status was unknown for 39 (17.8%) cases. The incidence of CPO has remained stable from 2010 (0.10 per 10,000 patient-days) to 2013 (0.11 per 10,000 patient-days). The incidence of CRE has nearly doubled from 0.15 per 10,000 patient-days in 2010 to 0.26 per 10,000 patient-days in 2013. However, this increase in the rate of CRE in 2013 is largely due to an ongoing outbreak at one hospital and is not reflective of a national trend. From 2010-2013, a total of three (1.6 %) deaths were attributedReference o to CPO; all were in patients with BSIs.

Figure 10. Carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing organisms (CPO) infection rates per 10,000 patient-days

Carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing organisms (CPO) infection rates per 10,000 patient-days - Text Description
Figure 10. Carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing organisms (CPO) infection rates per 10,000 patient-days
Year CRE CPO
2010 0.15 0.10
2011 0.23 0.16
2012 0.18 0.12
2013 0.25 0.12

The clustered bar graph presents the incidence rate of carbapenem resistant Enterobacteriaceae (CRE) and carbapenamase-producing organisms (CPO) infection rates (each rate represented by its own bar) per 10,000 patient days in Canada from 2010 to 2013. The horizontal axis represents the year and the vertical axis the incidence rate per 10,000 patient-days.


The NML has also been working closely with provincial public health laboratories to monitor the total number of CPO cases identified in Canada. Between January 1, 2008 and June 30, 2014, 725 CPOs were reported to the NML by provincial public health laboratories.

CIPARS routinely screens all its Salmonella and E. coli isolates for the possibility that they are carbapenem resistant. To date, no carbapenem resistance has been observed through routine screening.

Staphylococcus aureus

Antimicrobials of Importance: penicillinase-resistant penicillin (methicillin, oxacillin, nafcillin), vancomycin, cefoxitin (as a surrogate for oxacillin resistance)

Staphylococcus aureus (S. aureus) is a common Gram-positive bacterium normally found on the skin of healthy individuals. The bacteria can also be found in the interior of the nose and the groin region of healthy individuals without causing disease (colonization). S. aureus can cause a variety of infections, most notably in the skin and soft tissue, bone and bloodstream (BSI). When penicillin was first introduced, it was an effective treatment for S. aureus infections, but resistance developed soon after. S. aureus that are resistant to β-lactam antimicrobials (e.g., penicillins such as oxacillin, methicillin and dicloxacillin) are called methicillin-resistant Staphylococcus aureus (MRSA).

S. aureus, including MRSA is one of the most common causes of health care-associated infections in Canada and is spread from person to person through direct contact and by contact with contaminated surfaces. Initially, MRSA was found mainly in health care settings but over the past decade, community-associated MRSA (CA-MRSA) has been increasing in Canada, especially in certain vulnerable populations (e.g., homeless people, intravenous drug users). MRSA can cause serious infections such as BSI in the hospital setting, which can lead to death. In the community it causes mostly skin and soft tissue infections. Canadian prevalence studies have estimated that approximately 4.2% of hospitalized patients will become infected or colonized with MRSA resulting in an annual hospital cost of about $36.3 millionFootnote 17Footnote 18.

Hospital data presented here were reported to CNISPFootnote 19. In 2013, the rate of MRSA infection in patients was 2.18 per 1,000 patient admissions and 2.84 per 10,000 patient-days (Figure 11). Since 2009, national MRSA infection rates have decreased, with the most dramatic reduction seen in health care-associated MRSA (HA-MRSA) infection rates. However, current MRSA infection rates still exceed rates observed in the late 1990s and early 2000s, consistent with trends seen in other developed countries.

In 2013, 368 (19.9%) of MRSA infections were from blood and 1485 (80.1%) were from clinical sources other than blood. Skin and soft tissue infections (SSTI) represented the largest proportion (43%) of MRSA infections identified from clinical sources other than blood. The rate of MRSA BSI was 0.56 cases per 10,000 patient-days in 2013. The proportion of MRSA infections (all clinical sources) identified as CA-MRSA has steadily increased from 25% in 2008 to 33% of cases in 2012. In 2012, 8.6% of patients with a clinical MRSA infection died, and the following year, 25% of patients with a MRSA BSI died 30 days after the date of positive cultureFootnote 19.

Figure 11. Incidence of methicillin-resistant Staphylococcus aureus infections per 1,000 patient admissions and per 10,000 patient-days in Canada, 2001-2013

Incidence of methicillin-resistant Staphylococcus aureus infections per 1,000 patient admissions and per 10,000 patient-days in Canada, 2001-2013 - Text Description
Figure 11. Incidence of methicillin-resistant Staphylococcus aureus infections per 1,000 patient admissions and per 10,000 patient-days in Canada, 2001-2013
Year Per 1,000 patient admissions Per 10,000 patient-days
2001 1.11 1.37
2002 1.41 1.73
2003 1.60 1.19
2004 2.04 2.65
2005 2.75 3.22
2006 2.65 3.37
2007 2.57 3.45
2008 2.90 3.60
2009 2.90 3.78
2010 2.43 3.40
2011 2.23 2.83
2012 2.17 2.8
2013 2.35 2.88

The clustered bar graph presents the incidence of methicillin-resistant Staphylococcus aureus infections per 1,000 patient admissions and per 10,000 patient-days (each represented by its own bar) in Canada from 2001 to 2013. The horizontal axis represents the year and the horizontal axis the incidence rate.


Although intravenous vancomycin is one of the primary antimicrobials recommended for treatment of MRSA, both linezolid (IV and oral) and daptomycin (IV) are used within Canadian health care settings. Other antimicrobials are treatment options for specific sites of MRSA infections including: telavancin (IV) for SSTIs, doxycycline for SSTIs, trimethoprim-sulfamethoxazole (TMP-SMX) (IV) as well as clindamycin (IV and oral) for treating SSTIs and pneumoniaFootnote 20.

In rare cases, S. aureus may become resistant to vancomycin, the antimicrobial most frequently used to treat serious MRSA infections. This leaves few treatment options available as vancomycin-resistant S. aureus (VRSA) identified to date were also resistant to oxacillin and other classes of antimicrobials. Although VRSA has been identified in the United States and the United Kingdom, there have been no identified cases in Canada to dateFootnote 21. There has also been no documented resistance to tigecycline, linezolid or daptomycin in the isolates tested from 2008 to 2012. The proportion of tested MRSA isolates across Canada that were resistant to ciprofloxacin, erythromycin and clindamycin has remained relatively unchanged over this period (Figure 12). There has been a slight decrease in the proportion of tested isolates that were resistant to tetracycline and TMP-SMX.

Antimicrobial susceptibility patterns can vary widely by geographical region. In Canada resistance in MRSA to ciprofloxacin, erythromycin and clindamycin is slightly higher in the eastern region (Atlantic provinces), while resistance to tetracycline and TMP-SMX is lower in the east compared to the rest of Canada.

Figure 12. Antimicrobial resistance of Methicillin-resistant Staphylococcus aureus isolates, 2008-2012, Canada

Antimicrobial resistance of Methicillin-resistant Staphylococcus aureus isolates, 2008-2012, Canada - Text Description
Figure 12. Antimicrobial resistance of Methicillin-resistant Staphylococcus aureus isolates, 2008-2012, Canada
Antimicrobial 2008 2009 2010 2011 2012
Clindamycin 64.43 46.11 64.42 63.87 56.27
Erythromycin 85.41 89.69 86.52 86.78 83.92
Ciprofloxacin 85.25 90.60 87.62 86.78 83.33
Tetracycline 8.52 5.24 4.70 3.72 3.73
Trimethoprim-sulfamethoxazole 7.38 4.34 3.61 2.61 2.35

The clustered bar graph presents the percentage of methicillin-resistant Staphylcoccus aureus isolates that were resistant to different antimicrobials (each represented by its own bar) collected in Canada from 2008 to 2012. The horizontal axis represents the year while the vertical access the percentage of isolates.

Vancomycin-Resistant Enterococci

Antimicrobials of Importance: Aminopenicillin (ampicillin and amoxicillin), linezolid, lipopeptide (daptomycin)

Enterococci are part of the normal intestinal flora of both humans and animals but can also cause a range of illnesses including bloodstream, surgical site and urinary tract infections. The majority of human infections are caused by E. faecalis and E. faecium. The naturally high level of AMR found in E. faecalis and E. faecium makes infections difficult to treat.

Vancomycin-resistant Enterococci (VRE) are strains of Enterococcusthat have acquired resistance to this antimicrobial of last recourse, leaving few or no treatment options. VRE infections most commonly occur in patients in hospitals who are more susceptible or who have been previously treated with vancomycin or other antimicrobials for long periods of time.  Those who have undergone surgical procedures or who have medical devices such as in-dwelling urinary catheters are more at risk of infection. VRE infections are often difficult to treat. In Canada, treatment can consist of one of the following antimicrobials: linezolid, daptomycin, tigecycline, combination therapy with gentamicin, or nitrofurantoin, depending on the type of infection. Although VRE is considered a low-virulence pathogen, infection rates have been increasing in Canada and in other developed countries. There is also a concern that vancomycin-resistant genes may transfer from VRE to Staphylococcus aureus resulting in few alternative treatments for the more severe VRSA infectionsFootnote 22.

CNISP has collected data on ongoing surveillance of VRE in patients in participating hospitals since 1999Footnote 22. The VRE infection rate has increased since 2008 (Figure 13). In 2013, 324 VRE infections were reported to the Agency for a rate of 0.53 per 10,000 patient-days. Information on where the VRE was acquired was available for 223 patients. Of these, the majority (97%) were health care-associated with 54% of total infections affecting patients 65 years or older. Urinary tract infections (UTI) were the most commonly reported type of VRE infection (31%, n=100), followed by BSIs (29% n=95).

Figure 13. Incidence rates of vancomycin-resistant Enterococcus infections per 1,000 patient admissions and per 10,000 patient-days, 2001-2013

Incidence rates of vancomycin-resistant Enterococcus infections per 1,000 patient admissions and per 10,000 patient-days, 2001-2013 - Text Description
Figure 13. Incidence rates of vancomycin-resistant Enterococcus infections per 1,000 patient admissions and per 10,000 patient-days, 2001-2013
Year Per 1,000 patient admissions Per 10,000 patient-days
1999 0.02 0.02
2000 0.04 0.06
2001 0.01 0.02
2002 0.05 0.07
2003 0.05 0.06
2004 0.04 0.05
2005 0.03 0.04
2006 0.06 0.07
2007 0.08 0.10
2008 0.16 0.20
2009 0.24 0.32
2010 0.35 0.47
2011 0.51 0.68
2012 0.48 0.62
2013 0.44 0.54

The clustered bar graph presents the incidence of vancomycin-resistant Enterococcus infections per 1,000 patient admissions and per 10,000 patient-days (each represented by its own bar) in Canada from 2001 to 2013. The horizontal axis represents the year and the vertical axis the infection rates.

Organisms Transmitted Primarily in the Community Setting

Infections that are contracted outside the hospital setting are commonly referred to as "community-acquired". The organisms cause a range of infections that, in most instances, are treatable with antimicrobials. AMR is particularly significant in this setting as organisms are more difficult to control if treated with an inappropriate antimicrobial. In addition, community-acquired infections can be severe and easily transmitted which could lead to large community outbreaks. When these infections are caused by an AMR organism there is a potential for life-threatening disease.

The end of this section deals with two organisms that are viruses (Human Immunodeficiency Virus and Influenza) both of which are treatable by antivirals. Antibiotics (that treat bacteria) are not effective against either of these pathogens.

Streptococcus pneumoniae

Antimicrobials of Importance: Macrolides (erythromycin), lincosamides (clindamycin), penicillin, extended-spectrum cephalosporins (cefuroxime, cefotaxime, ceftriaxone, cefepime), trimethoprim/sulfamethoxazole

Diseases caused by S. pneumoniae include common, mild, self-limiting infections such as acute otitis media (middle ear infection) as well as severe invasive pneumococcal disease (IPD) with high mortalityFootnote 23. Only a few of the 93 currently recognized pneumococcal serotypes cause the majority of disease and have been incorporated into effective vaccines. Incidence of IPD in children under five years has declined in Canada since the implementation of the seven valent pneumococcal conjugate vaccine (PCV7) from 40 cases per 100,000 in 2003 to 15 cases per 100,000 in 2006. However the emergence of a multi-drug-resistant (MDR) non-PCV7 serotype soon occurred and paediatric incidence rates increased to 20 cases per 100,000 by 2009. In 2010, a 13-valent vaccine (PCV13) that included the MDR non-PCV7 serotype in its formulation was introduced. As of 2013, paediatric incidence has now declined to 17 cases per 100,000 in children less than one year and to 11 cases per 100, 000 in children two to four years. Incidence rates in older age groups remain constant with a rate of nine cases per 100,000 in 2013.

The vaccine-induced decline of PCV13 serotypes (including the MDR strainFootnote 23) has driven a concurrent decline in overall AMR in pneumococci (Figure 14). While PCV13 serotypes have declined from 50% of the isolates in 2011 to 35% in 2013, resistance to three or more classes of antimicrobials has declined from 8.0% to 7.5%. The impact of the S. pneumoniae vaccine on resistant strains illustrates the importance of vaccines as part of a strategy to mitigate the impact of AMR.

Figure 14. Multi-drug resistance and proportion of PCV13 serotypes of pneumococci in Canada, 2001-2013

Multi-drug resistance and proportion of PCV13 serotypes of pneumococci in Canada, 2001-2013 - Text Description
Figure 14. Multi-drug resistance and proportion of PCV13 serotypes of pneumococci in Canada, 2001-2013
IPD serotype 2011 2012 2013
PCV13 serotype 49.9 42.5 35.3
Resistance to ≥3 classes 8.0 7.6 7.5

The graph represents the percentage of Streptococcus pneumonia isolates that are resistant to three or more classes of antimicrobials (represented by a bar) and the overall percentage of Streptococcus pneumonaie isolates that are PCV13 serotype (represented by a line) in Canada from 2011 to 2013. The horizontal axis represents the year. The left vertical axis represents the percentage of isolates while the right vertical axis represents the percentage of isolates that are PCV13.


Resistance of S. pneumoniae to penicillin has decreased from 12% in 2011 to 10% in 2013 (Figure 15). Resistance to clindamycin (7% to 6%) and to doxycycline (10%) has remained relatively stable since 2010, both of which are common first-line treatments for pneumoniaFootnote 24. In contrast, resistance to clarithromycin, which can be used in community-acquired pneumonia, increased from 21% in 2001 to 25% in 2013 and TMP-SMX resistance has increased from 5 to 7%. To date, there has been no resistance reported to linezolid, tigecycline or vancomycin. S. pneumoniae has now developed resistance to less commonly used antimicrobials such as carbapenems for which resistance has been detected at levels less than 3% in 2013, with meropenem resistance increasing slightly from 2.0% in 2011 to 2.6% in 2013.

Figure 15. Antimicrobial resistance of Streptococcus pneumoniae isolates, 2011-2013

Antimicrobial resistance of Streptococcus pneumoniae isolates, 2011-2013 - Text Description
Figure 15. Antimicrobial resistance of Streptococcus pneumoniae isolates, 2011-2013
Year Ceftriaxone Cefuroxime Clarithromycin Clindamycin Doxycycline Penicillin (meningitis) Penicillin (oral) Trimethoprim-sulfamethoxazole
2011 0.97 4.24 21.36 7.06 9.18 11.92 3.71 5.12
2012 0.8 3.72 24.65 6.74 10.2 10.9 3.1 5.85
2013 0.66 3.58 24.76 5.84 9.89 9.99 3.39 7.37

The line graph presents the percentage of Streptococcus pneumoniae isolates that are resistant to different antimicrobials (each represented by its own line) in Canada from 2011 to 2013. The horizontal axis represents the year and the vertical axis the percentage of isolates.

Streptococcus pyogenes (Group A Streptococcus (GAS))

Antimicrobials of importance: penicillin, macrolides (erythromycin) and Lincosmaide (clindamycin)

GAS causes many illnesses, including invasive diseases such as streptococcal toxic shock syndrome, necrotizing fasciitis ("flesh-eating" disease) and bacterial sepsis, as well as non-invasive diseases like pharyngitis ("strep throat"), scarlet fever, rheumatic fever and skin infections such as impetigo.

The most predominant types of invasive GAS in 2013 were emm types 1 and 89, accounting for 23% and 8% of the isolates tested, respectively. The majority were from blood samples (68%), followed by synovial fluid (8%). Notably, all GAS were susceptible to penicillin and vancomycin. Resistance to clindamycin, a second-line drug for treatmentFootnote 24, has remained relatively unchanged from 2010 to 2013, while resistance to erythromycin and non-susceptibility to chloramphenicol has decreased over the same time period (Figure 16).

Figure 16. Antimicrobial resistance of invasive Streptococcus pyogenes, 2010-2013

Antimicrobial resistance of invasive Streptococcus pyogenes, 2010-2013 - Text Description
Figure 16. Antimicrobial resistance of invasive Streptococcus pyogenes, 2010 - 2013
  2010 N=383 2011 N=1230 2012 N=1122 2013 N=1290
Chloramphenicol non-susceptible 9.40 4.47 2.05 0.62
Erythromycin resistant 14.36 9.51 10.01 8.52
Clindamycin resistant 2.35 1.79 2.58 2.25

The line graph presents the percentage of invasive Streptococcus pyogenes isolates that were found to be non-susceptible to chloramphenicol, resistant to erythromycin or resistant to clindamycin (each represented by its own line) in Canada from 2010 to 2013. The horizontal axis represents the year and the total number of isolates tested, while the vertical axis represents the percentage of isolates.

Invasive Streptococcus agalactiae (Group B Streptococcus)

Antimicrobials of importance: penicillin, macrolides (erythromycin), and lincosamides (clindamycin)

Invasive Group B Streptococcus(GBS) is commonly associated with neonatal disease where the highest infection risk is during childbirth and often treated prophylactically with antimicrobials. GBS is also an increasing health concern in adults causing septicemia, meningitis, pneumonia, and bone, joint and tissue infections. At risk adults groups include the elderly, those with underlying medical conditions, pregnant women and those residing in extended health care facilities.

Antimicrobial resistance towards macrolide drugs has increased, with erythromycin resistance rising from 41% to 49% between 2012 and 2013 (Figure 17). Clindamycin resistance has also increased from 26% to 29% while chloramphenicol non-susceptibility has remained constant since 2010.

Figure 17. Antimicrobial resistance of invasive Streptococcus agalactiae (iGBS) tested, 2010 to 2013

Antimicrobial resistance of invasive Streptococcus agalactiae (iGBS) tested, 2010 to 2013 - Text Description
Figure 17. Antimicrobial resistance of invasive Streptococcus agalactiae (iGBS) tested, 2010 to 2013
  2010 N=235 2011 N=392 2012 N=329 2013 N=420
Chloramphenicol non-susceptible 2.13 2.55 2.74 1.90
Erythromycin resistant 39.15 41.58 40.73 48.81
Clindamycin resistant 24.25 25.51 25.53 28.81

The line graph presents the percentage of invasive Streptococcus agalactiae isoaltes that were found to be non-susceptible to chloramphenicol, resistant to erythromycin or resistant to clindamycin (each represented by its own line) in Canada from 2010 to 2013. The horizontal axis represents the year and the total number of isolates tested, while the vertical axis represents the percentage of isolates.

Neisseria gonorrhoeae

Antimicrobials of Importance: macrolide (azithromycin), cephalosporin (cefixime, ceftriaxone), aminocyclitol (spectinomycin), aminoglycoside (gentamicin), fluoroquinolone (ciprofloxacin)

Neisseria gonorrhoeae causes gonorrhoea, a highly infectious sexually transmitted disease. It results in an acute infection of the reproductive tract that may be symptomatic or asymptomatic. If untreated or inappropriately treated, it may cause genital/reproductive tract inflammation and damage as well as infertility. The treatment and control of gonorrhoea is complicated because it develops resistance to the antimicrobials used to treat it, including penicillins, tetracyclines, macrolides and quinolones. Recently, resistance to azithromycin and isolates with decreased susceptibility to the cephalosporins are emerging and threatening the last available treatment options.

Gonorrhoea is the second most commonly reported bacterial sexually transmitted infection in Canada. Rates of reported cases have more than doubled from 15 cases per 100,000 population in 1997 to 36 cases per 100,000 population in 2012. Of the 3,195 N. gonorrhoeae isolates cultured in public health laboratories across Canada in 2013, 1,183 were submitted to the NML for antimicrobial susceptibility testing (samples are submitted to NML when the provincial laboratories identify resistance to at least one antibiotic or if the provincial laboratories do not perform any antimicrobial susceptibility testing). A total of 1,153 of these were found to be resistant to at least one antibiotic tested, indicating that 36.1% of all N. gonorrhoeae cases diagnosed by culture in 2013 were resistant to one or more antibiotics (1,153/3,195) (Figure 18). Since 2012, isolates with resistance to azithromycin and decreased susceptibility to cephalosporins (cefixime and ceftriaxone) have been observed in N. gonorrhoeae isolates in Canada, with a total of seven (2012) and eight (2013) isolates observed. Despite the small numbers, this is of concern as it represents a threat to the success of currently recommended dual therapy treatment options.

Figure 18. Percentage of gonorrhoea isolates resistant to azithromycin, reduced susceptibility to cefixime and ceftriaxone in Canada, 2009-2013

Percentage of gonorrhoea isolates resistant to azithromycin, reduced susceptibility to cefixime and ceftriaxone in Canada, 2009-2013 - Text Description
Figure 18. Percentage of gonorrhoea isolates resistant to azithromycin, reduced susceptibility to cefixime and ceftriaxone in Canada, 2009-2013
  Azithromycin (≥2 mg/L) Cefixime (≥0.25 mg/L) Ceftriaxone (≥0.125 mg/L)
2009 2010 2011 2012 2013 2009 2010 2011 2012 2013 2009 2010 2011 2012 2013
Resistance 0.35 1.25 0.39 0.86 1.16 1.19 3.30 4.20 2.24 1.75 3.12 7.34 6.20 5.53 3.51

This bar graph presents the percentage of gonorrhoea isolates found to be resistant to azithromycin, have reduced susceptibility to cefixime or reduced susceptibility to ceftriaxone (each represented by its own bars) in Canada from 2009 to 2013. The horizontal axis is represented by the antimicrobial (including the breakpoint) and year, while the vertical axis represents the percentage of isolates.


According to the data available on indications and antimicrobial recommendations for patients seeking medical treatment from office-based physiciansFootnote 2, antimicrobials were recommended for the treatment of all cases of gonorrhoea included in the physician dataset. In 2013, the most commonly recommended treatment reported by physicians was a combination of cefixime and azithromycin (34% of cases), followed by cefixime alone (33%). A small number of cases also received treatment with azithromycin (17%) alone or the combination of ceftriaxone and doxycycline (17%).

The data demonstrates a pattern of use different from what is currently recommended by use guidelines.  The departure from current guidelines advising the use of a combination of antimicrobials is concerning. These guidelines are developed with relevant knowledge of resistance and treatment effectiveness based on Canadian information. It is essential to follow Canadian-based guidelines because international guidelines may not be applicable in Canada.

Physicians are now discouraged from using tetracyclines and penicillinsFootnote 16 due to high levels of resistance. In response to rates of decreasing susceptibilities to cephalosporins, the recommended treatment of gonorrhoea infection was updated to third-generation cephalosporins (ceftriaxone or cefixime) as the remaining first-line treatment regimen in combination with the macrolide azithromycin. There is no ideal alternative to the third-generation cephalosporins and there are very few new treatment options being developed. Early identification of emerging patterns of AMR and timely public health notification of cefixime, ceftriaxone or azithromycin treatment failures will assist in identifying effective treatment regimens and preventing the emergence of untreatable gonorrhoea in Canada.

Salmonella enterica

Antimicrobials of Importance: Carbapenems (ertapenem, imipenem, meropenem, doripenem), extended-spectrum cephalosporins (ceftazidime and ceftriaxone, or cefotaxime), fluoroquinolones (ciprofloxacin, levofloxacin, pefloxacin), macrolides (azithromycin)

Salmonella gastrointestinal infections are common and often self-limiting. Because gastrointestinal salmonellosis does not generally require clinical treatment, the majority of cases are not reported. Treatment of Invasive salmonella infections are indicated as these infections can become life threatening. Recent guidelines published in the Canadian Medical Association Journal recommend treatment of salmonellosis when infection occurs in those less than six months, older than 65 years, are immunosuppressed, and suffer from other comorbiditiesFootnote 26. If treatment is required, recommended antimicrobials are azithromycin in children and those with travel history and ciprofloxacin in adults for outpatients, while ceftriaxone is recommended for those patients requiring hospitalization, children under the age of 6 months, adults over 50 years of age, pregnant women or if suffering from bacteremiaFootnote 27Footnote 28.

Antimicrobial resistance for Salmonella has been monitored through CIPARS since 2002. Current levels of ciprofloxacin resistance in non-typhoidal Salmonella are relatively low and are not considered a significant problemFootnote 29. However, as with other organisms, the potential for ciprofloxacin resistance is high due to the frequency with which Canadians travel abroad.

Typhoidal Salmonella (Salmonella Typhi, Paratyphi A, Paratyphi B and Paratyphi C)

Humans are the only reservoir of typhoidal Salmonella. Infection (enteric fever) is caused by contact with another infected person or through contaminated water or food prepared by a person carrying this organism. In Canada, this type of infection is mainly acquired through exposure to contaminated food/water while traveling to countries where typhoidal infections are endemic. Typhoidal infections are potentially life-threatening as they are more likely to move from the intestines into the bloodstream than other enteric infectionsFootnote 30Footnote 31. For Canadian travelers, the Agency recommends that those traveling to South Asia obtain the typhoid vaccine, as this is the area of greatest riskFootnote 32.

The rate of infection observed in Canada has ranged from a low of 0.5 cases per 100,000 individuals in 2003 to a high of 0.7 cases per 100,000 individuals in 2008. A total of 177 cases of typhoidal infections were reported in 2013 and submitted to NML for AMR testingFootnote 29. Only two and 11 isolates have been identified as resistant to azithromycin and ceftriaxone, respectively since 2003 (Figure 19). In contrast, resistance to ciprofloxacin has increased from no resistance in 2003 to 17% in 2013. In 2013, 83% of the ciprofloxacin-resistant infections were identified from blood samples, implying that these were from bloodstream infections. Thirteen percent of typhoidal isolates were resistant to two or more antimicrobial classes.

Figure 19. Resistance to azithromycin, ciprofloxacin and ceftriaxone in typhoidal Salmonella in Canada, 2003-2013

Resistance to azithromycin, ciprofloxacin and ceftriaxone in typhoidal Salmonella in Canada, 2003-2013 - Text Description
Figure 19. Resistance to azithromycin, ciprofloxacin and ceftriaxone in typhoidal Salmonella in Canada, 2003-2013
Antimicrobial 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Azithromycin                 0 0 1.13
Ciprofloxacin 0 0 0 0 0.99 0 1.40 3.79 2.38 8.05 16.95
Ceftriaxone 0.65 0 0 0.87 0 0.40 0.47 0 0 0 0

The line graph showing the percentage of typhoidal Salmonella isolates in Canada that are resistant to azithromycin, ciprofloxacin or ceftriaxone (each represented by its own line) collected from 2003 to 2013. The horizontal axis represents the year while the vertical axis represents the percentage of isolates. Note that azithromycin was not included in the panel of antimicrobials prior to 2011.

Non-typhoidal Salmonella

In Canada, it is estimated that non-typhoidal Salmonella causes 88,000 cases per yearFootnote 33. There are over 2,000 different strains of non-typhoidal Salmonella that cause human salmonellosis. In Canada the top three Salmonella strains causing human infection are Salmonella Enteritidis, Salmonella Heidelberg and Salmonella Typhimurium. Non-typhoidal Salmonella is found in the intestines of many food-producing animals such as poultry and pigs. Human infection is usually acquired by consumption of contaminated food of animal origin, mainly undercooked meat, poultry, eggs and unpasteurized milk. Fruits and vegetables can become contaminated with human or animal faeces, leading to foodborne outbreaks if not handled properly.

Salmonella Enteritidis

A total of 746 human Salmonella Enteritidis were received from provinces in 2013 for AMR testing out of 2,987 samples. Fifteen percent (111/746) were resistant to at least one antimicrobial. Resistance to nalidixic acid (a fluoroquinolone) was observed in 12% (91/746) of the S. Enteritidis human samples. In terms of antimicrobials of human clinical importance, resistance to ceftriaxone and azithromycin was present in less than 1% of samples and has remained stable over time (Figure 20). Resistance to ciprofloxacin was present in 1% of samples in 2013, a slight increase from 0.2% in 2011, the first year this resistance was observed.

Salmonella Heidelberg

In 2013, there were 418 human Salmonella Heidelberg samples tested for AMR. Of the 418 cases, 41% were resistant to at least one antimicrobial. Of these resistant infections 75% were resistant to the combination of amoxicillin-clavulanic acid, ampicillin, cefoxitin and ceftriaxone. In terms of antimicrobials of human clinical importance, resistance to ceftriaxone was present in 31% (129 cases) of samples in 2013, an increase from 27% observed in 2012 (Figure 20). There was no resistance to azithromycin or ciprofloxacin in 2013.

Salmonella Typhimurium

A total of 385 human Salmonella Typhimurium samples were tested for AMR of which 128 (33%) were resistant to at least one antimicrobial. The majority (68/128) of these resistant samples were resistant to the combination of ampicillin, chloramphenicol, streptomycin, sulfisoxazole and tetracycline. In terms of antimicrobials of human clinical importance, resistance to ceftriaxone and ciprofloxacin was present in 2% (seven cases and six cases, respectively) of samples in 2013, while resistance to azithromycin was present in 1% of samples. Resistance to these antimicrobials has remained stable over time (Figure 20).

Figure 20. Resistance to azithromycin, ciprofloxacin and ceftriaxone in Salmonella Enteritidis, Salmonella Heidelberg and Salmonella Typhimurium in Canada, 2003-2013

Resistance to azithromycin, ciprofloxacin and ceftriaxone in Salmonella Enteritidis, Salmonella Heidelberg and Salmonella Typhimurium in Canada, 2003-2013 - Text Description
Figure 20. Resistance to azithromycin, ciprofloxacin and ceftriaxone in Salmonella Enteritidis, Salmonella Heidelberg and Salmonella Typhimurium in Canada, 2003-2013
  Enteritidis Heidelberg Typhimurium
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Azithromycin                 0 0.08 0.27                 0.26 0 0.24                 0 0.55 0.78
Ceftriaxone 0.28 0.55 0.65 0.14 0.11 0.16 0.09 0.4 0.2 0.33 0.40 22.4 32.7 28.9 13.3 14.8 14.1 13.9 19.1 33.1 27.2 30.9 1.18 1.34 4.47 1.48 1.37 2.32 1.68 1.32 2.74 2.38 1.82
Ciprofloxacin 0 0 0 0 0 0 0 0 0.2 0.84 1.47 0 0 0 0 0 0 0 0 0 0 0 0.33 0.17 0.54 0 0.45 0 0 0 0 0.79 1.56

The line graph presents the percentage of Salmonella Enteritidis, Salmonella Heidelberg, and Salmonella Typhimurium isolates that exhibited resistance to azithromycin, ceftriaxone and ciprofloxacin (each represented by its own line) in Canada from 2003 to 2013. The horizontal axis represents the Salmonella serovar and year, while the vertical axis represents the percentage of isolates. Note that azithromycin was not include in the panel of antimicrobials prior to 2011.

Shigella

Antimicrobials of Importance: Extended-spectrum cephalosporins (ceftazidime in combination with either ceftriaxone or cefotaxime)

Shigella usually causes diarrhea (sometimes bloody), fever and abdominal pain. High-risk groups include young children, individuals with inadequate hand washing practices and hygiene and men who have sex with men. Infections resistant to traditional first-line antimicrobials can last longer than those where bacteria are susceptible. Resistant Shigella is a significant cause of morbidity and mortality internationallyFootnote 34. In Canada Shigella is reported through the Canadian Notifiable Disease Surveillance System (CNDSS). Shigellosis in Canada averaged about 813 cases per year, with an unknown level of resistance to first-line antimicrobials. A survey conducted in 2002 on Shigella isolates collected from 1993-2001 showed that approximately 80% were resistant to at least one of the 35 antimicrobials testedFootnote 35. The highest rate of resistance was in folate pathway inhibitors, tetracycline and penicillin. Low levels of resistance were seen for nitrofurantoin (0.52%), quinolones (0.84%) and other beta-lactams (1.7%). In Canada, provinces are able to handle the vast majority of Shigella identification and characterization in their laboratories.

Tuberculosis (TB)

Antimicrobials of Importance: isoniazid, rifampin, ethambutol and pyrazinamide

TB is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It is spread through the air when individuals who are sick with pulmonary TB expel bacteria (e.g., by coughing). One-third of the world's population is estimated to be infected with the TB bacterium and although they do not have active TB, they may develop it in the near or remote futureFootnote 36. Those with weakened immune systems are at greater risk of becoming illFootnote 37 and those living with Human Immunodeficiency Virus are 15 times more likely to develop an active form of the diseaseFootnote 38.

Antimicrobial-resistant strains represent a significant challenge in the management and control of TBFootnote 37. In 1998, in response to a growing concern about TB drug resistance worldwide, the Agency established the Canadian Tuberculosis Laboratory Surveillance System in partnership with the Canadian Tuberculosis Laboratory Technical Network to monitor trends and patterns in anti-tuberculosis drug resistance in Canada over time.

Four main antimicrobials are considered first-line drugs for treating tuberculosis: isoniazid, rifampin, ethambutol and pyrazinamide. These are used in combination to maximize their effectiveness. Once susceptibility testing identifies a susceptible infection, the use of ethambutol is not neededFootnote 39. Ethambutol is not recommended in the treatment of children and can be replaced with streptomycin, kanamycin, or amikacin when necessary.

The following resistance patterns are of concern:

  • Mono-resistance - defined as resistance to one first-line anti-TB drug only (isoniazid, rifampin, ethambutol or pyrazinamide).
  • Multidrug-resistant tuberculosis (MDR-TB) - defined as resistance to isoniazid and rifampin with or without resistance to other anti-tuberculosis drugs.
  • Polyresistance (other patterns) - defined as resistance to more than one first-line anti-TB drug, not including the isoniazid and rifampin combination of MDR-TB.
  • Extensively drug-resistant TB (XDR-TB) - defined as resistance to isoniazid, rifampin, any fluoroquinolone and at least one of the three injectable second-line drugs (amikacin, capreomycin or kanamycin).

Surveillance data indicate that TB drug resistance in Canada has remained relatively stable since reporting began (Figure 21). In 2013, a total of 1,380 TB isolates were tested for AMR. Of these, 7% were classified as mono-resistant, 1% multidrug-resistant and 0.1% extensively drug-resistantFootnote 40. Prince Edward Island did not report any cases of TB in 2013 and all the isolates from Northwest Territories, Nunavut, Yukon and Newfoundland and Labrador were fully sensitive to all TB drugs. The majority of isolates showing any resistance (56%) or resistance to both isoniazid and rifampin (67%) were in females. All of the MDR-TB isolates were from individuals between the ages of 15 and 64 years and there were no MDR-TB cases reported for ages less than 15 years of age or over 65 years of age.

Figure 21. Tuberculosis drug resistance patterns as percentage of isolates tested, 2002-2013

Tuberculosis drug resistance patterns as percentage of isolates tested, 2002-2013 - Text Description
Figure 21. Tuberculosis drug resistance patterns as percentage of isolates tested, 2002-2013
  2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Resistance to one or more drugs 9.8 10.5 8.6 9.6 9.1 10.5 8.6 9.5 8.8 10.5 9.9 8.1
Monoresistance 7.7 8.3 6.8 7.7 7.7 8.8 6.9 7.4 6.9 9.0 9.1 6.7
Multidrug-resistant TB 1.4 1.4 0.9 1.6 1.1 0.9 1.1 1.4 1.3 1.4 0.6 1.0
Other patterns 0.6 0.7 0.9 0.2 0.2 0.9 0.4 0.8 0.5 0.1 0.1 0.3
Extensively drug resistant TB 0.1 0.1 0 0 0.1 0 0.1 0 0.1 0.1 0.1 0.1

This line graph presents the percentage of tuberculosis samples that exhibited different types of resistance (each represented by its own line) in Canada from 2002 to 2013. The horizontal axis represents the year and the vertical axis represents the percentage of isolates.


The incidence of new and re-treated TB disease has decreased since 2002, with the lowest rates observed in 2010 (Figure 22Footnote 41). Since then, rates have remained relatively stable over time and the Agency will continue to monitor this trend.

Figure 22. Reported number of tuberculosis cases and incidence rate per 100,000 population, Canada, 2000-2013

Reported number of tuberculosis cases and incidence rate per 100,000 population, Canada, 2000-2013 - Text Description
Figure 22. Reported number of tuberculosis cases and incidence rate per 100,000 population, Canada, 2000-2013
  2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Cases 1724 1772 1667 1631 1612 1640 1653 1575 1644 1654 1586 1621 1699 1640
Rates 5.6 5.7 5.3 5.2 5.0 5.1 5.1 4.8 4.9 4.9 4.7 4.7 4.9 4.7

The graph presents the total rate of tuberculosis cases per 100,000 populations (represented by bars) and the total number of cases of tuberculosis (represented by a line) in Canada from 2000 to 2013. The horizontal axis represents the year. The left vertical axis represents the total number of reported cases and the right vertical axis represents the incidence rate per 100,000 population.

Human Immunodeficiency Virus (HIV)

Drugs of Importance: Nucleoside Reverse Transcriptase Inhibitors, Non-nucleoside Reverse Transcriptase Inhibitors, Protease inhibitors, Integrase inhibitor, Fusion Inhibitors, Co-receptor inhibitors

Since it was first identified in the early 1980s, HIV has emerged as a significant public health challenge. The WHO estimates that 35.0 million people worldwide are living with HIV. Of these, 2.1 million were newly infected with HIV in 2013 and 1.5 million died that same yearFootnote 42. Despite significant advances in the understanding of the virus, control of this infection remains a challenge in many parts of the world. By the end of 2013, a cumulative total of 78,511 HIV cases had been reported to the Agency since HIV reporting began in Canada in 1985. In 2013 alone, 2,090 newly diagnosed HIV cases were reported. This represents a small decrease (0.4%) from the 2,099 newly diagnosed cases reported in 2012 and is the lowest number of annual HIV cases since reporting began in 1985Footnote 43.

There are over twenty antiretroviral drugs available in Canada to treat HIV infection. Each is assigned to one of six different drug classes. Treatment regimens are composed of a variety of possible drug combinations, usually consisting of three antiretroviral drugs from at least two different classes.  The Canadian HIV Strain and Drug Resistance Surveillance Program monitors genetic mutations in HIV that confer resistance to three major drug classes: Nucleoside Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease inhibitors (PI).

Among 4,521 newly diagnosed, treatment-naïve individuals from 1999 to 2008Footnote 44, an overall proportion of 9.8% had resistance to at least one antiretroviral drug class. Of those with drug resistance (n=442), the majority were mono-resistant to NRTI (38.2%) or NNRTI (32.4%) drug classes, while approximately 10.2% had resistance to two or more drug classes (MDR).

Resistance varied over time, as shown in Figure 23. Overall drug resistance increased from 8.1% in 1999 to 13.4% in 2008, largely attributed to an increase in NNRTI resistance over time (up to 6.6% in 2008Footnote 44).  The proportion resistant to NRTI or PI was relatively stable over time; NRTI mono-resistance varied from 2.1% (2002) to 5.4% (1999), and PI mono-resistance was below 3% annually from 1999 through 2008. Multi-drug resistance was consistently below 2% (range: 0.4% in 2007 to 1.5% in 2005).

Figure 23. Prevalence of transmitted HIV drug resistance, by drug class and year of diagnosis, 1999-2008

Prevalence of transmitted HIV drug resistance, by drug class and year of diagnosis, 1999-2008 - Text Description
Figure 23. Prevalence of transmitted HIV drug resistance, by drug class and year of diagnosis, 1999-2008
Year NRTI NNRTI PI MDR Total
1999 5.4 0.7 1.7 1.0 8.1
2000 4.2 1.2 1.4 0.9 7.0
2001 4.7 2.9 1.8 0.9 9.5
2002 2.1 3.7 2.1 1.3 8.3
2003 2.7 2.9 2.7 0.9 8.3
2004 3.6 3.3 1.7 1.3 9.1
2005 2.9 5.0 1.5 1.5 9.9
2006 5.2 3.1 2.2 0.7 10.7
2007 3.2 6.5 2.3 0.4 12
2008 4.3 7.5 1.4 1.1 13.4

The line graph displays the percentage of HIV isolates resistant to different antimicrobial classes (each represented by its own lines) in Canada from 1999 to 2008. The horizontal axis represents the year and the vertical axis the percentage of isolates.


Preliminary data for 196 persons newly diagnosed with HIV in 2013 within two participating provinces found 12% resistant to at least one drug class. Of all specimens tested, 6% were mono-resistant to NRTI while 5% were mono-resistant to NNRTI. Two isolates (1%) exhibited PI resistance while one isolate exhibited multi-drug resistance (unpublished data). Caution must be taken in applying these results widely as they are not representative of all participating provinces.

Transmission of antiretroviral resistant HIV is concerning from a clinical point of view because it may be associated with reduced treatment options for patients. Transmission of drug resistant strains also complicates the selection of appropriate medication for post exposure prophylaxis.  HIV drug resistance among newly diagnosed, treatment-naïve persons may be associated with ongoing HIV transmission by persons who are on treatment, and, therefore, indicates suboptimal HIV prevention and control from a public health perspective. Continued surveillance of transmitted drug resistance is needed to inform antiretroviral treatment guidelines and interventions aimed at reducing the spread of drug resistant HIV.

Influenza

Drugs of Importance: Oseltamivir (Tamiflu); Zanamivir; Amantadine

Influenza is a viral respiratory infection that usually causes some or all of the following symptoms: fever, cough, sore throat, muscle aches and fatigue, loss of appetite, runny or stuffy nose. Some individuals (especially children) may also have stomach upset and pain, vomiting and diarrhea. Influenza is highly contagious and spreads easily from person to person by coughing and sneezing or through contact with objects in the environmental that are contaminated by the virus.

Influenza is caused primarily by the influenza A and B viruses and can be prevented by annual immunization with the influenza vaccine. Most individuals with influenza become only mildly ill and do not need medical care or antivirals. Some are more likely to suffer influenza-related complications or to be hospitalized because of these complications, including the elderly, young children, pregnant women, Aboriginal people and those with an underlying medical condition such as cancer, diabetes, heart disease or lung disease, obesity.

During the 2013-2014 influenza season, 5,457 hospitalizations and 344 deaths were reported to FluWatch from participating regions. During the 2013-14 flu season NML tested 2,496 influenza viruses for resistance to oseltamivir and all but five were sensitive (0.2% resistant). All 2,493 viruses tested for resistance to zanamivir were sensitive. All 1,699 influenza A viruses tested for amantadine were resistant.

During the 2013-2014 influenza season the largest proportion of prescriptions for antivirals were in children two to 18 years of age and adults 19-64 years of age. The rates observed in the 2013-2014 season were lower overall than those observed during the 2012-2013 season (Figure 24).

Figure 24. Prescription sales for influenza antivirals by week, Canada 2013-14Reference p

Prescription sales for influenza antivirals by week, Canada 2013-14 - Text Description
Figure 24. Prescription sales for influenza antivirals by week, Canada 2013-14
Year Week of the year Number of antiviral prescriptions per 100,000 prescriptions
2013 35 3.4
36 5.1
37 5.0
38 7.1
39 8.3
40 11.0
41 10.4
42 12.1
43 15.3
44 14.4
45 16.4
46 19.3
47 21.7
48 21.7
49 25.8
50 37.3
51 54.7
52 133.9
2014 1 202.9
2 252.6
3 213.0
4 165.7
5 127.5
6 93.4
7 83.5
8 70.1
9 70.0
10 48.9
11 51.7
12 52.4
13 46.8
14 47.6
15 46.0
16 38.0
17 41.2
18 39.6
19 27.9
20 28.6
21 13.8
22 8.7
23 7.4
24 8.5
25 5.9
26 5.7
27 4.4
28 5.1
29 4.2
30 4.7
31 3.8
32 4.8
33 3.0
34 3.9

The line graph displays the total number of antiviral prescriptions per 100,000 prescriptions sold through pharmacies in Canada during 2013 from week 35 to 52 and in 2014 from week 1 to 34. The horizontal axis represents the number of the week and year, while the vertical axis represents the rate of antiviral prescriptions sold.

Food and Animals

The WHO Global Strategy for Containment of Antimicrobial Resistance was developed in 2012 to limit the impact of AMR on human health. This document includes a chapter on the use of antimicrobials in food-producing animals, with associated recommendations arising not from the perspective of animal health, but because of the impact that drug use in animals and developing resistance has on human health.

Organisms that move between humans and food producing animals through contact or from exposure to contaminated food or environments are known as foodborne organisms. Escherichia coli¸ Salmonella and Campylobacter are foodborne organisms of particular interest as they represent a means to measure the movement of antimicrobial resistant organisms from animals to humans. Because the same or similar antimicrobials are used in humans and animals, AMU in both sectors contributes to the emergence and spread of resistance along the food chain. These enteric organisms of interest may cause a diarrheal illness, or go un-noticed and share their AMR genes freely among other bacteria residing in the human gut. The bacteria picking up the resistant genes may go on to cause other potentially more untreatable infections as skin, urinary tract or surgical site infections.

Generic Escherichia coli

Antimicrobials of Importance: Carbapenems, extended-spectrum cephalosporins, fluoroquinolones (e.g., ciprofloxacin)

Surveillance of generic Escherichia coli is considered a good measure of how resistance develops after antimicrobial exposure because they are so widespread in the intestines of animals and people. Generic E. coli is tested for among samples collected from farm animals, slaughtered animals, and from retail meat. E. coli are found everywhere and it is estimated that for every Salmonella that may inhabitthe gastrointestinal tract, there are potentially thousands of E. coli that are capable of carrying resistance genes that are available to swap with other organismsFootnote 6. Additionally, monitoring AMR in generic E. coli in the food chain can help us understand potential risk factors for resistance in pathogenic E. coli human infections, such as urinary tract infectionsFootnote 45Footnote 46 (that may be considered in part of zoonotic origin) and E. coli infections in sites other than the gastrointestinal tract.

The Agency does not currently monitor resistance in generic or pathogenic E. coli in humans in the community (see Next Steps, below). In 2013, E. coli was isolated from retail meat with recovery rates of 93% for chickens and turkeys, 50% for ground beef and 29% for pork. Of the E. coli isolates recovered from chickens, 81% were resistant to at least one antimicrobial. For other commodities, the percentages of isolates resistant to at least one antimicrobial were 68% in turkeys, 65% in pigs/pork and 25% in cattle/beef. Resistance to carbapenems has not been detected in any E. coli isolates.

In 2013, the prevalence of resistance to ceftriaxone in E. coli isolates from cattle/beef, pigs/pork and turkeys was less than 4% across all surveillance componentsFootnote 29. In contrast, for chickens, the prevalence of ceftriaxone resistance was 34% for farm samples, 21% for slaughter chickens and 30% for retail chickens. Fluoroquinolone resistance was detected in three E. coli isolates in 2013: two chicken isolates and one beef isolate. Resistance to nalidixic acid was found in E. coli from all commodities, but always less than 5%. For multi-class resistance, 50 E. coli isolates resistant to six to seven antimicrobial classes have been detected since 2002. While the total number of isolates remains low year-to-year (e.g., nine isolates in 2013), retail beef, pork, chickens and turkeys have all been contaminated with these highly multiclass-resistant E. coli.

Regarding the integration of data on animal AMU and AMR in agri-food E. coli, for ceftriaxone resistance, the prevalence of resistance in E. coli from chickens appears to correlate better with reported AMU on chicken farms (i.e., provinces with more farms that reported using these drugs had higher resistance rates (Figure 25) in comparison to the situation with all Salmonella (data not shown). The correlation between resistance in E. coli and reported use supports maintaining surveillance of this organism as an indicator of overall selective pressure. Furthermore it provides an opportunity to examine the genetic relatedness between animal and human E. coli if surveillance of resistant commensal or pathogenic E. coli in humans is undertaken.

Figure 25. Category I β-lactam resistance in generic E. coli from chickens on farm, at slaughter and at retail along with reported ceftiofur use in participating broiler flocks (2003-2013)

Category I β-lactam resistance in generic E. coli from chickens on farm, at slaughter and at retail along with reported ceftiofur use in participating broiler flocks (2003-2013) - Text Description
Figure 25. Category I β-lactam resistance in generic E. coli from chickens on farm, at slaughter and at retail along with reported ceftiofur use in participating broiler flocks (2003-2013)
  British Columbia Prairies Ontario Quebec Atlantic
'07 '08 '09 '10 '11 '12 '13 '05 '06 '07 '08 '09 '10 '11 '12 '13 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13 '08 '09 '10 '11 '12 '13
Abattoir 0.49 0.51 0.52 0.66 0.61 0.63 0.5 0.07 0 0.09 0 0.06 0.1 0.14 0.05 0.07 0.17 0.23 0.25 0.26 0.33 0.29 0.32 0.32 0.11 0.04 0.14 0.44 0.47 0.28 0.24 0.11 0.1 0.31 0.42 0.13 0.16 0.26 0.2 0.17 0.43 0 0 0.2
Retail 0.33 0.54 0.49 0.49 0.49 0.44 0.61 0.14 0.09 0.17 0.21 0.25 0.22 0.29 0.25 0.23 0.24 0.29 0.25 0.30 0.27 0.28 0.23 0.24 0.29 0.20 0.24 0.42 0.43 0.33 0.08 0.19 0.22 0.23 0.31 0.23 0.26 0.25 0.27 0.28 0.22 0.36    
Farm             0.65                 0.55                     0.16                     0.20            

The line graph presents the percentage of generic Escherichia coli isolates recovered from chicken samples purchased from retail, collected at farms and slaughter (each represented by its own lines) that are resistant to category one beta-lactam antimicrobials across provinces and the Atlantic region in Canada from 2003 to 2013 (depending on the province/region the start date might differ). A text box below the graph presents the total number of broiler flocks that reported using ceftiofur in 2013. The horizontal axis represents the year and province/region and the vertical axis represents the percentage of isolates.

Campylobacter

Antimicrobials of Importance: fluoroquinolones and macrolides

In chickens and cattle, the predominant Campylobacter species is C. jejuni, whereas in pigs the predominant species is C. coli. Among retail meat samples, Campylobacter in 2013 was isolated at rates of 30% for chickens and 12% for turkeys. CIPARS does not test retail pork or beef for Campylobacter due to very low recovery rates from previous testing.

In 2013, at the farm-level, 20% of pre-harvest chicken Campylobacter isolates were resistant to fluoroquinolonesFootnote 28. At slaughter, 5% of cattle isolates, 13% of pig isolates and 14% of chicken Campylobacter isolates were resistant to fluoroquinolones. At retail, 11% of chicken and 16% of turkey Campylobacter isolates were resistant to fluoroquinolones. There are provincial differences in the prevalence trends of ciprofloxacin-resistant Campylobacter from poultry. Most notably in 2013, ciprofloxacin resistance in isolates from retail and slaughter chickens and retail turkeys increased in British Columbia. Conversely, in Ontario in 2013, there was a decrease in the proportion of ciprofloxacin-resistant retail chicken isolates.

Macrolide resistance was high in Campylobacter isolates from pigs at slaughter, with 48% of the isolates resistant to either azithromycin or erythromycin. For Campylobacter isolates from chickens, 0%, 5% and 7% of the isolates from farm (at slaughter and from retail meat respectively) were resistant to either erythromycin or azithromycin. For turkeys at retail, resistance rates were 1% for azithromycin and 9% for erythromycin. There was no macrolide resistance detected in the cattle isolates at slaughter.

In terms of integration of AMR and AMU data, British Columbia was the only region that reported any fluoroquinolone use in poultry farms in 2013 and also had the highest level of resistance in Campylobacter farm, slaughter and retail meat isolates. One year of data is not sufficient to draw conclusions about the association between fluoroquinolone use and resistance in broiler chickens. Monitoring use and resistance data from the broiler chicken sector will continue to be monitored.

Non-typhoidal Salmonella

Antimicrobials of Importance: Carbapenems (ertapenem, imipenem, meropenem, doripenem), extended-spectrum cephalosporins (ceftazidime and ceftriaxone, or cefotaxime), fluoroquinolones (ciprofloxacin, levofloxacin, pefloxacin)

In 2013, 34% of chicken and 22% of turkey store samples purchased by CIPARS were found to be contaminated with Salmonella. The top three Salmonella strains causing human salmonellosis can be found in the top five serovars isolated from agri-food sources. In Canada, the prevalence of Salmonella for pork or beef/cattle at slaughter is too low for ongoing reportable surveillance.

In terms of the drugs of importance to human medicine, no resistance to carbapenems has ever been detected in agri-food Salmonella isolates in Canada and in 2013, there were no Salmonella agri-food isolates resistant to ciprofloxacin. Resistance to ceftriaxone has been found in Salmonella from all animal species under surveillance, but is most common in chickens (overall 24% in 2013) and clinical isolates from cattle (44%). It is important to recognize that for many drugs (ceftriaxone in particular) resistance in Salmonella is very serovar specific.

Salmonella Enteritidis

All S. Enteritidis recovered from retail meat, slaughtered animals, animals on farm or from veterinary diagnostic isolates were not resistant to any of the antimicrobials tested.

Salmonella Heidelberg

No isolates were resistant to azithromycin or ciprofloxacin. Resistance to ceftriaxone has demonstrated both temporal changes and regional differences. In 2013, ceftriaxone resistance from retail chickens ranged from 26% to 80% by region, while temporal resistance trends in poultry isolates mirrored changing AMU practices. For example, in 2003 the prevalence of ceftriaxone resistance in S. Heidelberg from retail chickens in Quebec was 65% (during high levels of ceftiofurReference q use in chicken hatcheries). This figure dropped significantly during a period of little use in 2006 (to 7%) and rose again during a period of rotational use (43% in 2013).

Salmonella Typhimurium

Salmonella Typhimurium is most commonly isolated from healthy pigs and pork meat, with S. Typhimurium representing 31% of all Salmonella isolatesFootnote 29. The relative proportion of S. Typhimurium recovered from other animal species (healthy animals or meat) was much lower (<2%). In 2013, 90% of isolates overall from healthy animals/meat were resistant to one or more antimicrobials. No isolates were resistant to ciprofloxacin or azithromycin. Three percent were resistant to ceftriaxone. These prevalences of resistance have remained stable over time.

Among Salmonella isolates submitted from sick livestock, S. Typhimurium was the most common serovar recovered from cattle (45%) and pigs (41%). Eleven of the cattle isolates (10%) were resistant to six antimicrobial classes. It should be noticed that sick animals do not enter the food chain for human consumption.

AMR Conclusion

The emergence of antimicrobial-resistant organisms is a major public health concern in Canada, particularly in health care settings and in vulnerable populations. Agency surveillance programs have identified that these organisms appear to be thriving in both health care and community settings and are capable of causing severe, life-threatening infections that may be more difficult to manage because of limited treatment options. This leads to the use of more expensive, last-recourse antimicrobials. Because AMR may emerge in bacteria as a response to selective antimicrobial pressure, there is a potential risk that fewer and fewer antimicrobials will remain effective in the future. The use of last-recourse antimicrobials to treat serious infections (after all other treatment options have failed) is becoming more common in both health care and community settings.

Clostridium difficile, multi-drug-resistant Enterobacteriaceae (including ESBL and CRE), MRSA, and VRE are organisms of clinical significance in Canadian hospitals. The prevalence of many of these organisms continues to increase and they are causing more illness and death. These organisms are also responsible for multiple hospital outbreaks and contribute to the overall burden in Canada's publically-funded health care system.

Antimicrobial-resistant organisms are also becoming more prevalent in community settings. For example, of the Neisseria gonorrhoeae isolates submitted to the Agency for susceptibility testing, almost 4% are resistant to antibiotics according to current treatment guidelines, and over 10% of Streptococcus pneumoniae isolates are resistant to the most commonly prescribed antibiotics. MDR-TB is of significant concern because susceptible TB is difficult to treat. The prevalence of TB in vulnerable populations is high and the introduction of MDR-TB in community groups such as those living on First Nation reserves and incarcerated individuals can be devastating. Viral infections are also a growing concern. Overall drug resistance in HIV strains tested in Canada has increased since surveillance began in 1999. Preliminary 2013 data from two participating sentinel sites showed an overall resistance of 12%. For the Salmonella strains identified in this report, it does not appear that ciprofloxacin or azithromycin resistance from the Canadian agri-food sources under surveillance is contributing to the resistance observed in Salmonella-causing human illness. However, changing rates of ceftriaxone resistance for one Salmonella strain (S. Heidelberg) do appear to correlate.

Treatment of these resistant infections is associated with substantial morbidity and mortality and utilizes considerable health care resources. Antimicrobial prescriptions have also increased significantly. Unfortunately, the increase in the incidence of antimicrobial-resistant organisms and the use of antimicrobials in both the human and animal sectors is occurring at a time when the development of new drugs is decreasing. The collection of new information must be a priority in order to better understand the burden of disease caused by AMR and the impact of prescribing practices on the emergence of resistance.

Next Steps

The Agency has a strong foundation for AMR and AMU surveillance and generates robust data on AMR in a specific number of settings. However, there is a need to expand the scope of surveillance in order to provide more representative and comprehensive data for public health action. In collaboration with stakeholders, the Agency is currently developing a list of priority pathogens for AMR surveillance in Canada. Although the Agency is already monitoring many of the highest-ranked organisms of interest, there are some organisms not currently under surveillance. Moving forward, the Agency will regularly review and revise priority organisms of interest and target surveillance accordingly. As a first step, the Agency will conduct surveillance of resistance on an additional priority foodborne bacterial organism causing human illness.

The Government of Canada is working with provincial partners and academia in the animal sector to improve knowledge about additional veterinary pathogens that are currently submitted to diagnostic laboratories for antimicrobial susceptibility testing. This information will better inform veterinary prescribing behaviours, identify potential resistance determinants that could be transmitted to human pathogens, and provide an indicator of potential treatment failures due to resistance in animals.

To increase our understanding of community-associated AMR infections and how these spread beyond hospitals, the Agency will implement a community-level surveillance pilot to gather and analyze existing susceptibility data generated by front-line diagnostic laboratories. This will include information for all organisms identified in the priority exercise and will position the Agency to provide additional information about organisms that cause blood and urinary tract infections.

These new and enhanced initiatives will improve the Agency's understanding of how AMR is spread in the community and how it travels between the community and hospitals and along the food chain. New and emerging public health threats may be identified earlier which will direct new activities and enable the development of new policies and guidelines to reduce the burden and impact of AMR on the health of Canadians.

Conclusion

This report has illustrated that AMR is a serious and potentially growing threat to the health of Canadians. Increased national and international surveillance will be essential to inform targeted effective actions that will prevent the worst-case scenario, where infections are no longer treatable with antimicrobials.

The good news is that continued progress towards mitigating the impact of AMR and enhancing the stewardship of antimicrobials across sectors is well within the influence of actors in Canada. The Agency has established robust surveillance programs for AMR/AMU and the implementation of CARSS will be an important step towards providing decision-makers with the integrated information they need to make further progress in reducing the threat of AMR and preserving the efficacy of today's antimicrobials.

The Agency will continue to monitor its enhanced efforts to mitigate AMR and improve AMU, and will report on its progress in future reports.

Annex 1

Public Health Agency of Canada's Antimicrobial Resistance and Use Surveillance Systems
System name Pathogens Scope Moving forward
Canadian Nosocomial Infection Surveillance Program (CNISP) Methicillin-resistant S.aureus, Clostridium difficile,
Vancomycin-resistant Enterococci,
Carbapenem-resistant Enterobacteriaceae and
Carbapenemase producing organisms
Monitors health care- and community-associated infections in patients admitted to select acute-care hospitals. Expansion of coverage to include other resistance mechanisms, e.g., Antibiogram in hospitals.
Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) Campylobacter
Salmonella
E. coli
Salmonella from cases reported in the community and hospital, as well as that isolated from retail food and animals. Campylobacter and E. coli isolated from retail food and animals. CIPARS collects AMU information from sentinel grower-finisher pig and broiler chicken farms. Antimicrobial quantities distributed for sale for use in animals is provided to CIPARS from the Canadian Animal Health Institute. Human Campylobacter, E. coli and Enterococcus data will be obtained through the Antibiogram Project. In addition, human Campylobacter samples will be obtained from FoodNet Canada sites for AMR testing and will be linked to outcome information.
FluWatch Influenza A and B (of human, avian or other lineages, isolated from human cases) Monitors circulating strains of the flu virus and assesses their sensitivity to antiviral medications. Ongoing
Canadian Tuberculosis Laboratory Surveillance System (CTBLSS) Multi-drug-resistant Tuberculosis Sentinel laboratories report their results on anti-tuberculous drug susceptibility testing for every patient for whom a specimen or an isolate has been received for each calendar year. Ongoing
Antimicrobial-Resistant Neisseria gonorrhoeae Surveillance System Neisseria gonorrhoeae Monitors antimicrobial susceptibility of Neisseria gonorrhoeae in Canada.
Passive, voluntary submission by provinces and territories.
Ongoing
Invasive Streptococcal Disease Surveillance Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae Voluntary passive system. In 2013, isolates include 82% of S. pneumoniae, and 78% of S. pyogenes, cases reported to Canadian Notifiable Diseases Surveillance System. Ongoing
HIV Strain and Drug Resistance Surveillance System Human Immunodeficiency Virus Monitors drug resistance in HIV isolates from patients with newly diagnosed infections.  Five provinces currently participate. Ongoing
Antimicrobial usage (AMU) n/a National and provincial information on antimicrobials dispensed through community pharmacies, purchased by hospitals and clinical indication for which they were recommended by physicians. Integrate data from the Non-Insurable Health Benefits program from FNIHB and from hospital pharmacies within the CNISP network

Annex 2

Infections and pathogens for initial global surveillance compared to the Agency's current surveillance data
Infection Proposed metric Pathogen Canada BaselineTable 27 - Footnote * Source
Bloodstream infections Number of resistant infections per 10,000 patient-days Acinetobacter spp. Carbapenem resistance: 0.005/10,000 patient-days CNISP
Escherichia coli Carbapenem resistance: 0.007/10,000 patient-days CNISP
Klebsiella pneumonia Carbapenem resistance: 0/10,000 patient-days CNISP
Pseudomonas aeruginosa
Salmonella spp.
Staphylococcus aureus MRSA: 0.56 /10,000 patient-days CNISP
Streptococcus pneumoniae
Percentage resistance infections/total infections Acinetobacter spp.
Escherichia coli
Klebsiella pneumonia
Pseudomonas aeruginosa
Salmonella spp. Ceftriaxone: 11%
Ciprofloxacin: 1%
CIPARS
Staphylococcus aureus
Streptococcus pneumoniae Clindamycin: 6%
Penicillin: 10%
Ceftriaxone: 0.7%
Cefuroxime: 4%
Sulfamethoxazole trimethoprim: 7%
NML
Urinary tract infections Percentage resistance infections/total infections Escherichia coli
Klebsiella pneumonia
Diarrhea Percentage resistance infections/total infections Salmonella spp.
(Non-typhoidal)
Ceftriaxone: 6%
Ciprofloxacin: 1%
CIPARS
Shigella spp. Ceftriaxone: < 0.17%
Ciprofloxacin: < 0.10%
CIPARS (2002)
Gonorrhoea Percentage resistance infections/total infections Neisseria gonorrhoeae Azithromycin: 1.2%
Ceftriaxone and/or Cefixime: 3.9%
NML
Tuberculosis Percentage resistant isolate/total isolates tested Multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) 0.6% CTBLSS
Extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) 0.1% CTBLSS

The purpose of collecting data for global surveillance of human pathogens resistant to antimicrobial agents is to assess those infections and antimicrobial-resistant organisms that are the greatest global threat. For this reason, the WHO has selected, for initial surveillance, those organisms that are resistant to several drugs, thus limiting treatment options; and that are spreading across the globe. The WHO acknowledges that not all organisms included in the first phase of surveillance priorities are representative of the population being monitored. As a next step, the Agency will review the WHO priority infections and pathogens to determine which additional infection or pathogen is of concern in Canada.

References

Footnotes

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