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Antimicrobial Resistance
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Antimicrobial resistance is an increasingly serious health issue in Ontario and worldwide. As more antimicrobial drugs become ineffective and fail to treat a growing number of infections, those infections persist and increase the risk of disease, poor health and death. Action is required to ensure the use of antimicrobials only when necessary to safeguard the availability of future treatments for both common and serious infections.

Highlights

In Canada, total medical care costs associated with antimicrobial-resistant organisms (AROs) are estimated at $1 billion annually.

Antimicrobial resistance puts many achievements of modern medicine at risk, and there is considerable urgency to ensure effective antimicrobials are available.

Between 2010 and 2014 nearly half of Escherichia coli and Klebsiella pneumoniae tested from urinary tract infections were resistant to the antibiotics commonly used for treatment.

Resistance to cephalosporins, the last class of drugs available to treat gonorrhea, has remained relatively high at 10.1% of isolates tested in 2014.

From 2011 to 2014, the percentage of carbapenemase-positive isolates increased from 11% to 17% of all suspected carbapenemase-producing Enterobacteriaceae (CPE) isolates, indicating that this organism has the potential to become a more widespread problem.

Due to the complexity of the problem, addressing the growing threat of antimicrobial resistance is a shared responsibility and coordinated action is required to minimize emergence and spread of disease.

Size of the problem

Antimicrobial resistance is a serious and growing issue globally that threatens the ability to prevent and treat a range of infections from common urinary tract infections to more serious bloodstream infections. In Canada, total medical care costs associated with antimicrobial-resistant organisms (AROs) have been estimated at $1 billion annually (1). AROs are spread in a number of different environments, including in the health care setting and in wider community settings outside of hospitals.

Laboratory testing for resistance and whether or not it is increasing over time provides a warning that treatment may lose effectiveness. Many organisms, primarily acquired in community settings, are showing concerning levels of resistance. Between 2010 and 2014 nearly half of Escherichia coli and Klebsiella pneumoniae tested from urinary tract infections were resistant to antibiotics commonly used for treatment. Resistant specimens of Shigella, which can cause severe intestinal illness, made up 4.7% of all samples tested in 2014 compared to only 1.8% in 2010. Resistant specimens made up 11% of isolates tested in 2014 from invasive Candida glabrata infections (Figure 1).

Since 2009, Ontario routinely monitors more common AROs in hospitals, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Emerging AROs in health care settings, such as carbapenemase-producing Enterobacteriaceae (CPE), have not been routinely monitored, therefore, little is known about their true impact. CPE have become resistant to the most potent class of antibiotics used to treat these infections, while also showing resistance to an extremely broad range of other antibiotics. From 2011 to 2014, the percentage of carbapenemase-positive isolates increased from 11% to 17% of all suspected CPE isolates, indicating that this organism has the potential to become a more widespread problem.

Figure 1: Antimicrobial resistance in selected organisms, {{geoSelect}}, 2010–2014

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Data source:  Public Health Ontario Laboratory Information management System. Public Health Ontario, extracted 2015 Sep 29.










Populations at risk

Drawing on available data, resistance levels found in these same organisms show no clear distribution among age groups (Figure 2). Compared to females, twice as many males were likely to have a resistant isolate of CPE and N. gonorrhoeae. Conversely, females were twice as likely to have a resistant Shigella isolate. The distribution of the number of resistant isolates by age group and sex largely mirrors the overall distribution of the infection in the population. Because infections can be more serious in the very young and the very old, the lack of effective antimicrobial treatment options have the most severe impact on these age groups, with higher rates of complications and death.

Figure 2: Antimicrobial resistance in {{vis2OrgRadio}} by {{vis2CategoryRadio}}, Ontario, {{vis2YearSelectNameToDisplay}}

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Data source: Public Health Ontario Laboratory Information management System. Public Health Ontario, extracted 2015 Sep 29.

 

Focus on gonorrhea

Over the last several decades, Neisseria gonorrhoeae, the bacterium that causes the sexually transmitted disease gonorrhea, has become increasingly resistant to a number of antibiotics used for treatment. Many antibiotic classes are no longer effective: penicillins (discovered in 1928, resistant since 1976), sulfonamides (discovered in 1932, resistant since 1944), tetracyclines (discovered in 1944, resistant since 1985), macrolides (discovered in 1948, resistant since 1977), and quinolones (discovered in 1961, resistant since 1994) (2,3). Cephalosporins, the gonorrhea treatment of last resort, are now showing increased resistance, affecting up to 10.1% of isolates tested in 2014. The minimum inhibitory concentration, which is the lowest amount of a drug required to stop Neisseria gonorrhoeae microbial growth, has significantly increased between 2006 and 2011 (Figure 3).

Figure 3: Cephalosporin (cefixime) susceptibility of Neisseria gonorrhoeae (µg/mL), Ontario, {{vis3YearSelect}}

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Data source: Laboratory Information Management System. Streptococcus and STI Unit, National Microbiology Laboratory, extracted 2016 Jan 07.

 

Antimicrobial resistance

Antimicrobial resistance is resistance of an organism to an antimicrobial drug that was previously effective for treatment. It happens because of a change in the biological makeup of the organism, either naturally during replication or by picking up resistant genes from other microbes. Resistance is expedited when antimicrobials are not taken properly (the right drug, at the right dose for the right duration). Microbes that survive treatment multiply, leading to the emergence of strains that are partially or fully resistant to treatment (Figure 4) (4). While many organisms become weaker and less virulent when they become resistant to antimicrobials, recent studies show that some actually become stronger and more dangerous (5).


Figure 4: How organisms become resistant

Antimicrobial stewardship is the practice of using antimicrobials only when necessary, which lessens the opportunity for organisms to become resistant. Stewardship is a shared responsibility across multiple sectors and settings, including physicians, pharmacists and patients. Stewardship remains important as the use of antimicrobials in Canada is higher than in many other countries. For example, Canada ranks 11 of 29 countries based on use of antimicrobials for patients outside of hospitals, with use that is 60% higher than in the Netherlands, the country with the lowest use (1). Control of antimicrobial therapies is also important in agricultural and industrial use (6). While the use of antimicrobials in health care and community settings has declined in Canada over the past decade, their use in animals has remained unchanged in that time period (1).

Health Impacts

With the advent of antibiotics 75 years ago, many bacterial infections that posed a significant threat became treatable and manageable. Since then, bacteria have become resistant to these antibiotics, so today, some previously treatable infections can no longer be quickly or easily resolved. Patients infected with antimicrobial-resistant pathogens may experience increased morbidity and recovery time leading to greater emotional and financial burdens for families, as well as a greater economic burden to society due to increased health care costs and absenteeism (7).

Antimicrobial-resistant infections are also associated with increased mortality. For example, patients infected with MRSA are 64% more likely to die than those infected with non-resistant bacteria (8). The longer the infection persists, the greater the opportunity for its transmission to other individuals. People with weakened immune systems are at greater risk of infection, including infants, seniors and those with chronic diseases (9).

To manage resistant infections, physicians may recommend alternative antimicrobials for treatment. These drugs may be less effective, more toxic or more expensive than standard treatments (10). Furthermore, use of other types of antimicrobials to treat already-resistant infections may facilitate the emergence of new multidrug-resistant organisms (1).

Antimicrobial discovery is a very slow and costly process. Only two novel antibiotic classes have been approved for sale since 1962, compared to 20 in the period from 1940 to 1962 (11). Preserving the effectiveness of established treatment options is vital for protecting population health (12).

Importance

Antimicrobial resistance is a serious and growing public health threat not only in Ontario, but also globally. Overuse and misuse of antimicrobials has increased the rates of resistance and the risk of the spread and impact of infections. Many of the most effective antimicrobials available to treat infection are now less effective, or in some cases, completely ineffective. Antimicrobial resistance puts many achievements of modern medicine at risk, and there is considerable urgency to ensure effective antimicrobials are available.

People who have what were once considered "nuisance" infections, such as urinary tract infections or infectious diarrhea, may be at higher risk of complications such as kidney disease and sepsis. Longer durations of illness and treatment, often in hospitals, increases health care costs as well as the economic burden on families and society. Without effective antimicrobials to prevent and treat infections, the success of organ transplantation, cancer chemotherapy and major surgery may be compromised.

Surveillance of antimicrobial-resistant organisms is crucial to ensure the availability of comprehensive data to inform public health decision-making and the implementation of appropriate interventions and preventative measures. In Ontario, public health laboratories provide clinical microbiology testing and primary testing for infectious disease, test organisms for antimicrobial susceptibility and contribute to provincial and national monitoring efforts (13). The Canadian Antimicrobial Resistance Surveillance System (CARSS) is a federal initiative to integrate existing surveillance systems to enhance surveillance and response at the federal level (1).

Addressing the growing threat of antimicrobial resistance is a shared responsibility in Ontario and across Canada and the world. Stopping the spread of antimicrobial resistance relies on good antimicrobial stewardship at every level – from every patient-clinician interaction in hospitals and community health care settings to intersectoral collaboration across governments at the local, provincial and federal levels. A coordinated approach is needed among public health, health care, agriculture and the public and private sectors.

References

  1. Public Health Agency of Canada. Canadian antimicrobial resistance surveillance system - report 2015. Ottawa, ON: Her Majesty in Right of Canada; March 2015. Available from: http://healthycanadians.gc.ca/alt/pdf/publications/drugs-products-medicaments-produits/antibiotic-resistance-antibiotique/antimicrobial-surveillance-antimicrobioresistance-eng.pdf
  2. Unemo M, Shafer WM. Antibiotic resistance in Neisseria gonorrhoeae: origin, evolution, and lessons learned for the future. Ann N Y Acad Sci. 2011 Aug;1230:E19-28.
  3. Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev. 2014 Jul;27(3):587-613.
  4. Centers for Disease Control and Prevention. About antimicrobial resistance [Internet]. Atlanta, GA: Centers for Disease Control and Prevention; 2015 Sep 8. Available from: http://www.cdc.gov/drugresistance/about.html
  5. Roux D et al. Fitness cost of antibiotic susceptibility during bacterial infection. Sci Transl Med. 2015 Jul 22;7(297):297.
  6. Public Health Agency of Canada. The Chief Public Health Officer's report on the state of public health in Canada, 2013: Infectious disease — The never-ending threat. Ottawa, ON: Her Majesty in Right of Canada: March 2015. Available from: http://www.phac-aspc.gc.ca/cphorsphc-respcacsp/2013/index-eng.php
  7. Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2006 Jan 15;42 Suppl 2:S82-9.
  8. World Health Organization. Antimicrobial resistance: Global report on surveillance [Internet]. Geneva, Switzerland: World Health Organization; 2014. Available from: http://www.who.int/drugresistance/documents/surveillancereport/en/
  9. Government of Canada. Impacts of antibiotic resistance. Ottawa, ON: Her Majesty in Right of Canada; September 2014. Available from: http://healthycanadians.gc.ca/drugs-products-medicaments-produits/buying-using-achat-utilisation/antibiotic-resistance-antibiotique/impacts-repercussions-eng.php
  10. Ontario Medical Association. When Antibiotics Stop Working. Toronto, ON: Ontario Medical Association; March 2013. Available from: https://www.oma.org/resources/documents/antibiotics03192013.pdf
  11. Coates AR, Halls G, Hu Y. Novel classes of antiobiotics or more of the same? Br J Pharmacol. 2011 May;163(1):184-94.
  12. Silver LL. Challenges of antibacterial discovery. Clin Microbiol Rev, 2011, 24(1):71-109.
  13. Public Health Ontario. Laboratory Services [Internet]. Toronto, ON: Queen's Printer for Ontario. Available from: http://www.publichealthontario.ca/en/ServicesAndTools/LaboratoryServices/Pages/default.aspx

Report last updated: March 15, 2016

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