Opinion

Turning back the tide: The challenge of antimicrobial resistance and its impact on our health

A major lesson learned from the pandemic is that in today’s interconnected world, what happens in a seemingly distant region can expand rapidly and globally with devastating consequences. Antimicrobial resistance (AMR) is no different.

In a contribution to Healthy Debate last November for World Antimicrobial Awareness Week 2022, we wrote about how AMR is a fast and furious public health threat rather than a slow-moving tsunami. A year on, we ask: Is it too late to turn back the tide?

Let’s start with the magnitude of the problem. A published analysis estimated that globally, 4.95 million deaths were associated with antibiotic resistant bacteria, among which 1.27 million were considered attributable deaths. People living in sub-Saharan Africa have the highest mortality burden attributable to antibiotic resistance, at a staggering 27.3 deaths per 100,000 population. Lower respiratory tract infections such as pneumonia accounted for the highest mortality, with 1.5 million deaths associated with antibiotic-resistant bacteria. In terms of culprit, six bacteria (E. coli, S. aureus, K. pneumonia, S. pneumoniae, A. baumannii, and P. aeruginosa) were responsible for 3.57 million deaths associated with antibiotic resistance.

The COVID-19 pandemic may have hastened the emergence and transmission of resistant bacteria in hospital settings, particularly gram-negative rods such as E. coli. Furthermore, among patients who experienced bacterial infections in the backdrop of COVID-19, more than 60 per cent were infected with antibiotic-resistant pathogens.

A group of drug-resistant gram-negative rods capable of breaking down many classes of antibiotics, known as carbapenemase-producing Enterobacterales, has been increasing globally for the past two decades, and are increasingly reported in Canada, including Ontario.

Devastatingly, patients with the greatest medical needs are also most at risk of contracting multidrug resistant organisms. An Ontario man who received a life-saving liver transplant but experienced significant setbacks due to multiple infections caused by antibiotic-resistant pathogens perfectly illustrated the distressful situation. The truth is that this happens way more often than you think. Without effective antibiotics, infection risks following routine joint replacement and C-sections will become unacceptably high. Life-saving treatment such as chemotherapy, immunotherapy and organ transplant procedure will not be feasible without the support from antibiotics, essentially reversing decades of medical progress.

Life-saving treatment such as chemotherapy will not be feasible without the support from antibiotics, essentially reversing decades of medical progress.

The climate crisis has been on many Canadians’ minds after a summer plagued by immense forest fires, successive suppressive heat waves, as well as ruinous storms. Emerging data suggest that climate change is contributing to AMR as rising local temperatures may be associated with the spread of antibiotic resistant genes. Widespread floods following major storms have been linked to widespread, difficult-to-treat invasive fungal infections. Tick-borne infections such as Lyme disease, caused by the bacteria Borrelia burgdorferi, have also been linked to climate change. Notably, this summer the U.S. issued the first alert of locally transmitted malaria in Florida and Texas in 20 years – malaria is an infection transmitted by mosquitoes and causes a medical emergency.

To compound the problem, Canada has been facing its own “Bad Bug, No Drug” moment. This was a well-publicized public health situation faced by the U.S. nearly two decades ago. To tackle the problem, cross-sectoral efforts were undertaken that combined mandates for antimicrobial stewardship in health-care settings, investment in surveillance infrastructure and incentivization for research and development of new compounds. Many initiatives have paid off, particularly on the availability of new antibiotics, national benchmarking, implementation of antimicrobial stewardship programs and diagnostic technologies.

Unfortunately, Canada has fallen significantly behind. A 2015 study indicated that Health Canada’s lengthy approval processing time compared to the U.S. and European Union result in delays in accessibility to new drugs in Canada and contribute to higher drug cost. A 2023 study  identified that a third of the active substances approved in the U.S. and Europe between 2016 and 2020 had not been submitted for Health Canada review by February 2023. Of the 17 infectious disease treatments, eight were antibiotics or add-ons to antibiotics indicated for specific or complicated cases. This gap translates into significant bureaucratic barriers and logistical delays for health-care providers to access optimal antibiotics effective against highly resistant bacteria. In the meantime, clinicians have had to reach for more toxic, less desirable alternative antibiotics that would have been relegated to second- or third-line agents in international published guidelines. The magnitude of this problem was recently articulated in the Report of the Auditor General of Canada.

As 2023 World Antimicrobial Awareness Week approaches, let’s end this article on a positive note. In lockstep with the Auditor General’s Report, the Public Health Agency of Canada has embarked on the initial consultation with health-care providers to address the needs and urgency to access new antibiotics. Recently, the Council of Canadian Academies published its findings to stimulate the provision of new antibiotics to the Canadian market through pull incentives that ensure developers’ financial viability for antibiotics that have successfully proven scientific viability and relevancy.

All Canadians can play a part through regular handwashing and vaccination, using antibiotics only when indicated and limiting exposure to antibiotics used as growth stimulants in meat production. As health-care providers, we must practice antimicrobial stewardship principles such as The Four Moments of Antibiotic Decision Making. As antimicrobial stewardship clinicians, we implement system-level interventions and engage with prescribers to promote behaviour change in antimicrobial use.

Returning to our initial question, “Is it too late to turn back the tide?”, we believe the answer is no, it is not too late but collectively we – Canadians, patients, caregivers, legislators, politicians, policymakers, health-care providers – have to act now!

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Authors

Miranda So

Contributor

Miranda So, PharmD, MPH, is the Antimicrobial Stewardship Program Lead-University Health Network, of the SH-UHN ASP. She is a Clinician-Investigator with the Toronto General Hospital Research Institute, an Assistant Professor (Status-Only) at the Leslie Dan Faculty of Pharmacy, University of Toronto, and a Lecturer (Clinical), Division of Infectious Diseases, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia

Jennifer Curran

Contributor

Jennifer Curran, PharmD, is a Pharmacotherapy Specialist-Antimicrobial Stewardship, University Health Network, of the SH-UHN ASP. She is an Assistant Professor (Status-Only) at the Leslie Dan Faculty of Pharmacy.

Shahid Husain

Contributor

Shahid Husain, MD, MS, is a Transplant Infectious Diseases Consultant and Research Director of the Ajmera Transplant Centre, UHN, a physician member of the SH-UHN ASP, and a Professor of Medicine at the University of Toronto.

Mark McIntyre

Contributor

Mark McIntyre, PharmD, is the Antimicrobial Stewardship Program Lead-Sinai Health, of the SH-UHN ASP. He is an Assistant Professor (Status-Only) at the Leslie Dan Faculty of Pharmacy, University of Toronto.

Andrew Morris

Contributor

Andrew Morris, MD, SM is the Medical Director of the SH-UHN ASP, an Infectious Diseases Consultant and a Professor of Medicine at the University of Toronto.

Jenna Sauve

Contributor

Jenna Sauve, PharmD, is a Pharmacotherapy Specialist-Antimicrobial Stewardship, UHN, of the SH-UHN ASP.

Shreeya Thakrar

Contributor

Shreeya Thakrar, PharmD, is a Pharmacotherapy Specialist-Antimicrobial Stewardship, UHN, of the SH-UHN ASP.

Bohang Zhao

Contributor

Bohang Zhao, BScPhm, is a Pharmacist in the Antimicrobial Stewardship Program at Sinai Health, of the SH-UHN ASP. He is a University of Toronto graduate with antimicrobial stewardship experience at a community teaching hospital.

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