Antimicrobial Resistance
By John Lorinc
When Alainna Jamal (PhD ’20, MD ’22) ponders the threats that truly worry her, she focuses on one particular statistic in the unfurling story of the spread of CPE (known more formally as carbapenemase-producing Enterobacterales), an antibiotic-resistant pathogen that attacks almost any system in the body and is rapidly gaining a foothold in Canadian health care settings.
Interestingly, the detail she mentions isn’t a fatality rate that can run up to 50 per cent.
Rather, Jamal, a second-year internal medicine resident at the Temerty Faculty of Medicine, is preoccupied with the way the pathogen is proliferating.
The germs are transmitted through touch via the unwashed hands of health care personnel, contaminated medical equipment and splash from hospital sink drains.
Though commonly associated with infections picked up while hospitalized outside the country, especially in the United States and South Asia, Jamal says almost a third of new CPE cases in Ontario afflict people who haven’t travelled abroad but have had exposure in a Canadian health care facility.
“It spreads within our health care system because we either don’t pick it up fast enough, or our infection prevention and control measures maybe weren’t good enough,” she says. “And then you just get local dissemination, which is the part to me that’s actually the scariest and the most interesting because the pathogen itself doesn’t really know or care where it lives.”
Jamal belongs to a network of researchers studying antimicrobial resistance (AMR) at Temerty Medicine and its affiliated teaching hospitals. They’re pushing to not only expand the state of scientific knowledge about emerging treatment-proof infections but are fighting to put the related public health issues back on the radars of policymakers.
“The World Health Organization still calls antimicrobial resistance a silent pandemic,” says Jamal. “I mean, you can spend a day in our hospitals, and there’s absolutely nothing silent about antimicrobial resistance if you come on the wards or the ICUs. We see these difficult-to-treat infections literally every single day. It’s not a future problem. It’s a problem now, so I’m not sure what’s silent about this pandemic.”
The rising tide of AMR has many and diverse causes. Certainly, the best known involves the over-prescribing of antibiotics, particularly for viral infections of the upper respiratory tract. In the 15 or so years prior to the COVID-19 pandemic, public health officials and epidemiologists sought to spotlight C. difficile outbreaks in hospitals and other congregate care settings where infectious diseases spread rapidly, either through direct contact or by airborne droplets.
But there are many other drivers of AMR, notes Scott Gray-Owen, a molecular geneticist and the director of the Emerging and Pandemic Infections Consortium (EPIC), a partnership between the University of Toronto and five major hospital research institutes.
Gray-Owen focuses his research on the bacteria responsible for rapidly progressing invasive meningococcal meningitis and gonorrhea. Until fairly recently, many public health professionals regarded gonorrhea as a disease of the past, eradicated by antibiotics, says Gray-Owen. But the growing incidence of sexually transmitted diseases in an era when HIV-AIDS is no longer a death sentence has produced new, difficult-to-treat strains, he says.
“Gonorrhea has rapidly acquired resistance to any antibiotic that’s been used against it,” Gray-Owen observes, adding that WHO estimates there were 82 million cases in 2023. “This has become a real problem to the point that it was one of three bacteria that were considered an urgent threat by the U.S. Centers for Disease Control and Prevention. This is something that has not gone away.”
COVID-19 played a curious dual role in the growth of AMR. With emergency rooms inundated with patients, many of them suffering from suspected secondary bacterial infections, Jamal says COVID-19 hugely accelerated the spread of a range of infectious diseases within health care settings, as well as the use of antimicrobials to treat them — a veritable hot house for the evolution of drug-resistant strains.
“Hospitals became overrun through the various stages of the pandemic,” says Susy Hota (MD ’02, MSc ’11, PGME ’07), an associate professor in Temerty Medicine’s Department of Medicine’s Division of Infectious Diseases, and the division head for infectious diseases at University Health Network and Sinai Health.
“That really pressured the system in terms of being able to isolate patients appropriately for the various types of infections that they had. When the hospital is so full, we no longer have isolation rooms that we would normally use to keep people who carry antimicrobial-resistant organisms separate from others,” she says. “It became less of a priority to isolate patients with antimicrobial-resistant organisms than preventing the transmission of COVID-19, which is highly contagious.”
With the intense public focus on the infectiousness of COVID-19, and the scientific fights over whether it is transmitted on surfaces, through droplets or by tiny aerosols, vast sums of funding poured into pandemic-oriented research at the expense of other priorities, among them AMR, says Jamal.
“The impact of COVID-19 on AMR has been quite devastating,” she adds, citing a 2022 CDC report noting a spike of AMR in the U.S. early in the pandemic. “To those of us who do antibiotic resistance, we knew this was going to happen,” says Jamal. “There was a massive diversion of resources from all infectious disease initiatives to COVID-19, including within our group. For a good few years we were not doing any CPE research. Nobody had the bandwidth.”
EPIC was established at U of T in 2022 to fund infectious disease/AMR research and undertake related projects, such as driving improvements to prescribing practices through stewardship programs that provide expert advice on best practices for antimicrobial use to front-line physicians.
As Natasha Christie-Holmes (PhD ’08), a longtime manager of U of T’s high containment labs, and the director of strategy and partnerships for EPIC, says, “It’s probably been 15-plus years of consistent efforts to inform the clinical community about best practices and about standards of care in terms of antibiotic use. There’s now standardized stewardship practices in a lot of major hospitals, but it’s harder in rural settings, which tend to have smaller teams and less resources.”
There’s a wide range of AMR-related research, including interdisciplinary projects that EPIC’s granting programs deliberately seek out. One area that’s attracting a lot of attention is the use of genomics and sequencing to essentially map the trajectory of an outbreak within a health care setting in real time.
“Say you had an outbreak of an infection on a specific unit in a hospital,” says Hota. “You’ve identified three patients. The microbiology lab would send their clinical specimens off to a research lab that can perform specialized molecular analysis.”
By looking at and then comparing nucleic acid from the microbes causing the infections, it might be possible to determine the relatedness of cases or a path of infection between infected patients, even if they’d never met or were in different parts of the hospital.
Hota is a co-author of a study published in December 2023 in the Journal of Clinical Microbiology that demonstrates how whole genome sequencing could be used to investigate the transmission of an antimicrobial resistant form of fungus called Candida parapsilosis in a pair of Ontario hospitals.
The authors conclude, “Timely access to genomic epidemiological information can inform targeted infection control measures.”
But, as Hota cautions, the use of this approach is still a work in progress. The task of identifying transmission patterns using genomics is highly complex because the sequencing data can be very difficult to interpret.
What AMR researchers ultimately hope to achieve, besides scientific breakthroughs, is increased recognition of the grave risks associated with the kind of pandemic that hasn’t generated enormous amounts of public and media attention, yet claims thousands of lives each year. Citing a 2019 study by the Council of Canadian Academies, Jamal notes that about 5,400 people in Canada die from drug-resistant infections each year, and the cost to the health care system now runs to about $1.4 billion annually. Countless other patients will endure lengthy and painful recoveries that may only partially resolve or leave them with permanent disabilities.
“How,” she asks, “is that not front-page news?” •