By George Zhanel
As we head into another season of influenza and the associated bacterial superinfections that will result, monitoring bacterial pathogens for resistance to our current antimicrobials will take on even greater importance. Antimicrobial resistance surveillance is a priority as, worldwide, we continue to witness the global public health threat of increasing antimicrobial resistance. We can also see that Canada is not immune to this rise of antimicrobial-resistant pathogens.
Recently, the Canadian Antimicrobial Resistance Alliance (CARA, www.can-r.com) in partnership with Health Canada, published the results of the CANWARD study, a 10-year (2007-2016) review of trends in antimicrobial-resistant organisms identified among patients seeking care in Canadian hospitals. The eight separate medical paper supplement, published in the Journal of Antimicrobial Chemotherapy (September 2019), reviews the epidemiology of pathogens, the degree of antimicrobial resistance within specific hospital wards (medical, surgical, ICUs, emergency rooms and clinics), as well as infection sites (urine, blood, respiratory and wound).
The outcomes highlight both good and bad news. Some antimicrobial-resistant pathogens (eg. MRSA) are declining in Canada, while others (eg. extended spectrum b-lactamase producing Enterobacterales [ESBL], carbapenem-resistant Enterobacterales [CRE] and vancomycin-resistant enterococci [VRE]) are increasing in Canada. In addition, antimicrobial resistance and multi-drug resistance (MDR) in Pseudomonas aeruginosa continues to be a problem.
Action required to remain on the forefront of treating and preventing MDR infections
Overall, in terms of infections caused by antimicrobial-resistant pathogens, Canada is doing better than some countries, such as the United States, but not as well as some Nordic European countries, such as Denmark, Sweden, Norway and Finland. Thus, Canada must not take its eye off the proverbial ball as infections caused by MDR and extremely-drug resistant (XDR) pathogens continue to increase in our hospitals. The worry is that as MDR and XDR pathogens continue to spread across Canadian hospitals and cause infections, existing antimicrobial treatments will be limited and associated with greater microbiological and clinical failure rates.
Hospitals and patients will benefit from new antimicrobial agents
Canada is entering an exciting new era of treatment. While ongoing surveillance, stewardship, and infection prevention and control are imperative, so is the availability of new antimicrobials active and effective against infections caused by resistant pathogens. Canadian hospitals and patients need access to these new antimicrobials, especially those with novel, bactericidal mechanisms of action and activity against MDR and XDR pathogens. Approved treatments would ideally possess an excellent safety profile, outstanding pharmacokinetic and pharmacodynamic properties, and be available as both intravenous and oral therapies. In addition, these agents would be associated with limited resistance development during treatment, would be available to be used alone or in combination with other antimicrobials, and would demonstrate synergistic activity/efficacy when used in combination with existing antimicrobial agents.
Many new antimicrobials have recently been introduced into the Canadian market, or will soon be approved by Health Canada. These include: IV ceftolozane/tazobactam, IV ceftobiprole, IV/PO fosfomycin, IV/PO lefamulin and IV amoxicillin/clavulanate.
The challenge for medical microbiologists, infectious disease specialists, hospital pharmacy clinicians and antimicrobial stewardship programs will be identifying the patients who will most benefit from these agents and using them in a manner that optimizes their microbiological and clinical efficacy. It is important to understand that new IV antimicrobials typically receive FDA and Health Canada approval based on limited clinical trials, and as a result, the approved indications are limited. It will be common that these new IV agents will be used “off label” or “off indication”. Off-label usage, although necessitating a benefit/risk assessment, does not preclude an effective clinical outcome.
Canadian hospitals need to continue their focus on what they do best – surveillance of antimicrobial-resistant pathogens, antimicrobial stewardship, and infection prevention and control. At the same time, we are heading into a new era of agents that will help hospitals to treat their patients. This is welcome news as antimicrobial-resistant and MDR infections increase. For the first time in many years we will have several new IV agents developed to target MDR infections.
As a next step, hospitals will need guidance on the use of new antimicrobial agents. It will be a difficult balancing act for Canada to assure that antimicrobial stewardship programs are aware of when, and how, to use new antimicrobials in patients with infections caused by difficult-to-treat and antimicrobial-resistant pathogens. Canada will also need a national registry for clinicians to share their clinical experiences – documenting when, how and why they use these new IV antimicrobials, as well as their effectiveness and safety.
Knowing the impactful work conducted by Canadian hospitals in the areas of surveillance, infection control and prevention, and stewardship, we should be confident that Canada will remain at the forefront of treatment with new antimicrobial agents. Strengthening our response to the increase in drug-resistant infections is the best medicine!
George Zhanel is Professor-Department of Medical Microbiology and infectious Diseases at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba and Director-Canadian Antimicrobial Resistance Alliance (CARA, www.can-r.ca).