Thanks for meeting us at the Canadian Breakpoint, a Canadian infectious disease podcast by infectious
disease physicians.
I'm your host, Summer Stewart, and I'm excited to introduce infectious disease physician and
author Dr. Rupeena Purewal.
Dr. Purewal is a Canadian pediatric infectious disease physician from Edmonton, Alberta.
She completed her medical school at the University of Pecs in Hungary and her three-year residency
program at West Virginia University.
She returned to Canada in 2017 to start a pediatric infectious disease fellowship at
the University of Manitoba.
Upon completing her fellowship, Dr. Purewal moved to Saskatchewan as a clinician and
as an academic physician at the University of Saskatchewan.
For our first episode, Dr. Purewal will present the Canadian Antimicrobial Resistance Surveillance
System update.
Welcome, Dr. Purewal.
Hello everyone.
Thank you, Summer, for that great introduction.
I'm very excited to be here today to start our very first episode of our podcast.
And as Summer mentioned, my name is Rupeena Purewal and I'm a pediatric infectious disease
physician here in Saskatoon, Saskatchewan at the Jim Patterson Children's Hospital.
I've taken the initiative to start a Canadian-based podcast for my Canadian colleagues, whether
it be infectious disease specialists, microbiologists, family physicians, pharmacists, or really
anybody dealing with prescribing antibiotics and the use of antibiotics.
On our podcast, we'll be doing monthly episodes with interesting areas.
I'll be discussing current and up-to-date topics related to antimicrobials, stewardship,
and really all sorts of infectious diseases.
Some of our podcasts will be more informative, while others will be more interactive with
specific guests.
So thank you so much for tuning in.
Today's episode will be a summary of the Canadian Antimicrobial Resistance Surveillance
System, the CARS report that was updated in 2020.
As most of you are aware, CARS is a Canadian national system for reporting on antimicrobial
resistance and antimicrobial use.
And it's one of Public Health Agency of Canada's commitments as a part of the Pan-Canadian
Framework for Action on Antimicrobial Resistance and Use.
And by reporting findings on antimicrobials, it provides really us, decision-makers, with
evidence to support policy and programs to foster prudent antimicrobial use to prevent
and control resistance in Canada.
So our very first episode will be a condensed update with the main focus really on the priority
pathogens listed in the report that are showing a trend in Canada that's getting worse.
Antimicrobial data for certain pathogens and antimicrobial use in humans, along with emerging
threats that are being identified in Canada.
As most of you are aware, antimicrobial resistance is increasing in Canada.
And surveillance is one technique to identify resistance rates and create awareness to reduce
overuse and overprescribing of antibiotics.
The report really highlights some concerning trends in Canada that we should all be aware
of.
And therefore, it's a very important topic, especially for us in the clinical world.
So to begin with, we will be talking about three pathogens.
So there'll be MRSA, methicillin-resistant staph aureus, vancomycin-resistant enterococcus,
also known as VRE, and then also carbapenemase-producing entrobacteriaceae.
So starting off with what the report went through in regards to MRSA, in 2014 to 2018,
it did identify this pathogen as a trend towards getting worse.
So over 65 hospitals reported to the Canadian Nosocomial Infection Surveillance Program,
and 2,900 MRSA bloodstream infection cases were reported, and over 550 deaths were reported
due to MRSA in 2014 to 2018.
Now, whenever we speak about MRSA, we always discuss either healthcare-associated versus
community-associated MRSA bloodstream infections.
And so those are the areas that we will be talking about today that were mentioned in
the reports in regards to their mortality, in regards to their resistance patterns, and
also agents for non-bloodstream MRSA infections.
So starting off with healthcare-associated MRSA, it was noted that the all-cause mortality
during this 2014 to 2018 period was noted to be close to 24%.
They did notice that all the strains were susceptible to vancomycin, and less than 1%
were non-susceptible to daptomycin.
Now, looking at those agents that are used for non-bloodstream MRSA infections and the
healthcare-associated MRSA strains, they noticed no resistance to lenazoline, resistance to
rifampin, trimethypim, sulfamethoxazole, and tetracycline were reported as low, ranging
from anywhere from 1% to 4%, and notably for tetracycline around 4%.
And resistance to clindamycin has decreased from 75% to 50%.
So those are some reassuring numbers for clindamycin.
Now comparably, looking at the community-associated MRSA bloodstream infections, these have increased
by 140% between 2014 to 2018.
And it was reported that this was largely driven by the increase in cases attributed
to the community, so the number of cases overall had increased in the community as well.
Now, all-cause mortality was lower for the community-associated MRSA bloodstream infections
than it was for the healthcare-associated MRSA infections, and notably at 14% as compared
to the 24% we had just mentioned.
Now, in the report, they also went through more details for the community-associated
MRSA infections, and specifically outlining the different strain types.
So, historically based on Canadian standards, strains 7 and 10 were associated with community-associated
MRSA, and strain type 2 was historically associated with healthcare-associated MRSA.
However, they had noticed that strain types 2 and 10 were decreased overall, but the community
MRSA type 7 had increased from 8 to up until 9% between this 2014 to 2018 period.
For the community-associated MRSA, they did state that all isolates were susceptible to
vancomycin, and there was less than 1% non-susceptibility to daptomycin, so very similar to our healthcare-associated
MRSA.
And then comparing the non-bloodstream or agents that we use for non-bloodstream infections
for MRSA, they did note that trimethopram, sulfamethoxazole, and rifampin resistance
rates were low, ranging anywhere again from that 1 to 3 to 4%, but something that was
considerably different was that the tetracycline resistance rates were higher than compared
to the healthcare-associated.
So, like I mentioned before, it was at 4% resistance to tetracycline for the healthcare-associated,
and now for the community-associated MRSA infections, the resistance for tetracycline
was close to 10%.
And so that was important information.
And clindamycin, kind of similar to the healthcare-associated MRSA, had decreased for the community-associated
isolates, as well, down to 30% from 40%.
Now, moving on to our second pathogen that we're talking about today, which is vancomycin-resistant
enterococcus.
It's also notably a priority pathogen, indicated as getting worse for its trend summary.
So similar to MRSA, 62 hospitals reported information to CNISP, and 649 cases of VRE,
vancomycin-resistant enterococcus bloodstream infections were reported, and over 200 deaths
during this time period of 2014 to 2018.
Now, the rates of healthcare-associated vancomycin-resistant enterococcus bloodstream infections more than
doubled between this 2014 and 2018 period.
So those are significant numbers.
The all-cause mortality was also higher for cases with healthcare-associated VRE.
31% of patients died within 30 days of diagnosis between this 2014 to 2018 period.
Now, another important area that notably was mentioned in this report and updated was that
98% of the isolates for VRE were enterococcus faecium, and less than 2% were reported as
or speciated to enterococcus faecalis.
So really goes to show that the numbers of enterococcus faecium were significantly higher.
And there's a rapid emergence of a specific sequence type that was mentioned also in the
report.
The specific sequence type, the ST1478, that was reported for enterococcus faecium, it
was actually initially first reported in 2013 in Canada, but now it's representing over
40% of the isolates between this 2014 to 2018 period.
And the reason why it's important is because this actual sequence type, ST1478, was associated
with rising levels of resistance to important antimicrobials such as gentamicin and daptamicin.
And so I think that was a significant point in the report that they wanted to convey that
these, especially for us clinicians thinking about empiric management or even synergy,
it was an important key point that resistance rates are increasing for these agents.
In terms of antimicrobial susceptibility, so it was available for over 70% of the isolates,
and it was noted that daptamicin non-susceptibility had increased from back in 2014 where it was
0% up to 7 to 8% in 2018.
And so that was a significant change.
Resistance to high-level gent also increased from 9 up until 43%, and resistance to linase
lid also was notably increased from 0 up until 1.3%.
Now finally moving on to our third pathogen, our priority pathogen I should say, that is
showing a trend towards getting worse between this 2014 and 2018 period, the carbapenemies-producing
intrabacteria group.
So again, over 60 hospitals reported around 290 hospital or healthcare-associated colonizations,
73 healthcare-associated infections due to CPE organisms, and a total of 365 healthcare-associated
CPE cases, and 16 deaths in between 2014 to 2018.
So looking at the Canadian hospital data, it reported a nine-fold increase in patients
that have been colonized with healthcare-associated CPE organisms.
And so really, although infection rates remain low and stable, it was disclosed that increased
rates of colonizations were being reported, and this could be due to either heightened
awareness, increased screening, however it's still of concern.
The all-cause mortality was high for cases that had healthcare-associated CPE infections,
ranging at 16% of patients that died within 30 days of the diagnosis between this four
years.
Healthcare-associated CPE cases were reported that often are associated with international
travel and international healthcare exposure, as many of us are aware, and these are kind
of the screening questions and the reasons for screening in Canada.
However, domestic nosocomial transmission also appears to be increasing, and that was
mentioned in the report.
In 2018, around 40% of patients that were identified with healthcare-associated CPE
had traveled outside of Canada within the past 12 months, and 84% of the reported isolates
for these patients, they had received medical care while abroad.
And so an important point again for the reasons that why we screen such high-risk patients.
So the carbapenemase, another interesting kind of report for the CPE was looking at
what types of carbapenemases were identified.
And so when they looked at over 147 isolates, they were all reviewed, the proportion of
the carbapenemase that were identified, majority of them were KPC, so Klebsiella pneumonia
carbapenemase producing in 54% of those isolates.
So 80 out of 147 of them had KPC carbapenemases being produced.
The second highest was the NDM, which is the New Delhi metallo-betalactamase at 23%.
And then in decreasing order was oxalinase, the oxa-48 at around 10% and seracea, MarSense's
enzyme SME at 2%.
So this was the overall kind of trends and some information regarding these three priority
pathogens that I wanted to discuss.
And I think they definitely highlighted significant changes that are important for us as clinicians.
So I'm going to move on to talking about some antibiogram data for specific pathogens that
were discussed in the report because I felt like this was a very crucial point in this
2014 to 2018 report that they wanted to emphasize because these are agents that we are seeing
some worrisome changes.
So the data that was reported by hospitals was both from inpatient and outpatient and
duplicate isolates were removed when this antibiogram data was established.
Now many of us are probably more familiar with having a minimum cutoff point for reporting
around 30 isolates per hospital.
However, as of 2018 or during this report, prior to 2018 that was the minimum cutoff
and now that's changed and there's no longer this minimum cutoff for the number of isolates
and reported.
So just keep that in mind.
So the couple of pathogens we're going to talk about here are E. coli, Acidum abactor
species and then Salmonella species.
So let's start off with what the report kind of emphasized about E. coli.
So between 2015 and 2018 the proportion of E. coli non-susceptible to carbapenems was
less than 1% for both blood and urine isolates.
So that was a reassuring component.
For E. coli specifically looking at the antibiogram data for blood isolates that they reviewed,
non-susceptibility for pipercillin and tasobactam had increased from 26 to 30%.
Our trimethoprim sulfamethoxazole non-susceptibility also increased ranging around the same so
26 up to 30%.
And non-susceptibility however for ciprofloxacin remained unchanged.
Unfortunately like I mentioned the carbapenem remained less than 1%.
Now comparing that with the E. coli urine isolates that were reported from 2016 to 2018,
it was noted that non-susceptibility rates for pipercillin and tasobactam had increased
from 4 up to 6%.
For trimethoprim sulfamethoxazole they actually decreased slightly from 24 to 21%.
P to ciprofloxacin also decreased from anywhere from 19 to 17%.
And then the non-susceptibility to carbapenem as mentioned before was remained less than
1%.
In terms of acinetobacter something that was mentioned in the report was in 2018 the non-susceptibility
to meropenem was close to 5%.
And I think that's an important number in terms of considering what our empiric management
is and taking care of these patients.
In moving on to the salmonella species, so majority of the isolates that were submitted
for lab tests were cultured from blood for salmonella.
We will talk about both typhoidal and non-typhoidal salmonella in Terica.
So the data was restricted to isolates of salmonella and Terica were serovars typhi,
paratyphi and then there were several non-typhoidal serovars.
So overall most antimicrobial resistance remained stable except for the following.
Between 2014 and 2018 the frequency of salmonella typhi and paratyphi that was resistant to
ceftriaxone increased from nearly undetectable, so 0% in 2014 up to levels of 3%.
Between 2014 and 2018 it was also reported that the frequency of typhoidal salmonella
resistance to ciprofloxacin increased by 34%.
I think that was a very very important point and why empiric management has changed as
well.
In 2018 11% of typhoidal salmonella was resistant to either three or more classes of antimicrobial
so really putting it into this multi-class resistant category and of no resistance to
zithromycin was identified.
Now comparing this to the non-typhoidal salmonella species the number of isolates that were submitted
for lab testing overall had decreased from 2500 to close to 2100 and notably 85% of the
non-typhoidal samples were recovered from stool specimens as opposed to blood or urine
which were really only less than 5 to 7%.
In 2018 13% of the non-typhoidal salmonella were resistant to three or more classes and
really looking at resistance to tetracyclines had increased from 11 to 16%.
The other classes like trimethyprim, sulfamethoxazole, and ciprofloxacin had remained stable and
there was no identified resistance to meropenem that was seen and so that was quite reassuring
for that fact.
Now that was the main components that I wanted to discuss from those categories and I think
an important point that we should take from reading this report and reviewing this report
is kind of also focus on not only the resistance patterns that have been predicted because
those are helpful during our clinical practice but also looking at some of the statistics
that are alarming for antimicrobial use in humans.
So for the next section of the podcast I do want to focus on antimicrobial use in humans
and some of the statistics that were quite alarming to me were that one in four Canadians
received at least one antibiotic course in 2018 and when you look at either surveillance
at a global level or even respectively at a regional level it was tremendous to see
kind of the differences and so globally just to kind of give you an overview there is a
European surveillance of antimicrobial consumption network where Canada it was listed in this
report and they had a good graph on that and showing Canada was at the 12th lowest consumer
of listed as the lowest 12th lowest consumer of antimicrobials per capita.
So if you looked at kind of the lowest consumption country which was the Netherlands and you
looked at Greece which is the most consumption Canada fit at the 12th lowest and so just
kind of to put you put that into perspective Canada consumed nearly twice as an amount
of antimicrobials than the Netherlands but half the amount of Greece.
So I think that's an important consideration to see where we are fitting globally but we'll
talk a little bit about the regional differences as well but really kind of pinpointing on
the fact that along with surveillance increasing awareness of antimicrobials I think it also
impacts us as prescribers and just to think about is this appropriate use of this antibiotic
and do we need to be using these antibiotics and I think part of the surveillance understanding
the surveillance numbers and and why we're doing surveillance is to really drive you
know see what the pattern is showing for resistance but antimicrobial use as all of us are aware
is one of the key drivers of the resistance patterns and so I think it's important to
kind of just remind ourselves of what is going on nationally.
So the report identified that the situation in Canada is worsening we talked about some
of the priority pathogens we talked about some of the resistance patterns we talked
about how the anti-biogram data is changing so let's talk a little bit about the prescription
rates overall.
So in the report antimicrobial use and antimicrobial prescription rates whether you know consumption
or dispension of antimicrobials was all discussed so overall our antimicrobial prescription
rates have increased in this 2014 to 2018 period almost close to 6 percent.
In 2018 64 percent of prescriptions originated from other family physicians general physicians
compared to other medical or non-medical specialties prescribing around 35 percent.
Notably antimicrobial purchasing by hospitals increased by nearly 30 percent and the key
example they gave there was Dapdomycin had a 58 percent increase in purchasing by Canadian
hospitals.
It was also reports that there's increase in purchasing of doxycycline and penicillin
G and these are currently being investigated as part of the next report.
There was also mention further of antibiotics and antimicrobials that are put under WHO's
aware category of being reserve antimicrobials and so these are antimicrobial that should
really be reserved for treating multi-drug resistant infections and their overall kind
of purchasing rates had nearly increased to 10 percent although fortunately their use
remained less than 1 percent.
So these some of these reserve antimicrobials would include Dapdomycin, Linazolid, Ceftaz,
Avibactam just to give you a few examples.
It was also mentioned in the report that carbapenem use has increased by more than 120 percent
in the community setting and as most of us are aware Ertapenem being a common carbapenem
used in the community setting there had been reports of doubling in its use during this
2014 to 2018 period.
So I think in order to again really understand the depth and degree of antimicrobial use
we have to remind ourselves and refresh the definition of defined daily dose.
So as most of us are aware that's abbreviated as DDD and this is the assumed average maintenance
dose per day for an antimicrobial drug that's used for its main indication in adults.
So this DDD provides usually a fixed unit of measurement it's independent of the price,
currency, size and strength but really gives us an easy way to assess trends in drug consumption.
So I'm going to use some of those numbers just to give you an overall kind of review
of the consumption.
So in 2014 to 2018 annual antimicrobial consumption so either dispensed by community pharmacies
and purchased by hospitals was close to 17.5 antimicrobial doses were consumed each day
for every thousand population days or that's close to 6300 doses annually consumed every
thousand inhabitants.
So really this trend more likely was listed to be driven by the 29% increase in purchasing
of antimicrobials by hospitals but just to give you kind of an overall consumption data
important to kind of key in these numbers here.
So if we compare that to let's say we were talking about the carbapenem increase so in
the community setting up by 120% for instance if we look at that urtapenem use went from
2.5 ddd's per thousand inhabitants up to close to 5 so that's where that near doubling
in use of urtapenem numbers are reflective.
So like I mentioned in promise we look at a regional perspective of antimicrobial use
so in 2018 as per the report Canadian provinces in the eastern part of Canada so PEI in New
Finland consumed the largest quantity per capita and then the lowest consumption was
in the territories and British Columbia.
So in 2018 90% of the ddd's were dispensed in the community sector and only 10% purchased
by hospitals so I think that gives you kind of the consumption or dispensing rates as
well based on where they're occurring whether in the community or the hospital setting.
And whenever we talk about antimicrobial use I think we always have to bring up the estimated
health care costs because as most of us are aware these are usually directly affected.
So in the report they had indicated that for both community and hospital the estimated
costs of all antimicrobials that were consumed during 2014 to 2018 had gone up from close
to 810 million to 825 million in just four years.
So another kind of component of the antimicrobial use and really focusing on dispensing of antimicrobials
in which classes because I thought that was quite interesting and well laid out in the
report and an important point for us clinicians as well is that in the community setting the
top five antibiotic classes that were dispensed going from the most to the least were the
extended spectrum penicillins, tetracyclines, then macrolides, then fluoroquinols and then
our first generation cephalosporins being the least dispensed.
In the hospital setting for dispensing antimicrobials it really depended on if the patients were
in the ICU or non-ICU and so the report was able to separate those two settings and report
out the most to the least dispensing.
And so in the non-ICU setting the most dispensed were was cefazolin, then pipercelin, tasobactin,
then metronidazole, then ceftriaxin with the least being ciprofloxacin.
Whereas in the ICU setting you had a cephalosin was still the most dispensed but then also
with pipercelin tasobactin being number two and then more of your broader antimicrobials
like vancomycin and then meropenem and then least was cephtriaxin.
So those are just interesting kind of top five antibiotic classes that were dispensed
differently in the two settings that I thought was quite important to share.
So I think for some of the key points there about antimicrobial use and just looking at
those numbers and how they directly affect you know the initial part that we talked about
today which was resistance was important just to kind of key in some of those important
statistics in Canada.
So this we're coming kind of closer to the end of our podcast today or in our episode
so we're going to finish off by just identifying some of the emerging threats because I did
want to convey that information as an important part of the CARS 2020 report.
So as most of us are aware Canada oris back in between 2012 and 2019 there was 24 cases
that were reported of Canada oris to phac and so the public health agency of Canada
and some of which were multi-drug resistant so just keeping that in mind.
Notably we didn't talk a lot about nysere gonorrhea today although an important pathogen
with its increasing rates and also notably the in 2017 and 2018 it was identified as
an emerging threat because the first chef triaxone resistant case of nysere gonorrhea
was reported in Canada and it was associated with travel to Southeast Asia.
So really kind of keying in on importance of empiric management there.
And then finally the carbpennimase genes there was an identified emerging threat that's been
detected in acinetobacter isolate from a patient or from patients in health care settings.
So there was 41 cases that were reported with carbpennimase producing acinetobacter species
between this 2014 to 2018 period and this really represents a threat to the continued
effectiveness of carbpennims against acinetobacter species so just keeping that in mind.
Alright so I want to thank everyone for tuning in today for our very first episode in discussing
the surveillance report.
I hope you found this short segment a great review of antimicrobial resistance use and
some of our common pathogens and priority pathogens that were discussed today.
Please reach out to us via email if you would like to have specific topics discussed or
would like to come on to the podcast and discuss a specific area in infectious diseases.
We would be grateful to have input regarding that and I want to end off today by thanking
Verity Pharmaceuticals for its ongoing support for this podcast and I hope that you enjoyed
this episode and I look forward to creating new up to date episodes in the near future.
Thank you so much for tuning in.
Thank you Dr. Peerwal and to Verity Pharmaceuticals.
Thanks for listening to our very first episode.
Email us at thecanadianbreakpoint.gmail.com if you have any comments or if you have any
infectious disease topics you'd like to hear about and for us to discuss.
We look forward to seeing you again at the Canadian Breakpoint.