July 11, 2023 • 41 mins
Dr. Rupeena Purewal invites Dr. George Zhanel, Infectious Diseases and Medical Microbiologist and Research Director for CARA, to discuss the CLEAR registry.
To join CLEAR, email Dr. Zhanel at ggzhanel@pcsinternet.ca
CARA www.can-r.com
Canadian collaborative AMR Awareness campaign: www.antibioticawareness.ca
Pan-Canadian Action on Antimicrobial Resistance: www.canada.ca/en/public-health/services/publications/drugs-health-products/pan-canadian-action-plan-antimicrobial-resistance.html
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Episode Transcript
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Thanks for joining us at the Canadian Breakpoint, a Canadian infectious diseases podcast by
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Canadian infectious diseases physicians.
I'm Summer Stewart here with Dr. Rupeena Purewal, pediatric infectious diseases physician
in Saskatoon.
In this episode, we are excited to welcome Dr. George Zhanel, department head for infectious
diseases and medical microbiology at Max Rady in Winnipeg, and the research director for
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CARA, the Canadian Antimicrobial Resistance Alliance.
Today we'll discuss CLEAR, or the Canadian Leadership on Antimicrobial Real-Life Usage
Registry.
Dr. Purewal.
All right.
Thank you, everyone.
Welcome to another episode of our podcast, the Canadian Breakpoint.
Today we have a very, very special guest with us, and after I do his introduction, I think
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the viewers will also feel the same way.
So thank you, Dr. Zannell, for joining us today and taking time out of your busy schedule,
because you're a very, very busy person, to be on the podcast.
It's honestly an honor for us to have you on the podcast today.
So Dr. Zannell is a microbiologist and pharmacologist who received his PhD in the Department of
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Medical Microbiology and Infectious Diseases at the Faculty of Medicine, University of
Manitoba, and a doctor of clinical pharmacology at the University of Minnesota.
He is presently professor and associate head in the Department of Medical Microbiology
and Infectious Diseases, MaxRady College of Medicine, and research director of the Canadian
Antimicrobial Resistance Alliance, CARA.
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Dr. Zannell is the founding and chief editor of the Canadian Antimicrobial Resistance Alliance
website.
Dr. Zannell has published over 1,100 papers, chapters, and abstracts in the area of treatment
and prevention of infectious diseases.
He has presented over 1,200 lectures as an invited speaker at international, national,
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and local meetings, speaking on the topics of antimicrobial resistance infections, as
well as treatment and prevention of infectious diseases in Canada, the US, Central and South
America, Western and Eastern Europe, including Russia, Australia, Southern and Northern Africa,
the Middle East, and Asia.
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He has been extensively involved in treatment guidelines for a variety of infections in
Canada, the US, and internationally.
Dr. Zannell has received or been nominated for more than 100 teaching awards, including
the Canadian Association for Medical Education Merits Teaching Award in 2020.
Congratulations, Dr. Zannell.
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Thank you.
Dr. Zannell is also a member of the Who's Who in Medical Sciences Education, and in
2022, he was elected as a fellow of the Canadian Academy of Health Sciences in recognition
of sustained excellence in research and teaching within health sciences.
Participating in the Academy is considered one of the highest honours for individuals
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in the Canadian health sciences community.
In 2022, Web of Science identified Dr. Zannell as one of the world's most influential researchers
selected among elite group recognized for exceptional research influence, demonstrated
by the production of multiple highly cited papers that rank in the top 1% by citations
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for the field and year.
Also in 2022, Dr. Zannell received the Dr. Fred Aoki Career Achievement Award in recognition
of a career of dedication and excellence in multiple domains of medical microbiology and
infectious diseases, including research, education, clinical practice, service, and administration.
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So amazing.
I'm so honoured to have you here today, Dr. Zannell.
And today we're going to be talking about a very, very important topic, which is known
as the CLEAR registry that Dr. Zannell will give us more information about.
And so why don't we just start off, Dr. Zannell, by telling the audience a little bit about
what CLEAR is and when it was established and how did this come about?
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How did this registry, this national registry come about?
So Rapina, let me start by saying how delighted and honoured I am to be with you on this podcast.
And I also apologize, my mother sent in this mini biography and I apologize.
It just goes on and on and on.
She didn't even put in there that I finally got out of diapers when I was 15 years old.
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Lots of accomplishments.
I'm delighted to be with you.
So CLEAR, let's talk CLEAR.
CLEAR stands for the Canadian Leadership on Antimicrobial Real Life Usage Registry.
CLEAR, C-L-E-A-R.
And how this came about, it came about in 2019.
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It was traveling extensively across Canada before COVID, speaking at every hospital and
university about new IV antimicrobials in Canada, their properties, et cetera.
And colleagues would stop and talk to me and one of them was Dr. Ted Steiner, an ID doc
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in Vancouver.
And he said, you know what, it's great you're talking about these antibiotics and you're
doing research on them, but when they come to Canada, we need some sort of platform,
infectious disease specialist, medical microbiologist, clinical pharmacologist, when they're using
these drugs, they can actually share their experiences with other Canadians.
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And that way we know in the Canadian setting, treating patients with the Canadian antimicrobial
resistance rates we have, how are we using these drugs, for what infections, what pathogens,
and you should do something, he said to me, and that's how it all started.
That's fantastic.
And honestly, I think having that, I think the emphasis on having real life experience
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and real time experience.
And I think we've talked about this before.
It's fantastic that this information is presented to prescribers and it's real time data.
So we can actually use this information in that moment, especially when all of us are
being exposed to such new drugs and don't have a lot of data or information.
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So obviously this is a very, very new approach and it's a fantastic approach.
So in terms of what are some of the advantages that you've, since the establishment, what
are some of the advantages of such a registry do you think in Canada, besides having that
real time information?
So what we've got currently sitting in front of us is about 360 participants nationally.
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Half of those are infectious disease medical microbiology and the other half are clinical
pharmacists specializing in infectious diseases, antimicrobial stewardship.
And these individuals, every two, three months, get the latest information of how these antibiotics
are being used from us.
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So what we're doing is we're sharing the information that they themselves have told us.
So we have data submitters across Canada, pharmacists, infectious disease specialists.
They submit data when they use these antibiotics.
We crunch it and every two, three months we send them all the data.
So it's Canadians, teaching Canadians how these antibiotics are being used in their
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hands.
The other benefit is it's Canadians helping Canadians sharing Canadian experiences.
And as many of us know in the infectious disease world and microbiology world is that definitely
anti-biograms differ from different countries and our experience and access to medications.
And so having this data for us nationally is super helpful, especially myself being
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a prescriber.
I think this is the information that we're always looking for, especially when providing
patient care.
So I'm more interested to hear what type of data is being gathered in the registry.
And you did mention that it's collaborated data.
And so where is this data stored or how is it analyzed on your guys' end?
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So on our end, we decided in 2019 that every single new IV antibiotic that was health Canada
approved and marketed in Canada would have on the clear registry.
So we currently have four IV antibiotics.
Cephalopipral, ceftozentazobactam, intravenous phosphomycin, and dalbovansin.
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And so what we do is for our 360 participants, and by the way, how do you become a participant?
It's free.
You send Zanelle an email and just say, hey, make me a part of clear, boom, it's done and
you're a part of clear.
That's awesome.
And if you choose to submit data, that's fantastic.
But you're going to be educated.
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So for these four IV antibiotics, we have a link.
And we send out to all of our participants, if they have treated a patient with one of
these new drugs or will treat a patient, you hit that link and it's easy peasy.
It's three minutes on your own iPad, laptop, desktop, 17 questions pop down and it's point
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and click.
You're done in three minutes.
And it's asking you things like, well, what infection are you treating?
What is the pathogen?
Are you using the antibiotic alone or in combination?
What dose are you using?
By the way, did you do antimicrobial susceptibility testing?
And if so, what method, what was the M.I.C.
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Why did you use it?
Was it because of resistance to other antibiotics?
Is it because you failed previous therapy?
Was it because of intolerance to other agents?
Microbiologically, did it work?
Clinic, did it work?
Were there adverse effects?
So you point, click, point, click, point, click, you are done.
And then what we do is the data is stored on red cap.
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This is electronic data capture system.
And Melanie Baxter in our group is the guru.
She crunches it all.
And then we put PowerPoint slides together, send it out to the group.
We also present ideally each year a poster on every drug at AMI, at the AMI CACBID meeting.
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And then we also publish papers.
Once we get to about 30 to 50 patients, we'll actually write up a paper and publish it.
So we've done that for all of the antibiotics already, except double bands.
And we have yet to publish a paper on this.
We presented a poster because we're still not where we want in terms of the numbers
of patients.
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That's fair.
And when you say that in terms of number of patients, what is the threshold that you're
hitting before this data becomes finalized?
Rupina, the threshold is whatever Jordan Zanell thinks the threshold is.
It's terrible.
So I've kind of set a bar of if we hit 30-ish, 20, 30 patients, we'll put a poster together
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at AMI so Canadians can see what's going on.
Even well before that, we crunch the data, send it to all the participants, even if it's
only patients.
But once we start to hit around 50, the journals get interested because then you start some
substantial data.
So once we hit 50, we published a paper on cephtalbibral, we published a paper on cephtalzentazo,
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we published a paper on Intravenous Phosphamycin, and we're still not at 50 for the Dalbovansin,
but once we're there, we'll publish a paper on that.
But there is no hard and fast rules, but that's kind of the threshold.
Yeah, no, that's fantastic.
And you kind of mentioned that you're really looking at novel IV antibiotics.
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So in terms of, is there other criteria in how you decide which medications to review?
No, so my criteria really are if you're a new IV antibiotic, health Canada approved
and you're on the market, we want you in clear.
So try not to bias and say, we don't want this one, we don't want that one, we want
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them all.
But I will tell you, when intravenous amoxicillin clavulinate came to the market, which was
relatively recently, I hummed in a hard whether I should put this on the clear registry.
And initially I thought, well, of course it should be.
But then a colleague said to me, we know exactly how it's used.
It's used like the oral, which we've had for 35 years, when you can't use the oral.
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So didn't put it on the clear registry.
And yet I have some colleagues bugging me to say, hey, put it on there.
So it may actually, in fact, join the registry sooner than later.
Yeah, I think honestly being, so I'm a pediatric infectious disease physician and so amoxiclav,
we use a lot.
And I think there is a different, I guess there is a couple of indications where sometimes
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I feel more comfortable using the IV version and IV amoxiclav, for instance, if you do
have a polymicrobial infection where you're not necessarily worried about pseudomonas.
And I think it's some of that information that's really good to disseminate because
sometimes we don't really think about using amoxiclav in an initial setting like that,
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but remembering that the IV formulation, or again, just knowing that there is an IV formulation,
because I think that is some data that hasn't been, I guess, widely spread just because
it is a novel agent or a novel formulation.
Well, you've inspired me, Rupina, this summer to put a proposal together to put IV amoxiclav
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onto the clear registry.
I'll put together the 17 important questions we need to ask and run it by the clear group
that we have across Canada, get their input.
You may get an email yourself.
Oh, I'm already joining, so there's no doubt about that.
You can get an email, are these the best questions or should we add or delete, have other questions?
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But perhaps this fall, we should have IV amoxiclav join the clear registry.
Yeah, and I think it's important also from an adverse event standpoint, right?
Different formulations may have different adverse effects, right?
Or how quick, for instance, bone marrow suppression may occur, et cetera.
So I think it's important if something is new and novel, because I know that people
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definitely are looking out there for data.
I'm always doing that as a prescriber.
Thank you so much.
You've inspired me and you've made strong cases.
We're going to do whatever we can to put IV amoxiclav on the clear registry this fall.
Awesome.
And just like how you informed me that right now, so do you inform participants that are
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newer drugs are being added to the registry for review?
So do they receive an email for once they are a participant in the registry?
Do they receive an email once a new questionnaire comes on the market?
Yes.
So it's a balancing of not wanting to bombard them because everyone gets so many emails.
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I don't want them to shut down.
I'll typically send somewhere around three to four emails a year and it's always loaded
with here's the new information.
Here's the slides of the four drugs for your information.
And then if there are new developments.
So for example, recently when intravenous Dalba Vansin came onto the market, we immediately
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sent an email to all the participants saying great news.
Dalba Vansin has been Health Canada approved and is marketed with this indication.
Here is the clear link to IV Dalba Vansin.
If you have treated or will treat a patient with this drug, please consider joining.
And again, as always, it's voluntary, but it's ethics approved.
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We're not asking for any confidential patient information.
Please consider joining.
And we frequently get emails back saying, oh, I didn't even know it was on the market.
We're serving an educational tool at times.
Exactly.
I think a lot of that is that's very important, right?
Because it's really important to know which medications are out there.
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And then also knowing the detail of data that you're providing, including indications and
contraindications and really uses and anecdotal experience from our colleagues.
I think that there's multiple times in a day when I'm practicing, when I have to reach
out to friends across the nation to ask questions about this.
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And so what better way to do this than in a registry where people have already inputted
this data.
So I think this is honestly fantastic and it's the future of Canada.
And I think it's great to have local data.
So I'm very impressed.
Rupina, you said something really important.
It's this almost unexpectedness when you actually start to crunch the data per drug.
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You think you know what's going on in Canada and you realize you don't because the users
of drugs inform you what they're doing and it's on label, it's off label, all types of
dosing.
There are clear partnerships with infectious diseases and clinical pharmacy using, you
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know, renal function to customize dosing and optimize pharmacodynamics.
So it's very educational when you find out what's going on by crunching the data, what
Canadians are doing.
And so currently which centers or participants, I think you mentioned over 300 participants.
And so is it pretty much national?
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You have representation from most provinces?
Representation from all provinces.
It's been, I was a little bit shocked and surprised that the uptake was so vigorous
and so positive.
Other countries have tried this and they have not been able to make it work.
But you know, in Canada, I think we all kind of love each other and realize that we're
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just a bunch of Canadians who were born somewhere else.
So we contribute.
So coast to coast, I'm going to say 98% of all the participants are infectious disease,
microbiology and clinical pharmacy.
And then we've got sprinklings of intensivists, respirologists, internists, just other groups.
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I'm going to say about 98% of the participants are Canadian.
But interestingly enough, we have a bunch of people from all over the world, from Italy
and Chile and South Africa following the clear registry.
I don't know if they're Canadians working off site or just colleagues interested in
antimicrobial usage, but that's the demographic.
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In terms of data submitters, the people who actually point and click, it's 50-50.
Half of the submissions are infectious disease, microbiology, half are clinical pharmacists.
And frequently these groups are working together.
They just say, look, I'll submit the data on this patient.
I frequently get asked, well, what about duplications?
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We don't have duplications.
We look for them very, very carefully, but clearly the team is talking to each other
and saying, hey, why don't you enter this data on the clear registry?
Yeah.
And that's fantastic.
I think for listeners as well to know that it's not just physicians that are part of
the registry.
And we do have really anybody that's involved in prescribing and who's aware and working
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in that multi, and most of us are working in a multidisciplinary team environment these
days.
And so we have pharmacists on board and other specialties as well.
So I think it's nice to know that anybody could be involved who knows some information
about the medication.
So I think some of our audience are probably more eager to know some of the data.
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So why don't we walk through maybe one of the medications that you guys have reviewed
and just have a quick data synopsis for one of the medications that you have reviewed
in the clear registry.
It's a great idea.
And I'm going to start with ceftobiprol.
The reason is this is the drug that really started the clear registry.
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When it came out, colleagues were asking, who's using this drug and what for, and this
really drove the development of clear.
So it's a good drug to start with.
So ceftobiprol, we have had, we've now published a couple of posters at AMI, a paper in the
journal of global antimicrobial resistance.
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We crunched the data in May, sent it out to all the clear participants, but this is the
excitement of it, of what you find out how this drug is being used.
So to give you a little bit of data, our clinicians in Canada using intravenous ceftobiprol, well,
first of all, it's mostly for adults, but we do have some pediatric data to the clear
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registry.
It is primarily used because of resistance to other agents.
So clinicians, because of resistance to other drugs, they choose ceftobiprol.
What kind of infections are being treated with ceftobiprol on label, health candidate
approved indications and non.
It's everything under the sun.
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Arcteremia, a lot of endocarditis, bone and joint infections, hospital acquired pneumonia,
community acquired pneumonia, central nervous system infections, all types of infections,
but it's being used almost invariably as directed therapy when a clinician grows MRSA.
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Okay, all of the cases, these are documented infections caused by MRSA.
And typically the patient is not responding to vancomycin or not responding to Dapto my
son.
Indian clinicians are saying, I'm going to add ceftobiprol to the treatment.
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They don't take away the bank or Dapto add the ceftobiprol to treatment.
So whether you've got endocarditis or a vector in your bone and joint or a pneumonia documented
to be caused by MRSA, they start ceftobiprol treatment.
And then you have these other interesting things.
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Do you do antimicrobial susceptibility testing?
More than a half of the center said, no, we don't need to know from the can war data,
the national can war data, all of the MRSA are susceptible to ceftobiprol.
So we know the answers, it will be susceptible.
So half of them don't even do it.
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The other half do, discs, e-tests, whatever they're doing.
And then it comes down to the dosing and the dosing is fascinating because I'm going to
say about two thirds of the time it's 500 milligrams every eight hours, but in almost
everyone it's the prolonged two hour longer infusion as per the label to optimize the
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pharmacodynamics.
And then the other third, it is being dosed in relation to renal function.
Every single patient who's being treated with ceftobiprol has had their creatine clearance
calculated.
So this is what I talked about, clinical pharmacy working with infectious diseases and customizing
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the treatment to that patient.
And then when you get into the outcomes, the microbiological success astonishingly is over
90%.
Wow.
The clinical cure rates are around 85%.
And these are patients who've been failing vancotes, failing DAPTO.
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They've got MRSA in the blood, they've got MRSA endocarditis, bones, lungs, and they're
being treated.
I don't want to call it as salvage therapy, but they failed the initial therapy.
Now it's being added on.
And surprisingly, they're doing astonishingly well knowing that over 90% of these patients
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are back to remit.
Right.
Whether it's the pneumonia or endocarditis or whatever, the vast majority are back to
remit.
They're doing well microbiologically.
We're eradicating the organism and clinically they're doing well.
And then on the adverse effects side, we basically got the news that we expected it's a beta
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lactam.
It's a cephalosporin.
So the safety has been outstanding.
We've had a couple of patients with gastrointestinal intolerance.
We had one patient with some hypersensitivity, but none of the three necessitated drug discontinuation.
You know, for me, I always ask, well, I know you've had a side effect.
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Did you stop the drug?
You don't stop the drug.
It means the side effect was reasonably tolerated and you decided to persevere.
So lots of exciting data.
We know when it's being used, how it's being used.
The outcomes are quite good and it's safe.
Yeah, that's fantastic.
I mean, Justin, a few of those sentences there, I mean, definitely gave me more information
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as to when to use septibipral.
And I think really the role of the registry and the purpose of the registry is to provide
this real time data and give us information on when can we use it.
Because I think that's always the question, especially when you're in a crunch like that,
when you have a patient that's not responding, you know that there's not very many drugs
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out there that are going to treat MRSA.
And so having more information on a drug that you can add for combination therapy, I think
from a prescriber standpoint, the comfort of having such data also and knowing that
there is success rates of more than 90% is such helpful information.
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And the great news is this isn't American data or data from Italy or Spain or France
or South Korea.
This is what your colleagues are doing across the country in neighboring Alberta, neighboring
Manitoba, British Columbia to Newfoundland, Ontario, Quebec.
This is what we're all doing.
No, that's fantastic.
Yeah.
You did mention, and this is just out of interest because I'm a pediatric subspecialist.
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And so in terms of some of these medications, I mean, it's always a challenge for getting
dosing for us and further knowing which indications because we extrapolate most of our data from
adult data just because there aren't a lot of RCTs in pediatrics.
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And so within the same data, do you include the pediatric data and then provide that to
all physicians or is that only if somebody is specifically interested in having access
to the pediatric data or is this all combined?
We do make it clear that there's pediatric use to all of our participants.
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I've got a lot of really important women in my life, a really important person, Dr. Joanne
Embry, who was my boss for 12 years here in the medical school for a long time, pediatric
infectious diseases specialist like yourself, would always say to me, kids are not little
adults.
No.
They're different.
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And it stuck with me for the last 35 years.
So unfortunately, as you know, we frequently forget about children when it comes to antimicrobial
development.
We study adults, frequently more men than women.
And we say, well, we think this is appropriate guidance for everyone.
So we're late to the game with studying children, dosing efficacy or their unique side effects.
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And many of these drugs are not even indicated to be used in children.
But like most things, clinicians in Canada don't really necessarily care what all the
indications are.
Their job is risk versus benefit.
In my patient, if I think the benefit of using septobiprote or setozintazobac, or intravenous
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phosphomycin or dalbovansin, if the benefit outweighs my perceived risk, I'm going to
use it in this patient for this infection or this age group, even though it may be off
label.
So I did find it somewhat surprising.
But yes, we share the pediatric data with the participants.
Whatever data we get, it goes to them and they see it.
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Okay.
And I think just for our listeners, I think this is also important for especially the
pediatricians out there, is that being part of this registry is going to be helpful for
us too, right?
And so I think encouraging that more pediatric data be inputted into the registry and analyzed
similar to adult data.
I think that really, for me, would be helpful in the coming years, especially as we're seeing
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more antimicrobial resistance in the younger populations.
Well, Rapina, you got me all excited today because I think intravenous amoxicillin and
clavulinate could be what ignites our pediatric infectious disease specialists across Canada
to clear even more.
That's great.
So we know a little bit more about the future of the registry.
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So what else?
What else is what's new?
Like, what are we bringing in?
What other newer drugs are coming in?
So my vision is what I would like to happen is that a typical IV antibiotic is on the
registry maximum two to three years.
And once we've had two to three AMI posters over the years, a paper or two, we've presented
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this data in hospitals across Canada, our clear participants have had slide package
after slide package.
At some point, there's a time where clinicians in Canada say, well, this is not a new agent
anymore.
We know how to use it.
We know when to use it.
And I'd like to see it fall off the registry.
And I'd like to see new drugs come into the registry.
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So I would love two, three years once you've been in, you fall off the registry.
And then ideally every single new antimicrobial that comes in joins the registry.
So what could be the future?
You've inspired me with a box club, so I will get on that over the summer.
But we're trying to work, we're working, we're doing research with all the companies and
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trying to convince in the pen and Rella back down, Merrill Pen and Vabor back down, has
it in Abbey back down, so fitter a call potentially a tree and Abbey back down, which just got
approved in the United States and many others come to Canada.
You know, in Canada, these agents are not going to be used a lot.
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They're going to be used within the context of an antimicrobial stewardship program by
specialists.
But we know that the special access program doesn't work well for acute infectious diseases.
When Dr. Rupina has a patient with a multi drug resistant pathogen and they're critically
ill, you can't wait five days or eight days for this drug to come from Health Canada.
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You need to have the drug used within an hour or two.
So we're trying to convince companies that Canada is important, bring these agents to
Canada.
We really need them in select cases to maximize patient outcomes.
So every single one of the new ones that comes in, we're going to have them join clear.
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We're going to help Canadians educate other Canadians of how and why these drugs are being
used.
And I'm hoping this is a mobile process, so drugs are coming out, drugs are coming in,
and it just keeps moving forward over the next several years.
Yeah.
And I think you bring a very important point to, you know, to the front of the list here
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is that we really need newer agents and we need data on newer agents.
And I think some of the approvals are always lacking because we don't have local national
data.
But because we are looking at these medications in real time, I think that provides us with
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even a stronger case to bring in such drugs into Canada and have them at our fingertips
when we are in a tight situation where we are struggling to manage a patient.
So I think that's really another advantage of such a registry that's national.
You're absolutely right.
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And I can tell you from traveling again within Canada post COVID, the infectious disease
community is relatively small.
We all know each other coast to coast.
And there's a real need for some of these new agents to be used in select cases.
Clinicians would like them on the shelf, ready to go if and when I need them.
(34:24):
The good news is that I think Health Canada really understands this as well.
Yeah.
I've been to Health Canada several times over the last few years.
I've presented some of our national Canward resistance data.
They get resistance is a problem in Canada.
We have ESDLs.
We have CREs.
We have MRSA.
We have VRE.
We have multi-drug resistance pseudomonas.
(34:47):
We have these pathogens and we need some new treatments.
They understand the need for new antimicrobials.
They're ready to partner with industry to facilitate the approval process.
I think we just need some bold companies to want to come to Canada, say, look, I know
the patient clientele will be small, but we need to do this for Canada and we'll find
(35:11):
a way to make it work.
And I'm confident that with our strong infectious disease community in Canada, Health Canada
working together with industry, we'll find a way to get this done.
Yeah, exactly.
Well, thank you, Dr. Zanel so much for being such a strong advocate for all of us prescribers
because I know that all of us every single day are talking about this, but sometimes
(35:36):
you just don't have the pathway to how do you get to getting a new drug approved?
And so I think the clear registry is one of those gateways and I'm super excited that
we have such a registry and I'm also excited to hear all about this because now I'm aware
of it and I can share this information.
And that's what I would suggest to our viewers today is share with others that there is something
(36:02):
like a registry like this that exists within Canada.
It's a very easy process and it's really information spreading and it's important for us to have
such important data locally.
Rupina, for me, three quick thank yous, a big one to you.
I'm super honored to be part of this podcast with you.
I was delighted when you emailed me.
(36:23):
Thank you so much and thank you for what you're doing with your podcasts.
Two, thanks to your listeners for listening and perhaps even joining CLEAR and being a
participant or data submitter.
And lastly, I want to thank the CLEAR participants and the data submitters.
Without them, you and I are not talking.
Without them, it's just George Zanell intellectually masturbating, but they're the ones who actually
(36:47):
do all the work.
So I'm really thankful to Canadian clinicians, infectious disease specialists, clinical pharmacists,
microbiologists for everything they are doing to make CLEAR such a success.
Thank you.
Thank you to all of them.
Yeah, no, that's great.
Of course.
And so for, I guess, our listeners out there, I know you mentioned last time that it's just
a quick email to yourself.
(37:09):
So is this email something that they can find online for you and then just email you and
be part of the registry?
Absolutely.
So, you know, you can just Google George Zanell, Z-H-A-N-E-L and you'll find it right there.
Or you know, it's G G Zanell, Z-H-A-N-E-L at PCSinternet.ca.
(37:37):
And the email says, hey, CLEAR, C-L-E-A-R, I want to join.
Boom, it's done.
Awesome.
That's fantastic.
And then I know you did mention that previously because there's no demographics or patient
information that's being shared.
So I don't think that centers would have to have any prior like ethics approval from their
center to be part of the registry.
(37:58):
Is that correct?
We have had no center tell us this is a problem.
We are ethics approved.
We took it through the University of Manitoba, but there are there's absolutely no patient
identifiers that we are requesting.
No confidential patient information.
We are asking for the basics, the infection, the pathogen, the dose, all that.
(38:20):
So we have never had a site say that this is a problem for them.
That's fantastic.
So really easy, just an email away and you know, they could, the center could be involved
and maybe the future of the registry is to get more and more centers involved.
So we, you know, can amplify our data and have quicker turnaround time.
(38:41):
Maybe we could review medications at a quicker pace when we have larger participant involvement.
So I think that's fantastic.
So for our listeners and our viewers today, is there anything that one key message that
you want to provide before we finish off this podcast today?
I guess my only last message would be clear has been an unbelievable success story because
(39:09):
Canadians, Canadian clinicians wanted to be a success story.
And I'm just very thankful to the people who take the time to hit that link and spend the
three minutes point and click point and click.
And we've had tremendous success coast to coast, but you're right, the more the merrier.
(39:30):
Thank you all for what you're doing with the clear registry.
Thank you to you, Rapina for helping me advertise it.
Of course.
Yeah.
It's been a fun ride with it.
And I'm just hoping that it continues to be a success.
All right.
Well, we are so grateful to have you on this podcast today.
And as I always let our viewers and listeners know that this podcast is mainly for informational
(39:52):
purposes and in no way to endorse a product or in place of an infectious disease consult.
As we kind of exit the podcast today, I really am honored to have you here today, Dr. Zanell.
And I'm so excited for the future of clear.
And it's honestly so fantastic because all of us want to do certain things like this,
(40:14):
but you know, everybody has a busy schedule.
You have a very, very busy schedule and you were able to establish such an important registry.
And so we're super thankful.
And it's really an honor to have you today.
Thank you again.
Thank you, everyone.
Thank you, Dr. Pirwal and Dr. Zanell.
For more information on the clear registry and to join, please email Dr. Zanell at ggzanellatpcsinternet.ca.
(40:44):
Have a topic suggestion?
Email us at thecanadianbreakpoint.gmail.com and follow us on Twitter at CA Breakpoint.
See you again soon at the Canadian Breakpoint.
Thanks for joining us at the Canadian Breakpoint, a Canadian infectious diseases podcast by
(00:12):
Canadian infectious diseases physicians.
I'm Summer Stewart here with Dr. Rupeena Purewal, pediatric infectious diseases physician
in Saskatoon.
In this episode, we are excited to welcome Dr. George Zhanel, department head for infectious
diseases and medical microbiology at Max Rady in Winnipeg, and the research director for
(00:34):
CARA, the Canadian Antimicrobial Resistance Alliance.
Today we'll discuss CLEAR, or the Canadian Leadership on Antimicrobial Real-Life Usage
Registry.
Dr. Purewal.
All right.
Thank you, everyone.
Welcome to another episode of our podcast, the Canadian Breakpoint.
Today we have a very, very special guest with us, and after I do his introduction, I think
(01:00):
the viewers will also feel the same way.
So thank you, Dr. Zannell, for joining us today and taking time out of your busy schedule,
because you're a very, very busy person, to be on the podcast.
It's honestly an honor for us to have you on the podcast today.
So Dr. Zannell is a microbiologist and pharmacologist who received his PhD in the Department of
(01:24):
Medical Microbiology and Infectious Diseases at the Faculty of Medicine, University of
Manitoba, and a doctor of clinical pharmacology at the University of Minnesota.
He is presently professor and associate head in the Department of Medical Microbiology
and Infectious Diseases, MaxRady College of Medicine, and research director of the Canadian
Antimicrobial Resistance Alliance, CARA.
(01:47):
Dr. Zannell is the founding and chief editor of the Canadian Antimicrobial Resistance Alliance
website.
Dr. Zannell has published over 1,100 papers, chapters, and abstracts in the area of treatment
and prevention of infectious diseases.
He has presented over 1,200 lectures as an invited speaker at international, national,
(02:10):
and local meetings, speaking on the topics of antimicrobial resistance infections, as
well as treatment and prevention of infectious diseases in Canada, the US, Central and South
America, Western and Eastern Europe, including Russia, Australia, Southern and Northern Africa,
the Middle East, and Asia.
(02:31):
He has been extensively involved in treatment guidelines for a variety of infections in
Canada, the US, and internationally.
Dr. Zannell has received or been nominated for more than 100 teaching awards, including
the Canadian Association for Medical Education Merits Teaching Award in 2020.
Congratulations, Dr. Zannell.
(02:52):
Thank you.
Dr. Zannell is also a member of the Who's Who in Medical Sciences Education, and in
2022, he was elected as a fellow of the Canadian Academy of Health Sciences in recognition
of sustained excellence in research and teaching within health sciences.
Participating in the Academy is considered one of the highest honours for individuals
(03:16):
in the Canadian health sciences community.
In 2022, Web of Science identified Dr. Zannell as one of the world's most influential researchers
selected among elite group recognized for exceptional research influence, demonstrated
by the production of multiple highly cited papers that rank in the top 1% by citations
(03:41):
for the field and year.
Also in 2022, Dr. Zannell received the Dr. Fred Aoki Career Achievement Award in recognition
of a career of dedication and excellence in multiple domains of medical microbiology and
infectious diseases, including research, education, clinical practice, service, and administration.
(04:04):
So amazing.
I'm so honoured to have you here today, Dr. Zannell.
And today we're going to be talking about a very, very important topic, which is known
as the CLEAR registry that Dr. Zannell will give us more information about.
And so why don't we just start off, Dr. Zannell, by telling the audience a little bit about
what CLEAR is and when it was established and how did this come about?
(04:30):
How did this registry, this national registry come about?
So Rapina, let me start by saying how delighted and honoured I am to be with you on this podcast.
And I also apologize, my mother sent in this mini biography and I apologize.
It just goes on and on and on.
She didn't even put in there that I finally got out of diapers when I was 15 years old.
(04:53):
Lots of accomplishments.
I'm delighted to be with you.
So CLEAR, let's talk CLEAR.
CLEAR stands for the Canadian Leadership on Antimicrobial Real Life Usage Registry.
CLEAR, C-L-E-A-R.
And how this came about, it came about in 2019.
(05:14):
It was traveling extensively across Canada before COVID, speaking at every hospital and
university about new IV antimicrobials in Canada, their properties, et cetera.
And colleagues would stop and talk to me and one of them was Dr. Ted Steiner, an ID doc
(05:35):
in Vancouver.
And he said, you know what, it's great you're talking about these antibiotics and you're
doing research on them, but when they come to Canada, we need some sort of platform,
infectious disease specialist, medical microbiologist, clinical pharmacologist, when they're using
these drugs, they can actually share their experiences with other Canadians.
(05:56):
And that way we know in the Canadian setting, treating patients with the Canadian antimicrobial
resistance rates we have, how are we using these drugs, for what infections, what pathogens,
and you should do something, he said to me, and that's how it all started.
That's fantastic.
And honestly, I think having that, I think the emphasis on having real life experience
(06:21):
and real time experience.
And I think we've talked about this before.
It's fantastic that this information is presented to prescribers and it's real time data.
So we can actually use this information in that moment, especially when all of us are
being exposed to such new drugs and don't have a lot of data or information.
(06:46):
So obviously this is a very, very new approach and it's a fantastic approach.
So in terms of what are some of the advantages that you've, since the establishment, what
are some of the advantages of such a registry do you think in Canada, besides having that
real time information?
So what we've got currently sitting in front of us is about 360 participants nationally.
(07:14):
Half of those are infectious disease medical microbiology and the other half are clinical
pharmacists specializing in infectious diseases, antimicrobial stewardship.
And these individuals, every two, three months, get the latest information of how these antibiotics
are being used from us.
(07:34):
So what we're doing is we're sharing the information that they themselves have told us.
So we have data submitters across Canada, pharmacists, infectious disease specialists.
They submit data when they use these antibiotics.
We crunch it and every two, three months we send them all the data.
So it's Canadians, teaching Canadians how these antibiotics are being used in their
(08:01):
hands.
The other benefit is it's Canadians helping Canadians sharing Canadian experiences.
And as many of us know in the infectious disease world and microbiology world is that definitely
anti-biograms differ from different countries and our experience and access to medications.
And so having this data for us nationally is super helpful, especially myself being
(08:24):
a prescriber.
I think this is the information that we're always looking for, especially when providing
patient care.
So I'm more interested to hear what type of data is being gathered in the registry.
And you did mention that it's collaborated data.
And so where is this data stored or how is it analyzed on your guys' end?
(08:49):
So on our end, we decided in 2019 that every single new IV antibiotic that was health Canada
approved and marketed in Canada would have on the clear registry.
So we currently have four IV antibiotics.
Cephalopipral, ceftozentazobactam, intravenous phosphomycin, and dalbovansin.
(09:15):
And so what we do is for our 360 participants, and by the way, how do you become a participant?
It's free.
You send Zanelle an email and just say, hey, make me a part of clear, boom, it's done and
you're a part of clear.
That's awesome.
And if you choose to submit data, that's fantastic.
But you're going to be educated.
(09:37):
So for these four IV antibiotics, we have a link.
And we send out to all of our participants, if they have treated a patient with one of
these new drugs or will treat a patient, you hit that link and it's easy peasy.
It's three minutes on your own iPad, laptop, desktop, 17 questions pop down and it's point
(10:01):
and click.
You're done in three minutes.
And it's asking you things like, well, what infection are you treating?
What is the pathogen?
Are you using the antibiotic alone or in combination?
What dose are you using?
By the way, did you do antimicrobial susceptibility testing?
And if so, what method, what was the M.I.C.
(10:23):
Why did you use it?
Was it because of resistance to other antibiotics?
Is it because you failed previous therapy?
Was it because of intolerance to other agents?
Microbiologically, did it work?
Clinic, did it work?
Were there adverse effects?
So you point, click, point, click, point, click, you are done.
And then what we do is the data is stored on red cap.
(10:47):
This is electronic data capture system.
And Melanie Baxter in our group is the guru.
She crunches it all.
And then we put PowerPoint slides together, send it out to the group.
We also present ideally each year a poster on every drug at AMI, at the AMI CACBID meeting.
(11:08):
And then we also publish papers.
Once we get to about 30 to 50 patients, we'll actually write up a paper and publish it.
So we've done that for all of the antibiotics already, except double bands.
And we have yet to publish a paper on this.
We presented a poster because we're still not where we want in terms of the numbers
of patients.
(11:28):
That's fair.
And when you say that in terms of number of patients, what is the threshold that you're
hitting before this data becomes finalized?
Rupina, the threshold is whatever Jordan Zanell thinks the threshold is.
It's terrible.
So I've kind of set a bar of if we hit 30-ish, 20, 30 patients, we'll put a poster together
(11:51):
at AMI so Canadians can see what's going on.
Even well before that, we crunch the data, send it to all the participants, even if it's
only patients.
But once we start to hit around 50, the journals get interested because then you start some
substantial data.
So once we hit 50, we published a paper on cephtalbibral, we published a paper on cephtalzentazo,
(12:16):
we published a paper on Intravenous Phosphamycin, and we're still not at 50 for the Dalbovansin,
but once we're there, we'll publish a paper on that.
But there is no hard and fast rules, but that's kind of the threshold.
Yeah, no, that's fantastic.
And you kind of mentioned that you're really looking at novel IV antibiotics.
(12:36):
So in terms of, is there other criteria in how you decide which medications to review?
No, so my criteria really are if you're a new IV antibiotic, health Canada approved
and you're on the market, we want you in clear.
So try not to bias and say, we don't want this one, we don't want that one, we want
(12:57):
them all.
But I will tell you, when intravenous amoxicillin clavulinate came to the market, which was
relatively recently, I hummed in a hard whether I should put this on the clear registry.
And initially I thought, well, of course it should be.
But then a colleague said to me, we know exactly how it's used.
It's used like the oral, which we've had for 35 years, when you can't use the oral.
(13:23):
So didn't put it on the clear registry.
And yet I have some colleagues bugging me to say, hey, put it on there.
So it may actually, in fact, join the registry sooner than later.
Yeah, I think honestly being, so I'm a pediatric infectious disease physician and so amoxiclav,
we use a lot.
And I think there is a different, I guess there is a couple of indications where sometimes
(13:47):
I feel more comfortable using the IV version and IV amoxiclav, for instance, if you do
have a polymicrobial infection where you're not necessarily worried about pseudomonas.
And I think it's some of that information that's really good to disseminate because
sometimes we don't really think about using amoxiclav in an initial setting like that,
(14:11):
but remembering that the IV formulation, or again, just knowing that there is an IV formulation,
because I think that is some data that hasn't been, I guess, widely spread just because
it is a novel agent or a novel formulation.
Well, you've inspired me, Rupina, this summer to put a proposal together to put IV amoxiclav
(14:35):
onto the clear registry.
I'll put together the 17 important questions we need to ask and run it by the clear group
that we have across Canada, get their input.
You may get an email yourself.
Oh, I'm already joining, so there's no doubt about that.
You can get an email, are these the best questions or should we add or delete, have other questions?
(14:58):
But perhaps this fall, we should have IV amoxiclav join the clear registry.
Yeah, and I think it's important also from an adverse event standpoint, right?
Different formulations may have different adverse effects, right?
Or how quick, for instance, bone marrow suppression may occur, et cetera.
So I think it's important if something is new and novel, because I know that people
(15:22):
definitely are looking out there for data.
I'm always doing that as a prescriber.
Thank you so much.
You've inspired me and you've made strong cases.
We're going to do whatever we can to put IV amoxiclav on the clear registry this fall.
Awesome.
And just like how you informed me that right now, so do you inform participants that are
(15:44):
newer drugs are being added to the registry for review?
So do they receive an email for once they are a participant in the registry?
Do they receive an email once a new questionnaire comes on the market?
Yes.
So it's a balancing of not wanting to bombard them because everyone gets so many emails.
(16:05):
I don't want them to shut down.
I'll typically send somewhere around three to four emails a year and it's always loaded
with here's the new information.
Here's the slides of the four drugs for your information.
And then if there are new developments.
So for example, recently when intravenous Dalba Vansin came onto the market, we immediately
(16:28):
sent an email to all the participants saying great news.
Dalba Vansin has been Health Canada approved and is marketed with this indication.
Here is the clear link to IV Dalba Vansin.
If you have treated or will treat a patient with this drug, please consider joining.
And again, as always, it's voluntary, but it's ethics approved.
(16:50):
We're not asking for any confidential patient information.
Please consider joining.
And we frequently get emails back saying, oh, I didn't even know it was on the market.
We're serving an educational tool at times.
Exactly.
I think a lot of that is that's very important, right?
Because it's really important to know which medications are out there.
(17:12):
And then also knowing the detail of data that you're providing, including indications and
contraindications and really uses and anecdotal experience from our colleagues.
I think that there's multiple times in a day when I'm practicing, when I have to reach
out to friends across the nation to ask questions about this.
(17:37):
And so what better way to do this than in a registry where people have already inputted
this data.
So I think this is honestly fantastic and it's the future of Canada.
And I think it's great to have local data.
So I'm very impressed.
Rupina, you said something really important.
It's this almost unexpectedness when you actually start to crunch the data per drug.
(18:01):
You think you know what's going on in Canada and you realize you don't because the users
of drugs inform you what they're doing and it's on label, it's off label, all types of
dosing.
There are clear partnerships with infectious diseases and clinical pharmacy using, you
(18:22):
know, renal function to customize dosing and optimize pharmacodynamics.
So it's very educational when you find out what's going on by crunching the data, what
Canadians are doing.
And so currently which centers or participants, I think you mentioned over 300 participants.
And so is it pretty much national?
(18:43):
You have representation from most provinces?
Representation from all provinces.
It's been, I was a little bit shocked and surprised that the uptake was so vigorous
and so positive.
Other countries have tried this and they have not been able to make it work.
But you know, in Canada, I think we all kind of love each other and realize that we're
(19:04):
just a bunch of Canadians who were born somewhere else.
So we contribute.
So coast to coast, I'm going to say 98% of all the participants are infectious disease,
microbiology and clinical pharmacy.
And then we've got sprinklings of intensivists, respirologists, internists, just other groups.
(19:29):
I'm going to say about 98% of the participants are Canadian.
But interestingly enough, we have a bunch of people from all over the world, from Italy
and Chile and South Africa following the clear registry.
I don't know if they're Canadians working off site or just colleagues interested in
antimicrobial usage, but that's the demographic.
(19:52):
In terms of data submitters, the people who actually point and click, it's 50-50.
Half of the submissions are infectious disease, microbiology, half are clinical pharmacists.
And frequently these groups are working together.
They just say, look, I'll submit the data on this patient.
I frequently get asked, well, what about duplications?
(20:13):
We don't have duplications.
We look for them very, very carefully, but clearly the team is talking to each other
and saying, hey, why don't you enter this data on the clear registry?
Yeah.
And that's fantastic.
I think for listeners as well to know that it's not just physicians that are part of
the registry.
And we do have really anybody that's involved in prescribing and who's aware and working
(20:41):
in that multi, and most of us are working in a multidisciplinary team environment these
days.
And so we have pharmacists on board and other specialties as well.
So I think it's nice to know that anybody could be involved who knows some information
about the medication.
So I think some of our audience are probably more eager to know some of the data.
(21:05):
So why don't we walk through maybe one of the medications that you guys have reviewed
and just have a quick data synopsis for one of the medications that you have reviewed
in the clear registry.
It's a great idea.
And I'm going to start with ceftobiprol.
The reason is this is the drug that really started the clear registry.
(21:28):
When it came out, colleagues were asking, who's using this drug and what for, and this
really drove the development of clear.
So it's a good drug to start with.
So ceftobiprol, we have had, we've now published a couple of posters at AMI, a paper in the
journal of global antimicrobial resistance.
(21:49):
We crunched the data in May, sent it out to all the clear participants, but this is the
excitement of it, of what you find out how this drug is being used.
So to give you a little bit of data, our clinicians in Canada using intravenous ceftobiprol, well,
first of all, it's mostly for adults, but we do have some pediatric data to the clear
(22:10):
registry.
It is primarily used because of resistance to other agents.
So clinicians, because of resistance to other drugs, they choose ceftobiprol.
What kind of infections are being treated with ceftobiprol on label, health candidate
approved indications and non.
It's everything under the sun.
(22:31):
Arcteremia, a lot of endocarditis, bone and joint infections, hospital acquired pneumonia,
community acquired pneumonia, central nervous system infections, all types of infections,
but it's being used almost invariably as directed therapy when a clinician grows MRSA.
(22:55):
Okay, all of the cases, these are documented infections caused by MRSA.
And typically the patient is not responding to vancomycin or not responding to Dapto my
son.
Indian clinicians are saying, I'm going to add ceftobiprol to the treatment.
(23:16):
They don't take away the bank or Dapto add the ceftobiprol to treatment.
So whether you've got endocarditis or a vector in your bone and joint or a pneumonia documented
to be caused by MRSA, they start ceftobiprol treatment.
And then you have these other interesting things.
(23:36):
Do you do antimicrobial susceptibility testing?
More than a half of the center said, no, we don't need to know from the can war data,
the national can war data, all of the MRSA are susceptible to ceftobiprol.
So we know the answers, it will be susceptible.
So half of them don't even do it.
(23:58):
The other half do, discs, e-tests, whatever they're doing.
And then it comes down to the dosing and the dosing is fascinating because I'm going to
say about two thirds of the time it's 500 milligrams every eight hours, but in almost
everyone it's the prolonged two hour longer infusion as per the label to optimize the
(24:23):
pharmacodynamics.
And then the other third, it is being dosed in relation to renal function.
Every single patient who's being treated with ceftobiprol has had their creatine clearance
calculated.
So this is what I talked about, clinical pharmacy working with infectious diseases and customizing
(24:44):
the treatment to that patient.
And then when you get into the outcomes, the microbiological success astonishingly is over
90%.
Wow.
The clinical cure rates are around 85%.
And these are patients who've been failing vancotes, failing DAPTO.
(25:04):
They've got MRSA in the blood, they've got MRSA endocarditis, bones, lungs, and they're
being treated.
I don't want to call it as salvage therapy, but they failed the initial therapy.
Now it's being added on.
And surprisingly, they're doing astonishingly well knowing that over 90% of these patients
(25:24):
are back to remit.
Right.
Whether it's the pneumonia or endocarditis or whatever, the vast majority are back to
remit.
They're doing well microbiologically.
We're eradicating the organism and clinically they're doing well.
And then on the adverse effects side, we basically got the news that we expected it's a beta
(25:45):
lactam.
It's a cephalosporin.
So the safety has been outstanding.
We've had a couple of patients with gastrointestinal intolerance.
We had one patient with some hypersensitivity, but none of the three necessitated drug discontinuation.
You know, for me, I always ask, well, I know you've had a side effect.
(26:06):
Did you stop the drug?
You don't stop the drug.
It means the side effect was reasonably tolerated and you decided to persevere.
So lots of exciting data.
We know when it's being used, how it's being used.
The outcomes are quite good and it's safe.
Yeah, that's fantastic.
I mean, Justin, a few of those sentences there, I mean, definitely gave me more information
(26:31):
as to when to use septibipral.
And I think really the role of the registry and the purpose of the registry is to provide
this real time data and give us information on when can we use it.
Because I think that's always the question, especially when you're in a crunch like that,
when you have a patient that's not responding, you know that there's not very many drugs
(26:54):
out there that are going to treat MRSA.
And so having more information on a drug that you can add for combination therapy, I think
from a prescriber standpoint, the comfort of having such data also and knowing that
there is success rates of more than 90% is such helpful information.
(27:15):
And the great news is this isn't American data or data from Italy or Spain or France
or South Korea.
This is what your colleagues are doing across the country in neighboring Alberta, neighboring
Manitoba, British Columbia to Newfoundland, Ontario, Quebec.
This is what we're all doing.
No, that's fantastic.
Yeah.
You did mention, and this is just out of interest because I'm a pediatric subspecialist.
(27:39):
And so in terms of some of these medications, I mean, it's always a challenge for getting
dosing for us and further knowing which indications because we extrapolate most of our data from
adult data just because there aren't a lot of RCTs in pediatrics.
(27:59):
And so within the same data, do you include the pediatric data and then provide that to
all physicians or is that only if somebody is specifically interested in having access
to the pediatric data or is this all combined?
We do make it clear that there's pediatric use to all of our participants.
(28:22):
I've got a lot of really important women in my life, a really important person, Dr. Joanne
Embry, who was my boss for 12 years here in the medical school for a long time, pediatric
infectious diseases specialist like yourself, would always say to me, kids are not little
adults.
No.
They're different.
(28:44):
And it stuck with me for the last 35 years.
So unfortunately, as you know, we frequently forget about children when it comes to antimicrobial
development.
We study adults, frequently more men than women.
And we say, well, we think this is appropriate guidance for everyone.
So we're late to the game with studying children, dosing efficacy or their unique side effects.
(29:08):
And many of these drugs are not even indicated to be used in children.
But like most things, clinicians in Canada don't really necessarily care what all the
indications are.
Their job is risk versus benefit.
In my patient, if I think the benefit of using septobiprote or setozintazobac, or intravenous
(29:30):
phosphomycin or dalbovansin, if the benefit outweighs my perceived risk, I'm going to
use it in this patient for this infection or this age group, even though it may be off
label.
So I did find it somewhat surprising.
But yes, we share the pediatric data with the participants.
Whatever data we get, it goes to them and they see it.
(29:52):
Okay.
And I think just for our listeners, I think this is also important for especially the
pediatricians out there, is that being part of this registry is going to be helpful for
us too, right?
And so I think encouraging that more pediatric data be inputted into the registry and analyzed
similar to adult data.
I think that really, for me, would be helpful in the coming years, especially as we're seeing
(30:18):
more antimicrobial resistance in the younger populations.
Well, Rapina, you got me all excited today because I think intravenous amoxicillin and
clavulinate could be what ignites our pediatric infectious disease specialists across Canada
to clear even more.
That's great.
So we know a little bit more about the future of the registry.
(30:38):
So what else?
What else is what's new?
Like, what are we bringing in?
What other newer drugs are coming in?
So my vision is what I would like to happen is that a typical IV antibiotic is on the
registry maximum two to three years.
And once we've had two to three AMI posters over the years, a paper or two, we've presented
(31:05):
this data in hospitals across Canada, our clear participants have had slide package
after slide package.
At some point, there's a time where clinicians in Canada say, well, this is not a new agent
anymore.
We know how to use it.
We know when to use it.
And I'd like to see it fall off the registry.
And I'd like to see new drugs come into the registry.
(31:28):
So I would love two, three years once you've been in, you fall off the registry.
And then ideally every single new antimicrobial that comes in joins the registry.
So what could be the future?
You've inspired me with a box club, so I will get on that over the summer.
But we're trying to work, we're working, we're doing research with all the companies and
(31:51):
trying to convince in the pen and Rella back down, Merrill Pen and Vabor back down, has
it in Abbey back down, so fitter a call potentially a tree and Abbey back down, which just got
approved in the United States and many others come to Canada.
You know, in Canada, these agents are not going to be used a lot.
(32:14):
They're going to be used within the context of an antimicrobial stewardship program by
specialists.
But we know that the special access program doesn't work well for acute infectious diseases.
When Dr. Rupina has a patient with a multi drug resistant pathogen and they're critically
ill, you can't wait five days or eight days for this drug to come from Health Canada.
(32:39):
You need to have the drug used within an hour or two.
So we're trying to convince companies that Canada is important, bring these agents to
Canada.
We really need them in select cases to maximize patient outcomes.
So every single one of the new ones that comes in, we're going to have them join clear.
(33:00):
We're going to help Canadians educate other Canadians of how and why these drugs are being
used.
And I'm hoping this is a mobile process, so drugs are coming out, drugs are coming in,
and it just keeps moving forward over the next several years.
Yeah.
And I think you bring a very important point to, you know, to the front of the list here
(33:21):
is that we really need newer agents and we need data on newer agents.
And I think some of the approvals are always lacking because we don't have local national
data.
But because we are looking at these medications in real time, I think that provides us with
(33:42):
even a stronger case to bring in such drugs into Canada and have them at our fingertips
when we are in a tight situation where we are struggling to manage a patient.
So I think that's really another advantage of such a registry that's national.
You're absolutely right.
(34:02):
And I can tell you from traveling again within Canada post COVID, the infectious disease
community is relatively small.
We all know each other coast to coast.
And there's a real need for some of these new agents to be used in select cases.
Clinicians would like them on the shelf, ready to go if and when I need them.
(34:24):
The good news is that I think Health Canada really understands this as well.
Yeah.
I've been to Health Canada several times over the last few years.
I've presented some of our national Canward resistance data.
They get resistance is a problem in Canada.
We have ESDLs.
We have CREs.
We have MRSA.
We have VRE.
We have multi-drug resistance pseudomonas.
(34:47):
We have these pathogens and we need some new treatments.
They understand the need for new antimicrobials.
They're ready to partner with industry to facilitate the approval process.
I think we just need some bold companies to want to come to Canada, say, look, I know
the patient clientele will be small, but we need to do this for Canada and we'll find
(35:11):
a way to make it work.
And I'm confident that with our strong infectious disease community in Canada, Health Canada
working together with industry, we'll find a way to get this done.
Yeah, exactly.
Well, thank you, Dr. Zanel so much for being such a strong advocate for all of us prescribers
because I know that all of us every single day are talking about this, but sometimes
(35:36):
you just don't have the pathway to how do you get to getting a new drug approved?
And so I think the clear registry is one of those gateways and I'm super excited that
we have such a registry and I'm also excited to hear all about this because now I'm aware
of it and I can share this information.
And that's what I would suggest to our viewers today is share with others that there is something
(36:02):
like a registry like this that exists within Canada.
It's a very easy process and it's really information spreading and it's important for us to have
such important data locally.
Rupina, for me, three quick thank yous, a big one to you.
I'm super honored to be part of this podcast with you.
I was delighted when you emailed me.
(36:23):
Thank you so much and thank you for what you're doing with your podcasts.
Two, thanks to your listeners for listening and perhaps even joining CLEAR and being a
participant or data submitter.
And lastly, I want to thank the CLEAR participants and the data submitters.
Without them, you and I are not talking.
Without them, it's just George Zanell intellectually masturbating, but they're the ones who actually
(36:47):
do all the work.
So I'm really thankful to Canadian clinicians, infectious disease specialists, clinical pharmacists,
microbiologists for everything they are doing to make CLEAR such a success.
Thank you.
Thank you to all of them.
Yeah, no, that's great.
Of course.
And so for, I guess, our listeners out there, I know you mentioned last time that it's just
a quick email to yourself.
(37:09):
So is this email something that they can find online for you and then just email you and
be part of the registry?
Absolutely.
So, you know, you can just Google George Zanell, Z-H-A-N-E-L and you'll find it right there.
Or you know, it's G G Zanell, Z-H-A-N-E-L at PCSinternet.ca.
(37:37):
And the email says, hey, CLEAR, C-L-E-A-R, I want to join.
Boom, it's done.
Awesome.
That's fantastic.
And then I know you did mention that previously because there's no demographics or patient
information that's being shared.
So I don't think that centers would have to have any prior like ethics approval from their
center to be part of the registry.
(37:58):
Is that correct?
We have had no center tell us this is a problem.
We are ethics approved.
We took it through the University of Manitoba, but there are there's absolutely no patient
identifiers that we are requesting.
No confidential patient information.
We are asking for the basics, the infection, the pathogen, the dose, all that.
(38:20):
So we have never had a site say that this is a problem for them.
That's fantastic.
So really easy, just an email away and you know, they could, the center could be involved
and maybe the future of the registry is to get more and more centers involved.
So we, you know, can amplify our data and have quicker turnaround time.
(38:41):
Maybe we could review medications at a quicker pace when we have larger participant involvement.
So I think that's fantastic.
So for our listeners and our viewers today, is there anything that one key message that
you want to provide before we finish off this podcast today?
I guess my only last message would be clear has been an unbelievable success story because
(39:09):
Canadians, Canadian clinicians wanted to be a success story.
And I'm just very thankful to the people who take the time to hit that link and spend the
three minutes point and click point and click.
And we've had tremendous success coast to coast, but you're right, the more the merrier.
(39:30):
Thank you all for what you're doing with the clear registry.
Thank you to you, Rapina for helping me advertise it.
Of course.
Yeah.
It's been a fun ride with it.
And I'm just hoping that it continues to be a success.
All right.
Well, we are so grateful to have you on this podcast today.
And as I always let our viewers and listeners know that this podcast is mainly for informational
(39:52):
purposes and in no way to endorse a product or in place of an infectious disease consult.
As we kind of exit the podcast today, I really am honored to have you here today, Dr. Zanell.
And I'm so excited for the future of clear.
And it's honestly so fantastic because all of us want to do certain things like this,
(40:14):
but you know, everybody has a busy schedule.
You have a very, very busy schedule and you were able to establish such an important registry.
And so we're super thankful.
And it's really an honor to have you today.
Thank you again.
Thank you, everyone.
Thank you, Dr. Pirwal and Dr. Zanell.
For more information on the clear registry and to join, please email Dr. Zanell at ggzanellatpcsinternet.ca.
(40:44):
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See you again soon at the Canadian Breakpoint.
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