Thanks for joining us again at the Canadian Breakpoint,
a Canadian infectious diseases podcast by Canadian
infectious diseases physicians. I'm Summer Stewart
here with Dr. Rupina Pirwal, Pediatric Infectious
Diseases Physician in Saskatoon. For today's
episode, we welcome back Dr. George Zanell to
share clear registry results for IV AmoxClab.
Dr. Pierwal. All right. Welcome, everyone, to
another episode of our podcast, The Canadian
Breakpoint. Today, we have Dr. Zanell back with
us to discuss the CLEAR registry. And as many
of you know, he's a microbiologist and pharmacologist
who received his PhD in the Department of Medical
Microbiology and Infectious Diseases, the Faculty
of Medicine, University of Manitoba, and a doctor
of clinical pharmacology at the University of
Minnesota. the Magna Cum Laude. He's presently
professor and associate head, Department of Medical
Microbiology and Infectious Disease, Max Rady
College of Medicine, and research director of
the Canadian Antimicrobial Resistance Alliance.
Dr. Zanel is the founding and chief editor of
the CAR website. Dr. Zanell has published over
1 ,200 papers, scientific abstracts and posters,
and book chapters in the area of treatment and
prevention of infectious diseases. He's presented
over 1 ,300 lectures, is an invited speaker to
international, national, and local meetings.
speaking on the topics of antimicrobial resistance
infections, as well as the treatment and prevention
of infectious diseases in pretty much all over
the world, in Canada, U .S., Central and South
America, Western and Eastern Europe, including
Russia, Australia, Southern and Northern Africa,
the Middle East, and Asia. He's been extensively
involved in the treatment guidelines for a variety
of infections in Canada, the U .S., and internationally.
Dr. Zanell has received or been nominated for
more than 110 teaching awards, including the
Canadian Association for Medical Education Merit
Teaching Award in 2020. Dr. Zanell is a member
of the Who's Who in Medical Sciences Education.
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 the health sciences. Fellowship in the
Academy is considered one of the highest honors
for individuals in the Canadian health sciences
community. Also in 2022, Dr. Zanella 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.
Each year since 2022, Web of Science identifies
Dr. Zanell as one of the world's most influential
researchers, selected among an elite group recognized
for exceptional research influence, demonstrated
by the production of multiple highly cited papers
that rank in the top 1 % by citations for field
and year. We have an amazing speaker today, and
we are talking about one of probably the most
awaited topics for me, because I wanted to bring
up IVMOX -CLAV into the Clear Registry, and super
excited to hear some of the results and analysis
that you guys have done with the Clear Registry.
Thank you, Dr. Zanell, for being here today,
and always taking the time to support the podcast.
Dr. Repina, for me, it's an honor to be with
you. I do apologize. My mother sends out these
prolonged biographies and your listeners have
to suffer through them. So I apologize for that.
Hopefully the rest of the podcast will be much
shorter and clearer. No, we love hearing about
all of your accomplishments. And honestly, they're
commendable. So we are just honored to have you
here. And so I think for some of our listeners,
they have heard of other Clear Registry episodes
and tuned in. But for some of them who have not
or haven't had the chance to yet, can you remind
our listeners what the Clear Registry is, what
it does, what does it encompass, and what's the
ultimate purpose of the registry? CLEAR stands
for, and it's just spelled C -L -E -A -R, stands
for the Canadian Leadership on Antimicrobial
Real Life Usage Registry. And essentially it's
a voluntary and free. data sharing service. I
have some 450 clear participants across Canada.
About half of those are infectious disease microbiology
specialists and about 50 % of those are clinical
pharmacists interested in infectious diseases
and stewardship. And what happens is if Canadian
clinicians are using new IV antibiotics like
IV Amox Clav, they teach each other about when,
how, and why they use these new IV antibiotics
in the Canadian setting. And all we do is just
facilitate this. So right now on the CLEAR site,
we have links. to antibiotics such as IV amoxicillin
clavulinate. And what happens is all of our participants
have these links. I send them out every three,
four months. And the participants who've used
IV amoxicillin clav, for example, or will use
it, they can hit one of these links. and 17 questions
pop up, point and click, point and click, point
and click. You're done in three minutes. And
then I share the data. I crunch it and I share
it with all the CLEAR participants every three
to four months. So the good news is we're going
to have another data crunch of IV Amox Clav first
week of September. So if you're a CLEAR participant,
you'll get that. If you're not a CLEAR participant,
it's a great opportunity to join. Awesome. It
sounds like fantastic work. And we've seen it
with the other antimicrobials and how much information
that you've been able to provide Canadian prescribers
and also international prescribers. So super
excited to see more of this data come through.
And so specifically for IVMOX -CLAV, when did
we start collecting this data and what specific
data have you collected thus far? We started
collecting data in June of 2024 for IV Amoxclav,
and we've collected a whole variety of data of
why clinicians in Canada use this drug, when
and for what types of infections and pathogens
they use the drug, and how they use it in terms
of dosing and infusion. And we also have very
good data on safety. Perfect. Yeah, and we're
going to go right into this and talk about...
What specific age group then are you seeing most
often that prescribers are prescribing IV amoxiclav
and which indications? In terms of age, 5 % of
all the usage is in pediatrics. And I'd love
to get more pediatric use because this agent
is indicated for all ages. And then we have a
lot of use in patients 65 years of age and older,
and then patients 18 to 64. So 95 % of the use
is in adults and 5 % use in children. In terms
of infections, it's very interesting. use IV
Amoxclav for both on -label, so infections that
are covered by Health Canada, but also off -label,
which is very consistent with the way clinicians
work. They basically look at, look, I know about
the drug. It's safe, effective. I'm going to
use it when I think I need to use it. Our biggest
use, 23%, is intra -abdominal infections, followed
by acute bacterial skin and skin structure infections.
Thereafter, cystitis and pyelonephritis community
acquired pneumonia is also a big indication as
well as ear nose and throat infections bone and
joint infections and also a variety of female
genital type infections so it's used all over
a whole variety of infections okay and are you
looking at the the status of the patient. So
are they admitted to the ward? Are they in the
ICU? Are they very ill? Are you able to see some
of that prescriber information as well? Yes,
we are. So in terms of bacteremia, only about
19 % of the patients have bacteremia when they're
being treated with IV amoxclav, and only about
11 % are in the unit. So the majority of these
patients are on the medical ward, surgical ward,
or in the emergency room. Not many are critically
ill. Interestingly, About 50 % of the time it's
used as directed therapy where clinicians actually
identify and culture a pathogen, whether it's
a staph or a strep or E. coli or proteus or other
organisms. And the other 50 % of the time it's
used empiric. Clinicians don't really know what
the pathogen is yet, but they have a pretty good
idea based on the infection that they are treating.
50 % directed, 50 % empiric use. Okay. Yeah.
And then for the directed use, what's kind of
the number one pathogen that was identified that
it was used towards? Was it mainly E. coli? So
50 % of the time, no pathogen was identified.
And the drug was used in 26 % of the time. It
was actually a mixed infection, a combination
of E. coli or another gram negative and another
gram positive or even an anaerobe. And then the
other 25 % organisms grew out, E. coli. streptococci,
klebsiella, enterococcus, staphylococci, or potentially
even an anaerobe. So the majority of the time,
patients are IVM, OX, CLAV, they don't have an
identified pathogen. The treatment is simply
empiric, but in a significant chunk, it's a mixed
infection, mixed gram positives and gram negatives,
or potentially even an anaerobe. Right. And you
mentioned like intra -abdominal infections being
kind of one of the common uses. And obviously,
as clinicians, we know that those are usually
polymicrobial infections. And so that's kind
of the comfort with using the Aviumox Cloud because
of its broad range of coverage. In terms of the
providers, is there a specific dose? Because
I know that in pediatrics, there is kind of a
standard IV dose and then there's also a higher
IV dose that you can use. And so I don't know
if that's been looked at or is it mainly kind
of the adult information because the majority
of the participants have registered kind of adult
use. Is there a specific dose that you've seen
that providers have been using? Yes, so we've
captured dosing and also renal function. All
of these patients have had their renal function
assessed and dosing has been based on a combination
of infection, severity of illness, but also renal
function. By far the most common dose is 1 ,000
slash 200 milligrams Q8H. The 1 ,000 is the amoxicillin,
200 is the clavulinate every eight hours. And
then two other doses that seem to be quite common
are 2000 slash 200 Q8, as well as 500 slash 100
Q12. And again, that's based on renal function.
But by far the most common dose is 1000 milligrams
slash 200 every eight hours. Okay. All right.
And then in terms of once prescribers are using
this in terms of therapy, is it often used as
monotherapy or combination therapy? By far, 84
% of the time it's used alone. When it is used
in combination, it's used in combination with
a whole variety of different agents because of
the different infections that are being used.
But frequently it's used along with vancomycin.
or a fluoroquinolone, such as ciprofloxacin or
levofloxacin, or with a macrolide, azithromycin,
or doxycycline. But the majority of the time,
it is used alone. All right. And then in my experience,
I've used it and not had any specific adverse
events that were severe. And so is that kind
of what you're seeing in the registry as well?
Or are there any specific side effects that should
be brought to our attention? As expected, you
know, we've had hundreds and hundreds of patient
cases reported now, and overwhelmingly, the drug
is unbelievably safe. In 98%, we've just had
no side effects reported whatsoever. Sometimes
the clinician doesn't know if any side effects
have occurred, but overwhelmingly, 98 % of the
time, no side effects. We had two side effects
reported. One was rash. The other was a transient
leukopenia. But I'll say that neither one of
these two resulted in drug discontinuation. So,
you know, no surprise. It's a beta -lactam. It's
a penicillin. This is an astonishingly safe drug.
Sounds fantastic. So in terms of obviously all
the clinicians and pharmacists out there and
nurses are thinking, so what are the outcomes
in our patients? I know that clear looks at microbiological
curates and then also clinical outcomes. And
so what have you seen with IVM Oxclav? So I'm
going to talk about both the microbiological
success and the clinical success. But it's very
interesting. And I think your listeners will
be interested. You know, why? Why are clinicians
choosing IVM Oxclav? This is an antimicrobial
stewardship play, I think, in most hospitals.
40 % of the time, they're using it instead of
piperacillin -tazobactam. They're choosing the
narrower spectrum. 15 % of the time, they're
using it instead of ceftriaxone. They're using
it instead of... meropenem and ertapenem. They're
using it instead of other antimicrobials, such
as fluoroquinolone. So large part of its use
is an antimicrobial stewardship strategy. Use
it instead of things like peptazo, ceftriaxone,
a carbapenem, a fluoroquinolone, which is wonderful
in terms of trying to preserve drugs such as
piperacillin, tezobactam for the future. Now,
in terms of microbiological outcomes and clinics,
outcomes. The data is overwhelmingly supportive.
Microbiological success, which is what we call
eradication of the pathogen or presumed eradication.
As you know, Dr. Rupina, I'm a microbiologist.
I like to kill bugs and moxclav, no surprise,
you know, it's killing them. 87 % microbiological
success, meaning the pathogen has been eradicated
or it can't be found after treatment, which is
really great news. And in terms of clinical outcomes,
you know, you're very interested in making patients
clinically better. 87 % clinical success based
on either improvement or clinical cure. So, you
know, wonderful news regarding safety, but also
very, very good news in terms of efficacy. Yeah.
And like you mentioned, it gives us an alternative
option, right? So sometimes when you don't want
to use Piptase or you don't feel like there's
a need to use it, you have another option. And
I think when IV, the formulation came out, because
I think oral Amoxiclav, everyone's been using
for a long time. And then when the IV formulation
was released, I think a lot of us benefited from
that from both like an antimicrobial resistance
standpoint, stewardship standpoint, like you
mentioned, but just awesome clinical curates.
also patient compliance, and then, and just patient
satisfaction as well, because it's that one drug
kind of method. And oftentimes, you know, for
intra intra abdominal infections, we sometimes
have to use combination therapy, we're using
like ceftriaxone, because we need better anaerobic
coverage with that and, and or even with ciprofloxacin
sometimes. And so I think IV amoxiclav has really
helped with patient satisfaction as well, because
You can present to them that, you know, it's
a single three times a day medication that we
can give through your IV. And so they can go,
especially for pediatric patients who want to
go on passes in between antibiotics, it really
helps. So, you know, you talked about oral amoxicillin
clavulate, which has been available in Canada
since the 80s. And just so your listeners know
how old I am, I published a paper on... oral
amoxicillin clavulinate back in 1986 dr rupina
so your listeners are listening to a dinosaur
talking about this drug but you know we we've
been trying to get the intravenous version to
canada for many many years because it's been
available in many countries such as france for
many many years and we're delighted to have it
here because 15 of the time clinicians want to
use a mox club but they want to use the iv and
that's the reason why they're using it is look
i I really want to use this drug, but I need
the IV. Patients can't take oral. So it's wonderful
we have this drug in Canada. Yeah, it's fantastic.
And we have information analysis of how it works
and side effect profiling because of a clear
registry. So I think it helps prescribers. So
moving on to any specific resources, obviously
they have clear registry data and information.
Are there any publications and posters that our
prescribers can review or present locally to
their centers if anyone has any questions? So
we had a poster in Calgary in April at the AMI
meeting. That's the Canadian Infectious Disease
Microbiology meeting. And reviewer and your listeners
can look at that poster. But I also want to throw
out a pitch. You know, if you're not a clear
participant, just send me an email. You know,
Google George Zanell. You'll find my email address.
If you've got a pen and you can write it down,
it's G -G -Z -N -E -L, Z -H -A -N -E -L, at P
-C -S, internet, all one word, dot C -A. You
can just send me an email and you become a clear
participant for free. And it's voluntary. We're
going to be doing a data cut this September,
probably in the first week of September. So in
two through weeks, I'll send out the most current
data of IBMog's cloud. And if you're a CLEAR
participant, hit that link. Let us know how things
work for you when you use the drug. And if you
just joined CLEAR, I will send you all the data
come the middle, late September. So if you're
not a member, join and you'll get the latest
data on IV Amoxicolab. Awesome. Sounds fantastic.
And then in terms of how long we're collecting
this information for IV amoxicillin in the clear
registry, should prescribers continue submitting
the data up to a certain date? Are you planning
on doing some long -term work with this? So thanks
for this. I see each of these new IV antimicrobials
being on the clear registry for about three years.
So as of today, we have intravenous Dalba -Vansin.
intravenous meropenem, they bore back dam, and
also intravenous ceftobiprol, but only if you're
treating endocarditis, of course, along with
IV amoxclav. And I see each of these drugs being
on the clear registry for about three years,
where We send enough data to all the Canadian
clinicians, show enough AMI posters, publish
enough papers so that Canadian clinicians feel
very comfortable with this drug. Where are we
with IV Amoxclav in this cycle? We're about a
year and a half in. I'd like to get a lot more
data. before Christmas of this year, put together
another AMI poster, which will be presented in
St. John's in 2026. Then we'll also put together
a paper and the most common contributors to the
IVM Oxclav site will be invited to be authors
like they are on the AMI poster. So I'm hopeful
that we would continue. gathering data for IV
amoxiclav for at least another year and a half.
But my big goal now is between now and Christmas,
trying to really ramp up lots of data and especially
pediatric data if clinicians are using the drug
in children. Awesome. Sounds fantastic. So we
will all submit our cases and get some more information
on IV amoxiclav. I think it's been in my practice.
I use it all the time and I'm excited to see
what other prescribers are doing across the nation.
So thank you so much for this wealth of information.
Is there anything else that you'd want our listeners
to know about the Clear Registry or about IBM
Ox Club in general? Dr. Rupin, I think just two
thank yous. One to you for this wonderful podcast
series that you put together. And two is for
all the clear participants. Thank you for all
of the individuals across Canada, all the clinicians
who are part of the site. They follow it. And
thank you to the ones who actually click the
links and enter the data so we can all teach
each other. So a couple of thank yous to go around.
Awesome. Thanks so much. We really appreciate
you taking the time to come on the podcast. You've
done several episodes for us and all of them
have had so much listener love and we're super
excited to hear more about this and maybe we
can do an updated episode when you get some more
information in the next year and a half here.
Thank you so much. It's been my pleasure. Thanks.
Thank you, Dr. Zanell, for joining us. Please
see the episode description for Dr. Zanell's
email if you'd like to be included on the Clear
Registry. Be sure to follow us at cabreakpoint
on X if you haven't already, and we'll see you
again soon at the Canadian Breakpoint.