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New Antibiotics for Multi-Drug Resistant Gram-Negative Infections - HHS Medical Grand Rounds — Transcript

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0:01Okay, I should unmute myself before I
0:04speak, which I just did. Uh,
0:08welcome to the uh, Department of
0:10Medicine Grand Rounds. And, uh, thank
0:13you uh, all for joining us uh, this
0:16afternoon. This grand rounds is hosted
0:18by Hamilton Health Sciences today. Um,
0:21for those who don't know me, I'm Kazam.
0:23I'm the physician chief for Hamilton
0:25Health Sciences. And I'm excited today
0:27to introduce uh our speaker Dr. uh
0:31Broady uh Duncan. Dr. Duncan is an
0:34assistant professor in the department of
0:35pathology and molecular medicine and he
0:37is also a member of the department of
0:39medicine.
0:41Broady completed his uh residency uh
0:44training in medical microbiology at
0:46McMaster University and um has been
0:49working as a medical mic microbiologist
0:52and infectious disease specialist uh at
0:54Hamilton Health Sciences since 2023.
0:57Uh he's the lead for pediatric
1:00microbiology
1:01providing support for clinical care
1:03infection control and microbiology
1:06research at McMaster Children Hospital.
1:09uh his research interests also include
1:11using uh biioinformatics
1:14tools uh like whole genome sequencing to
1:16predict antimicrobial resistance and he
1:19is currently completing a master's
1:21degree in the lab of Dr. Andrew
1:23MacArthur.
1:24Broady is keen has keen interest in
1:26medical education and he is currently uh
1:29the program director for medical
1:31microbiology residency program. very
1:34impressive for a young man's broad I'm
1:37uh really excited to hear today about uh
1:40this is a topic which is you know we
1:42facing sometimes you know on medicine
1:43and most of subsp specialists also deal
1:46with it when needed we call you to help
1:49us broad is going to talk to us about
1:51new antim micro antibiotics sorry new
1:54antibiotics for multi-drug resistance
1:56crime negative infections broady without
1:59further ado I will pass it on to you
2:02>> perfect [snorts] uh thank you so much
2:03And thank you again for inviting me to
2:05present today. I'm really excited today
2:07to talk about new antibiotics for
2:09multi-drugresistant gram negative
2:11infections. This is an area which is
2:12really like one of the reasons that I
2:14got into microbiology and infectious
2:16disease because I think it's so
2:17interesting and so important for
2:18patients and uh hopefully today's
2:20presentation is not too uh not too dry
2:23for all of you and we all get to learn a
2:25little something.
2:26So I'll start with the land
2:27acknowledgement. Today we meet on the
2:29traditional territories of the Missaga
2:31and Hodnoson nations and within the
2:33lands protected by the dish with one
2:36agreement.
2:39In terms of our outline for today so
2:41we'll start talking about the rise of
2:42multi-drugresistant gram negatives
2:44specifically talking about carbopen
2:46resistant enoractor alleyis and
2:47multi-drugresistant pseudo. We'll
2:50briefly go over some mechanisms because
2:51I know it's not the most interesting to
2:52everybody although I think it's very
2:54interesting. um mainly so that we can
2:56get into the meat of today's
2:57presentation which is about new
2:58antibiotics and how they work and the
3:01evidence behind using them and we'll
3:03also tie into that resistance to some of
3:05these new antibiotics.
3:09So starting with the changing
3:11epidemiology um this is a slide that I'm
3:14sure we've all seen many variations on
3:15over the years. This is the most recent
3:17uh version that I can find from 2025
3:19where we really are in this antibiotics
3:21arms race where the war between humans
3:24and bacteria just continues to escalate.
3:26On the top side of this timeline, you
3:28can see how humans have done all sorts
3:30of, you know, great science and
3:33pharmaceuticals and marketing and
3:35treating patients and medicine in order
3:37to treat infections with all these
3:40different antibiotics. And on the
3:42bottom, you can see how despite all of
3:44our best efforts, bacteria continually
3:47evolve all these different mechanisms of
3:49resistance. And this is just something
3:50that has continued to date. So today,
3:52we're talking about the stuff that's on
3:54the far right side of the slide. Uh
3:56mainly the stuff on the top and a little
3:58bit some of the stuff on the bottom.
4:01Unfortunately, this is a word where
4:03really we're kind of at a stalemate. I
4:05wouldn't say that we are winning and but
4:07we're doing our best to keep the
4:08bacteria at bay. Um here is a recent
4:11systematic review of uh deaths that are
4:14directly attributable to AMR. So you can
4:16see that in uh 2021
4:20it really is something that is not
4:22distributed equitably across the globe.
4:24Most deaths from AMR right now are
4:26happening in places like subsaharan
4:27Africa, South Asia where there is a lot
4:30of resistance and difficulties with
4:32accessing antibiotics that are needed to
4:34treat that. Luckily, right now in North
4:36America, even though we are starting to
4:38see quite a bit of antimicrobial
4:40resistance, we also do have access to a
4:41lot of these fancy new antibiotics that
4:43allow us to still treat it and prevent
4:45death at least, even if there's still a
4:47lot of mority from it. In 2050, that
4:50might not necessarily be the case
4:52globally. Um, so there's definitely
4:54going to be a shift in where AMR is
4:56across the world. Lots of places are
4:58going to be really heavily affected,
5:00including South Asia, Central and
5:02Eastern Europe, South America. In North
5:04America like Canada, it's not predicted
5:06that things are going to be awful in
5:082050, but certainly rates of death
5:10directly attributable to AMR are
5:11probably going to at least double. Um,
5:14so again, this is a word that we really
5:15have to continue all fighting.
5:20In terms of the deadliest causes of AMR,
5:23specifically in high income countries
5:24like ours, MRSA is right at the top, but
5:27then there's still a lot of gram
5:28negatives. Uh, today I'm going to be
5:30focusing on multi-drugresistant pseudo
5:32and E.coli coli because these are
5:34obviously you know like top five causes
5:36of death from AMR and these are some of
5:38the most rapidly increasing uh causes of
5:41antimicrobial resistance in our
5:43healthcare setting.
5:46So starting with some definitions today
5:49we'll be talking a lot about carbopen
5:50resistant entroacteralis which is CR
5:53specifically we'll also be talking about
5:55carbopenise producing entraacttoralities
5:58or CPE
6:00most CRA in Canada are CPE but it does
6:03require specific testing to actually
6:05label a CR as a CPE so you will see that
6:08in some of the studies we talk about
6:10some of them are about CRE some of about
6:12CPEs but practically they're mostly the
6:14same when we talk about CRES and CPEs,
6:17it's almost always cleella pneumonia and
6:19E.coli. All inrobacttors can pick up
6:23these things like enrobacttor proteella,
6:25but on a global level kleb and ecoli
6:27really are like the two big bad ones.
6:30Although I'll say here in Hamilton, we
6:31do have a decent amount of enoractor
6:32that is um MDR.
6:36We'll also be talking about multi-drug
6:37resistant sudamonusa.
6:39Um here I'll be using multi-drug
6:40resistance kind of as a standin for this
6:43phrase difficult to treat which is where
6:45it's resistant to all routinely
6:46available betalactans and fluoroquin
6:48like taso muro septas and mcphopine
6:51cyproloal um again like different places
6:54use definitions for MDR but this is the
6:56idea of what we'll be talking about
6:58throughout this presentation
7:01I won't be talking about esbl and
7:03enteractalities because even though
7:04they're very important I think all of us
7:07are very familiar with them now that
7:08they are endemic here in Ontario. And I
7:12also won't be talking about carbon
7:13resistant asbactor for the opposite
7:15reason that this is exceedingly rare in
7:17Canada um and especially here in
7:19Hamilton. So just in the interest of
7:21time we'll focus on CR and pseudo.
7:26I'll also briefly introduce the types of
7:28carbopenamases that we see in our
7:29carbopenamase producing entrabacular
7:32specifically KPC NDM and ox48 like these
7:35are the three most common enzymes that
7:38cause CPE and you will see these
7:40specific names coming up again
7:42throughout the presentation there's lots
7:44of other ones but right now
7:45epidemiologically they're not as
7:46important the reason they're not as
7:48important is because all of these can be
7:50transmitted between strains via plasmids
7:52on the right you can see you know
7:54bacteria have all these different
7:55mechanisms that they can transfer
7:56genetic material between each other and
7:59unfortunately KPCNDM and oxo48 like
8:02enzymes have put themselves onto
8:05plasmids that are very widely
8:07transmitted. So the sort of one of those
8:08things where once Pandora's box is
8:10opened and these things started to
8:11transmit horizontally it just has had
8:14this total global spread and arrived
8:16here in Canada.
8:20So specifically about CPE in Canada, CPA
8:23rates have more than doubled in the past
8:25five years in Canada. On the right you
8:26can see a figure of nationwide
8:28surveillance data showing that from 2018
8:31to 2022 the rate of CPEs has more than
8:34doubled and although we don't have
8:36formal reports yet, it does seem that
8:38since then rates have doubled again. Um
8:41which is obviously a big problem that
8:42things are exponentially increasing.
8:45Luckily the overall rate on the
8:47population level remains very low. So on
8:50the bottom you can see the 2025 report
8:52from Public Health Ontario looking at
8:54CPE and you can see that going up until
8:57August we've had 780 cases this year to
9:01date which is you know more than double
9:02of what we normally would have in uh
9:05over the past five years but the overall
9:07rate per million population is only 47.
9:09So again, all of us individually,
9:13we could see this in some of our
9:15patients, but it's not something we
9:16really need to be empirically worried
9:18about very much on a population level.
9:20It still remains mostly an individual
9:22problem.
9:24Part of this is that CPE in Canada are
9:26generally healthcare associated
9:28infections. So again, here is a chart
9:30specifically looking at Canadian acute
9:32care facilities showing that as rates
9:34have doubled, this is almost entirely
9:35because of CPE infections that are being
9:37diagnosed in the hospital. We're not
9:39seeing a lot of people getting sick in
9:41the community with CPEs and then being
9:43diagnosed that way.
9:46This ties into some of the risk factors
9:48for CPE in Canada. So the vast majority
9:51of patients with CPE have a strong
9:53history of recurrent hospitalizations
9:55and chronic illness. Um so these are
9:58patients that are sick that get lots of
10:00antibiotics you know have lots of other
10:02coorbidities where they get pneumonas
10:03and UTI and things like that and then
10:05they acquire CPE. Another major factor
10:08is international travel especially to
10:10South Asia and I think that makes sense
10:12to all of us that you know we don't have
10:14these things endemically in Canada right
10:15now but if you travel to a place where
10:17it is endemic you can get colonized with
10:19it. it becomes part of your normal
10:20flora. Then you come to Canada and then
10:23when you get hospitalized and exposed to
10:24antibiotics, you select for these
10:26multi-drug resistant organisms.
10:28Combining those two, healthcare outside
10:30of Canada is probably the single
10:31strongest risk factor for CPE. Um, but
10:34actually a minority of patients with CPE
10:37have that specific strong risk factor.
10:39Most cases are in older adults and
10:41there's a site male predominance, but
10:42again that probably more reflects the
10:44coorbidities than it does anything
10:45pathophysiologically about these. And
10:48you can see in this uh figure on the
10:50right that looking at Ontario specific
10:53data uh it really does vary depending on
10:56geographic local which probably reflects
10:58underlying demographics. The highest
11:00rates are in this western part of the
11:02GTA probably related to international
11:04travel but in Hamilton area we do have
11:07somewhat uh significant amount of CTE
11:13in terms of outcomes. So this is a
11:16serious condition to be diagnosed with.
11:18The all cause mortality in hospital is
11:20about 15 to 25% for a patient with a CPE
11:23infection. And this has been shown in
11:25multiple studies in multiple contexts in
11:26many different countries. This specific
11:29number is a bit difficult to interpret
11:30because a lot of these patients are very
11:32comorbid, very elderly, maybe they're
11:35dying from different things, but it does
11:37seem that CPE itself probably
11:39significantly increases directly
11:41attributed mortality. Um it's hard to
11:43put a number on it. Some studies are not
11:45significant. Some studies are
11:46significant. Here I have a data from
11:49this study where the figure is below
11:51that suggest that the odds ratio of
11:52death is potentially between two and
11:54five depending on what CTE you're
11:57infected with. And uh specifically NDM,
12:00which we'll talk about a lot later, is
12:02the hardest to treat and has the highest
12:04excess mortality compared to patients
12:06that have more susceptible infections.
12:08So this is very serious
12:13in terms of CPE in Canada. As I
12:15mentioned, CPE has not yet had a major
12:17impact on a population level in Canada.
12:19So here is a national antibiogram
12:21looking at E.coli from 2021 submitted to
12:24this uh to this uh resistance alliance
12:26surveillance mechanism and you can see
12:28that mirrorenm resistance is essentially
12:31not present on a population level. This
12:33is a rounding error, right? So you might
12:35see the occasional patient every once in
12:36a while but this is not our dayto-day
12:38that we're worried about CP.
12:41I'll contrast that with MDR sudamonus.
12:44So MDR sudamonus has had a population
12:46level impact from that same data set
12:49looking at septacadine cyproloxisen
12:52miraen pipaso these susceptibility rates
12:55are awful because this is kind of like a
12:58uniquely selected population. If we look
13:00at our own local antibiotics here in
13:02Hamilton, MDR pseudo is also a local
13:04problem here in Hamilton. It's quite sad
13:07that now there really is no single
13:09empiric antibiotic that is guaranteed to
13:11be effective for patients infected with
13:13sudamon. So on the bottom here um you
13:15can see the line for sudamon serotinosa
13:17for data from 2024 from Hamilton General
13:20Hospital and you can see that for
13:21sepasime pipaso muropenam and
13:24cyproloxisin all of these have
13:26susceptibility rates of less than 90%.
13:30>> [sighs]
13:31>> So this is not good and what are the
13:33mechanisms behind this? So as I already
13:36mentioned for carbopenum resistant
13:38E.coli and cle cell pneumonia it's
13:40almost always because they are
13:41carbopendamase producers where
13:42carbopendamases are betalacttoases where
13:45if you have your carbopenum that wants
13:47to go in and kill the bacteria your
13:49enzyme comes in binds to it destroys the
13:51betalactam ring and now your antibiotic
13:54doesn't do anything.
13:56Most carbopenamases give resistance to
13:58all classes of betalactam except for
14:00some of the novel agents that we'll talk
14:01about. And that's why CRES and CPEs are
14:04so difficult is because we don't just
14:08see that we can't use carbopen anymore.
14:10They're resistant to all betalactams and
14:13usually they picked up resistance to
14:14lots of other classes of antibiotic
14:15along the way too.
14:20Every carbopenise is different. So as I
14:22mentioned KPC, NDM and ox48 like are the
14:25ones that we worry about the most in
14:28terms of differentiating these. They
14:31fall in different molecular classes
14:33where KPC is in class A. You can see
14:35that down here and these are most common
14:37betalacttoes. NDM is class B which are
14:40metallobalacttoases
14:42and ox48 is in class D which is our oxa.
14:45Right now there aren't really any
14:47significant carbopenases that fall in
14:49class. So I don't think that as
14:51internists you need to necessarily
14:52memorize all these different classes but
14:54I do think it is important to know that
14:55KPC NDM and ox48 like enzymes are all
14:59different and in particular these class
15:01B metalloactinases are very tricky um to
15:04treat because their mechanism with this
15:06metallic enzyme is so different
15:13in terms of the epidemiology of these
15:15mechanisms. So the top three CPE in
15:17Canada are KPC and NDM kind of fighting
15:20for first and second place and then
15:22slightly less oxy 48. There is a lot of
15:24variation province to province. So on
15:26the left you can see Ontario specific
15:28data that shows that NDM is numerically
15:30the most common CPE in Ontario. On the
15:33right you can see national data looking
15:35at all of these and you can see that
15:37right now KPC is the most common uh
15:41enzyme. But again, if you go through
15:42different provinces just related to the
15:44different ways that different underlying
15:46patient populations, some places KPC is
15:48more common, some places NDM is more
15:50common, but there is a lot of variation.
15:54One thing that's scary is that we have a
15:56new problem which is co-irculation of
15:58carbopenases. So we'll see not just NDM
16:01but having NDM and oxo or NDM and KPC or
16:04less common enzymes co-irculating like
16:06NDM with vim, KPC within. This is
16:09obviously problematic. Um on the right
16:12is a uh global map from a recent paper
16:16looking at reports of these
16:17co-irculating strains. And you can see
16:19that right now it's primarily in Asia
16:21that they're seeing a lot of these
16:22double caropenases, but we are starting
16:24to see these in North America as well.
16:27And we have actually seen a couple of
16:29these in our laboratory here in
16:30Hamilton. Anecdotally, I'll say most of
16:33those cases that I'm aware of are
16:35directly related to international
16:36travel. But again five or 10 years from
16:38now who knows what will be.
16:44I'll briefly talk about multi drug
16:46resistance sudamonus mechanisms of
16:47resistance because you could spend like
16:48a whole hour just talking about this one
16:50slide. Um essentially sudamonus becomes
16:53resistant to individual betalactams like
16:55carbopenants through many different
16:56mechanisms. So they can acquire these
16:59chromosomally encoded resistance genes
17:01like KPCNDM but they also have all these
17:04other things like hyperproduction of
17:06their intrinsic betalacttoases mutations
17:09of targets down reggulation of porin so
17:11antibiotics can't get in upregulation of
17:14elux pump so once the antibiotic gets in
17:16it just gets pushed right out um so this
17:18is something that is a lot more
17:20complicated with sudamonus compared to
17:22ecoli and klepsiala because there are so
17:24many different mechanisms that could be
17:26involved
17:30in terms of in Canada what we see with
17:33pseudo. So this data from a Canadian
17:35surveillance study from very recently
17:38shows that the main drivers of multid
17:39resistance pseudo in Canada are
17:41mutations in foreign genes, mutations in
17:43chromosomal betalacttoesis and
17:45overexpression of chromosomeal
17:46betalacttoases. So this is really
17:49important that most of these are
17:50happening on individual levels to
17:52patients that are being exposed to lots
17:53of antibiotics. It's not like there's
17:55horizontal transmission of super
17:57resistant pseudomones. In this study,
18:00they found it was quite uncommon to have
18:01outbreaks of MDR pseudo strains. And you
18:03can see that here on the right where
18:05just a minority of the pseudos that they
18:07were looking at fell into specific
18:09outbreak clades. And it's actually
18:11extremely rare in Canada to have
18:12transmitted carbopenases. Less than 1%
18:15of pseudo in Canada have carbopenases.
18:18None of them in this study had KPC or
18:20NDM. It's important to know that that's
18:23just luck that Canada is like that. In
18:25other countries, they actually do have
18:27major problems with KBC and NDM
18:29students, but luckily has not hit our
18:31shores yet.
18:35So, that's all of the wonky microbiology
18:37stuff. Now, I'll move into some more
18:39clinically relevant stuff talking about
18:41new antibiotics.
18:44So most new effective antibiotics are
18:47combination betalactam betalacttoise
18:50inhibitors. Um so just as a reminder
18:52that why we talk about betalacttoase
18:54inhibitors so much is that carbopenases
18:57what they do in the bacteria is you have
19:00the carbopenise it cleaves your
19:02betalactto antibiotic so then it can't
19:04do anything and then your bacteria is
19:06nice and healthy and able to cause nasty
19:08infections. However, if you put in this
19:11betalacttoase inhibitor, it will inhibit
19:14the carbopenamise and then your
19:15betalactam can still go do its thing and
19:17then hopefully kill the bacteria and
19:19treat the patient and save their life.
19:22So that's why betalacttoase inhibitors
19:24work in vitro and in vivo they do seem
19:26to work quite well too.
19:29So we know that traditional blis like a
19:33Moxclav pipaso amps back don't really
19:35work on these KPC NDM ox48 broad
19:38carbopenamases but we have all these new
19:41novel BLBLIS that can be effective for
19:45specific carbopenases. We still don't
19:47have an antibiotic that treats every
19:49single one of these but we have a bunch
19:52of these new tools and this is what I'll
19:54be going into more detail on now.
19:58Starting with septasine abactam. So
20:00septazi is a combination betalactam
20:02betalactinase inhibitor. Septazzine we
20:05all know is a thirdgen sephosporin. It
20:07has good activity to enteract and
20:09sudamonus and for other GMBB2. It's not
20:12great for GPCs and anorobes but for our
20:13gram negatives it gets the job done for
20:15sure. Abibactam is a novel reversible
20:19non-balact based BLI that inhibits class
20:23A and D betalacttoes importantly
20:26including KPC and ox48 m like it does
20:28not have any activity on NDMs. So this
20:31is where if you had a patient with EC
20:32coli that had KPC, Septes Aavi should
20:36work on it in theory, right? Um while if
20:39you had a pseudo with NDM, you would not
20:41expect this to work.
20:44In terms of the clinical evidence that
20:46this actually does help patients, we
20:49have two big big enough studies. Uh so
20:52reprise was published in 2016. It was an
20:54RCT of septaz avi with or without
20:56metronizol versus the best available
20:58therapy to treat UTI and intraabdominal
21:00infections. The included population was
21:03septaz resistant and anorobactralis and
21:05pseudo. So not necessarily these
21:07carbopenum like super
21:08multi-drugresistant ones but kind of
21:10halfresistant ones and so best available
21:13therapy was often muropenum and they did
21:15not do any formal statistics but they
21:17did not see a significant difference in
21:19test of cure when they were just
21:20descriptively describing the outcomes
21:22between septazi and murupen
21:27if we look at reprove a 2018 study this
21:30was a non-inferiority RCT of septazavi
21:32versus muripen specifically for
21:34hospitalacquired pneumonia
21:36big study. This included mostly
21:38susceptible enroact
21:42um and this did have a non-inferior
21:45result for clinical cure. I'll say it's
21:46a little bit funny that they chose a uh
21:49non-inferiority margin of 12.5% instead
21:51of 10 but good thing they did that
21:54because it almost went to you know above
21:5710 but anyways this is the final result
22:00from that. So on the basis of these two
22:02studies, the brand AviAZ was FDA
22:05approved in 2015 for these indications
22:08just based off of this evidence that
22:10like it clearly seems to work in
22:12patients that have these serious
22:13infections. Um it's not Health Canada
22:16approved. So we can only access it via
22:17SAT here.
22:20However, this is not evidence that this
22:21necessarily helps patients that do have
22:23these super drugresistant bacteria.
22:26Luckily, since then, we have gotten more
22:28of that clinical evidence. So here I
22:29have uh two systematic reviews. The
22:31first one published in 2022 was a
22:33systematic review of septaz avi versus
22:35best available therapy for CPE. Best
22:37available therapy at that time is often
22:39kistan and ticy because right we're not
22:41really going to be using carbopen to
22:43treat our cpes. This systematic review
22:46did find significantly better mortality
22:49and clinical cure when using septazi and
22:52lower nephrotoxis.
22:54The second review from Yang 2023
22:57similarly found that comparing Septazavi
22:59versus Kaliston for CPE had
23:00significantly better mortality, much
23:03better treatment success and lower
23:04nephrotoxicity with this novel agent.
23:07Notably, this study explicitly talked
23:09about how often these arms included
23:13combination therapy with all sorts of
23:15things like ticycanidones
23:17etc. And it didn't seem like combination
23:19or not really had a big impact. Just the
23:22fact you're using septazi at all led to
23:24better outcomes for these patients with
23:26CP.
23:29So that's septazi. Moving on to miro
23:32vapor. So mopen voractam is a
23:34combination of mirropenum which I think
23:35we all know and love unfortunately these
23:38days. Treats lots of gram negatives
23:40pretty okay for gram positives pretty
23:41good for anorobes. Vorbactam is another
23:44novel bli that has bonic acid in it.
23:47This one inhibits class A and C
23:49betalacttoases including KPC but does
23:52not treat oxa or endia.
23:56Clinical evidence for efficacy is
23:58supported by these two RCPs tango one
24:00and tango 2. The first was a large study
24:02of patients with UTI that was generally
24:05quite susceptible. There was almost no
24:06CR in the study and they found that
24:08murovore was non-inferior to pipaso for
24:12clinical cure of UTI. Tango 2 was a
24:16study specifically looking at serious
24:18carbopenum resistant antacteralis
24:21infections. This was a smaller study
24:22with only 77 patients and the comparison
24:25here was again trying to use
24:27combinations of everything available at
24:30the time. One patient actually did get
24:31septazim monotherapy in the best
24:33available therapy. Um and overall they
24:36still found that their interpretation is
24:38neuropenactum had superior cure rates
24:41with a 32% difference and a trend
24:43towards lower mortality and le less
24:45nephrotoxicity although I don't think
24:46this is actually technically like a
24:48prespecified uh hypothesis testing to
24:51look for superiority but evidence looks
24:53pretty good in this RCP anyways so on
24:56the basis of this vomir which is the
24:58brand name for miro vore was FDA
25:00approved in 2017 and actually hot off
25:02the presses although I guess It's a year
25:04old now. Health Canada has approved
25:07neuropen vibroactam in Canada
25:09specifically with the indication of
25:10infections by carbopenum resistant.
25:16Moving on to amipenabactam. So
25:18imipenabact is a combination of
25:20immipenum which is a carbopenum that we
25:22don't use a lot here in Hamilton but is
25:24a good one. It treats grand negatives
25:26quite well except for bizarre reasons.
25:29It does not work very well in this MPP
25:30group proteus provenency morella. It's
25:33pretty good for grandposits including
25:34enterus which is kind of nice to have as
25:36an option and it's pretty good for
25:37animals. Reabactam is another one of
25:40these novel reversible non-balactin
25:42blis. It only inhibits class A and C
25:45including KPCs. Sometimes in vitro it
25:48works on class D but I would not say
25:49it's reliable for oxes and it definitely
25:51does not work on any
25:54the clinical evidence is based off of
25:57restore ME1 and restore ME2. Restore ME1
26:00was this very small RCT with 31 patients
26:03comparing imipen reabactim versus kiston
26:06with meipenum for imenum resistant
26:09pseudo and enerobactor outs. This was
26:12too small of a study for them to have
26:13any preplanned statistics but
26:15numerically it looked like there was a
26:17better clinical response mortality in
26:19ephrotoxis.
26:21Restore ME2 is a much larger trial of
26:24MELI versus pipaso for pneumonia but
26:27this was not in a super resistant
26:29subset. It was primarily regular old
26:32pseudo and clesella and here they did
26:34find again non-inferior mortality. I
26:37think this is actually in favor of
26:38imenelabactam with this confidence
26:40interval. So it seems to work and on the
26:44basis of this recarbrio the brand name
26:46for me panamelabactin was FDA approved
26:48in 2019 for patients with limited
26:50treatment options but this is actually
26:51quite controversial because that was
26:53made just based off of restore ME1 and
26:56then after restore ME2 the FDA added the
26:58indication of pneumonia with this study
27:01showing that like it really seems to be
27:03non-inferior to our other commonly
27:05antibiotics.
27:06Recarbio is also not Health Canada
27:08approved. So if you need it, you access
27:10it through the special access program.
27:13Just for a minute talking about the
27:15controversy here because I think this is
27:16interesting. Um did the FDA break its
27:19own rules in approving the antibiotic
27:20recar? So in the package insert it says
27:23that for this antibiotic approval of the
27:26UTI and introdal infection indications
27:28is based on limited clinical safety and
27:30efficacy data for recarrio which is
27:32based off of that in Really one trial.
27:34So, you know, I'm not an expert in uh
27:37how drugs get approved and things like
27:39that, but essentially, I just think it's
27:40very interesting that obviously as we're
27:42in this antibiotic arms race, it is very
27:44important for us to have access to the
27:46tools that we need um as quickly as
27:48possible because patients certainly do
27:50die without them. But, uh I think it's
27:52it is an interesting point that this is
27:55an antibiotic that really did not have
27:57the robust clinical trial data to
27:59support approval the way that these
28:02antibiotics normally do. And there's a
28:04question of if the FDA might have
28:05skirted around some of its uh typical
28:08decision-making policies in giving
28:10approval for this antibiotic. So that's
28:13all I'll say on it. I think just
28:14something in this political environment
28:15for us all to think about is that FDA
28:17decisions are not necessarily always the
28:19decisions that other countries are going
28:21to make when it comes to looking at
28:22antibiotics.
28:26Okay, so I talked about these three
28:28novel BLBLIS. How do we pick one?
28:33There is some clinical data to inform
28:37this decision. Here's one example of a
28:39particular study from a in 2019 which
28:41was a retrospective cohort of septes
28:43versus neurovvore specifically for
28:45carbopen resistant enteractis and they
28:48did not find any significant difference
28:49in mortality clinical success or adverse
28:51events. There are no direct prospective
28:55trials comparing any of these BLBLIS,
28:58but there are multiple other smaller
28:59studies that all seem to have similar
29:02findings of they're all pretty okay.
29:05In terms of in vitro data, we do have
29:07multiple studies that show that there is
29:08occasionally resistance to septazavi
29:10developing although it is still very
29:12uncommon while resistance is more rare
29:14for me and vibroactton and then imire is
29:17not used as often and there's not as
29:20much data kind of commenting on that.
29:23And in terms of access, as I said, vomir
29:25is now Health Canada approved. It's not
29:27unformulated to HHS, but it certainly
29:29has less paperwork for us to do in order
29:32to prescribe this antibiotic. And the
29:34other ones are only available through
29:35SAP.
29:38So in terms of treatment decisions, what
29:40I would recommend and this is in line
29:42with the IDSA 2024 guidance is that for
29:44KPCs we really can pick any of them but
29:47I probably would lean towards mirror pen
29:49and vapor back first just because it is
29:51more easily accessible now and there are
29:53rare reports of resistance. Sephres is
29:56also a perfectly good option and I would
29:58have no hesitation going to that if
29:59that's the one I could get my hands on.
30:01It is definitely the most wellstudied
30:03has the strongest clinical evidence
30:05efficacy although there are slightly
30:07higher reports of resistance compared to
30:09neuro vapor when you look at the primary
30:11literature and then imipenella dam for
30:15me would probably be my third choice
30:16just because there's less clinical
30:17evidence of efficacy but again if this
30:19was the only one I had access to I would
30:21have no hesitation to use this to treat
30:23um a KPC
30:26when it comes to oxa48 like only septas
30:28avy has efficacy for this class decarb
30:31enemies. So that is the one I would pick
30:32every time for NDM. None of these seem
30:36to work. So we'll talk about that more
30:38in a few minutes.
30:40And if you have a CR that you do your
30:43special testing on it actually turns out
30:44not to be a CPE. That's where if it's
30:47still miros susceptible, you could
30:49certainly use mirror penum. Um but other
30:52than that like any of these three agents
30:54should be perfectly acceptable to treat
30:55a caropen resistant antibacterial that
30:58is through other sorts of mechanisms.
31:03So now let's talk about these NDMs. Do
31:06we have any antibiotics that can treat
31:08these? I would say 5 years ago the
31:10answer would have been no. What an awful
31:12situation. Now we are starting to get
31:15some tools. So astractam
31:17is a combination of asrianam which is a
31:19monoactam and aviactam which we've
31:21already talked about as part as test
31:23avi. So astrianam is notable because
31:26it's a monoactam slightly different from
31:28other betalactams. It treats gram
31:30negatives but they're almost always
31:32resistant which is why all of us on this
31:33call have probably never described asm.
31:36Um however one thing that's notable is
31:38that as trienm is unaffected by class B
31:41metal betalacttoises just the way that
31:43the structure of the molecule is these
31:45NDMs cannot cleave it.
31:48So if you take estrianam and you combine
31:51it with avibactam the theory is that
31:53this monobactam
31:55would be able to treat entropius and
31:57sudamonus at baseline but they can't
32:00because there's so much other
32:01betalacttoases but then if you add in
32:03the aviactam this takes care of all of
32:05those. So between the two of them, we're
32:08covering our class A, we're covering our
32:09class C, we're covering our class D and
32:12class B doesn't work at all in Astrianm.
32:14So in theory, it should work. Does it
32:17work in practice? Luckily, yes. So our
32:20two pieces of evidence both of these
32:22published this year we have assemble
32:24which was a small very small RCT looking
32:27at specifically metallobalacttoise G&D
32:30infection mostly enterbacks like equal
32:32and cle a couple of pseudo and steno too
32:35small to do statistics but it really did
32:37look like better mortality 8% versus 3%
32:40and clinical cure where again just to
32:42emphasize for me five years ago the best
32:44available therapy would not work. You
32:46can see the clinical cure rate for best
32:48available therapy was 0% in the study
32:50which matches up with I think a lot of
32:52our clinical experience.
32:54Revisit was a larger RCT not
32:57specifically looking at resistant
32:59organisms. So it was much larger 422
33:02comparing asam abactam with muripenum
33:05plus minus kiston. It was mostly E.coli
33:08infections of which a decent proportion
33:10were carbopen producing. Not very much
33:12pseudo on this. They did not do formal
33:15uh prespecified non-inferiority testing,
33:17but the clinical cure difference was
33:19very similar with only a 2.7%
33:20difference. Mortality is quite low in
33:22both of these arms, which again I think
33:24emphasizes that these were not MBL's for
33:27the most part. It was mostly just kind
33:28of regular intraabdominal infections in
33:30the so on the basis of this year and
33:34Blavio which is an awful name uh is now
33:36FDA approved for intraabdominal
33:38infection if there are limited or no
33:40other treatment options. Right now this
33:42is not accessible in Canada period. I
33:44actually don't know if Emblavio is
33:45really like properly for sale in the USA
33:47yet. Um so maybe this will become
33:49accessible in Canada in the future but
33:51right now I do not have any mechanism to
33:53get my hands on this.
33:56But there's this very funny thing which
33:58is actually explicitly recommended in
33:59the IDSA guidelines that even though we
34:02don't have access you can replace it
34:04with a dual infusion of septazavi and
34:06astrianame where again the theory is
34:09that if you put the septazavi in one
34:11port and the astrianame in the other
34:13once they're in the patient's blood
34:15you've kind of got asam aviactam along
34:18with the septazadine floating around in
34:19there and this should work just as well
34:22as if it had been like a real proper uh
34:25compounded antibiotic. Um, so this is
34:27obviously not FDA approved. Um, but in
34:31the limited clinical studies that use
34:33this, it really seems to work. Um, so
34:36again, like we know that as a backdam
34:38should work. So there's no reason to
34:40think that this would act differently.
34:46Moving on to sephidol. So sephidol is
34:49another option that we have for MBLs
34:51because it has this novel Trojan horse
34:54mechanism. So it's called a Trojan horse
34:55because sephidaracol is a cederaphor
34:57that binds to iron and you can see that
35:00this combination of iron with a
35:02sephiderol
35:03the bacteria says hey I love iron I'm
35:06going to bring this in so I can use it
35:08and it gets transported directly into
35:11the cell right to the inner membrane
35:13where then sephidacol can say aha I've
35:16tricked you into bringing me in and I'm
35:17going to kill you now uh this is notable
35:20because again in theory by going through
35:23this iron transport system the
35:25antibiotic avoids the betalacttoases and
35:28ellex pumps and poor mutations that
35:30normally would prevent it from working.
35:32So even if the bacteria has NDM the
35:35sephiderol just gets pulled right past
35:37it and then can uh kill the bacteria. So
35:42in vitro this certainly works and
35:45mechanistically it's super interesting
35:47and you know I think a lot of us were
35:49hoping that this would really be like
35:50our savior for all of these awful source
35:52of infections
35:55the clinical evidence for sephidol.
35:58So if we start with credible CR which is
36:00a 2021 study of uh sepheracol versus
36:03best available therapy for carbopen
36:05resistant G&Bs which was mostly
36:07asintoidal factor but also significant
36:09amount of cleb and pseudo.
36:12The best available therapy for these was
36:14generally kaliston based and there was
36:17actually numerically higher mortality
36:18with sephidacol which is mainly due to
36:21patients with acne having really bad op
36:23outcomes. Even in the klepsiala and
36:26pseudo smaller subsets um there was not
36:30a obvious clinical benefit to sephidol
36:33over the best available therapy.
36:36Game changer is an RCT that came out
36:39this year again looking at sepharol
36:40versus best available therapy usually
36:42kiston based. This included a larger
36:45proportion that were carbopenise
36:46resistant mostly antibacter alleys and
36:48this one did find a non-inferior
36:50mortality overall but if they looked at
36:54a subset which again like statistically
36:56interpret as you will but there was a
36:58higher mortality for sephidarol for
37:00carbopen resistant uh organisms.
37:04So this is very interesting in that it's
37:06important for us to distinguish that
37:08this clinical evidence is very different
37:10than the clinical evidence we had for
37:12our other things like sepami and muro
37:15vapor those other ones like it seems
37:18relatively clear that they improve
37:21outcomes compared to these awful
37:22antibiotics like kalistin and ticycline
37:25and stuff that I'm not confident really
37:26works all that well the evidence for
37:29sephidol seems to suggest that sephidol
37:32is noninferior to all of these awful
37:35things. So that's just something for us
37:37all to think about is that sephidol is
37:39not necessarily better than kaliston.
37:44In terms of access on the basis of this
37:46and lots of other kind of uh various
37:49trials in various settings, fatroia
37:51which is named after the iron trojan
37:53horse is approved in the USA. It is not
37:56health Canada approved. You can only
37:58access it through.
38:01So with that evidence in mind if we're
38:03treating CR that is NDM and it's a
38:06serious infection our first line
38:07treatment options would be estranam
38:09abactam but it is not accessible. So
38:11instead we have septazavi estrianam and
38:13sephidacol where septazavi estrianam is
38:16this weird dual infusion so very limited
38:18clinical data for it specifically and we
38:20can't do susceptibility testing but in
38:23theory it should work and ideally be
38:25better than standard of care right now.
38:27Sephiderol on the other hand like in
38:30vitro works a lot uh you know has a very
38:33clear mechanism is FDA approved but the
38:36clinical data is still kind of limited
38:38and it's not clear if it's superior to
38:40kalista so again these are difficult
38:43things to think about I'd say
38:44anecdotally most of my colleagues would
38:47probably choose sephasg&m over septicol
38:50but there's really not strong evidence
38:52to push you one way or another
38:56what about non-balactin options or this
38:58best available therapy. So I'll just
39:00very briefly in one minute go through
39:02like why not use things that aren't
39:04betalactives and uh sometimes you can.
39:06So for example fluquinones and usually
39:09they're resistant just because the genes
39:10are on the same plasmids but if you are
39:12lucky and you get one that is
39:14susceptible sure use it. I think that's
39:16great. Aminoides have significant
39:19toxicities which I think we all know. So
39:21what guidelines would say and what I
39:23would agree with in practice is that if
39:24you need to use a short course for
39:26example to treat a UTI where it
39:28concentrates really well I think that's
39:29an acceptable option. I generally would
39:32not turn to this for other serious CR
39:34infections.
39:36Toscycline is often susceptible in vitro
39:38but it really does not have good
39:40clinical efficacy for serious
39:41infections. So I would only consider
39:43this I really know other options and I
39:45would go to SAP for these other things
39:47before I would use ticycan as first line
39:49therapy. Kaliston is awful. I won't say
39:52anything more about this. It doesn't
39:53even have a susceptible breakpoint
39:55anymore because of what an awful
39:56antibiotic is. So, I wouldn't use that.
39:58And then IV phosphomy really does not
40:01have evidence of efficacy as
40:02monotherapy. And even as combination
40:03therapy, I'm not convinced that it's
40:05doing a whole lot. So, it's something
40:06you can keep in your pocket, but is not
40:08dependable to treat.
40:12So, that's treatment of CR. I will very
40:15quickly talk about MDR pseudo.
40:17So the big thing for NDR pseudo
40:19septtolazine tasobactam I think a lot of
40:22us have seen this in action in the past
40:235 years so I'm not going to spend a lot
40:25of time on this septtolazine is doing
40:27the heavy lifting here where it's a
40:29novel sephilis that has very high
40:30affinity for sudamis targets so most mdr
40:33pseudo are still susceptible to
40:35septtolazine and then tasobactam is you
40:37know to add on some of this uh helpful
40:39inhibition of other activities I won't
40:42go through the evidence for this in the
40:44interest of time but again like it does
40:46seem to work for serious infections in
40:48many different uh body sites. So if
40:51we're trying to treat MDR pseudo we have
40:54four options. We have septtolaso
40:58septazavi inelli and then maybe
41:01sephidacol
41:03does something notably I would not use
41:05mir pen and vorback dam because voractam
41:08actually doesn't do a whole lot for
41:09pseudo um so if it's mirror resistant
41:11it's probably this is not going to work
41:12either and similarly as treemakdam
41:15really doesn't do a whole lot compared
41:17to septas avi because these mls is not
41:20really something we're seeing a lot soon
41:22but one thing that's important when
41:24choosing is that it really needs to be
41:25based on resistance patterns and this
41:27brings us into the last thing we'll talk
41:29about which is resistance to these new
41:30antibiotics.
41:32So if we talk about pseudo um this is
41:35Canadian specific data from relatively
41:37recently showing that in this study
41:40which is like you know more resistant uh
41:42isolates than we normally have septalas
41:45susceptibility 78% septaz avi 60% inelli
41:4863% and then muro vabbor uh was 39% or
41:53lower if we looked at this study which
41:55specifically includes sephidol you can
41:57see here that in vitro 98% susceptible
42:01which significantly higher than any of
42:03our newer uh betalactase inhibitors that
42:06I like so much.
42:09And here we can see uh two studies that
42:12I won't go through in detail, but they
42:14were both observational trials comparing
42:16patients getting sephalasone and
42:17septazavi where both of them seem to do
42:20pretty decently, but there was
42:21significant emergence of resistance
42:22after treatment. So for example in this
42:24study 38% and 25% with septalas and
42:27septazi if they got a recurrent
42:29infection the recurrent infection was
42:31resistant to the first one that they
42:33got.
42:35So on the basis of this
42:38this is where there really is still no
42:40single antibiotic that you can always
42:42turn to for multi-dug assistant pseudo.
42:45My recommendation would be to repeat
42:46susceptibility testing every time you
42:48were considering one of these agents.
42:50And on the basis of that study showing
42:52those multiple studies showing that uh
42:55you do develop resistance relatively
42:57quickly after getting treated with one
42:58of these, I would avoid using the same
43:01agent empirically for a serious
43:02recurrent infection. If it's something
43:04where like sepsis where you need to get
43:06treatment active within a day or two, I
43:08would not repeat test repeat treatment
43:11based off of old susceptibility results.
43:15And then sephida call is problematic
43:16because again in vitro super susceptible
43:18the most susceptible of all of these but
43:20does it work as well? A bit hard to say.
43:25Finally resistance in CPE. So uh tying
43:29back to the first slide about how we're
43:31in the antibiotic arms race. So
43:33septazavi was FDA approved February
43:362015.
43:37The first reports of sethazi resistance
43:40was May 2015. So it has only take a
43:43couple of months for us to find uh high
43:46resistance to these novel agents which
43:49is very scary.
43:52There's now hundreds of case reports of
43:53KPC variants around the world. All sorts
43:55of different ways this particular enzyme
43:57can mutate and all of these give septas
43:59resistance. So again on a population
44:01level this is exceedingly rare but is
44:03something we are seeing more of in the
44:05past few years and 10 years from now who
44:07knows how reliable septazi is going to
44:09be empirically.
44:13Even scarier is that we do see
44:14co-resistance between some of these
44:16newer antibiotics. For example, there's
44:18been quite a few reports of
44:19co-resistance to septazavi and
44:20sepheracol where you have a patient with
44:22KPC, you treat them with septazavi and
44:24then the next time they get sick, it's
44:26resistant to both septazavi and
44:28sephidacol just because of the specific
44:30mutations in that enzyme. So proceed
44:32with caution.
44:36The last thing I'll say is we have all
44:38of these even newer antibiotics come
44:40coming down the pipeline like Tanny
44:41Borbactam. Tannibactam is very exciting
44:43because this is the first BLI that
44:45itself is directly active against class
44:47B metallobalacttoases and it's got
44:49buronic acid inside of it. Tanny
44:52Borbackdam actually does have a big RCT
44:55published in NGM in 2024 that shows that
44:57it seems to work and that was in 2024
45:02and a whole year earlier as they were
45:04doing pre-clinical studies they had
45:06already found an NDM that had mutated to
45:09become resistant to tanning back. So
45:11this is an antibiotic that isn't even
45:13available yet and we already have
45:15bacteria showing that they can become
45:17resistant to it. Um, so this is
45:19obviously very scary stuff but exciting
45:22for us to keep an eye on over the next
45:24few years.
45:26So that's the end of my presentation.
45:28Our take-home points are carbopene
45:30producing entacles and MDR pseudo are on
45:33the rise in Canada and difficult to
45:34treat and to me like as a infectious
45:37disease uh physician really some of the
45:39scariest most difficult sorts of
45:40infections that we deal with. The new
45:43standard of care is to treat with these
45:45novel BLBLIS, which I've put in the box
45:47on the right. You should always check
45:49for susceptibility and resistance
45:51mechanisms if you're treating one of
45:52these super MDRs. These novel agents are
45:55often not approved in Canada, but still
45:58can be accessed for individual patients.
45:59And so you really should consult
46:01infectious disease for difficult to
46:03treat serious infections which actually
46:05now is like a formal hospital policy
46:07that if we find CPE you really should
46:10consult infectious disease. And finally
46:13the callol is an option but to me the
46:16efficacy is unclear. I would say I would
46:18use it only when you must. I don't think
46:20that this is the magic bullet to to fix
46:22this problem but is certainly something
46:24we need to keep available in our
46:26armamentarium.
46:27And finally, if you want more details
46:30on, you know, specific guidelines and
46:31stuff, this IDSA 2024 guidance on the
46:34treatment of resistant gram negative
46:35infections is very good. I think that
46:37they go through the evidence quite well.
46:38I think that my clinical and
46:40microbiology experience matches up a lot
46:42with what that guideline has to say. Um,
46:44so that's a great reference for
46:45everybody.
46:47And that is my presentation. So, thank
46:48you again for uh taking the time to
46:51listen to me today. And I'm happy to
46:52take any questions.
46:55>> Amazing. Thank you. Thank you so much
46:57Rodie for taking us uh through this and
46:59I absolutely hear the excitement uh
47:02about all these new drugs from your end.
47:05Uh if you have any question please uh
47:07raise your hand to bring you in to ask
47:09your question or you can write it in the
47:11Q&A section or if you want to chat in
47:14the chat as well that works. I have Dr.
47:17Hullbrook uh which I am got lit and uh
47:23and I think
47:26>> I am thanks very much that was really
47:29interesting Broing and very troubling
47:31actually as somebody who's a real
47:32veteran of uh you know therapeutics. I
47:35have a a quick comment and a couple of
47:36questions for you regarding the
47:38regulatory aspect and it being odd that
47:40the FDA would put something on the
47:42market with limited evidence in in
47:44Canada. We have an additional concept
47:47around allowing something on the market
47:49called notice of compliance with
47:50conditions. So if you see that applied
47:52to a medication, it means that there's a
47:54high high need, but the evidence isn't
47:57really all there and the company's
47:59expected to produce more data. So I
48:01suspect FDA just doesn't have that
48:03aspect, but it is a kind of a nice part
48:05of Health Canada. Um, my questions are
48:08twofold. One is adverse effects.
48:12Do you find the adverse effects of these
48:14agents any worse, excuse me, than their
48:17anchor drugs? So, you know,
48:19sephilisborns, allergy, neurotoxicity,
48:22etc. Is there anything worse about the
48:24new drugs? Um, and then the second part
48:27is I take every opportunity I can for
48:30our infectious disease colleagues uh to
48:32rant a bit about our infection control
48:34practices.
48:36What is the evidence, you know,
48:37particularly because these are so
48:39important. Have we learned anything with
48:41these resistant organism? You talked
48:43about some of them not being it doesn't
48:45sound like direct patient to patient
48:47spread. Um, in terms of these organisms,
48:50do we need to be doing anything
48:52differently around our infection
48:54control, gowning, gloving, you know,
48:55etc., etc. Those two questions if you
48:58wouldn't mind.
48:59>> Yeah, thank you so much. Those are both
49:01great questions, things I would have put
49:02into this talk if I had more time. So
49:04good. I get to talk about them now. So
49:06in terms of your first question about
49:08adverse effects, so luckily in basically
49:11all of the clinical trials, there is
49:12really not any signal to higher
49:14toxicities or specifically concerning
49:17adverse effects with most of these
49:19antimicrobials. Um the even though these
49:23novel betalactinase inhibitors are not
49:25structurally similar to other things we
49:27have like clabulin and tasobactam it
49:29doesn't seem that they have their own
49:33specific toxicities in humans beyond
49:36what we have from the primary betalactin
49:38itself. Um so for example that's where
49:41as you mentioned like neurotoxicity
49:43these are things that we do see in
49:45trials that seem to be associated with
49:47these antibiotics but they are not worse
49:49than the traditional comparators. Um so
49:54I really have no hesitation with using
49:56any of these. I do think because they
49:58are still relatively new, it is
50:00important that we should be monitoring
50:01for toxicities, especially because a lot
50:03of these are going to be used in our
50:05very sick, you know, ICU level patients
50:07where they're more vulnerable to having
50:08adverse effects. For example, sephidaol,
50:11it's not super hpattoxic, but monitoring
50:14liver enzymes is something important to
50:15do. Um but in general I really don't
50:17have any significant toxicity concerns
50:19and certainly treating sepsis
50:21appropriately is going to be much better
50:23for all of their organs than whatever
50:25small risk we have from these
50:26antibiotics.
50:28So that's a great question. In terms of
50:30the second question on infection
50:31control, I really wanted to talk about
50:32this but thought it might be a little
50:33too uh not not interesting for people.
50:36So these bacteria actually do spread
50:38directly personto person. um
50:42they are similar to ESBLs and uh you
50:47know like a lot MRSA and stuff like that
50:50where it's almost entirely through
50:51direct contact especially close contact.
50:54So we do see for example family members
50:57that where the whole family just you
50:58know because they're all so close
51:00sharing you know clothes and materials
51:01and stuff like that do become infected.
51:03Motherto child transmission as well
51:05where if mothers colonized the child can
51:07pick it up as well. Um in hospital we do
51:10know that these do spread person to
51:12person. The mechanism of spread is
51:14almost always through health care worker
51:17fulommites and touching and hands and
51:19stuff like that. So contact precautions
51:21with gowns, gloves, regular handashing
51:24should be effective at cutting off
51:26transmission. And uh something that
51:29again I think that because MRSA and ESBL
51:31are so common in our community now, a
51:33lot of us like don't pay attention to
51:35contact precautions as much as we
51:36should. But for CPEs and MDR pseudo, it
51:39really is important. In fact, uh there's
51:41actually been very recent changes at our
51:43hospital system that we are actually no
51:45longer screening for ESBL as routinely
51:47as we used to do, but we are starting to
51:49screen quite routinely for CPEs. And
51:52that's because now we do know in
51:54Ontario, even patients without
51:56international travel do pick up CPE,
51:58whether it's from other healthcare
52:00institutions or from their friends and
52:01family. So we are quite routinely
52:03screening for CPE now. If we find PPE,
52:06that patient needs to go in contact
52:07precautions. And it's all of our
52:09responsibility to make sure that us, our
52:11learners, our other health care
52:12professionals are respecting those
52:14contact precautions.
52:18>> Good uh good points and and back to the
52:21idea of of of surveillance. I I've
52:24noticed that actually now the MRS say
52:26the SPL and the CP results you know
52:29coming from these uh swaps you know so I
52:32think more and more uh uh you know have
52:36to be more careful with this is pretty
52:38scary to be honest uh in terms of uh for
52:41patients and in terms of how this is uh
52:43spreading and increasing but also to be
52:45honest from I look at it from a human uh
52:47resources as well uh means you know we
52:50want more of you uh infectious disease
52:52dogs you because I don't think that
52:54generalists will ever be able to manage
52:56those things uh with this complexity uh
52:58in the compass 7x
53:00uh fantastic I don't see any uh other uh
53:05questions coming in unless I'm missing
53:07anything double check all right I think
53:10you've covered it uh very well it's uh
53:13was pretty in-depth I love the evidence
53:15around it I love the microbiology around
53:17it around it and uh thank you very much
53:20for your time I think we're going to
53:21give people a few minutes uh back. Thank
53:25you.
53:25>> Great.
53:26>> Thank you so much.
53:27>> And thank you everyone for attending. I
53:29will Oh, there's something in the chat.
53:31>> Maybe they just uh did I miss something
53:32in the chat?
53:34>> Uh antibiotic stewardship, you know, I
53:37think that's a comment coming in. I
53:39think yeah, Dr. Darami and I we all
53:42agree with that. Absolutely. Uh well,
53:46next week it's going to be uh St. Joe's
53:49grand round. So, we'll see you all uh
53:51then and uh I'll see you around. Thank
53:53you, Dr. Duncan again and uh have a
53:55great uh uh rest of the day, everyone.

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