Artwork for podcast Febrile
108: StAR: MDR GN
Episode 10812th August 2024 • Febrile • Sara Dong
00:00:00 00:45:24

Share Episode

Shownotes

This StAR episode features the CID State-of-the-Art Review on ##.

Our guest stars this episode are:

Arsheena Yassin (Robert Wood Johnson University Hospital)

Mariya Huralska (Robert Wood Johnson University Hospital)


Journal article link: Yassin A, Huralska M, Pogue JM, Dixit D, Sawyer RG, Kaye KS. State of the Management of Infections Caused by Multidrug-Resistant Gram-Negative Organisms. Clin Infect Dis. 2023;77(9):e46-e56. doi:10.1093/cid/ciad499


Journal companion article - Executive summary link: https://academic.oup.com/cid/article/77/9/1223/7408674


From Clinical Infectious Diseases


Episodes | Consult Notes | Subscribe | Twitter | Merch | febrilepodcast@gmail.com


Febrile is produced with support from the Infectious Diseases Society of America (IDSA)

Transcripts

Speaker:

Hi, everyone.

Speaker:

Welcome to Febrile, a cultured podcast about all things infectious disease.

Speaker:

We use consult questions to dive into ID clinical reasoning, diagnostics,

Speaker:

and antimicrobial management.

Speaker:

I'm Sara Dong, your host and a MedPeds ID doc.

Speaker:

I hope everyone is settling into the new academic year nicely.

Speaker:

I just thought I'd put out a quick call for volunteers message.

Speaker:

As a little reminder, Febrile is a pretty small operation and it is always improved

Speaker:

by our guests who come to talk about ID.

Speaker:

I am looking to highlight people on the show.

Speaker:

I welcome any ideas that you have and I am definitely in need of new cases and topics

Speaker:

for us to cover in the coming months.

Speaker:

It is really just as simple as emailing me at febrilepodcast@gmail.com.

Speaker:

If you want to be on an episode, have a recommendation or another idea,

Speaker:

especially for fellows, trainees and junior faculty, I think this is a really

Speaker:

great way to make your work count twice.

Speaker:

If you have a topic that you've previously presented on and it helps support

Speaker:

Febrile to keep us running , and if you're interested, but you don't have

Speaker:

an idea, I can brainstorm with you.

Speaker:

Thanks for letting me make that little plug.

Speaker:

Okay.

Speaker:

So back to business.

Speaker:

We are here with another Febrile StAR episode.

Speaker:

These feature topics and authors from the CID, Clinical Infectious Diseases

Speaker:

journal, State of the Art Reviews.

Speaker:

We've been spending the past few months getting caught up and still have a few

Speaker:

upcoming episodes, including this one.

Speaker:

Today, we have two guest stars here to discuss multidrug

Speaker:

resistant gram negative infections.

Speaker:

Hello, everyone.

Speaker:

I'm Arsheena Yassin.

Speaker:

I'm an ID pharmacist at the Robert Wood Johnson University Hospital in New

Speaker:

Jersey, and I'm excited to be here today.

Speaker:

Hi, everyone.

Speaker:

My name is Mariya Huralska.

Speaker:

I am an infectious disease fellow at Robert Wood Johnson,

Speaker:

and I work with Arsheena.

Speaker:

I'm also really excited to be here.

Speaker:

I really love the Febrile podcast.

Speaker:

As everyone's favorite cultured podcast, we always start off by asking

Speaker:

if you'd be willing to share a little piece of culture or something that,

Speaker:

uh, brings you joy or happiness.

Speaker:

You know, as the weather is getting warm, I actually saw a lot of sunlight

Speaker:

yesterday, so I'm looking forward to being outside more, but the music

Speaker:

is something that I really enjoy and something that I, you know, listen to

Speaker:

on my downtime, whenever I'm coming home from work or on the weekend.

Speaker:

And I like all types of music, depending upon my mood that day.

Speaker:

Yeah yeah it's nice, well depending on when this gets released, it's

Speaker:

flower blooming season outside, even though it's raining for me today.

Speaker:

It's very nice.

Speaker:

Mariya, what about you?

Speaker:

So one of my favorite shows right now that I'm watching with my mom, it's

Speaker:

called Servant of the People, and it's on Netflix, and it stars President Zelensky

Speaker:

from Ukraine and it's about a teacher who goes on a rant about politics and

Speaker:

corruption and his video goes viral and then he becomes president and then he

Speaker:

actually becomes president in real life.

Speaker:

And I just really love it.

Speaker:

It's a very satirical commentary on the disconnect between corrupt

Speaker:

politicians and the people that they're supposed to be serving.

Speaker:

So I really love it and I highly recommend it.

Speaker:

Nice.

Speaker:

So we're gonna walk through a case that also is featured in the review as well,

Speaker:

but just to talk through some of the key concepts that you covered in the article.

Speaker:

So I'll jump in with our case today.

Speaker:

We have an 82 year old female with hypertension, diabetes, CKD,

Speaker:

and a recent ruptured cerebral aneurysm, status post embolization,

Speaker:

so that was about 2 months ago.

Speaker:

She is transferred from a nursing home to the emergency department due to

Speaker:

hypotension and fevers, as well as one week of coughing and pleuritic pain.

Speaker:

She had received five days of piperacillin tazobactam at the nursing facility

Speaker:

without improvement in her symptoms.

Speaker:

And we'll note that that recent admission related to her cerebral aneurysm, she

Speaker:

was admitted for 10 days in the ICU and was overall in the hospital for 18 days.

Speaker:

And so during this time, she was treated for a ceftriaxone resistant E.

Speaker:

coli UTI with seven days of pip-tazo [piperacillin-tazobactam].

Speaker:

And then in the interim, she has also had one other reported UTI that was

Speaker:

treated with seven days of levofloxacin.

Speaker:

This time she's dyspnic, she's hypotensive, 80s over 40s, heart

Speaker:

rate's 120 and is febrile to 101.

Speaker:

2.

Speaker:

Her oxygen saturation is 86 percent on room air and she has

Speaker:

crackles at the left lung base.

Speaker:

For a little more objective info, her lab showed a leukocytosis

Speaker:

to 18, lactate of 4, and a serum creatinine of 3 from a baseline of 1.

Speaker:

5.

Speaker:

Her chest x ray demonstrates a dense infiltrate on the left side and she's

Speaker:

continuing to deteriorate and now is intubated and requiring a norepi drip.

Speaker:

Two sets of blood cultures and respiratory cultures are cooking in the lab.

Speaker:

So this is a pretty common scenario, the ICU or ED calls you, they're

Speaker:

asking, what empiric therapy to start.

Speaker:

So I was hoping you could walk us through how to approach this type of case,

Speaker:

and then what gram negative targeted antimicrobial you'd want to start?

Speaker:

For us in ID, it's getting a really good history on our patients is really key

Speaker:

because we're thinking about how to tie this into what pathogens we need to be

Speaker:

concerned about, and also how likely this patient is to have resistant organisms and

Speaker:

then be able to tailor our antimicrobials to the pathogens we are concerned about.

Speaker:

When we are seeing these patients that are coming in, and especially

Speaker:

when you are concerned about resistant gram negatives, is really trying

Speaker:

to see where that patient has been.

Speaker:

So some of this was also presented in the case, but really looking to see

Speaker:

what antibiotics this patient has been exposed to, which facilities and exposure

Speaker:

this patient has had, what infections this patient has, had past micro.

Speaker:

When I'm evaluating a patient that's coming in with a suspected resistant

Speaker:

organism infection, there's a systematic way that I evaluate high

Speaker:

risk risk factors, is what I call them.

Speaker:

So, firstly, where's the patient coming from?

Speaker:

Is the patient coming from the community, meaning from home?

Speaker:

or are they coming from another facility and the facility is also important.

Speaker:

So are they coming from a different hospital and they were only in that

Speaker:

hospital for a couple of days or are they coming from an ICU part of that

Speaker:

hospital where they were already trached or ventilated for a month and now they're

Speaker:

being transferred to your hospital.

Speaker:

Or are they coming from a long term care facility, which that in itself is

Speaker:

a pretty strong risk factor for having a resistant organism, especially if

Speaker:

they have foreign indwelling devices.

Speaker:

So a trach is a big one, chronic indwelling catheters,

Speaker:

long term PICC or midlines.

Speaker:

Those are all risk factors for having resistant organisms,

Speaker:

especially in the bloodstream.

Speaker:

I always review the prior culture results, I usually look about a year out.

Speaker:

You don't have to go a year out, but it is important to look at least within the past

Speaker:

30 days, I would say, to see if they've ever been in that hospital and if they've

Speaker:

ever grown anything resistant in the past.

Speaker:

Now that doesn't mean necessarily if they've grown a resistant organism

Speaker:

in the urine, let's say six months ago, that that is the exact same

Speaker:

organism that is presenting in our patient as a cause of her pneumonia.

Speaker:

However, knowing that this patient has grown a very resistant organism

Speaker:

even in the urine six months ago tells you that this patient is

Speaker:

colonized with this organism or could be colonized with this organism.

Speaker:

And so again might push you into starting broader therapy early.

Speaker:

And lastly, travel history, I think could be an overlooked risk factor, but

Speaker:

it's also really important, especially when we're talking about NDM organisms.

Speaker:

So recent travel to India is a really big risk factor that you

Speaker:

don't want to miss finding out about.

Speaker:

Other MDR Enterobacterales have been observed in southern Asia, South

Speaker:

America, and northern Africa as well.

Speaker:

Getting a good travel history, especially within the past month, I would say, um,

Speaker:

and if that patient is then coming in with a severe infection, you want to know the

Speaker:

epidemiology of the resistant organisms to the relevant country that they've traveled

Speaker:

to because that again may increase your pre test probability of this patient

Speaker:

being sick with something very resistant.

Speaker:

Yeah, and then just piggybacking off of the risk factors, the two that the

Speaker:

IDSA's AMR document really highlights is previous antibiotic exposure and

Speaker:

the past cultures, like Mariya said.

Speaker:

And then there are others that have been studied, such as advanced age,

Speaker:

other comorbidities, such as being immunosuppressed, being bedridden,

Speaker:

et cetera, that may put these patients at high risk for infections.

Speaker:

When you look at the studies that were done to look at which risk

Speaker:

factors we can use to really estimate the probability of a patient having,

Speaker:

whether it be a carbapenem resistant Enterobacterales or a difficult to

Speaker:

treat Pseudomonas, they've all been very different, including various patient

Speaker:

populations, various infection source.

Speaker:

So just being aware of the other risk factors that may play a role

Speaker:

in that patient presenting with drug resistance is important.

Speaker:

Locally at one of my previous hospitals, we really tried to see of the models

Speaker:

that were published, how we can use them in our patient population to

Speaker:

distinguish who will have a carbapenem resistant Enterobacterales or not.

Speaker:

And they really sort of varied in how they were able to predict those

Speaker:

infections in our patient population.

Speaker:

As ID fellows, we're usually the ones kind of seeing the patient first.

Speaker:

So when you're seeing a patient who potentially might have a resistant

Speaker:

gram negative infection, especially based on their history, it's really

Speaker:

important to figure out where their source might be because the source

Speaker:

will then change what antibiotics you use with respect to locations.

Speaker:

For example, if you're thinking that it might be a CNS

Speaker:

infection, you need CNS dosing.

Speaker:

If you're thinking that it might be a GU infection, then you need

Speaker:

an antibiotic that has good renal penetration and so on and so forth.

Speaker:

So in this case, she's coming in dyspneic.

Speaker:

She is hypoxic and eventually becomes intubated.

Speaker:

So I'm thinking that it's probably a respiratory source.

Speaker:

We already have a chest x ray.

Speaker:

We know that she has a left infiltrate, and so she gets intubated.

Speaker:

When you're working someone up, it's always really, really important

Speaker:

to get a good sample from wherever you think the infection is.

Speaker:

So if she's getting intubated and she has a lot of secretions, I would either

Speaker:

hope to get secretions to culture at that time or maybe down the line

Speaker:

when she's a little bit more stable.

Speaker:

We already have a CBC and I would want to get a CMP to look at

Speaker:

her kidney and liver function.

Speaker:

That will be helpful also in the future for antibiotic dosing, Say she has an AKI

Speaker:

or shock liver or something like that.

Speaker:

We would want to know that information for the future.

Speaker:

Lastly, you know, when choosing an empiric antibiotic, especially

Speaker:

when it's broad, you want to look at how sick is the patient.

Speaker:

So, you know, is the patient coming in with a diabetic foot ulcer and

Speaker:

you have some time to think about it and maybe even hold antibiotics

Speaker:

before you can get cultures?

Speaker:

Or in this case, she's coming in very sick, intubated almost right

Speaker:

away, and she started on pressers.

Speaker:

We don't have a lot of margin of error in this case.

Speaker:

We can't afford to be wrong.

Speaker:

And so if I were to have a patient like this where I'm asked what I start,

Speaker:

I would be more inclined to allow myself the freedom to go more broad

Speaker:

because again, we don't have the luxury of being wrong in this situation.

Speaker:

Now, specifically looking at when we're choosing an empiric regimen for

Speaker:

our patients, Where we're concerned about multidrug resistant infections.

Speaker:

Here I'm mainly talking about those gram negative infections where

Speaker:

you have resistance to one or more antibiotics in three or more classes.

Speaker:

When we're thinking about these patients, and as Mariya highlighted

Speaker:

, just looking at these three factors, looking at the local epidemiology,

Speaker:

looking at the patient specific risk factors and then also looking at the

Speaker:

acuity of illness for that patient.

Speaker:

So now I'll go into briefly, just more focusing on the local epi.

Speaker:

So when we're looking particularly at multi drug resistant gram negatives,

Speaker:

resistance really varies locally, globally, even within a hospital.

Speaker:

It's really important when you're looking at your patient, where

Speaker:

did that patient infection start?

Speaker:

Because the way we approach that patient is going to be different from whether

Speaker:

they're coming from the community versus coming from a facility versus

Speaker:

someone that's sick in your ICU or the floors, because again, the resistance

Speaker:

pathogens, the exposure that the patient has really varies from that location.

Speaker:

And one helpful tool that we in ID love to use are our antibiograms.

Speaker:

Most hospital has a local antibiogram.

Speaker:

It's not always easy to get antibiograms from a facility or somewhere else

Speaker:

that the patient's coming from.

Speaker:

And if you're so lucky, you may also have antibiograms that are syndrome

Speaker:

specific or even unit specific.

Speaker:

And all of this information is just very helpful.

Speaker:

Because it sort of gives you an idea as how well your agents

Speaker:

are against that particular pathogen you're concerned about.

Speaker:

So let's say we want to cover for Pseudomonas, for example.

Speaker:

And generally, you're thinking about using your backbone drug, cefepime.

Speaker:

You can look at your antibiogram and say, hey, how well does cefepime cover

Speaker:

this pathogen that I'm concerned about?

Speaker:

And depending upon the susceptibility rates in your antibiograms, you may

Speaker:

lean towards choosing cefepime or using something else, depending upon

Speaker:

that susceptibility rates within your antibiogram, if you're able to

Speaker:

get the nursing home antibiogram.

Speaker:

So this is all just very helpful information for us to use when we're

Speaker:

trying to choose which empiric regimen to use for that particular patient.

Speaker:

Just something to note, depending upon your hospital, and I think

Speaker:

this is probably true for most hospitals here within the U.

Speaker:

S., our antibiograms are almost always outdated.

Speaker:

It's usually based on microbiology results from the year prior.

Speaker:

So, for example, at our hospital, we're now creating our 2023 antibiogram.

Speaker:

It's not the most up to date information.

Speaker:

It's helpful, but it's just really important to be aware of some of these

Speaker:

downsides with using your antibiograms.

Speaker:

Also, another thing is that when you're looking at your antibiograms, you may

Speaker:

have changes in certain breakpoints.

Speaker:

So, the Clinical and Laboratory Standard Institutes, they're normally the ones that

Speaker:

review and set a lot of breakpoints for various antibiotics for various pathogens.

Speaker:

But there's often a lag from when they would suggest breakpoint changes to

Speaker:

when that actually happens in the lab, just updating all of those panels.

Speaker:

So when there are changes in breakpoints, it's just really important to communicate

Speaker:

to your micro lab to come up with a game plan on how to report those

Speaker:

susceptibility results and also how to incorporate that maybe when you're

Speaker:

creating your antibiogram as well.

Speaker:

And just briefly talking about specifically looking

Speaker:

at gram negative infections.

Speaker:

Here within the U.

Speaker:

S.

Speaker:

You know, most of the gram negative resistance that we see, it's

Speaker:

usually, you know, ESBL organisms.

Speaker:

So, 2020 CDC data shows about over 20 percent of hospital E.

Speaker:

coli are resistant to third generation cephalosporin and also Pseudomonas.

Speaker:

Those are, you know, two major pathogens that most hospitals would commonly see.

Speaker:

But when it comes to carbapenem resistant Acinetobacter, or difficult to treat

Speaker:

Pseudomonas, so these are pseudomonal strains that are resistant to most of

Speaker:

the commonly used antibiotics . This is often very rare that we would need to

Speaker:

cover empirically for patients, unless you're in an area where there is a

Speaker:

recent outbreak, for example, maybe a nursing home has a recent outbreak of

Speaker:

one of these pathogens, or even locally as well, or if they're just endemic

Speaker:

to maybe the area that you're in.

Speaker:

So, it's really important just know your local epi and also be

Speaker:

aware of trends that are happening within your community as well.

Speaker:

But most of the time, we usually do not have to cover these agents

Speaker:

empirically, unless you have a really strong suspicion for those pathogens.

Speaker:

But other than that, it's really covering those ESBL organisms,

Speaker:

Pseudomonas, and when it comes to CRE, it really depends upon the

Speaker:

area in the United States you're in.

Speaker:

I know the resistance that we see here in New Jersey may be different from

Speaker:

other places within the country, and then also the various strains within the U.

Speaker:

S.

Speaker:

It's mainly KPC right now.

Speaker:

But they're also, this is really changing as well.

Speaker:

And then also, this sort of ties in especially for your travelers.

Speaker:

So, in our example case, just based on her risk factors and her previous cultures,

Speaker:

we decided to cover for Pseudomonas just because she has previous hospitalization,

Speaker:

a recent past antibiotic use.

Speaker:

Also decided to cover for MRSA just based on those risk factors as well, following

Speaker:

the latest IDSA pneumonia guidelines.

Speaker:

And also because she's coming in pretty sick and has past cultures

Speaker:

with ESBL E coli, it was decided to cover for those as well.

Speaker:

And just based on the antibiogram, the empiric regimen that

Speaker:

was chosen was meropenem.

Speaker:

Based on the antibiotic, we're making sure we're covering for susceptible, usually

Speaker:

susceptible, not difficult to treat Pseudomonas and also that ESBL pathogen.

Speaker:

Vancomycin to cover a risk for MRSA and also just adding on an aminoglycoside

Speaker:

to help increase just based on meropenem susceptibility patterns in the hospital

Speaker:

and in the nursing home to really help expand that gram negative coverage

Speaker:

for better coverage of Pseudomonas.

Speaker:

Now, if for example, we chose not to cover and start this patient out

Speaker:

on one of the the newer agents, and here newer, I'm talking about

Speaker:

agents that we'll generally be using for carbapenem resistant pathogens.

Speaker:

And this is mainly because she did not present with past

Speaker:

cultures for these pathogens.

Speaker:

If for example, she, she did, we had a urine culture with a carbapenem resistant

Speaker:

Enterobacterales or she's coming from a facility that has recent outbreak or,

Speaker:

this is very common within their facility to have patients with these pathogens.

Speaker:

Or she's coming, maybe had a recent travel to an area where these pathogens

Speaker:

are endemic, then we would generally have a much lower threshold to start these

Speaker:

patients on one of the more targeted agents to cover those resistant pathogens.

Speaker:

And Arsheena kind of already touched on this, but let's say I have a septic

Speaker:

patient and she's coming in on pressors.

Speaker:

, is being intubated.

Speaker:

Maybe she's coming in from a long term nursing home facility,

Speaker:

but she has no history of resistant organisms in the past.

Speaker:

I've reviewed her micro cultures, I don't see anything.

Speaker:

Or let's say she's really never even been hospitalized.

Speaker:

I really would not be reaching for the newer agents in this case right away.

Speaker:

I would be relying on my local antibiogram that I always carry in my pocket.

Speaker:

And so in our cases, we have choices of antibiotics that we can

Speaker:

use based on whether the patient is in the ICU or whether the

Speaker:

patient is somewhere on the floor.

Speaker:

So in our case, a patient that's in the ICU that I would like to cover for a

Speaker:

severe infection, I would choose cefepime based on our local antibiogram, . but

Speaker:

I still would like to go broad because of how sick she is, tying it back to

Speaker:

what we talked about before, where the margin of error is small and I

Speaker:

can't afford to guess incorrectly.

Speaker:

Yeah, and, especially in these cases where patients have no real risk factors for

Speaker:

resistant pathogens, it's really helpful to use your local antibiogram to see how

Speaker:

well your backbone therapy is working.

Speaker:

For example, your backbone gram negative is the cefepime for your

Speaker:

hospital, and cefepime covers more than 90 percent of your gram negatives,

Speaker:

including Pseudomonas, depending upon how sick the patient is, you may

Speaker:

be okay with using one agent or not.

Speaker:

But it really depends on the patient as to what margin you're okay with,

Speaker:

but let's say you have maybe cefepime susceptibilities are in the 70s.

Speaker:

That's really when you want to consider adding on a second agent

Speaker:

to really increase that gram negative spectrum for that patient.

Speaker:

And then the opposite spectrum of the scenarios, you have a patient coming

Speaker:

in with, let's say, a diabetic foot ulcer and that ulcer's been there for

Speaker:

many weeks and the only reason the patient's coming in is because his sister

Speaker:

said, you're going to the hospital.

Speaker:

Meaning there weren't any preceding signs of sepsis, the patient wasn't

Speaker:

having chills or rigors at home, there wasn't increased drainage, it's

Speaker:

mainly a just situational admission to the hospital for a long term,

Speaker:

probably diabetic osteomyelitis in a patient who's otherwise stable.

Speaker:

Um, but, I review his cultures and I see that previously he's been admitted

Speaker:

for this ulcer before and he's had debridements before and he actually has

Speaker:

grown carbapenem resistant Klebsiella.

Speaker:

Am I reaching for a newer agent?

Speaker:

Probably not, at least not at this stage, because again, the overarching theme

Speaker:

here is that the patient is stable.

Speaker:

He's not having fevers, he's not having chills, rigors, he's hemodynamically

Speaker:

stable, and I have time to wait until we consult our surgical colleagues

Speaker:

so that they can get us really good specimens, and then we can send that off

Speaker:

to the lab and tailor our antibiotics based on what grows this time.

Speaker:

Um, so I may consider not starting anything despite the fact that

Speaker:

I know that he's grown very resistant organisms in the past.

Speaker:

So, I can briefly talk about optimizing the dosing for patients when we're

Speaker:

looking at Gram negative infections, and, the IDSA's AMR document is a

Speaker:

readlly helpful tool based on the resistance that you're seeing to

Speaker:

help choose the empiric regimen.

Speaker:

And also, it has a helpful table there on how to dose these

Speaker:

antibiotics for the resistant pathogens that you're concerned about.

Speaker:

Now, oftentimes, when we have patients and we're starting them on an antibiotic,

Speaker:

it usually involves beta lactams.

Speaker:

And especially in our very sick patients, really we just want to be careful on

Speaker:

how we're dosing to make sure we're using appropriate dose, especially

Speaker:

in our ICU patients where there may be altered volume distribution, their

Speaker:

clearance may be changing, they may be on continuous renal replacement therapy, etc.

Speaker:

So just taking all of these things into consideration when we're dosing

Speaker:

antibiotics and just making sure that we're using the appropriate dose

Speaker:

for a particular patient based on the pathogen we're concerned about.

Speaker:

Now, oftentimes specifically when we're using beta lactams, we can

Speaker:

either give them intermittent, so for example, infuse over 30 minutes, or we

Speaker:

can give it by a prolonged infusion.

Speaker:

So most of our beta lactams, after you give a dose, you have this high

Speaker:

concentration and peak, and usually with that short half life, you may have

Speaker:

a decrease in concentration eventually leading to concentrations below the MIC

Speaker:

of the pathogen you're concerned about, and this may lead to decreased efficacy

Speaker:

of the drug and even regrowth of those organisms and potential resistance.

Speaker:

If we prolong that infusion of the antibiotics, so giving piperacillin

Speaker:

tazobactam instead of 30 minutes over 4 hours, you're having a more constant

Speaker:

concentration in the blood above the minimum inhibitory concentration, and

Speaker:

really it's a way to help enhance the efficacy of that drug, decreasing the

Speaker:

resistance based on specific parameters.

Speaker:

And this is something, especially when we're looking at resistant gram negatives

Speaker:

that maybe have higher MICs, using this prolonged infusion to really help target

Speaker:

those higher MICs are useful tools.

Speaker:

Now, when it comes to clinical outcomes and use of prolonged infusion antibiotics,

Speaker:

mainly it's been retrospective studies that have shown mortality benefits,

Speaker:

particularly in really sick patients with documented Gram negative bacteremia.

Speaker:

It really has not shown in a lot of more retrospective studies.

Speaker:

But just based on the pharmacokinetic properties of the medications, the

Speaker:

international consensus guidelines on prolonged infusion beta lactams

Speaker:

really recommends using prolonged infusion if possible, especially for

Speaker:

those patients where you're looking at resistant gram negatives, especially

Speaker:

in patients that are critically ill.

Speaker:

Now, for in our example patient, that patient will also be started

Speaker:

on usually vancomycin, as you mentioned, as well as aminoglycoside.

Speaker:

And part of the monitoring for these antibiotics, as a lot of

Speaker:

our pharmacists like, will involve therapeutic drug monitoring.

Speaker:

And this involves measuring a concentration of the drug within the body.

Speaker:

And then being able to really calculate to see if your drug is

Speaker:

reaching its efficacy target and also as a way to help decrease toxicity.

Speaker:

So, very commonly in most hospitals, this is done for

Speaker:

aminoglycosides and vancomycin.

Speaker:

Not really done for beta lactams, but it is done in certain centers within the U.

Speaker:

S.

Speaker:

But I do think if you are using a beta lactam in a patient that's just you know,

Speaker:

their, their clearance may be different.

Speaker:

So patients with extremes of body weight, our CF patients, if your

Speaker:

patients are on ECMO or continuous renal replacement therapy, if your

Speaker:

patients are having side effects from some of these medications, for

Speaker:

example, of neurotoxicity from cefepime.

Speaker:

Or, if you're using, you know, you're stuck using beta lactam for a pathogen

Speaker:

with a higher MIC, this may be an area to incorporate using therapeutic

Speaker:

drug monitoring with our beta lactams to make sure we're reaching our

Speaker:

efficacy and as well as safety targets for those particular antibiotics.

Speaker:

And, we're getting more and more resistant pathogens.

Speaker:

We now have a large amount of various antibiotics to use and which

Speaker:

one to use for certain resistance genes will just become more and

Speaker:

more confusing in the future.

Speaker:

But really just involving an ID or maybe a stewardship specialist within

Speaker:

your hospital to really help guide that we're using these drugs for the

Speaker:

appropriate indication, and we're using it for the appropriate pathogen as well.

Speaker:

That's a great summary.

Speaker:

I mean, I think some of the points that you guys made of general considerations,

Speaker:

are obviously good for this case, but they're probably good for everything in

Speaker:

ID, like what's the source of infection?

Speaker:

What bugs do we think are there?

Speaker:

And like Mariya talked about the consequences if we don't have the

Speaker:

correct combo of antibiotics initially.

Speaker:

So at this point in our case, let's say, we have a working diagnosis

Speaker:

that our patient has a pneumonia.

Speaker:

The patient was empirically placed on vancomycin, meropenem, and tobramycin.

Speaker:

We mentioned some risk factors for MDR gram negative infection, so recent

Speaker:

antibiotic exposure and hospitalization.

Speaker:

And after some chart review, you also learn that she has had previous cultures

Speaker:

or colonization with the likely ESBL E.

Speaker:

coli.

Speaker:

You are lucky enough to get a little bit of information from her local nursing

Speaker:

facility antibiogram, which showed that Pseudomonas susceptibility to meropenem in

Speaker:

the ICU is 75 percent on that antibiogram.

Speaker:

So again, another, another place that we're often called, empiric therapy

Speaker:

has been started in this patient.

Speaker:

You have sort of pending partially returned diagnostic results.

Speaker:

And we are asked to help think about how do we adjust the antibiotic regimen?

Speaker:

Can you talk a little bit about some of the cautions or things

Speaker:

to think about related to sort of traditional testing and whether or

Speaker:

not we may have rapid diagnostics that can help impact our management?

Speaker:

Yeah, I can sort of start here, you know, especially when we're starting

Speaker:

broad antibiotics for our patients.

Speaker:

I'm wearing my stewardship hat right now.

Speaker:

It's really important for us to get additional testing, utilizing

Speaker:

rapid diagnostic testing, if you have that available, so you're

Speaker:

able to get your answers quickly.

Speaker:

And this really allows us to be broad when we need to be broad and then

Speaker:

be able to taper and streamline our antibiotics in a timely manner,

Speaker:

so we're not giving these patients unnecessarily broad antimicrobials.

Speaker:

Now specifically looking at our traditional culture methods, right now,

Speaker:

most laboratories in the United States, if you obtain blood cultures, those blood

Speaker:

cultures will then go to lab, has to be incubated, and then maybe within a couple

Speaker:

hours or a day or so may become positive.

Speaker:

And then, the techs are able to do gram stain results, and you're able to see

Speaker:

the gram stain and be able to tailor results based on the gram stain results,

Speaker:

which are negative or gram positive.

Speaker:

Then, that culture is then plated out and then further incubated for growth.

Speaker:

And once there's growth, usually most laboratories use susceptibility testing

Speaker:

panels such as Phoenix or Microscan to do identification susceptibilities.

Speaker:

Overall, for even a susceptible pathogen, it takes about three

Speaker:

days to get ID and susceptibility.

Speaker:

Now just think about that for resistant pathogens.

Speaker:

It's going to be much longer, especially, for example, if you are treating

Speaker:

a difficult to treat Pseudomonas.

Speaker:

So, on day three, when you have all your results returning, then there's

Speaker:

additional testing that has to be done on other antimicrobials, the newer

Speaker:

antimicrobials, and then that again delays that time to final susceptibility results

Speaker:

and really for us to be able to know if we're treating this patient appropriately.

Speaker:

Now, there have been some panels that are updated with some of the newer agents, so

Speaker:

when I say newer, it's really relative, but more of those agents that we use

Speaker:

for carbapenem resistant gram negatives.

Speaker:

So, some panels include ceftolozane tazobactam, ceftazidime avibactam at

Speaker:

this point, and it's really important to know what your micro lab has.

Speaker:

So when you have a patient that's coming in or you're in a hospital

Speaker:

that sees a lot of resistance, just so you're able to really decrease that

Speaker:

time to final susceptibility results.

Speaker:

For us, we, we do have some cases where we do see quite a

Speaker:

number of resistant pathogens.

Speaker:

So we worked with our micro lab to have reflex testing done.

Speaker:

So if there's a pathogen that tests resistant to particular antimicrobials,

Speaker:

certain antimicrobials are automatically tested without us even having to call the

Speaker:

lab and that just helps us with decreasing our time to final susceptibility

Speaker:

results and hopefully decreasing that time to appropriate antibiotic use.

Speaker:

And then to expand a little bit more on what Arsheena said, so she talked

Speaker:

about traditional culture testing and rapid diagnostics is a way that we can

Speaker:

test for possibly resistant organisms and then can get resistance patterns

Speaker:

in these organisms a lot quicker than traditional culture methods.

Speaker:

Like Arsheena said, with culturing, it might take 24, 48 hours or longer

Speaker:

to grow an organism, but with rapid diagnostics such as Accelerate Pheno or

Speaker:

Maldi TOF or Varigene for Gram Positives, we can get those results much quicker.

Speaker:

So one to eight hours.

Speaker:

Our lab, we can get the identification of an organism within three hours, and

Speaker:

we're usually expecting to get some kind of susceptibility results, at least

Speaker:

the earliest ones, within six hours.

Speaker:

So much quicker than with traditional culture results.

Speaker:

And so in these cases where patients are coming in septic, very sick,

Speaker:

intubated, and we're concerned for septic shock, losing time is detrimental,

Speaker:

waiting for cultures to grow, especially if you don't know how broad

Speaker:

you should go with your antibiotics.

Speaker:

So from the infectious disease fellow standpoint, I'm already

Speaker:

calling the micro lab pretty much as soon as I see the patient.

Speaker:

And firstly, I'm telling them, Hey, I have a concern for a

Speaker:

multi drug resistant organism.

Speaker:

Could you please, in addition to the early susceptibility antibiotics on the

Speaker:

standard panel, could you also please add the newer agent as well so that I'm not

Speaker:

losing time waiting for them to then add it on once it does come back resistant.

Speaker:

Yeah, and luckily for us, we have a lot of rapid diagnostic tools that we're

Speaker:

able to use for our patients, and I think this is just going to be more

Speaker:

and more common as we're seeing more resistant pathogens and using more of

Speaker:

these tools, I think it's really important to tie these results with some sort

Speaker:

of ID or stewardship feedback as well.

Speaker:

It's very difficult for frontline providers to understand the

Speaker:

results of these rapid diagnostic tools and how to use them.

Speaker:

So, for example, we have CARBA 5 that's being done for patients where

Speaker:

isolates test carbapenem resistant.

Speaker:

As you can tell, if something comes back, OXA positive, the primary team usually,

Speaker:

they don't understand how they should be tailoring regimens for these patients.

Speaker:

So currently, at our institution, when these results are positive, the

Speaker:

ID stewardship team, the ID fellows are made aware, and we sort of have

Speaker:

a schedule to call the team and make them aware to adjust antimicrobials.

Speaker:

So we're really utilizing the rapid diagnostic tools to decrease that

Speaker:

time to appropriate antibiotics.

Speaker:

And I know like multiple studies that have been done in the past,

Speaker:

really showing mortality benefits in using these tools in this way.

Speaker:

And it's also important when we talk about resistant gram negatives, how to

Speaker:

interpret an ESBL pattern in a isolate of E.coli that is ceftriaxone resistant or

Speaker:

pathogens with inducible AmpC resistance.

Speaker:

Because again, it's, it's something that may be familiar to us in ID, but

Speaker:

the teams will you know, not aware of what the meaning of these and usually

Speaker:

choose something that says susceptible on the panel that's being released.

Speaker:

Later in that day, after antibiotics have been started, we learned that the blood

Speaker:

cultures have returned positive for gram negative bacilli in two of two sets.

Speaker:

The rapid diagnostic results one hour after this showed Klebsiella

Speaker:

pneumoniae with the KPC gene detected.

Speaker:

So the patient was adjusted to meropenem vaborbactam.

Speaker:

So, about two days after this, the susceptibility results confirmed the

Speaker:

organism was resistant to standard antimicrobials, including meropenem,

Speaker:

but susceptible to tobramycin based on updated CLSI breakpoints.

Speaker:

Reflex susceptibility testing was done due to the resistant meropenem

Speaker:

result and showed us susceptibility to ceftazidime avibactam, imipenem

Speaker:

relebactam, and meropenem vaborbactam.

Speaker:

And in addition to these, our respiratory cultures also did show a carbapenem

Speaker:

resistant Kleb pneumoniae as well.

Speaker:

The patient has defervesced.

Speaker:

They are extubated over the course of the next 72 hours.

Speaker:

And so now we are being asked, well, what should we do for a duration of therapy?

Speaker:

Okay, so I can I can get started on kind of monitoring the patient first.

Speaker:

Well, when we start the broad spectrum antibiotic, so mero-vabor in this case,

Speaker:

we always want to make sure that we monitor and see signs of improvement

Speaker:

as in most infectious diseases.

Speaker:

So in her case, her fever curve improved and most importantly,

Speaker:

she was able to be extubated.

Speaker:

So, in our case, we picked the site of infection correctly.

Speaker:

We picked the right antibiotic and very quickly she was

Speaker:

able to come off of the vent.

Speaker:

However in other cases, especially in let's say intra abdominal

Speaker:

infections, which become a lot more complicated situations where duration

Speaker:

of therapy is not defined and it's really dependent on source control.

Speaker:

In those instances and or in cases where patients are intubated on top

Speaker:

of that and can't tell you any signs and symptoms, you're stuck kind of

Speaker:

monitoring things like, again, fever curve, but also sometimes lactate

Speaker:

and procalcitonin can be helpful.

Speaker:

Although those markers can be a little bit controversial and they're more

Speaker:

taken in the context of the patient.

Speaker:

So in this case, she's getting better and duration of therapy.

Speaker:

It's important to understand that with resistant gram negatives, IDSA

Speaker:

does not recommend extending duration of therapy just based on the fact

Speaker:

that the organism is resistant.

Speaker:

What's most important in terms of duration is, is the patient getting

Speaker:

better, and is the patient responding to the antibiotic that we've chosen.

Speaker:

Another key part of your review and really all of these state of the art reviews

Speaker:

that I wanted us to end on is how to use multidisciplinary approaches to not

Speaker:

only manage patients in the hospital, but also to help ensure they have a safe

Speaker:

transition to the outpatient setting.

Speaker:

So in our example in this case, the patient is ready for

Speaker:

discharge back to her facility.

Speaker:

It's about hospital day five, but you get a call that the facility

Speaker:

does not have meropenem vaborbactam.

Speaker:

They're not sure if they can get it.

Speaker:

So maybe as you talk about how you might handle the situation, you could

Speaker:

give us some insight into who is part of this multidisciplinary team that

Speaker:

is trying to help the patient get to a safe discharge from the hospital.

Speaker:

So from the clinical side, when we've said as consultants, okay, we would

Speaker:

like for this patient to go on this newer agent, probably the very first

Speaker:

people that we're consulting is, of course, case management, and I mean,

Speaker:

we always have our ID pharmacist on board with us, but I think those two

Speaker:

people early in the discharge process are really important because, you have

Speaker:

to make sure that the place that you're sending this patient to on this newer

Speaker:

agent or any really broad agent spectrum agent is available at the facility.

Speaker:

And so the social worker and the case manager, and in some cases, ID

Speaker:

pharmacist can help ensure that when the patient gets to the facility,

Speaker:

there is no delay in treatment because the antibiotic is or isn't available.

Speaker:

Additionally, we always want to send patients on an antibiotic that is

Speaker:

given the least amount of times.

Speaker:

If anybody's had to take antibiotics multiple times a day can appreciate that,

Speaker:

in theory, it doesn't sound like a big deal, but in practice, it can be very

Speaker:

challenging, especially for patients who already have other comorbidities going on.

Speaker:

So we really try to minimize the amount of times that the patient

Speaker:

receives the antibiotic per day.

Speaker:

Less frequent dosings are favorable.

Speaker:

There are studies that have found that OPAT regimens that are dosed once or twice

Speaker:

daily are closely associated with better adherence, than more frequent regimens.

Speaker:

And then, of course, whenever possible, we always try to consider oral agents.

Speaker:

Now, in very resistant organisms, that's almost never an option, but if we can,

Speaker:

we always consider sending the patient on an oral agent to minimize complications

Speaker:

from PICC lines or midlines that may further downline cause more infections.

Speaker:

Yeah, just just piggybacking off of the multidisciplinary team it's

Speaker:

really important to get ID involved, especially early in these cases

Speaker:

to really see and help determine the duration of antibiotics.

Speaker:

So, does that patient really need an additional 7 days of these agents outside

Speaker:

at a hospital and really determine what the correct duration is and if

Speaker:

those patients can switch to oral.

Speaker:

And then also to, especially if you're going to be on, for example, 6 weeks

Speaker:

of antibiotics after discharge, really making sure that we have the appropriate

Speaker:

labs are done and someone is following that patient outside to make sure

Speaker:

that you're having no toxicity and you're having clinical improvements.

Speaker:

And, the usual monitoring, especially for most antibiotics

Speaker:

is usually weekly CBC and CMP.

Speaker:

if you're giving maybe vancomycin, also therapeutic drug monitoring is needed.

Speaker:

So, I really think it's key to, to really have a broad team involved

Speaker:

when discharging these patients to make sure all of that is

Speaker:

really communicated on discharge.

Speaker:

And other members, if you have these in your hospital are OPAT liaisons,

Speaker:

your transition to care pharmacist that can work magic to help you get

Speaker:

some of these antimicrobials that you really need for your patients

Speaker:

at home, or even at a facility.

Speaker:

Looking at various formulary options, and again, just involving case management,

Speaker:

social work, and also the bedside nurse is going to be the one that's educating

Speaker:

that patient and their family member on how to, if it's an IV antibiotic, how

Speaker:

to administer that antibiotic, because most of the time, if they're going

Speaker:

home, they'll likely be administering those antimicrobials themselves.

Speaker:

When we do have these patients admitted to the hospital, I do

Speaker:

think this multidisciplinary approach also holds through.

Speaker:

So when we have these patients, especially that have these resistant pathogens and

Speaker:

intra abdominal infection, it's really important to get a multidisciplinary team

Speaker:

to really help ensure you have source control, because especially when we're

Speaker:

reaching for, agents such as, ceftazidime avbactam, the more likely that patient

Speaker:

still has that remaining source, the more likely that patient is going to develop

Speaker:

further and further resistance later on.

Speaker:

So I think just having that multidisciplinary approach involving

Speaker:

key stakeholders, that's important for that patient care, helping appropriate

Speaker:

antibiotic use in the hospital, appropriate source control if needed, and

Speaker:

then appropriate discharge is really key.

Speaker:

I want to add to what Arsheena just mentioned.

Speaker:

So, source control, especially in situations where source

Speaker:

control may never be achieved.

Speaker:

So, a good example is in a patient who has an LVAD infection, and that LVAD is a, is

Speaker:

destination therapy, and has, let's say, a drive live infection with an organism like

Speaker:

Pseudomonas, where the more antibiotics you give this patient, the more

Speaker:

resistant the Pseudomonas will become.

Speaker:

So, I think it's really important to start planning early in these

Speaker:

kinds of situations where source control is, may not be feasible.

Speaker:

What, what will be the plan once that Pseudomonas becomes so resistant

Speaker:

where there are no options available.

Speaker:

And, of course, involving the patient as well and making the patient

Speaker:

understand, there may come a time where we may run out of antibiotics.

Speaker:

And so these are one of the times where you want to involve the patient, the

Speaker:

surgeon, ID, the pharmacist, so that we have a plan for when that time arrives.

Speaker:

Awesome.

Speaker:

And then I just want to open it up just to see if there's any other

Speaker:

closing thoughts that you guys have.

Speaker:

Thank you so much , it's a huge topic that we can't always condense

Speaker:

into these episodes, but I think you've given people really valuable

Speaker:

initial steps to get started.

Speaker:

So closing thoughts would be that treating multi drug resistant gram

Speaker:

negative infections is certainly challenging, but it's exciting that

Speaker:

we have new agents that we can use.

Speaker:

It's encouraging, but I think it's really important to understand the

Speaker:

appropriate time of when to use them.

Speaker:

, it's really important to understand that just because these newer agents

Speaker:

are novel, we shouldn't be afraid to use them, especially if we have

Speaker:

strong risk factors, strong indications to reach for them, and especially

Speaker:

if the patient is very, very sick.

Speaker:

So don't be afraid of them, but also use them thoughtfully.

Speaker:

And just adding to what Mariya said, just really considering the whole

Speaker:

patient, their risk factors, how ill they are, your local epi, to really

Speaker:

determine which one of these agents to start, because now we have several.

Speaker:

And then also really utilizing, I think, rapid diagnostic testing

Speaker:

has really changed how we will be approaching these patients.

Speaker:

Really just taking advantage of those.

Speaker:

If you have them to really be able to modify therapy in an appropriate manner

Speaker:

based on the resistance, based on the results . And then also just adding the

Speaker:

duration should really just focus on the clinical improvement, how that patient is

Speaker:

doing versus just maybe this is resistant pathogen, we need to treat them longer.

Speaker:

And then also just involving a multidisciplinary team, and be

Speaker:

able to facilitate those patients leaving the hospital safely and

Speaker:

hopefully being able to prevent them from having further readmissions.

Speaker:

And just closing thoughts, this was an exciting article that we

Speaker:

did with some amazing co authors.

Speaker:

I just wanted to give them a shout out.

Speaker:

So shout out to co authors, Drs.

Speaker:

Jason Pogue, Deepali Dixit, Robert Sawyer, and Dr.

Speaker:

Keith Kaye.

Speaker:

Thanks to Arsheena and Mariya for joining today.

Speaker:

You can find their article linked in the episode description and Consult Notes

Speaker:

from CID entitled State of the Management of Infections Caused by Multidrug

Speaker:

Resistant Gram Negative Organisms.

Speaker:

Don't forget to check out the website, febrilepodcast.

Speaker:

com, where you'll find the Consult Notes, which are written complements to

Speaker:

the episodes with links to references, our library of ID infographics,

Speaker:

and a link to our merch store.

Speaker:

Febrile is produced with support from the Infectious Diseases Society of America.

Speaker:

Please reach out if you have any suggestions for future shows or want

Speaker:

to be more involved with Febrile.

Speaker:

Thanks for listening.

Speaker:

Stay safe and I'll see you next time.

Chapters

Video

More from YouTube