CEimpact Podcast

New IDSA guidelines to treat drug resistant gram-negative bacteria

Drug resistance to antibiotics continues to escalate. This week we do a deep dive into the Infectious Disease Society of America's (IDSA) brand new guidance on the treatment of antimicrobial resistant gram-negative infections.
 
The GameChanger
The new IDSA guidelines provide critical, evidence-based recommendations for managing drug-resistant gram-negative infections. The guidance offers health care providers clear strategies to improve outcomes and reduce the emergence of resistance.


Guests
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health

Amanda Bushman, PharmD, BCPS-AQ ID, BCIDP, FIDSA
Infectious Disease Pharmacist
UnityPoint Health

Tony Mannum, PharmD
PGY2 Infectious Disease Resident
UnityPoint Health
Reference

IDSA Guidelines for treating resistant gram negative organisms

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CPE Information
 
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Identify effective strategies for treating urinary tract and systemic infections caused by Extended-Spectrum Beta-Lactamase (ESBL)-producing organisms.
2. Discuss appropriate therapeutic agents for infections caused by AmpC beta-lactamase-producing bacteria, ensuring choices minimize the risk of resistance development during treatment.

0.05 CEU/0.5 Hr
UAN:  0107-0000-24-251-H01-P
Initial release date: 09/02/2024
Expiration date: 09/02/2025
Additional CPE details can be found here.

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Speaker 1:

Hey, CE Plan members from CE Impact, this is Game Changers. We talk a lot about antibiotic resistance and good stewardship of antibiotic use to prevent resistance, but unfortunately, even with stewardship measures in place, we still see a lot of antibiotic resistance, which increases costs to treat infection as well as mortality when we aren't successful. Today we are talking about a new set of guidelines that will hopefully have an impact on treating drug-resistant gram-negative bacteria, and those are from the Infectious Disease Society of America. Here to dig into that are not one, not two, but three pharmacists who are experts in infectious disease and are going to walk us through the guidelines and share their clinical experience in implementing them. So let's get into it. Amanda and Tony, would you introduce yourself and tell our listeners a little bit about you?

Speaker 2:

Yeah, my name is Amanda Bushman and I'm the infectious diseases pharmacist for UnityPoint Health Des Moines, and daily in my role I take care of lots of different patients with lots of different infections, so I utilize these guidelines quite a bit.

Speaker 3:

And I'm Tony Manum. I am UnityPoint Methodist's first PGY2 resident in infectious disease and, coincidentally enough, I have done quite a bit with the previous version of this guideline, the 2023 AMR guidance document. I taught that in grand rounds in my PGY1 institution and also for the North Dakota Society of Hospital Pharmacists and the North Dakota Infection Prevention Conference, so I've had a little bit of experience with this document.

Speaker 1:

Awesome. Well, thank you both for being with us today, and we also have Geoff Wall, who is our regular contributor. Geoff, I'm going to let you just remind the listeners about your practice and how you work with both Amanda and Tony on a daily basis, and then I'll let you all get into it.

Speaker 4:

All right, sounds good. So you know, for those long-term listeners, Geoff Wall, internal medicine clinical pharmacist here at Methodist for 25 years now Hard to believe so, and I'm I wouldn't consider myself an infectious disease expert. I'm just kind of a guy who goes along for the ride a lot of the time. So I'm glad Amanda or Tony here are kind of here to kind of give us a hand, because there are some major changes to these guidelines and they will absolutely impact primary care physicians and primary care providers and pharmacists. So, you know, I don't think you have to be a total ID nerd to go. You know, yeah, these are important and I think that they they fundamentally make some recommendations that are going to change practices for all types of healthcare providers. So that's why I think this is timely and again, I appreciate Amanda and Tony here giving us a hand with this.

Speaker 4:

As you point out, you know, antimicrobial resistance is a global crisis. About 1.3 million deaths are estimated to be directly attributable to resistant pathogens, so that's obviously a big deal. It's responsible for about 2.8 million infections and 35,000 deaths annually from 2012 to 2017. So this is a huge problem. It's getting worse, and so that's why these practice documents are coming out.

Speaker 4:

It is worth noting that this is a little bit different than official practice guidelines, because they don't really do kind of you know, the grade system and a PICO question and all that other stuff. It's more of a guidance document and I think that's also based on the fact that, you know, like so many things in infectious diseases, we don't have a huge evidence base. I mean, there's just, you know, there are a few randomized control trials, but this is just not an area of medicine where we have tons and tons and tons and tons of RCTs on, like, say, cardiology. So you know, keep that in mind that this is best practices. But if you want to get into the nitty gritty and say, well, gee, you know, you know what are they basing this on?

Speaker 4:

It is largely on small studies, retrospective papers, in vitro, you know data, stuff like that. But that's no different really than most other ID documents that we have. So it's a huge set of documents or guidelines. We could literally spend hours talking about them. But I think the three of us decided that the best way to focus on this was to focus on the types of resistant organisms that are more common in many areas of the United States and, I suppose, worldwide, and the ones that are less likely to have infectious disease consults involved. So again, primarily things like ESBL. So I mean, we see ESBLs quite a bit, even here in Iowa, and certainly it's become more common throughout the United States. So we thought we would focus mostly on that and then a little bit more common throughout the United States. So we thought we would focus mostly on that and then a little bit on some of the other stuff going on.

Speaker 4:

So extended spectrum beta-lactamases have been around now for a long, long time.

Speaker 4:

They are you know how I try to explain to students is kind of a super beta-lactamase that basically hydrolyzes a wide variety of that class, and you know at least for 25 years that I've been practicing, you know they've been an issue and they've just steadily risen in numbers.

Speaker 4:

Even here in Des Moines, where I think we're very, very lucky that we don't see a ton of these super resistant bacteria, it is now not uncommon at all for us to see ESBL producing organisms, particularly E coli, which I think is the most common one, but also Klepneuma and a couple others as well.

Speaker 4:

But E coli certainly leads that list, and so the dogma that I was taught I think the dogma that Amanda was taught for many years is that when you have an ESBL producer, you pretty much have to use a carbapenem, because carbapenems are the only beta-lactam that are stable to the hybrid hydrolyzation of ESBL producing bugs. And so you know that made it a real pain whenever we wanted to send somebody home, because then it had to be, you know, some sort of carbapenem. And then there was some evidence to suggest that maybe phosphomycin would work. But that was always a pain because a lot of hospitals don't carry it, it's expensive and the data was never really that good with phosphomycin to begin with. So this has always been a real clinical conundrum, and that's why I think the guidelines you know this really is probably the most important update from the guidelines is that when we're talking about simple cystitis.

Speaker 4:

So again, not you know things that are affecting the upper GU tract, that they actually say that it is reasonable to use traditional antibiotics if they're susceptible in vitro, in particular nitrofurantoin and Bactrim, and that is a huge change. That is is is well, I think, almost immediately kind of impact things.

Speaker 4:

The other thing that that I think is is worth discussing too is that one of the things we kind of struggle with is how long to treat patients with urinary tract infections. Again, this is a super bad bug. You want to make sure we kill every single little, teeny tiny organism in the GU tract and again the guides document says no. Basically, you know, just because it's an ESL, esbl producer does not mean you need to treat for soup for much longer, longer than you would treat normally. So that's again another big big difference. So it is entirely possible that if you had an ESBL E coli that was susceptible to Bactrim, that was uncomplicated cystitis, you could treat it like any other uncomplicated cystitis, which means three days of Bactrim or five days of nitroferantoin. Certainly, if you have pyelonephritis or some sort of other complicated UTI, you would use longer therapy, but again, that's a big big change. So, amanda, tony, what's your kind of take on all that?

Speaker 2:

Yeah, I think a couple of things to think about. You mentioned the phosphomycin drug potential concerns there, and I think one thing that people forget about is if you do need to use phosphomycin, it's not commercially available on any of the susceptibility panels. So that requires additional testing by e-test through micro labs, and so again that's delaying potential results and potential therapy switches. So again, you know, having the data this supporting the use of nitrofurantoin or Bactrim, those are on commercially available panels so you can have that information to treat your patient sooner and more readily. So I think that that's important too. I think the other thing to remember with the phosphomycin piece is in the United States IV phosphomycin is not available, that's not FDA approved. And so again thinking about different papers that you may read, again just thinking about the route of administration and the severity of infection, because, remember, phosphomycin should only be utilized in a similar manner to nitrofurantoin and Bactrim in the uncomplicated space as well.

Speaker 3:

Yeah, and with phosphomycin too. The main piece that we talk about is why we maybe only want to use it for E coli is we do have data ona, FosA hydrolyzed gene that is in many Enterobacterialis besides E coli that essentially the idea is that that gene can break down Fosamycin and lead it to not effectively treat that bacteria. And then also as just a whole on this whole guidance document, it's, you know, focused on pathogens and when you have the appropriate therapy for a pathogen, it shouldn't affect anything like duration or, you know, time until de-escalation, as long as you have something that you can appropriately go to shown on a susceptibility report.

Speaker 4:

It shouldn't delay those transitions, right? No, I completely agree, and but I think that's. I mean, I think everybody's just so terrified of ESBLs. I mean, they see that, you know, at least in our, in our hospital, there's a little like star thing that says ESBL produce and it just causes everybody to flip out, and I, I'm, I flip out as much as anybody else does. But I think that that I think these new set of guidelines really kind of say okay, let's all take a step back, just because this is an ESBL producer does not mean that, you know, we should run screaming from the room and not even touch the patient because we're terrified, we're going to get colonized with ESBL. So I, you know, I, I, I appreciate that, and but I think that this is going to be a bit of a change in paradigm.

Speaker 4:

No-transcript what? Okay, I don't even carry phosphomycin, which a lot of pharmacies don't. It might be worth a phone call to the physician and say you know, just kind of curious, why are you picking phosphomycin? And if they give you a big long lecture about ESBLs, this is a perfect time to educate, I think, the providers that are in the community. So it is worth noting. The guidelines also say that you know, quinolones can be used if they're susceptible, and a single dose of aminoglycosides, which I've actually had a couple of friends who are doing that and they're getting good results Um, uh, friends of mine who work in other hospitals. You know, I got it, I think. I think I'm going to start dabbling in that a little bit in my patients. I don't know, have you guys been using that?

Speaker 2:

at all. We've done it occasionally, not routinely, um, but the ones that we have done it in I know it has been successful. So it's just something to kind of you know, keep on the radar and see. I think again, you know, patient selection there is probably an important piece.

Speaker 4:

And then, of course, you know, the beauty is, no one's going to get nephrotoxic after a single dose of an immunoglycoside. Are you guys? Just, are you guys doing like what? Seven milligrams per kilogram, five milligrams per kilogram?

Speaker 2:

Usually we would do the seven milligrams per kilo for the IV product.

Speaker 4:

Okay, and of course, quinolones are from the devil, so we should not use them unless we absolutely have no choice.

Speaker 4:

I appreciate Tony pointing, I appreciate Tony pointing out that phosphomycin does not work against ESBL Klebneumo Um, I've, I've caught that mistake before. I know Amanda has um, because again, we all think that that extensory tetravenous vatolactamase scramnades are this kind of like homogenous group that all have the same problem. And again, you know that's not true anymore than it's true for any other infection. And and I think that, uh, that you know again, one of the things I really appreciate about these guidelines is they kind of call us back to the fact that you know we've learned over the last 20 years that, especially for urinary tract infections, you know we get such high concentrations of most beta-lactams and Bactrim and nitrofurantoin that you know you are going to get good clinical success and it isn't just an in vitro result you are going to get good, good clinical success.

Speaker 4:

Now, that being said, one of the things that the guidelines talk about too is, remember that uncomplicated cystitis in most patients tends to be a pretty, a pretty mild thing and in fact in some cases you don't even need to treat it. I mean people uh, occasionally women can just, you know, can, can, can, basically just push fluids and they do okay after a while. But you know, yes, antibiotics are often needed as well. But one of the things they point out for uncomplicated cystitis is that if you, you know, get a culture on a patient with uncomplicated cystitis, you start them on. You know again, you know back, let's say, you start them on, I don't know, bactrim or Nitroferanto and let's say it's resistant but the patient's getting better. You don't need to switch therapy, you can just go ahead and complete therapy because they are clinically improving. And you know, for years I've taught students, you know, treat the patient, not the lab. I think in this case it's treat the patient, not the culture. Result right If the patient's getting better.

Speaker 4:

You can go ahead and just complete courses. Now that is only for uncomplicated cystitis, for pylo, for complicated urinary tract infections or for any other, obviously, infection. If it's resistant you're going to want to use. You know, day one of therapy is going to be the effective therapy and that kind of transitions us into talking about effective therapy. And you know, in infections that are outside the urinary tract or again, or deep tissue urinary tract infections, and they, you know, in those patients, a carbapenem is still recommended as first line treatment for ESBL infections outside of the urinary tract. That is, of course, based on a classic study that they came out.

Speaker 4:

It seems like a million years ago that found that that, compared to PIP-TASO, that carbapenem has got better outcomes in patients with ESBL deep tissue infections, particularly ESBL blood infections compared to zosyn. So based on that, that is still the first-line agent. However, they also say that after appropriate clinical response is achieved and your in vitro results say it's susceptible to Bactro, susceptible to Cipro or levofloxacin, you can consider switching them to oral, a transition to oral therapy. So what do you guys think about that stuff?

Speaker 2:

I think that it, you know, has a positive impact on our patients in general for people to be aware of that, because if somebody is getting you know has a positive impact on our patients in general for people to be aware of that, because if somebody is getting you know an intravenous antibiotic, we know that potentially they could need a PICC line or outpatient infusions or coming to an infusion center and that might not be all be feasible or easy for our patients. So I think just educating and reminding people that you can safely step down to oral agents if the patient is clinically getting better and you have susceptibility data to support that, I think is a real important piece to the puzzle, just from all the potential other issues that you might have.

Speaker 4:

Yeah, I follow some of the big stud IED practitioners, twitter X whatever we're calling it this week and there's been a kind of a meme going around the church of the oral switch. Basically is what they're calling it. So I mean, you know, you know not being afraid, you know to use, you know the clinical data. Yes, the patient's getting better. Yes, the patient doesn't have a fever. Yes, the patient can eat food and keep it down and you've got a good drug with high bioavailability.

Speaker 5:

Yeah.

Speaker 4:

You know, I mean I think we've kind of forgotten that somewhere along the way, because I mean that was chapter and verse for me many years ago and it seems like kind of along the way we've kind of said, oh no, we better place a $5,000 pick line in this patient, it's like you know.

Speaker 4:

So, yeah, I agree that that's, that's. Yeah, I'm again resetting us and recentering us to kind of remember that sort of thing. Now, the one thing that that they talk about for for carbapenems and and again, I I did not know this, and so we talked a little bit before we started recording that in patients who are critically ill and or experiencing hypoalbuminemia which is pretty much everybody they actually call out meropenem or imipenem-celestatin as the preferred carbapenems. And the reason why they say that is that erdapenem is a highly protein-bound drug that has a long half-life. But in patients with hypoalbuminemia then there's more free fraction of the erdapenem that basically gets metabolized or excreted and so it significantly drops the half-life and it may not be optimal with just daily dosing this patient and I'm not going to lie, I'd never heard of that, and so we talked a little bit about beforehand. So, tony, what's your take on that?

Speaker 3:

Yeah, it's a it's kind of a tough area. There's pretty limited data about the subject so far. Most of the data do point that it's a possible piece you do have to consider a lot of these patients getting carbapenems are in the ICU. I think that there's been some pieces with some of the erdapenem group maybe having you know at baseline maybe a little bit higher risk, maybe higher like so far Apache scores. So there is that piece to consider. But there is also a study which is kind of the full backing behind this specific recommendation that did show a potentially five times increased mortality from a patient being treated with erdapenem an albumin of four compared to an albumin of two. So it really is an area that just needs a little bit more data. My research project for this year is we are going to be looking at that and seeing if we can find anything in our organization. So it really is just an area that needs a little bit more data to bring some more clarity to this.

Speaker 4:

I love it. We need some more data, so I'm doing it. You got to love those year-long projects for our PQI residents, so yeah.

Speaker 3:

So anyway, so yeah, so.

Speaker 4:

I had not heard of that. It sounds like it's somewhat controversial in the IB world. But, as Tony points out, there is this study that suggests that when you take a look at hypoalbuminemic patients, that erdapenem is associated with a higher clinical failure rate. I, you know. The only thing that makes me a little little like concerned about that is that I mean that would not just be true for ESBLs but be true really for all infections that we use erdapenem for. And you know the randomized control trial that I'm aware of, when they've looked head to head with with you know non, you know carbapenem antibiotics is they found pretty good results.

Speaker 4:

So yeah, it'll be very interesting, you know, I, I, you know a lot of times when, when, when we have our, our residents do projects, you know, some of them have really high clinical imports, some of them are more for like money. You know, where are we saving sort of thing. And I think this is going to, I think your project is going to have very high clinical import because, yeah, I don't really think so.

Speaker 2:

I think probably just kind of understanding how your micro lab reports things and what antibiotics like we've mentioned are ones that you should be choosing versus potentially other ones, and I just think that that's probably, you know one thing. Just to keep in mind, tony, and a quick add-on to the acute cystitis piece with essentially treating a patient with non-covering therapy.

Speaker 3:

That can even be beta-lactam. So if they've gotten, you know, four days of a five-day course of Keflex and you call the patient because they have an ESBL and they're saying they're clinically better, that is not, you know, a reason to bring them back in and treat them with new antibiotics or give them a new script um finish out the course of what was prescribed.

Speaker 4:

And we've done that in practice. You know, here was success so far, so right, and it is, and it is, yeah, and and that's. And it just to be totally clear that for deep tissue infection, for non urinary tract infections, that's a little bit different, right? So if you had somebody you started on, I'd help me Zosyn Banco, and it then came back as an ESBL producer. You switched to say meropenem. That would be day one of therapy for deep tissue infections.

Speaker 4:

So excellent, all right, so now we're going to turn our attention to AMP-C producers, and I'm not even going to attempt to explain AMP-C. I understand it kind of, but you know, amanda, what is AMP-C and why are we concerned about it?

Speaker 2:

Yeah. So I think it's one of those ID kind of mysteries out there, and the reason I say that is because it's not something that can be tested and reported in the micro lab, so it's just something that clinicians need to be aware of and think about. So I think about AMC, as a particular bacteria can produce this type of enzyme, so to say, and in the process, specifically if the course of therapy is going to be longer term, if the patient has a bacteria and we'll get into which ones of those potentially are more concerning than others produce AMP-C, it can actually go through a whole enzymatic process which then leads us to potentially develop resistance to a narrow-spectrum therapy and this is different from the narrow-spectrum therapy that might be intrinsically resistant to the bacteria in general. This happens more to the bacteria in general. This happens more. We see it specifically with the third generation cephalosporins, where we're concerned that they can develop resistance over time and it could look susceptible on culture results.

Speaker 2:

So when we talk about potential bacteria that can produce AMP-C, there's a whole gamut of reports and literature out there that say these bacteria might and these bacteria maybe and these ones are stronger, have a stronger correlation. So I think the ones that we think about are enterobactors, specifically the colloquiae, or Klebsiella erogenes, which used to be Enterobacter erogenes and that was renamed by the Microlaboratory Society, the CLSI, several years ago. So it was Enterobacter erogenes, now it's Klebsiella erogenes and then also the Citrobacter frondii, and, remember, there's multiple species of Citrobactors, so it's really important to specifically recognize that one. And again, there's a whole host of other pathogens or species of pathogens that could be potentially concerning. But again, I think you have to be cognizant of the fact that if you lump everything into a potential amp C producer again, what does that do to your potential epidemiology things? Along the way as well, Tony, did you have something you wanted to?

Speaker 3:

add yeah, and with those P's.

Speaker 3:

I mean I know some of the pharmacists out here are going to be familiar with these pieces because even I started to learn some of the acronyms going into my pharmacy school.

Speaker 3:

But we used to use the term space bugs in this area to define likely MC producers and this included things like serratia and proteus. So we have now kind of changed this. Now a new terminology that came out was kind of heck, yes, which, which included three that Amanda talked about Citrobacter freundi, Klebsiella orogenes, Enterobacter cloacae, but they added this Hophnia alvei and a Yersinia species to that. But this document only really calls out the three Enterobacter klebsiella orogenes and Citrobacter freundi, because we just haven't seen enough of this Hapnea or Yersinia in the US to kind of get a good firm stance on this. And so with these bugs they're particular to be marked as AMC, because in the findings it's around like 20% incidence, which is significant, and while some of the ones that are more minor, which are things like Morganella morgani, and while some of the ones that are more minor, which are things like Morganella morgani, Proteus, those things are less than 5% chance of being likely anti-producer.

Speaker 4:

So something to for sure be aware of when you're treating a patient, if maybe something's not getting better but not, you know, high enough percentage to just empirically treat differently, right? So so you know again, for for the you know, for for kind of everyone out there, you know, the reason this is important is that in, especially in long-term therapy, you have the potential that that that particular infection, that bug, can develop resistance as time goes on and you've actually the clinical failure. But also, if you're using a ton of of drugs that induce AMPC, the ecology of of your hospital can be affected by that and you can end up, you know, in a system of having more, more resistant organisms. So it's one of those. Because of this, if, again, if I remember correctly, ampc is spread, it's spread by plasmids, right? And so you know, basically it transfers to the next generation of organisms. So there's two reasons why you have to be careful about this the individual treatment as well as the surrounding resistance in your system. And yeah, I'm going to have to change.

Speaker 4:

Amanda knows that I've been teaching my bugs and drugs talk for 9 billion years. Here I'm finally going to have to retire the space bugs, and that, because that's what I was taught. I think part of that too, is that back in the day we used to give two, we used to do two drugs for that. Right Back in the day we used to give them, you know, glycosides with the beta-lactam, and I think that may have helped keep that from happening, because you were able to dust those bugs. You know, as I was always taught, that bugs don't retire that space.

Speaker 4:

Mnemonic or, and I like that. I've heard of heck yeah, heck, yeah, heck, yes, um yeah, and then you know, and you know, but, but bottom line is, we should not worry about mnemonics and just concentrate on, you know, kleb, uh, or enterobacter cloacae, Kleberogenes and citrobacter frondae, and if you see those, that really is the what you want to focus on. And then so you may ask yourself well, what? So it will be terrific. What am I supposed to do? Well, in my hospital, ceftriaxone is a workhorse that we use for lots of stuff and it is a terrific drug. I love it. I use it whenever I can because it's you know it really we. You know it keeps me from using a ton of Zosyn. It keeps me. It's once a day, which is really nice.

Speaker 5:

It's not renally cleared, which is really nice and all that stuff, but however, in these bugs in.

Speaker 4:

These. Bugs that are moderate are at risk for developing AMC production. We should not use ceftriaxone, so do you guys want to comment on that?

Speaker 2:

Yeah, so because you would want to avoid ceftriaxone potential use due to the AMP-C and then you would have resistance via other mechanisms to your more narrow spectrum agents as well. Probably, empirically a good place to start, I would say, is cefepime. That's where the literature leads us and again, a lot depends on the inducibility and the drug and there's lots of different theories out there. But I would empirically say that cefepime for potential amp C producers is a good choice and then, once you have susceptibilities back, looking at oral agents again, if the patient's improving, a step-down therapy again would be either the fluoroquinolones or Bactrim would be my go-to drugs in that.

Speaker 4:

So again, to be, you know, to make sure we're all kind of on the same page. So you know you're dealing with a deep tissue infection, abdominal infection, pneumonia, blood infection. With these three organisms enterobacter cloacae. With these three organisms enterobacter cloacae, cleborogenes, centrobacter frondae do not empirically or try to avoid empirically using ceftriaxone. In fact, empirically try cefepime in these patients. And we can do a whole other game changers on why almost nobody's allergic to cefepime. But that's a whole other thing for another day. You know that cefepime is a really good choice here.

Speaker 4:

And then, yes, stepping down based on your susceptibility. So again, don't go run screaming from the room If somebody has, you know, cleverogenies in their blood. You know, pay attention to the, to your, your in vitro susceptibilities and kind of go from there. So again, big, big change. I know this has kind of been brewing in IV circles now for six or seven years, but now I think you know these guidelines have really come in and clearly suggested that I'm going to have to watch out for that when I work in my ICU and I suspect a lot of the clinicians out there are just going to kind of keep an eye on that.

Speaker 4:

So any last things on that before we move on to our last little topic here.

Speaker 3:

No, I would just say, you know, when we talk about cefepime we kind of link it closely to Zosyn too as well.

Speaker 4:

But so far there's maybe just been a mix of data maybe not showing it to be as effective as cefepime, so cefepime really is going to be our workhorse for these bugs.

Speaker 4:

And you know, I've certainly seen and there's been increasing reports of neurologic toxicity with cefepime. I'm starting to get the feeling that's a you know. Yes, it happens. Yes, you have to watch out for it, but given the metric ton usage of Cefapime we have, if it, you know, it does happen, but it's pretty rare. So, again, don't be afraid of using Cefapime. You know, because, well, you know, gosh, they could get confused or they could. You know. Yeah, you know, that is certainly a possibility and you need to monitor the patient for that. But don't be afraid of using cefepime, especially again, for deep tissue infections or non-urinary tract infections with cefepime. You know for that point.

Speaker 4:

So then finally and we're just going to take a couple minutes on this for time reasons we're going to talk about CREs. So CREs are defined as members of the enterobacterioles group that is resistant to at least one carbapenem antibiotic, right? So obviously these are really scary organisms. I am so grateful that I rarely ever see these, but we're also aware of the fact that there are places in the United States, and certainly places worldwide, that this is common. They see it all the time. I shudder to think what practicing in those places must be like, but it can definitely be a problem. Now again, you know, I think at this point, if you're a general practitioner, time to get ID involved. You know, I think you know, unless you're just extremely comfortable and have a lot of experience dealing with this, this is where things start to get pretty difficult and trying to figure out what's going on.

Speaker 4:

So, and part of the reason for that is that you know we're not only talking about just the general, you know regular, you know enterobacteriolase type thing. But now we're starting to get into the weirdogram negatives like aciniobacter, stenotrophomonas, you know you've got a lot of these like unbelievably super duper resistant organisms. That again just gets very scary, to be honest with you. Now, fortunately, we now have about 87 antibiotics out there for super duper resistant gram negatives. But they all have one thing in common they're expensive as hell. And so you know again, smaller hospitals are simply just not going to carry them because they don't see them enough to deal with them.

Speaker 5:

So you know, rather than kind of break every single CRE down.

Speaker 4:

You know, I guess what I would say is you know, what would your guys' suggestions be besides getting ID involved for, especially for CRE infections outside? The urinary tract and then CRE infections inside the urinary tract, infections outside the urinary tract, and then CRE infections inside the urinary tract. So if the patient has, for example, cystitis and it's a CRE, and everybody again is kind of scared now what would you guys recommend?

Speaker 2:

Yeah, I think that's a really good question. I think I want to back up, though. When you talk about how would you approach these as your health system, I think a lot of it is. Again, partnering with the micro lab and knowing exactly what testing happens in-house is a send out, what things are available to you, what the turnaround time is, because those help you not only plan from a formulary standpoint about maybe what drugs you need to have on formulary or what drugs you need to be able to get in a certain timely manner, all of those things, but again, I think the testing results is probably a really important piece of it. You know, from that standpoint.

Speaker 2:

I think again, empirically I don't think, unless somebody has had a CRE, you're not going to empirically be treating, for you know a CRE pathogen and so I think really what you're going to do you're not going to empirically be treating, for you know a CRE pathogen and so I think really what you're going to do is you're going to say if Mr Smith has a history of CRE, you're going to look at his past cultures and sensitivity results, you're going to see what he was treated on in the past, how that infection was resolved, and then potentially pick your empiric therapy based off of that. I don't think there's like a one size fits all for, like your CRE, this is what I would empirically start. I don't know how you feel, tony.

Speaker 3:

Yeah, I think it's very difficult now for empiric starts, even with our even higher therapy for CRE, because before our main pieces was really just KPC and now we are starting to get more metallobatylaccomases in the US, likely not, you know, in some of our areas here, but across, you know, on some of the coastal sides, which you know we'll eventually get here, and that does limit our treatment.

Speaker 4:

So it really is important to get a specialist involved, an ID specialist, early, because if you get a metallobetalactamase, carbapenemase, you know organism that can be very difficult to treat and could lead to treatment failure. If you're not, you know, well-versed in how to successfully treat those infections, all right, yeah, and yeah, I mean I think yeah for this whole CRE part of this. I think the bottom line is, you know, as one of my favorite internal medicine docs says, know what you know, know what you don't know, and don't confuse the two. This is a place where, if you don't know, don't guess, don't you know, don't say, well, I can look up in Sanford, guide as good as anybody else, yeah, guide as good as anybody else. Yeah, don't do that.

Speaker 4:

Get infectious disease involved, because I think this becomes very specialized and you really need, I think, expert guidance to figure out what's going on there. So, yeah, you know. So we again, you know we could do two hours probably on the different you know types of CREs out there, but you know we're trying to focus on what primary care providers, pharmacists, physicians and other kind of you know ground level practitioners are dealing with. So any last thoughts from you guys.

Speaker 2:

No, I think you know, like I've mentioned before, it's kind of just the collaboration amongst your team, whether it's ID or your micro lab or your infection control. Knowing about your institution I think is so important because that helps you make empiric plans and it also helps you to understand how things are reported or the nuances and what you need to be cognizant of, and that 100% helps you. I know people sometimes are not fond of all the work that goes into all that planning and thought process, but really it will pay off when you need it to, because that will really help guide and direct a safe and effective patient care in a timely manner. Yeah, and I I completely agree with that.

Speaker 3:

I mean, some of the guidelines are very specialized, especially when we get into CRE stentropomonas, crab pseudomonas about more resistant coastal areas and you know, if you start start double therapy on stenotrophomonas in a population that you have that's 98% susceptible to Bactrim, I mean you're going to just create more resistance.

Speaker 4:

So so really knowing what you're seeing in your population, Right, and I mean you know again, pointing once again that you know a good antimicrobial stewardship team is worth their weight in platinum. A good ID pharmacist like Amanda is worth their weight in platinum. You know, utilize your experts. You know, don't assume you know everything in ID, because I think this is definitely an area where you know, yeah, get the experts involved and know your local antibiogram. You know, our team for years has tried to, like you know, get the word out. You know, make pocket cards, stick it up on the intranet of our system, and I still always have physicians going. So is this going to be susceptible? And it's like, well, why don't you look up the antibiogram? It's why they do all this work, you know. So back to you, jen. I think you know again. I think that's you know. I think there's some key pieces to this, but that's definitely one of them.

Speaker 1:

Yeah, absolutely, absolutely. Thank you for going through those, and I appreciate the expertise on this team. Tony, you're in good hands and it sounds like your project is super exciting, so best of luck with that as well. So thank you to all of you for being with us this week. This is a super important topic, you know. I think we take we take antibiotics for granted, so even at the most basic level, we need to be super, super diligent and have those stewardship programs in place. So so thank you for reminding us of all of that, and that is it for this week. So, if you are a CE plan member, be sure to claim your CE credit for this episode by logging in at CE impactcom and, as always, have a great week and keep learning. We'll talk to you next week.

Speaker 5:

Thanks for listening. Then claim your CE credit by clicking on the link in the show notes and check out CE impacts other education at CEcom, where we curate the most important information in pharmacy and medicine to deliver straight to you. Join today to connect your learning to practice.