Episode 108
108: StAR: MDR GN
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 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)
Transcript
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.
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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.
