The Next Frontier: Rapid AST to Optimize Care of Patients With Bloodstream Infections

7:47

The Ongoing Challenge of Antimicrobial Selection for Bloodstream Infections

I will start with a section on the ongoing challenge of antimicrobial selection for bloodstream infections. Just a bit of background where I'm coming from with this presentation. I'm a clinician. I spend the majority of my time on either a teaching clinical service with residents, fellows, students, or a non‑teaching clinical service with APPs. And so most of it is spent in clinical decision‑making and patient care. And so I'm going to be presenting to you just like what it is that we're doing on a daily basis when we're seeing these patients.

Clinical Case

We'll start off with a case. This is a 52 year old patient who has well‑controlled diabetes. The patient was admitted to a rural safety‑net hospital with fever, dysuria, and flank pain. The initial urinalysis that was obtained showed a 3+ leukocyte esterase, 2+ bacteria, WBCs. Seems like the person has a urinary tract infection. They also obtained procalcitonin. Pretty high, 6.2. Peripheral white blood cell count 18.5. The patient was empirically started on ceftriaxone 2 grams daily. Then a CT scan of the abdomen and pelvis done in the emergency room showed pyelonephritis. They obtained blood and urine cultures which showed on gram stain gram‑negative rods. The ceftriaxone was continued while the cultures were pending.

Worldwide Sepsis Incidence and Death: 2017

So that's the case that we're framing things for.

9:29

And so thinking about sepsis, September was Sepsis Awareness Month. It's something that is on many of our minds and there are about 48.9 million cases of sepsis that have been identified worldwide with 11 million deaths that were reported. 19.7% of deaths worldwide are due to sepsis. It is a really important problem for us as infectious diseases clinicians. Even if you're not an infectious disease clinician, you are taking care of folks as a hospitalist or other specialists, these are things that we need to deal with all the time. And the incidence of sepsis kind of varies worldwide depending on the geographic location, with higher incidences that we can see in South America and Sub‑Saharan Africa, as well as in some of the Asian countries.

BSI Burden and Mortality

So the burden of bloodstream infections and mortality globally has been also documented. So the global estimated burden of bloodstream infections, this was in 2019, was about 119.2 million disability‑adjusted life years, accounting for about 2.9 deaths. And 51% of the bloodstream infections and deaths from the bloodstream infections are from Gram‑negative bacteria. And so Gram‑negative bacteremia is a problem that we really need to be thinking about as we're considering the impact of sepsis on our patients.

There was 1 study that was done in Ontario in 2017 that looked at the burden of bloodstream infections, that found that the incidence was about 150 per 100,000 population. The most commonly identified organisms were E. coli with about 40 per 100,000 population, and then Staph. aureus with 22 per 100,000 population. And the mortality risk does vary by the organism, with Staph. aureus having higher adjusted odds of mortality than E. coli. This is something that we have experienced clinically, but Gram‑negative bacteremia is still a really big problem.

BSI Burden and Mortality: By Organism

And so this slide kind of shows the burden of bloodstream infections and mortality by organism. And you can see that the Staph. aureus and E. coli are the ones that have the largest mortality, as well as the highest number of episodes. And so even though E. coli is bacteremia more common than Staph. aureus, the mortality is slightly higher with Staph. aureus.

But you can also see on the left hand side where some of the other organisms that we do concern ourselves with, will be falling. And when we think about the burden of antimicrobial resistance, sepsis, and why we do what we do in terms of antibiotic stewardship, 1 of the things that come to play is Clostridioides difficile. And C. diff is an issue that causes—the bacteremia from C. diff less common, but the morbidity and mortality from C. diff is a problem that we do need to be concerned with.

Ongoing Threat of Antimicrobial Resistance

So speaking of antimicrobial resistance, we have an ongoing threat globally with about 1.14 million global deaths attributable to bacterial antimicrobial resistance. And this is expected to increase as we use more antibiotics, as we lose more antibiotics. And the threat is partially driven by this overconsumption and inappropriate use of antibiotics.

Percent MDR E. coli and P. aeruginosa CLABSI: 2023

So we're talking about, how can we use our antibiotics better? A couple of the organisms that are really important in our overall view of antimicrobial resistance. Thinking about Enterobacterales that are multidrug resistant as well as Pseudomonas.

CDC Antibiotic Resistance Threats Report 2019: AMR Threats in the US

You will see that the CDC has identified several types of organisms as urgent threats as well as serious threats. And thinking back to our case that we started off with, this patient had an E. coli bacteremia and when we look at the threat levels of serious hospital onset, ESBL‑producing Enterobacterales are really an important thing for us to be considering.

US and Global Health Disparities in Sepsis, BSI, and AMR

Just wanted to give you a slide on the US and global disparities in sepsis, bloodstream infections, and antimicrobial resistance. So it's important for us to understand that while these issues are important to us in general, sometimes they do not affect populations in the same way. And understanding disproportionate impacts of sepsis, bloodstream infections, and antimicrobial resistance can help us as we're thinking about how can we be intentional when we're developing our antimicrobial stewardship initiatives, or assessing what the potential risks are so that we can help our patients to be safe.

And so the data that you see on the screen, which you will be able to take a look at afterwards, looks at, you know, from a bloodstream infection, for example, disproportionately higher rates in people who are experiencing poverty, household crowding, and lower education rates. And there's also global disparities with increased rates seen in Western and Sub‑Saharan African countries.

From a sepsis standpoint, we have data in the United States that shows that Black, Native American, and Hispanic people have higher sepsis mortality compared with their White counterparts. And some of that may be related to the, you know, a delay in diagnosis, delay of recognition of the signs and symptoms of sepsis. And opportunities for us as your healthcare professionals to educate the different communities on what the signs and symptoms are of sepsis so that they can recognize it earlier and maybe bring these rates down.

And then from an antimicrobial resistance standpoint, we have data that suggests that groups from racial and ethnic minoritized groups may have higher risk for infections with pathogens that have increasing antimicrobial resistance. And that includes, you know, bacterial and fungal organisms.

Inappropriate Antimicrobial Prescribing Drives Resistance and is Inequitable

So when we think about the drivers of antimicrobial resistance, inappropriate prescribing is 1 of them. And that also translates to where there are inequities in inappropriate prescribing. And so this slide has a few of the data that has been collected looking at where some of this inappropriate prescribing occurs.

So we can see differences in antibiotic prescribing based on the patient race and ethnicity, geography and socioeconomic status. There's also data that shows that the clinician who is doing the prescribing, the prescriber, whether or not their age is greater or less than 30, or if they are a physician vs an APP, or how much years of experience that the prescriber has, can also play a role in how people prescribe. We see that there are data that suggests that people who are not White are less likely to receive empiric antibiotic broad spectrum therapy than the patients who are White. And this is a trend that is seen in the West and South Central regions of the United States. There's insurance disparities as well, where folks who have private insurance are more likely to receive antibiotics inappropriately and overall, compared with folks who have public insurance or uninsured.

So all of this is meant for us to understand that prescribing differences occur. And it's in the context of why do we need to prescribe antibiotics appropriately? We all know this. If we are not giving a patient appropriate antibiotic coverage, we have increased mortality, length of stay into the hospital, hospitalizations are more costly. If we give them broad spectrum antibiotics unnecessarily, we increase the risk of C. diff. We increase the risk of AMR, adverse events and mortality. And so it really requires us to be more judicious with how we prescribe our antibiotics.

Difficulties in Optimizing Antibiotic Use in BSIs

But there are difficulties with optimizing antibiotic use. Some of this is the diagnostic uncertainty. As a clinician, oftentimes we get called because the patient comes in with symptoms but we're not 100% sure what exactly is it. Is it sepsis? Is it not? Is it bacterial? Is it not? What is causing it? We don't know the answer to that yet. And so therefore the need to know the organism that's causing the bloodstream infection really can help us to reduce that diagnostic uncertainty and guide appropriate antibiotic choices.

We have our traditional culture methods that require 24-48 hours, and that delay is causing us to potentially be more broad in our initial antibiotic selection. And we have the issue of antimicrobial resistance, where we don't necessarily have the data that we need to know which antibiotic to choose upfront and perhaps if we choose wrong, if we guess wrong, we could be contributing to AMR in our population. If we guess wrong, we could also contribute to undertreatment of our patient and that's really, as clinicians, something that we wrestle with. And so that's that balance between prioritizing patient safety and stewardship.

Key Takeaways: Challenges Selecting Antimicrobials for BSIs

So the key takeaways from this, for me as a clinician thinking about selecting antimicrobials appropriately for bloodstream infections, is that sepsis and bloodstream infections are common. We see them all the time. They cause millions of deaths every year and are very costly. There are disproportionate burdens in low income, middle income countries. There are disproportionate burdens in rural vs urban settings and in different demographics. And we also see inequities in prescribing. And so there's a lot of work for us to do in trying to ensure that we're doing this appropriately. We know that inadequate antibiotic coverage can be linked to increased mortality in length of stay but unnecessarily broad antibiotics can cause adverse effects. And it comes down to, how can we optimize the selection of our antibiotics and reduce our commission bias of choosing things more broadly because we don't have all the information?

Clinical Case: Follow‑up

So in this particular patient, what happened was that patient was diagnosed with pyelonephritis, as we saw. The Gram‑negative bacteremia was initially treated with ceftriaxone. By Day 2, still wasn't improving. By Day 3, it grew the E. coli. Stewardship—or the susceptibility testing was in progress. Ceftriaxone was continued. By Day 4, fever was continuing, patient was not improving, CT scan revealed a developing renal abscess. And then finally we got the susceptibilities back, showing that the organism was resistant to ceftriaxone. At that point, ceftriaxone was changed to ertapenem. So now Day 4, Day 5, and the next couple of days patient became more stable, ready for discharge, and then sent home on oral levofloxacin.

How Rapid AST Could Have Helped In This Case

But there are ways that rapid AST could have helped in this case. So first, the resistance to ceftriaxone could have been identified within hours instead of several days and then we could have had an earlier switch to more effective therapy. That may have prevented the development of this renal abscess. Hard to know. But we do know that this patient had a prolonged fever and bacteremia sepsis symptoms, while they were on inappropriate treatment. They could have recovered a lot faster if we had switched them over to the appropriate treatment sooner and have been discharged from the hospital, therefore got less of a hospital bill, or at least less cost to the hospital itself. And so there's a lot of opportunities for implementing rapid AST to help out with our clinical decision-making.

[00:25:36]

Questions and Answers

With that, I'm going to pause for 3 minutes of questions and answers. Remember to use your iPads for your questions. If you would like to hold your question to the end with the panel, that's all right as well. But we'll have an opportunity for those who are online and in the room to be able to field any questions that might come in right now. Thank you.

Dr Veve: So while we're waiting for some questions to come in, I have 1 for you. Thanks for the really informative talk. So I know you were talking about geographic location and race as maybe predictors associated with inappropriate antimicrobial therapy. And I've seen you talk on this topic elsewhere, but I wondered what your thoughts were for social determinants of health and how those also kind of intersect with the global problem of inappropriate antibiotic use?

Dr Marcelin: Yeah. So just a clarification. It's not that it's a risk factor. It is that there are differences in the prevalence of these—of AMR, of these other—of sepsis and other complications in certain groups. And so the social and structural determinants of health play a huge role in that. And so if you think about what social determinants of health are, these are the things that are the environments in which people live, work, play, and they affect all of the ability of individuals to be able to have good health.

And so, for example, if we have a group of individuals who are living in a rural area, who have less access to health care that is reliable, the nearest healthcare facility is, you know, 4 or 5 hours away; and they also have less access to pharmacy because they're living in a pharmacy desert; and they also are employed in an occupation that puts them at increased risk of exposure to antibiotic‑resistant organisms, for example, farming; then when that person has an injury or develops an illness, the likelihood of that infection being antimicrobial‑resistant infection is higher just because of their risk of being in that environment where they are living and working and playing.

And the fact that they are 4 or 5 hours away from the nearest hospital makes it so that their risk of sepsis is higher because they have to wait that much longer to get to a place, and maybe they might make a decision, because it is a bit of an effort to get to that hospital, to maybe minimize the symptoms or say, “I'm sure it'll get over, I'll get over it pretty soon.” Or maybe they just don't recognize it. And until that person is very ill and EMS needs to be called, at that time, once they get to the hospital—remember, it's 5 hours away, or maybe they have to be life‑flighted somewhere—they are coming into the hospital critically ill in the ICU.

And so those are the ways that the social determinants of health intersect. And things like race and ethnicity are parts of the overall social determinants, because of how structural racism and redlining and other policies have made it so that people are living in those areas that are increasing their risk of exposure, etc. Thanks for that question.

Dr Veve: Thank you. We have some other questions that have come in, but I think we'll transition to Dr Alexander and then we'll go through some questions towards the panel at the end.

Dr Marcelin: Yes. Thank you.

[00:30:17]

Integration of Genotypic RDT With Rapid Phenotypic AST for Bloodstream Infections

Dr Jose Alexander (Advent Health): So now we’re going to transition to the laboratory portion. And I want you to see this in a very simplified way. When we talk about antimicrobial stewardship for bloodstream infection and laboratory diagnostics, let's see that antimicrobial optimization in 2 different ways: escalation and de‑escalation. What opportunity we have. The implementation of these technologies is always beneficial, or you can obtain the most benefit, if you have an antimicrobial stewardship program that is able to intervene. If you have this technology in the laboratory, you don't have a communication pathway and you don't have protocols as to what to do with those results, literally just wasting money. So these tests are expensive. These test can actually have an impact if they are utilized in the best way possible. The best way to start is with a poll.

[00:31:06]

Poll 3

How far into the process of implementing rapid phenotypic AST is your institution? So I'm going to give a few seconds.

• It's not on the radar;
• It's an early discussion;
• In process of implementation; or
• It's fully implemented.

Okay. Well, fortunately, we have implemented 40% and in early discussion, so I don't know what microphone am I using, but here we go. It’s back. So the idea is that what we can do and how can we implement rapid AST? Now, if there is a spot for rapid PCR, and let's just call it BCID, as we know the rapid PCR done in blood. So can we implement both of them or we have to implement 1, only 1?

[00:32:21]

Typical Patterns of Intrinsic Antibiotic Susceptibility and Resistance In Enterobacterales

So before I start it's important to put in perspective antimicrobial resistance. So Enterobacterales is the most typical Gram‑negative that we isolate in the group, that we isolate in the laboratory. E. coli is the most predominant 1. So based on our data from our institution we know E. coli is the main organism. In dividing Enterobacterales group into E. coli, Klebsiella, and Proteus vs SPiCE‑M group make a lot of sense for the perspective of what we're looking for and what we can do with them.

So we see E. coli, Klebsiella, and Proteus, that what we consider wild types to be susceptible to third generation, fourth-generation cephalosporin and carbapenems. There is a caveat with Imipenem and Proteus mirabilis that it could be resistant by porin restriction, not necessarily because there is a carbapenemase, and that is an important consideration with that particular organism.

In the group of SPiCE‑M they carry an intrinsic MC, that is a cephalosporinase could be or not susceptible to third generation cephalosporin, should be susceptible to fourth-generation cephalosporin, and susceptible to carbapenems. So that in the same group of the SPiCE‑M, there is some of those organisms that have a high risk of expressing MC quickly, and those are the ones that we need to make sure that the narrow spectrum that we use on them is cefepime if there is no any other resistant mechanism involved.

Having this in the perspective is critical to be able to know how this technology, the BCID and rapid AST, is going to feed into the equation to provide the patient with appropriate escalation or de‑escalation of treatment.

[00:33:54]

Mechanisms of Resistance in Grain‑Negative Bacteria

Antimicrobial resistance is multifactorial, but 1 advantage that we have right now with the Enterobacterales group is that most of the beta-lactam resistance is very well defined based on beta‑lactamases. We have ESBL. That is, CTX‑M is the most predominant gene circulating, and it can be identified using rapid BCID. We have a group of carbapenemases gene that can also be identified. We know that we have other mechanisms that we cannot, like porin restriction, efflux pump play a significant role.

And at this point, it's important to have, and also in perspective, there is this other group of Gram‑negatives that are the non‑fermenters: Pseudomonas, Acinetobacter. That group is very difficult or almost impossible to define phenotypically based on a BCID, because they have resistant mechanism that we don't have a gene specific target in the BCID, or the mechanism is mediated by mechanism that we cannot identify by PCR. So like porin restriction in Pseudomonas aeruginosa producing a carbapenem‑resistant Pseudomonas. The only way for us to be able to see that is having a full phenotypic profile of that organism. So rapid AST play a significant role for non‑fermenters because you can have access to a full phenotypic profile that is accurate and more reliable than using only BCID.

[00:35:14]

Clinical Case

And then back to the case. A patient was admitted on day zero due to a complicated UTI. The patient was in stable condition. Elevated procalcitonin and white blood cells. The initial UA was positive with ongoing urine culture. Patient started meropenem and vancomycin and the positive blood culture showed up in 24 hours incubation. Detected E. coli. No gene detected.

So to be able to use all those criteria, it's important for the facility to have a very well‑defined cumulative antimicrobial data. So if you can use those genes, how an E. coli that is ESBL compared with an E. coli that is not ESBL? How that E. coli compared with E. coli KPC, for example? So defining those antimicrobial resistance and profile can help the antimicrobial stewardship team to be able to escalate or de‑escalate based on the presence or absence of those genes.

And in this particular case on Day 2, the patient was responding well at treatment, normal renal function, no fever, white blood cell was improving, and the E. coli was confirmed in the urine culture using MALDI‑TOF.

[00:36:20]

Poll 4

So with no other clinical information and in a very simplified way, would you de‑escalate meropenem based on the rapid diagnostic, in this case the BCID, since the E. coli didn't have known any gene detected? You continue with Meropenem or you de‑escalate from meropenem?

Okay, 93.3% said de‑escalation, 6.7% continue with meropenem. Are any of you a physician in my facility, that say 6.7%?

So the de‑escalation and escalation is critical, right? But you need to understand the epidemiology of the gene that you have circulating. In our facility, we were able to determine that ESBL in blood is 97% CTX‑M. So we still have 3% that are not CTX‑M. So a risk assessment of the patient condition, the clinical condition, the multi‑drug resistance assessment is critical for this type of decision.

[00:37:33]

Genotypic Rapid Diagnostic Tests for BSIs

So we have multiple rapid diagnostic test, PCR, in clinical use currently. I always say that depending on the situation, depending on the condition that you have, we have the BioFire FilmArray, 3 different organisms. Detection of resistant genes have around 1 hour turnaround time. We have the Cepheid that is specifically for gram‑positive cocci in clusters to define MRSA for MSSA. We have the ePlex that used to be the GenMark, now is the – the Roche ePlex. They have organisms also beyond pathogens that can be identified as a contaminant that can help to d‑escalation. The famous Luminex Verigene battle horse that I don't know if it's still around. Some people using MALDI‑TOF with a specific protocol to be able to identify directly from blood. Some FISH technology and the T2 Biosystem that was actually based on direct blood, no actually a positive blood culture.

But in definitive, the important thing is there is still facilities across the US that don't use BCID. And this is kind of mind blowing that we have this amazing technology to be able to optimize treatment based on organism identification and with good cumulative data to antimicrobial resistance genes, and they still are not in use.

[00:38:50]

Rapid Diagnostic Tests: Resistance Markers for Earlier Targeted Therapy

So what is important of the resistant markers? Well, the rapid diagnostic actually shortened the time to appropriate therapy for escalation. And this is 1 of the critical aspects. So a Gram‑positive cocci, Gram‑negative rod that we identify in our facility with resistant genes, we know that CTX‑M and Enterobacterales, we have 100% susceptibility to meropenem because we define the organism ESBL vs CRE. We haven't found – or at least until this point, I think we just found the first – no carbapenemase producing CRE. And that's an important aspect, because now we start seeing those organisms circulating when the BCID may fail because there is no specific carbapenemase gene.

So when we have a KPC, meropenem, vaborbactam is a drug of choice. When we have a metallo‑beta‑lactamase in Enterobacterales, ceftazidime avibactam, plus meropenem, plus aztreonam is a drug of choice and we have an OXA 48. So the current dynamic of this epidemiology of metallo‑beta‑lactamase and KPC is changing in the US, so identification of the gene is critical. And this is 1 of the advantages of the BCID.

So from the perspective of the implementation that we are right now in the process, the detection of a gene based on the BCID is enough for us to escalate, since we know the profile of those particular resistant mechanisms. Do we need a ASD in this case in our facility? No, in the case of Enterobacterales, but we need it for in the case of the non‑fermenters.

[00:40:22]

RDTs: Benefits and Limitations

But there is benefit and limitation. So the benefit allow for early optimization of antimicrobial therapy. So we can escalate quickly. I don't see any situation when a patient will come to the hospital and we're going to put the patient on meropenem vaborbactam, empirically, right? So a patient that has a carbapenemase is by default a drug‑bug mismatch. So an escalation as soon as possible is critical to reduce mortality, and if you use with antimicrobial stewardship oversight.

Associated with decreased hospitalization, hospital length of stay, if it's used with antimicrobial stewardship program because we need that communication. In our facility with EPI, we have an in‑basket. Every time that that result automatically trigger to antimicrobial stewardship team and they're able to do the intervention.

But there is limitation. Supplement but cannot replace the full phenotypic AST. There is always variation of drug resistance. And knowing the risk and the – the different of that variation is critical. So knowing your data is important. Not all genetic marker resistant and included. If we looking for porin restriction, efflux pump or some obscure beta lactamases will not be there. Unable to detect resistance caused by porins, specifically non‑fermenter, is very difficult. If you find a Pseudomonas, there is a carbapenemase, but you don't find a Pseudomonas, that doesn't mean that carbapenem—Pseudomonas could be carbapenem resistant. And genetic markers are unreliable for the non‑fermenters group.

[00:41:51]

Conventional Blood Culture AST Workflow: Limitation

This is how the blood culture looks in a standard process. We have a positive blood culture that could be positive from 1-5 days. We have a gram stain, we report to the floor. We do a BCA – we plating that blood, and we wait for maybe 16, 24 hours. Now we have the blood, the growth, we have the organism we are able to identify, and then we have to wait 16, 24 more hours to have an antimicrobial and is when we do optimization. If we do BCID, we can optimize based on organism and genetic – and genetic profile. But a full optimization is done down – down the road of 48 hours with optimization, antimicrobial optimization.

[00:42:30]

Rapid Phenotypic AST Platforms for Blood Cultures

So this is the standard workflow, but when with the access now to rapid phenotypic AST, we can actually reduce that and not necessarily for escalation, but now we can optimize de‑escalation or have a better profile for non‑fermenters. We have multiple platforms that are being used. And these platforms, they use different techniques. So technically the blood, the positive blood culture that is set, the instrument have different approaches to be able to detect. Some of them use the morphogenetic cellular analysis based on FISH technology, microfluidic or resonant frequency to evaluate the mass and the amount of organism. We have some blood microdilution that use microscopy, like the Q‑Linea. We have the Selux, that evaluates also the viability by fluorescence. And we have the Vitek reveal that a blood microdilution that evaluates based on the volatility of some metabolism. So technically it's evaluating the metabolism of the organism and the organism is growing or is not, and that directly correlates with the activity of the antimicrobial.

The other significant aspect is where you get the ID. So 1 of the advantages of this new system is that they don't have an ID required, like in the case of the acetophenone that based on the FDA approval, you need to have an ID performed by the same instrument. In this, you can bring the ID from other instrument like a BCID, for example, or PCR.

And you see the average turnaround time, all of them are within seven hours. So that's an significant improvement vs 46 hours or 50 hours that we currently have with the traditional phenotypic testing. This can allow your team to be able to have a reliable full phenotypic profile for de‑escalation or escalation of unusual organisms.

[00:44:22]

Blood Culture Rapid Phenotypic AST Workflow

So this is how it looks or this is how we are foreseeing the implementation in our facility. So we have a blood culture that turned positive. We do a gram stain, we do a BCID, we have the organism ID, we set up the rapid AST, and we are expecting to have 8-10 hours optimization of therapy. So we are reducing between 36 and 40 hours.

Now, do we need data to see how these translate to clinical outcome? Sure. But every facility is different. If you look for a small community hospital, without the same resources from a big academic center, you will have a completely different outcome. You will have different impact. But just by a rational approach if you, as a pharmacy, as an infectious disease physician, are able to get a full AST for your patient that have a bloodstream infection 40 hours in advance, don't you think that that can make a big change for that patient?

[00:45:20]

Rapid Phenotypic AST: Clinical Impact

So what is the clinical impact? Well, rapid phenotypic AST significantly reduced time to actionable result and can improve antimicrobial decision making. You actually have the full susceptibility profile of the organism. The action depends on the effective implementation, workflow integration, clinical response, and collaboration with antimicrobial stewardship team.

So that is another aspect. If you don't have this communication and this action, that you are actually losing a lot of the potential of the utility for this diagnostic. The BCID of the rapid PCR have no definitively proven mortality benefits. Observational studies suggest improvement, antimicrobial use, and hospital length of stay.

[00:46:04]

Posttest 1

Now, I know you guys were very confident at the beginning, but I am confident in my ability to communicate the benefit of rapid phenotypic AST to decision makers at my institution.

Okay, so we have more confident people now. That's good.

[00:46:50]

When and How My Institution Uses Rapid Phenotypic AST

So when in our institution, how we are planning to use rapid AST. Enterobacteriaceae resistant gene detected? No, we have a good defined plan. We have a good understanding of the epidemiology. We have a good profile for each organism based on resistant genes. And rapid PCR can actually drive treatment escalation.

Enterobacterales with no resistant gene detected. That's the best target for us. Being able to— rapid phenotypic AST can facilitate the escalation by providing susceptibility to basic penicillins with inhibitor, quinolones, and even trimethoprim sulfate for do PO conversion as soon as possible.

But in the non‑fermenter group, yes, all non‑fermenters will be used directly to rapid AST, because we know that it's a Pseudomonas or it’s Acinetobacter. We know that the rapid diagnostic or the PCR are no reliable in detecting some of the resistant mechanisms they have.

So the primary goal is for the escalation and narrow spectrum beta‑lactamase LPO conversion. If you don't have access to BCID, the rapid AST can actually cover the entire spectrum of the organism. You will have phenotypic data for escalation and de‑escalation. But if you have the BCID, you can use the BCID but you have only the organism identification.

[00:48:09]

Case: E. coli With No Resistance Gene Detected by RDT

And this is how they look for us. So we have a Gram‑negative that is identified as an E. coli. There is no gene detected. We have a 3% chance that that E. coli is not a CTX‑M. And we know that they could be—it could be—could not be a CTX‑M because we have evaluated and see that some of the other SHV, OXA are present. So when we have these E. coli, we set up the phenotypic AST. So the trigger is an Enterobacterales with no resistant gene. We do a second screening for those 3% ESBL with ceftriaxone and ceftazidime.

If it's detected it's an ESBL, we don't do anything else. But if it's not detected, we are able to release antimicrobials that allow the clinician to de‑escalate. Rapid – rapid PCR, the BCID give you the evidence to de‑escalate the narrow spectrum if third generation. Lower than that, we don't have any evidence that we can continue de‑escalating. So now we have the opportunity to go all the way down to penicillin with inhibitors or even agents to provide a PO conversion.

The other advantages? Well, in 2024, we have around 1,652 organisms that met this criteria that we will be able to provide rapid AST and have a full susceptibility profile within 10 hours.

[00:49:27]

Integrating RDT and Rapid Phenotypic AST: Takeaways

So what is the takeaway? Conventional method may require 72 hours for identification of bacteria, antimicrobial susceptibility profile. The BCID of rapid PCR allow for early optimization of antimicrobial therapy for organisms with detected resistance genes, but not all resistant markers are included. Genetic markers are unreliable for some bacteria and non‑fermenters, and do not replace AST, but give you the option to avoid the drug mismatch of almost every single patient that have a highly resistant organism. Traditional phenotypic AST takes several days, so the opportunity with the rapid phenotypic AST is the short time, seven hours, within seven hours based on all the platforms that are currently available.

[00:50:08]

Posttest 2: Case

So this is the posttest case. A hospitalized patient that was started on empirical meropenem and vancomycin for a complicated UTI they found to be a bacteremia with a Gram‑negative bacilli. The genotypic of the PCR was a E. coli with no resistant genes, and that is the phenotypic AST result. Susceptible to ampicillin/sulbactam, cefepime, meropenem, trimethoprim/sulfamethoxazole, but resistant to ciprofloxacin. The condition of the patient is stable and the patient is improving.

[00:50:41]

Posttest 2

Assuming that there is no contraindication based on the rapid phenotypic AST result reporting susceptibility to all except for ciprofloxacin, what would be your recommended action in this case?

So we have an increase on discontinue meropenem and switching to PO conversion with trimethoprim/sulfamethoxazole. And – and I think that is the opportunity that now we have to do that discontinuation quickly not only for narrow spectrum avoid antimicrobial resistance, but also to be able to put the patient in an oral treatment as soon as possible. I think this is okay.

[00:51:51]

The Antimicrobial Stewardship Program Role in Implementing Rapid Phenotypic AST

Dr Veve: What's going on everybody? Good morning. My name is Veve. I'm a ID pharmacist at Henry Ford Health in Detroit and Wayne State University's College of Pharmacy. So, I'm going to talk a little bit about the implementation side and considerations. I know, looks like a mixed crowd. I'm sure there's a lot of folks considering adapting rapid phenotypic ASTs at their health system.

[00:52:22]

Blood Culture Rapid Phenotypic AST‑Considerations

So, you know, I wanted to start with—I don't think this is a test for every hospital, and the previous speakers kind of talked a little bit about some of the considerations to make or really some of the challenges, depending on where your practice site is. So, you know, it's not for everyone, but there really is an opportunity for the right site.

And, you know, Jose was kind of talking about the prevalence of genotypic rapid diagnostic testing and how maybe we've seen increases in the test utilization. And, you know, that might be enough with traditional AST for some sites, right? And a lot of that's going to be contingent on laboratory capacity and stewardship personnel to make sure that a rapid phenotypic AST is the right move for you.

And then, on the other hand, it's challenging to identify the right patients and organisms to treat. And you really have to dive into your local epi and potential practice barriers to identify the right person, the right patient, and the right organisms to apply rapid phenotypic testing.

[00:53:30]

Blood Culture Rapid Phenotypic AST: Implementation Considerations

So I'm going to touch on this slide a little bit. But these are considerations for adapting, really I would say, any rapid diagnostic test that your hospital or health system, but trying to spin it towards the rapid pheno AST platform. So, first thing could be the stewardship team, the micro team, and infectious diseases physician colleagues perform a gap analysis. So thinking about performance, the current landscape of performance at your health system, and maybe what are some of the goals that the C‑suite has. Or there's other directions for the stewardship team, and that can lead to some positive discussion about what org and who to test.

Combine that with some of the local epi data. Look at your antibiogram. Look at the frequency of organisms, particularly, maybe some of those that we don't have reliable genotypic markers from some of the bloodstream infection, PCR testing.

And communication. How are you going to do it? You can adapt rapid diagnostic tests, but if you don't have a good platform of communication or pathways, generally you're not going to see that return on investment or value for patient care and in this case, timely, appropriate antimicrobial therapy.

Other lab considerations, you know, is this going to be a 24/7/365 approach or is it batched? What about your stewardship personnel? How frequently are they working? Is there consistent stewardship coverage for the 24 hours or, you know, does third shift kind of get left off there?

And then education, right? Like who's the end user for this test, right? And I'm just thinking in my hospital, really think it's going to be hospitalists and intensivists who are primarily going to be seeing this, and a bunch of medical residents, fellows, and different clinical pharmacists. How do we educate them and how do we identify this in the electronic health record so that these results are actionable?

And then last but not least is kind of the quality assurance process. And I'm a big believer in, if you implement something, you really need to evaluate it to justify kind of the implementation process.

So these 6 things are some significant considerations for rapid pheno.

[00:55:38]

Decision Making Proposal for Rapid Phenotypic AST

But I wanted to take it a step further. And you're like, “All right, what is this guy talking about?” And I want to use a case example of hospital and site‑specific considerations. And I want to showcase how at my site we've done the same thing. So for hospital consideration, what's the landscape? What does that look like for you? What do you have available and where's that added value for rapid phenotypic tests? How's that? How's that going to look like?

Talking about the stewardship program and microbiology lab capacity and space and some of those workflow limitations.

And then location specific considerations. Do you care for a large population where timely antimicrobial or antibiotic therapy is most likely to see a benefit? And I think literature, the literature based approach would be critically ill patients in septic shock. We know that that's where time really matters most over the grand scheme of patients with infections. What about immunocompromised populations, solid organ transplant recipients, and maybe some other immunocompromised folks, where the prevalence of resistant organisms may be a little bit more common?

And then taking a step back and looking at challenging Gram‑negative bacteria at your site, how often do we see these from blood? Are they typically resistant? What's kind of like the resistance patterns there look like for your site? And how common do we think these tests would be useful within those populations?

[00:57:11]

Decision Making Proposal Example: My Health System

So I'm going to fill in the blanks here. And you know my health system, Henry Ford in Detroit, so some of the existing diagnostic tests we have, we have an MRSA nares. We use genotypic blood culture identification. We have some respiratory and meningitis/encephalitis panels and urine antigen testing. But we don't have an existing pheno. And how do we show value, given the – the landscape of rapid diagnostic tests, can be can – can be a challenge.

I think we have an excellent infrastructure, but I'm biased. But there are still some concerns about how these results get reported to frontline clinicians and how are they interpreted from or distinguished from genotypic testing?

And populations likely to benefit? We have a lot. We have high acuity illness. We're a large hospital and health system in an urban metropolitan area. We see everything. We see a lot of those populations that have those resistant infections where they're likely to be benefit.

And when we're thinking of how could we best utilize, and I think back to some of Jose's slides, is what about these organisms where our genotypic diagnostic tests just don't reliably identify common resistance mechanisms? And to us, we thought Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. And evaluating these in bloodstream and trying to identify opportunities to – to escalate therapy and get patients on more active – more active therapy sooner in their – their disease, their hospitalization.

We also looked at the prevalence of these organisms. So in a year's worth, you know, we have a lot of Pseudomonas. So 153 bloodstream isolates for individuals and then less for Acinetobacter and steno. But we know that those are commonly resistant organisms where timely antibiotic therapy can be a little bit more challenging.

[00:59:07]

Importance of Proper Implementation

Okay. So, you know, it's great. We know that these pheno tests identify susceptibilities much faster and can get patients on active therapy. But that's all great. If you don't do the proper implementation steps, I think it sets your health system up for failure. So without significant planning, with the lab, with ID consultants, with key stakeholders, and really the stewardship team, you might not see a benefit. So really, really important slide in my opinion, is getting all that key stakeholder advice and really planning this out and planning to evaluate to show that return on investment is also a key component.

I've talked about this a little bit more, about the incremental difference in turnaround time, like the bar just keeps getting narrower and narrower. So how can you justify using a test like this? And what kind of outcomes are you expecting?

Successful implementation relies on a really robust practice model just as much as the technology itself, I think. And, some of the automation in the microbiology lab, routing the phenotypic AST alerts within existing workflow is really essential in my opinion. Timing of the results in the electronic health record. I know some of you might not be familiar, but you know, some of these susceptibility results will result at different times. And then I also wanted to plug utilization of microbiology nudges, of course, because I think that's also an efficient way to get clinicians to prescribe the right antibiotic therapy without necessarily having stewardship personnel responding to it. So big nudge fan.

[01:00:52]

Role of ASP in AST Workflow

So this is kind of a snapshot of how this works for my—or we're in process of implementing a similar workflow. Rapid tests are used only for Pseudomonas, Acinetobacter, and Stenotrophomonas maltophilia in ICU populations. And you can see on the right hand side we – patients with a bloodstream infection. If it's a positive, they get flexed to a genotypic AST platform. That gets routed to the ID pharmacists and is resulted in the electronic health record while conventional AST is still being performed. And kind of where we're trying to pivot the phenotypic AST is of those select organisms that we've talked about, adding that on is going to show some benefit just because of the limitations to existing genotypic platforms. The key here is we try to make these results actionable and route them to stewardship personnel, who are routinely making recommendations to escalate or stop therapies.

[01:01:55]

Electronic Health Record: ASP Queue

How many of you guys are familiar with ID pharmacist workflow at a hospital setting? Some of you who are pharmacists probably. Or some of you, I think, have the wherewithal to ask some of these questions. But, you know, I actually on Friday had a session with 1 of our ID fellows and oriented him to our stewardship workflow, and he was like, “Whoa, I have no, I had no idea that this what you guys do.”

And I think this is an important slide, because if you're considering adopting some of these tests or 1 of these tests, it's really important to touch base with your pharmacist and talk about existing workflow and resources. So I'm an Epic hospital, and, you know, kind of our workflow here, we use the Bugsy module. And you can see on the left hand side that figure there, we have a cascade of different results that the stewardship pharmacists go through. 200 unreviewed results makes me a little bit stressed right now standing up here.

But on the right hand side, you can see that box there, AMS, BPA or Best Practice Advisory, or Practice Advisory. And that's where all of our genotypic results and eventually our phenotypic results will get routed as a priority for the ID pharmacist to review it. And the way that this  works is we have dedicated IT personnel who can create these alerts for us and route them to us to make this an actionable intervention, really. Right? Otherwise, it kind of gets blasted into the void.

So the summary on this slide is do you know your stewardship pharmacist workflow? Or maybe it's not a pharmacist who's routinely doing stewardship at your site. Does this fit into it? Do you have IT support? And what are some alternative approaches in the event that you don't have this robust platform?

[01:03:37]

Patient Case Example

I wanted to do a patient case example. So here's a 70 year old patient admitted to ICU with shock. Blood cultures are growing Gram‑negative bacilli. And he was started on vanco/pime: vancomycin and cefepime. The organism is identified as Pseudomonas aeruginosa. And from the genotypic results, that gets flexed to the rapid phenotypic results that are then routed to the antimicrobial stewardship pharmacist. And look at that. You know, we see that this isolate is resistant to cefepime and ciprofloxacin, intermediate to meropenem, piperacillin/tazobactam, and then susceptible to ceftolozane/tazobactam and tobramycin, for example. And really, what this would do is significantly increase the time to appropriate therapy in someone who is critically ill, who we know this is kind of the most vulnerable population in terms of timely antibiotic therapy. So in this case, the patient would get started on ceftolozane/tazobactam much more timely than conventional methods.

[01:04:37]

ASP Role in Education and Evaluation of Rapid Phenotypic AST

Education is also really important. And, you know, generally the stewardship team is responsible for dissemination. And I just wanted to emphasize this is particularly important depending on how you use the test. Are the end users—and in my, you know, my case, you know, the intensivists—are they going to be familiar with what the test is and how to respond to it? Right? And that's on us to educate that.

Formal evaluation of the workflow and opportunities. You know, anybody who's implemented anything in a hospital knows how challenging that could be. And I think the stewardship teams need to be really cognizant of that, and are there any changes that need to be tweaked or modified in order to get the best results.

[01:05:20]

Rapid Phenotypic AST: Future Opportunities?

So, you know, I really am excited about this technology. There's a lot of future opportunities. And, you know, the application, you know, a lot of applications focus on Gram‑negative bloodstream infections. But, what about other organisms where timely identification of susceptibility can be really important? And that's slow growing mycobacteria. Those are always really, really challenging cases. Different Candida species. The challenge with using fast AST or phenotypic AST in these populations is the real—the significant laboratory validation time‑suck that it is to validate these platforms in other organisms or other disease states such as urine sources, respiratory sources, bone and joint, and gastrointestinal.

And then I'm also interested in some of those other less common populations, so solid organ transplant and urosepsis with bacteremia is also very interesting to me to try to facilitate that early oral switch that Jose had kind of talked about.

[01:06:23]

Takeaways: Role of Antimicrobial Stewardship Program in Implementing Rapid Phenotypic AST

So takeaways are, you got to consider if this is the right fit for you. It's not right test for everyone and the decision should be institutional specific. Look at your organism prevalence and then really look at workflow opportunities and capacity for the lab and stewardship teams. If you don't have a good understanding of the workflow, and if there's not something actively responding to alerts, generally you're not going to see what you had intended. So that's a really key component of embedding that into stewardship workflow.

[01:06:56]

Posttest 3

Okay. Posttest 3. So to maximize the potential impact on patient outcomes, which of the following strategies should be the antimicrobial stewardship program’s highest priority when implementing blood culture rapid phenotypic AST? Is it:

1. Establishing criteria for which organisms and patients to test;
2. Is it batching tests to maximize laboratory efficiency;
3. Is it developing a workflow to actively report active – actionable results; or is it
4. Evaluating medication use early in implementation;

Oh, you guys got this already. You know, you got – got it at the beginning, right? So it's developing that workflow, right? I'm beating that drum here. Establishing criteria for which organism patients assess is really important, but you can have all that fleshed out, if you don't have a good workflow, it ain't going to work.

[01:07:59]

Question and Answers

Excellent. So I believe we're going to switch from questions and answers, and then we're going to do a panel discussion. And thanks for your time today. I hope you found that informational.

[01:08:12]

Panel Discussion

Dr Marcelin: Okay. Thanks, everyone, appreciate your interest. And we've been having a lot of – a lot of questions coming in and so I'm just going to jump into it. You know, we started off and pretty much throughout this entire discussion we've been using cases that are inpatient based cases. And 1 of the questions that came in, either of you could kind of touch on, would be, what is the possibilities of use of rapid AST, phenotypic AST in the outpatient setting to help primary care clinicians and make better decisions about those antibiotics for UTIs, etc.?

Dr Veve: Oh, I'll take that. So, I do a little bit of outpatient stewardship and I agree with commenter. That is a really great opportunity to expand in the ambulatory setting where it just takes a long time to get some of those results. I do think that there's an opportunity, particularly with maybe urinary tract infections or probably 1 of the more common disease states where we would get cultures. The challenge, and I look forward to hopefully figuring this out, is validating phenotypic tests on urine cultures, really. I think that's kind of – developing a platform where you can reliably use the pheno in patients with urinary tract infections to get them on more active therapy faster would be a good future direction. I just – we need some time to kind of figure that out a little bit more.

Dr Marcelin: What about if your institution already has an antibiogram that they use to help with making empiric decisions about antibiotics? How does the rapid pheno play a role in – how does it help to augment the antibiogram, or is – is the implementation of rapid pheno for institutions that don't use an antibiogram for those sort of decision making? That's a – I was looking at Jose when I asked that.

Dr Alexander: So the antibiogram is – is a tool that we use for guiding empirical treatment. So we have cumulative data. We evaluate the patient from the perspective of multidrug resistant risk for that patient, and decide what is the best approach based on the population. And if we know the organism, we have a very narrow point in the antibiogram. The advantage of the – having a rapid AST is actually can overpass the need for antibiogram for that particular case. You already have a susceptibility profile specific for that patient, and now you have not only the clinical component, but now you have a whole organism antimicrobial profile that will allow you to optimize the initial implementation of empirical treatment that was based on the antibiogram. So we still need the antibiogram because it's going to be – that will be the driver for that initial treatment. But the rapid AST, the advantage is that that optimization can be done faster and sooner, specifically in a patient – in a case‑by‑case scenario.

Dr Marcelin: Okay. So it's meant to help, not replace.

Dr Veve: Yeah. Only thing I would add is if you practice at a site that does not see Gram‑negative resistance at all, then I don't know if you're really going to see that additional value outside of using some traditional stewardship – stewardship antibiogram services, where you could try to facilitate that early switch in the same capacity, you're just not going to have the susceptibility results. But that just might not be, you know, depending on where you're at geographically, that might be the case.

Dr Alexander: I just want to add also for the perspective of rapid AST, there is a lot of discussion. Well, we should limit this specific unit in the hospital, right? Maybe ICU. And the test is the – the power that we can take, the benefit that we can take from this test is based on the action that we're going to take. A lot of patients, ICU, critical care patient, patients with high risk, if the patient is severely compromised and you tell the clinician, “Oh, this is just a pan‑susceptible E. coli, they just go from meropenem to, I don't know, ampicillin/sulbactam,” there is a fear factor that is not going to allow many of those patients to be de‑escalated. So that is another component to have in consideration. What is the clinical condition? Even if you have evidence that the organism is pan‑susceptible, is that – are we going to be able to break through that fear factor to keep patient on broad spectrum a little bit longer, even when we have evidence?

Dr Veve: That's a good point.

Dr Marcelin: So then what – so then what's the answer? How do you – how – how do you help? Because we're giving – we're going to give folks more tests, more opportunities to – to get that data. But what I'm hearing from you is ultimately, we may still be in a situation where we might continue broad spectrum antibiotics unnecessarily, more to treat ourselves than the patient. And so what's the solution to that?

Dr Alexander: I mean, there is the clinical judgment that play a big role. I don't know if we have a solution to be able to change. I mean, we can provide evidence, education, material data that support that de‑escalation is appropriate. But it’s this fear factor. I remember the case that, I mean – or MRSA – MRSA, MSSA, BCID is pretty accurate. And we have 1 case that we miss the gene. And that creates a whole change from the perspective of some of our providers, that they didn't want to trust the test anymore, just for 1 case. So when we proved that was probably less than 0.1% of the scenario. So I think the clinical judgment plays a big role. And I think part of the education and conversation with data is to be able to make sure that they continue using clinical judgment, but the clinical judgment can change the outcome of what is normally used for them.

Dr Marcelin: Okay. Thank you. I'm going to switch gears to another question. But before I do that, there is someone out here who asked a question, “Are there any bug‑drug combinations on your panel where you have no claim?” And if you can – whoever wrote that question, if you can clarify just a little bit more. I think you're asking an interesting question, but I just want to make sure I can ask it in the way that's going to get your answer. So just type it into the – thank you. Appreciate it. While you're doing that, I will move to a question about breakpoints. So what break points are the phenotypic results based on for these tests?

Dr Alexander: So they are based on FDA breakpoints and every manufacturer – it's important to check with the manufacturer and the package insert and the recommendation of the manufacturer. But all these platforms come with FDA breakpoints. We are – used to have automated AST platform that we can validate new breakpoints, CLSI breakpoint, make changes, users. So, I think those are some limitations that some of these platforms have. Hopefully, the future laboratories can – we can have more open access to these type of software that we can validate ourselves. And I think could be a limitation. And it's important for you to have that in consideration.

In regard to the drug class mismatch, a comment about that is, there is limitation of the platform and performance, but they also gap in regard of the FDA indication for certain drugs. So if there is no FDA indication for a specific drug‑bug combination or source, it's possible that many of these rapid AST are not going to give you that result. It's not that the instruments have any limitation. Technical is that there is a limitation in regard of the indication for that particular drug. Could be another gap. Some drug with bug mismatch that there is indication and the instrument doesn't give that information, because it could be some limitation of the performance. So that – that 2 different aspect is important to have well‑described or discussed with the manufacturer when you decide what platform is fit for you.

Dr Marcelin: Does that answer your question? Perfect. Okay. So, at the MAD‑ID meeting in May, so there was a presentation about using rapid diagnostics where no beta – with no beta‑lactamase enzymes detected but approximately 20% of the E. coli was resistant to ceftriaxone from different mechanisms. So what – the question is what is the benefit of rapid phenotypic AST in patients with E. coli in that situation? Either of you. Michael, do you want to?

Dr Alexander: So that is the perfect scenario for this type of technology. So we know that the epidemiology can be set with certain organisms. CTX‑M is the most global ESBL. Resistant to ceftriaxone is ESBL, AMC or carbapenemase. Some of them are already or most of them can be identified by genetic profile. But when you have a resistance to a specific class that is caused by a gene that is low prevalence or no presence in any other rapid PCR, the final result for that type of – that type of cases is to have a full phenotypic profile.

So that is the perfect scenario. If you have a high prevalence of ESBL there are no CTX‑M. This is the perfect scenario. If you're seeing a lot of AMC and E. coli, Klebsiella, this is the perfect scenario because we know that we don't have AMC markers. And if you're seeing a lot of carbapenemase, no carbapenemase producing Enterobacterales, this is also another. This is probably the best technology because you get the final AST rapid faster. And it's not based on resistance mechanism. It's based on the – the summation of all those mechanisms together, how they reflect in the phenotypic profiles.

Dr Marcelin: Okay. A question about just the implementation of the rapid AST, do – are you aware of any data that just kind of tells us how well – how widely this is implemented across the country and like, how many folks – how many hospitals are using this currently?

Dr Veve: Good question. I don't. I don't know. I think, I'm not aware of survey data specifically to phenotypic platforms. I don't know, Jose if you know any, any of those data, but I do think that's a need to get a better idea of who's using what in which areas as a future research direction. I know there's more – obviously, genotypic testing has been around for longer. So, you know, there's still a gap there.

Dr Alexander: I think the experience is mostly with LTT applications. So now we have some FDA approval method that is right now getting deployed through clinical settings. The experience that could be around is probably some LTT modification of other platforms.

Dr Marcelin: Sounds like a really cool fellow’s project or ID pharmacy resident project, we all think. Okay, we maybe have time for 1 or 2 more questions. One. Okay. All right. Let's make it good. Okay. So here's a question that, I mean, I just want your thoughts on this. I think we may not have a solution to it, but, you know, earlier we were talking about ways that the – there's the differences from a global standpoint in antimicrobial resistance and implementing things in resource‑limited settings. And so if we think about global resource‑limited settings, where the rates are higher, as well as in the United States and rural resource‑limited settings, what – what are some of the ways that clinicians in this room can help to address this with the rapid AST in resource‑limited settings?

Dr Veve: Ooh, that's like the Willy Wonka golden ticket. I wish – I wish I had an answer to that. I do think that is – it's a clear challenge. I think, you know, access to the testing, I think, is step 1 and trying to – to promote access to these low/middle income countries and other more rural countries and show justification of benefit within – within that population. I think we need more – we need funding to support this work. I think we need access to these tests and showcase how, you know, I think, Jasmine, to your point, you'd see larger incremental value in implementing these tests in those – those specific sites. And I think we need more data to showcase that.

Dr Marcelin: Thank you. Also, a call to action, I suppose –

Dr Veve: Yes!

Dr Marcelin: – for people with money to help us to address this issue. All right.

[01:21:40]

Go Online for More CCO Coverage of Bloodstream Infections!

And so I just want to remind you all to go online for more coverage of bloodstream infections. Questions that did not get answered in this session, we will be collating them and answering them online. And so if you still have questions that you'd like to put in really quickly, please go ahead and do so. We'll capture all of them and – and then try to address them. You will have access to downloadable slide sets of all of the data. And we have some clinical thought commentaries from our faculty experts that will be addressing these a little bit more. I want to thank you all for your participation, in the room as well as online. And go out and enjoy ID Week. Thank you very much. I appreciate you guys being here.

[END OF TRANSCRIPT]