Antibiotic Prescribing Dilemmas in The Face of Increasing Resistance: How Do Diagnostics Help?

Time index	Content
0:0:0.0 --> 0:0:29.970 Webinar Host	Hello and a very warm welcome to everyone joining us for today's Select Science webinar: Antibiotic Prescribing Dilemmas in the Face of Increasing Resistance: How do Diagnostics help? My name is Dora Wells and I'll be moderating today's presentation. I'm delighted to be joined by today's speaker, Doctor Jean Patel, principal of Scientific Affairs at Beckman Coulter Microbiology. Doctor Patel will give a short presentation and then run a panel discussion with our guest experts, Eric Myers, system pharmacy specialist
0:0:30.60 --> 0:0:59.840 Webinar Host	of infectious diseases at Adventist Health and Navaneeth Narayanan, clinical associate professor of infectious diseases at Rutgers University. After the discussion, we'll open the panel to audience questions. Please feel free to ask any questions for the Q&A session at any time during the webinar. You can submit your question at the speech bubble icon to the left of your screen, and now without further delay, I would like to hand over to Doctor Patel for today's presentation and I'd like to thank her for presenting to us today. Please go ahead.
0:1:0.70 --> 0:1:13.370 Jean Patel	Welcome everyone to Antibiotic Awareness Week with Beckman Coulter Microbiology today, we're going to talk about antibiotic prescribing dilemmas in the face of increasing resistance and the role diagnostics can play in helping.
0:1:14.320 --> 0:1:19.610 Jean Patel	And we're going to begin with a presentation and then move into a round table discussion.
0:1:21.460 --> 0:1:34.930 Jean Patel	We have some great infectious disease pharmacists with us today. For this round table discussion, we have Doctor Myers. He coordinates antibiotic stewardship programs for Adventist Health. This is a 23-hospital system.
0:1:35.550 --> 0:1:53.570 Jean Patel	And we have Doctor Narayanan for who is Co-director of the Antibiotic Stewardship Advisory Committee at Robert Wood Johnson University Hospital. Both are antibiotic stewardship experts, and we hope to learn from them today.
0:1:57.0 --> 0:2:17.80 Jean Patel	The learning objectives for today's session are to review a snapshot of some of the current antimicrobial resistant threats, learn about the antibiotic pipeline, understand challenging prescribing situations, and also understand how diagnostics can impact prescribing practices today.
0:2:19.450 --> 0:2:23.890 Jean Patel	So, let's begin with that snapshot of antimicrobial resistance.
0:2:26.170 --> 0:2:43.460 Jean Patel	The Centers for Disease Control and Prevention has identified a number of antimicrobial resistance threats, and these are categorized as urgent threats and serious threats. There are also some concerning threats that aren't listed here.
0:2:44.330 --> 0:2:58.0 Jean Patel	Today we're going to talk about carbapenem resistant Enterobacteriaceae and we're using this as an example of how an emerging antimicrobial resistant threat can really challenge on prescribing practices.
0:3:2.200 --> 0:3:17.800 Jean Patel	So, if we look at the numbers for burden estimates of carbapenem resistant Enterobacteriales, and I should say that Enterobacteriales is just another name for Enterobacteriaceae, and we'll sometimes refer to these organisms as CRE.
0:3:19.180 --> 0:3:36.990 Jean Patel	And these are bacteria that in the US are estimated to cause greater than 13,000 hospitalizations per year and an estimated 1100 deaths per year in the United States.
0:3:38.40 --> 0:3:51.310 Jean Patel	If we look at global burden estimates, there's an estimate of over 100,000 deaths per year due to CRE or carbapenem resistant Enterobacteriales.
0:3:52.370 --> 0:4:17.880 Jean Patel	Now this is an emerging antimicrobial resistant threat and when we look at these numbers there is concern that there's a lot of resistant infections out there that either aren't being detected or are detected and aren't being reported, and that these are underestimates of how many cases are occurring. We also know that CRE spreads easily, and we expect these numbers to increase over time.
0:4:21.230 --> 0:4:51.60 Jean Patel	The mechanism of resistance in these organisms is very complex. There are two primary mechanisms by which an isolate of Enterobacterales would become resistant. One is that the isolate would develop porin changes. Porin changes would limit the access of the drug to the microorganism. And then if you combine this porin change with the cephalosporinase. So, an enzyme that can hydrolyze
0:4:51.180 --> 0:5:8.640 Jean Patel	an extended spectrum cephalosporin. Those two mechanisms combined would result in carbapenem resistance, and that's because that cephalosporinase has little bit of activity for the carbapenems, so the little bit that does get into the cell, then are hydrolyzed.
0:5:10.670 --> 0:5:38.760 Jean Patel	And then there is plasmid-mediated carbapenemases. And so these are enzymes that can cleave the carbapenem drug, and they render the drug inactive. There are multiple carbapenemases out there. KPC is the most common one in the United States. There's Oxa 48-like enzymes which are also very common. And then there are NDM, VIM and IMP.
0:5:39.470 --> 0:6:12.780 Jean Patel	And all three of these are less common. They are all classified as metallo beta lactamase enzymes, and that's important because some of the beta lactamase inhibitors that are available today in an antimicrobial agent are not active at inhibiting these enzymes. And that means the drugs don't work. So, bacteria that produce these enzymes are the hardest infections to treat.
0:6:16.10 --> 0:6:22.490 Jean Patel	The epidemiology of resistance mechanisms varies greatly across the globe
0:6:23.160 --> 0:6:28.710 Jean Patel	And these are three examples, the epidemiology and the US and Europe and in China.
0:6:30.50 --> 0:6:41.30 Jean Patel	So, in the US, you see a lot of bacteria that do not produce a carbapenemase. These are the bacteria with the porin change and the cephalosporinase that's combined.
0:6:41.670 --> 0:6:48.580 Jean Patel	There are a lot of KPC producing isolates and then some NDM producing isolates and that's a smaller percentage.
0:6:49.610 --> 0:7:8.370 Jean Patel	The picture is similar, but a little different in Europe, so again there are a good number of isolates that do not produce a carbapenemase. But there are more Oxa-48 producing isolates and a few more NDM producing isolates.
0:7:9.830 --> 0:7:36.410 Jean Patel	And then if you look in China, the picture is very different. Here are most of the isolates are producing a carbapenemase KPC is still the most common, but there is a big hunk of the pie that it is caused by NDM producing isolates. We know that antimicrobial resistance is a global threat, and we expect that this epidemiology to change over time because bacteria are spreading.
0:7:39.60 --> 0:7:58.290 Jean Patel	So, this is a picture of what kind of drugs are available today to treat these infections. And here the infections are separated into what kind of resistance mechanism is present, which carbapenemase is produced and then also isolates that don't produce a carbapenemase.
0:7:59.70 --> 0:8:8.990 Jean Patel	And the first rows in this table are the drugs that are available today. They're on market in the United States.
0:8:10.300 --> 0:8:41.850 Jean Patel	There are some of these drugs that would be considered for treating serious infections are a big concern, so Colistin is a big concern. These are listed as red question mark because Colistin is a drug that has shown limited efficacy in treating serious infections. A lot of times when Colistin is used, it's used in combination with other antimicrobial agents, and it's often used as a drug of last resort because the efficacy issues that occur.
0:8:43.290 --> 0:8:58.480 Jean Patel	Tigecycline and Eravacycline are drugs that have good activity in vivo, but the distribution in the body is limited so they're not the best drugs for treating a bloodstream infection. They can be used in combination with other therapy.
0:9:0.0 --> 0:9:12.890 Jean Patel	We have some good new agents, Ceftazidime-avibactam, Meropenem-vaborbactam, Imipenem-relebactam, all with activity for some types of CRE, but not all types of CRE.
0:9:14.730 --> 0:9:47.240 Jean Patel	And then drugs like Plazomicin, this is a novel aminoglycoside. This is a drug that has to definitely be tested for susceptibility to an organism before it's used. And that's because there are mechanisms of aminoglycoside resistance that travel with carbapenemases on the same plasmid. So, on the same piece of DNA. And then when that piece of DNA moves, both types of resistance move with it.
0:9:47.520 --> 0:9:52.440 Jean Patel	And so, you really have to worry about co-resistance for this drug.
0:9:53.280 --> 0:10:15.680 Jean Patel	And Cefiderocol is a new drug. It has broad activity for multi drug resistant organisms. It is a drug that is recommended for complicated UTI and for ventilator associated pneumonia. It is not a drug that's recommended for treating bloodstream infections, at least not now.
0:10:16.900 --> 0:10:35.510 Jean Patel	And there are new drugs coming to the market. Aztreonam-avibactam and Cefepime-taniborbactam. And these are drugs that will be active for some NDM producing isolates. And this is good news because those drugs are definitely needed as NDM producing isolates become more common.
0:10:36.750 --> 0:10:52.270 Jean Patel	So, this is a complicated picture. It's hard to find a drug that would fit all types of infections, and this is one of the reasons why diagnostics are so important for using antibiotics appropriately.
0:10:54.500 --> 0:11:22.530 Jean Patel	Another reason why we worry about the future of CRE is that this is plasmid-mediated resistance and that means that this piece of DNA which is represented by the green circle in these bacteria - that green circle of DNA contains the carbapenemase and it can move from one bacteria to another and it can move from one species to another species or in a body.
0:11:23.300 --> 0:11:44.760 Jean Patel	Think about the GI track where there are lots of gram-negative organisms. If a patient becomes colonized with one of these resistant bacteria, that's where this plasmid can easily be transferred from one organism to another. They're all present in this GI tract.
0:11:45.220 --> 0:12:17.690 Jean Patel	They're not being treated with an antimicrobial agent there because they're not causing infection. And this is how you see antimicrobial resistance amplified. So, I at least think about spreading as a resistant bacteria moving from one person to another, and then this amplification is occurring when a person has a resistant organism. But now the types of resistant organisms that they carry is amplifying.
0:12:19.680 --> 0:12:38.630 Jean Patel	When we look at how this affects the number of infections that occurred, you can track the increased occurrence of CRE infections in the United States by looking at these maps that came from CDC. Very quickly from 2005 to 2015
0:12:39.810 --> 0:12:57.350 Jean Patel	cases of CRE moved from just outbreaks that were primarily occurring in the New York City area, to cases that have occurred in nearly all states in the US - and today there have been cases in every state in the US.
0:13:0.210 --> 0:13:32.40 Jean Patel	CDC also has reported the trend of CRE infections over time and a bit of good news is that this trend is pretty flat, and this is thought to reflect some of the efforts at preventing infections in the healthcare setting. And that's where CRE isolates are causing infections. It occurs in a healthcare setting and with implementing infection control measures, you can reduce the number of infections that occur
0:13:32.370 --> 0:13:49.310 Jean Patel	and keep this trend flat. We don't know yet the impact of COVID-19 on rates of resistance. This has been measured. So, CDC recently reported
0:13:50.680 --> 0:14:21.290 Jean Patel	the status of antimicrobial resistant threats post-pandemic and they report no increase in the number of infections, but they also report that there are challenges with data collection because resources were diverted to COVID-19 during the response. So, it's not clear that we have the best data to understand rates of resistance. Also, we know that there were a lot of
0:14:21.390 --> 0:14:29.890 Jean Patel	antibiotics used empirically, and it could be that it will be a couple of years before we see the impact of that empiric use of antimicrobials.
0:14:33.920 --> 0:15:4.20 Jean Patel	If we look at CRE cases across the globe and it's clear that in the United States rates of CRE infections are still pretty low, less than 5%, but there are parts of the world that are real hot spots for CRE infections. So, for example, in India, there are just very high rates of CFE infections and there are higher rates
0:15:4.100 --> 0:15:5.760 Jean Patel	in places like China,
0:15:7.570 --> 0:15:32.250 Jean Patel	in Russia, in Latin America, there are hot spots of higher rates. There are some places in the world where we don't have the exact data and this is actually a model where they took known data and then use models to estimate where infections, what infection rates might occur in different parts of the world.
0:15:33.730 --> 0:15:40.200 Jean Patel	So, this is very concerning that the number of cases is going to grow and grow quickly.
0:15:41.510 --> 0:15:46.100 Jean Patel	This is occurring at the same time that the antibiotic pipeline is slowing down.
0:15:47.190 --> 0:16:4.940 Jean Patel	This chart looks at different types of antibiotics in development. I think it's useful to look at this first column, which are traditional types of antimicrobial agents that can treat the most resistant infections that occur.
0:16:5.910 --> 0:16:16.580 Jean Patel	And there is only one drug that has filed an NDA with the FDA - that means a drug that is ready for FDA review.
0:16:17.600 --> 0:16:47.50 Jean Patel	There are four drugs that are in phase three and 11 drugs that are in phase one, so this is a big gap between the number of drugs that are ready to come on to the market and the number of drugs that are in a very early phase of development. So, you can think about phase one as approximately 10 years before the drug is going to be used in patients and the number here 11.
0:16:47.210 --> 0:17:9.730 Jean Patel	might look good, but there are lots of opportunities for these drugs to fall out of the pipeline because of technical error or technical challenges that occurred during development. So, this is not the robust antibiotic pipeline that we want to see when we're facing very drug resistant infections.
0:17:12.880 --> 0:17:20.970 Jean Patel	How bad can the CRE infection rate get? I think we can learn a lesson from ESBL producing Enterobacterales.
0:17:22.90 --> 0:17:52.500 Jean Patel	So, this is the type of infection that is increasing. You see a really clear trend in the number of ESBL infections that are occurring in the United States. And this is occurring because ESBL's are now causing community associated UTI infections. Anytime an infection or resistant type of infection moves from the healthcare setting to the community setting
0:17:52.820 --> 0:18:2.590 Jean Patel	there is the threat of infection rates increasing, and that's because it's very hard to prevent infections once they are community acquired infections.
0:18:4.290 --> 0:18:37.860 Jean Patel	So, the changing epidemiology we saw for ESBL producers are that infections were limited to the healthcare setting, but then there was a new type of ESBL that emerged, and it was found in E coli strain ST131. This is a strain that is a common cause of community associated UTI infections. And now you see these infections occurring in the community. They occur in patients who have no health care risk factors at all.
0:18:38.520 --> 0:18:53.370 Jean Patel	And this is why you see the upward trend now. All of this could also happen for CRE infections and if that does happen, that will be a very challenging prescribing environment.
0:18:54.920 --> 0:19:5.640 Jean Patel	So, in summary, CRE is an example of a really hard to treat infection. New drugs are available, but these are effective for only some types of infections and not all.
0:19:14.490 --> 0:19:25.270 Jean Patel	And CRE rates are expected to increase significantly, especially if the epidemiology shifts to community associated infections.
0:19:26.690 --> 0:19:38.960 Jean Patel	So, my goal here was to set the stage for the next discussion, and we'll be discussing challenging prescribing situations and the impact of diagnostics on today's prescribing
0:19:40.210 --> 0:19:44.160 Jean Patel	practices with both Doctors’ Myers and Doctor Narayanan.
0:19:46.110 --> 0:20:3.480 Jean Patel	A warm welcome to Doctor Myers and Doctor Narayanan. Thank you for joining us for Antibiotic Awareness Week so that our audience can learn more about each of you and what you do. Can you remind us of where you work and tell us about a typical day for you as an ID pharmacist?
0:20:7.590 --> 0:20:9.360 Jean Patel	Doctor Myers, would you like to go first?
0:20:10.130 --> 0:20:45.480 Eric Myers	Yeah. So, hi everyone. I'm Eric and thank you, Jean, for the invitation. So, I work with Adventist Health, which is a 23-hospital health system on the West Coast of the United States and I'm now working in more of a corporate role. So, what I typically do, it depends a lot on the day, but from a high level, I coordinate with our local antibiotic stewardship teams that each of our hospitals to try to identify kind of the common problems facing everyone and try to take that and come up with the systematic solution to try to address some of those problems.
0:20:47.650 --> 0:20:48.480 Jean Patel	Great. Thank you.
0:20:50.160 --> 0:20:53.650 Nav Narayanan	Hi everyone and Jean, thank you again for the invitation.
0:20:54.740 --> 0:21:23.970 Nav Narayanan	So, I actually I'm a faculty member at Rutgers University in New Jersey and I practiced at Robert Wood Johnson University Hospital in New Brunswick, NJ so I wear a few different hats just given my role as clinical faculty. So, I spent time at the university teaching and lecturing pharmacy students. I practice at the hospital with our medical schools’ infectious disease division, so clinical service.
0:21:24.170 --> 0:21:56.240 Nav Narayanan	As well as work with the ID physician, medical director on stewardship initiatives. So that includes a variety of things. So, sort of, as Eric mentioned, sort of systematic approaches. So, a high-level sort of projects to systematically adjust and ensure rational antibiotics throughout the hospital looking at metrics and working with our antimicrobial stewardship team just to think about what initiatives that we can sort of run to help and work with other services. So, a big part of my job is working with other
0:21:56.360 --> 0:22:1.170 Nav Narayanan	Non-infectious related services to think about stewardship and how we can sort of optimize care.
0:22:2.650 --> 0:22:3.560 Jean Patel	Great. Thank you.
0:22:4.630 --> 0:22:18.620 Jean Patel	So, I know both of you are involved in decisions about when to use antimicrobials for really hard to treat infections. Can you share with me what some of your biggest challenges today?
0:22:20.120 --> 0:22:25.480 Jean Patel, Nav Narayanan	Doctor Narayanan, could we start with you? Yeah. Yeah. So, when I think about
0:22:26.780 --> 0:22:40.870 Nav Narayanan	hard to treat infections, the first thing that comes to mind is sort of managing our formulary and thinking about sort of what antibiotics that we need sort of right away available versus sort of getting it after the fact so.
0:22:40.950 --> 0:23:10.900 Nav Narayanan	So, you know, unfortunately at our institution, we do have certain resistance patterns that warrant keeping some of the newer antibiotics on our formulary readily available. So, we're able to sort of keep these go through our pharmacy and therapeutics committee and sort of rationalize it. The use of it and the cost of it - and we're able to use these. And then we specifically sort of crossing over to our stewardship program, we make sure
0:23:11.0 --> 0:23:49.100 Nav Narayanan	that these antimicrobials are sort of positioned in terms of their formulary restriction appropriately. So, we have a pretty intricate restriction policy that tries to limit where we use these new antimicrobials obviously for the purpose of preserving them for the long run. So, when we think about sort of prescribing and whatnot, we try to make sure that infectious disease specialists or infectious disease physicians are involved in the cases. So, these are these newer drugs for hard-to-treat infections are generally limited to Infectious Disease Physicians to prescribe. So that's one major aspect from my point of view.
0:23:49.750 --> 0:23:57.590 Jean Patel	Thanks. Thanks - and Doctor Myers you need to do this across several healthcare institutions. What are your challenges?
0:23:58.390 --> 0:24:27.860 Eric Myers	Yeah, I think I'm going to look at this from sort of a broader or really broad sense, maybe too broad, but I think the challenge that I really struggle with is how do we ensure that all of our clinicians are really, really weighing the risks of antimicrobial use at the actual point of prescribing? And what I mean by that is I think at a global societal level, we're all well aware of the risks of antibiotic resistance and antibiotic over use.
0:24:28.340 --> 0:24:59.590 Eric Myers	And I think you'd be hard pressed to find a clinician that argues that isn't a problem at a societal level. But often when I discuss with our frontline clinicians at the point of actually making a clinician patient level decision, they almost always view more antibiotics as the safer choice. And they tend to view stopping antibiotics as inherently more risky than everyone in Healthcare is inherently risk averse. So that obviously over time just leads to more antibiotic use, more resistance and sort of perpetuates the problem.
0:25:0.160 --> 0:25:33.110 Eric Myers	And so, I feel like there's, and even when we have really high-quality data and we are, we're seeing a lot of data with short course durations now where it really across the multitude of indications, longer durations of antibiotics are actually less safe and not any more effective than shorter durations. So even when we have that data, it's still the perception is still at that provider patient level decision that more antibiotics are actually safer. So, what I really struggle with is how do we kind of bridge that gap and address that disconnect.
0:25:34.370 --> 0:25:39.780 Jean Patel, Nav Narayanan	Yeah, that's an excellent point. Go ahead. No, and Jean, just to just to jump in, I think
0:25:41.490 --> 0:26:11.800 Nav Narayanan	I agree with that Eric, pretty totally, I mean we hear it sort of when we're just making rounds, right? It's like, you know, and I do understand the perspective, right, you have a critically, I'll patient and you don't wat to sort of miss something, but it's always you know what if they have an infection or just in case. And I think the perception generally is that antibiotics are sort of low risk from that risk to benefit ratio. But the problem is that the sort of long-term risks are really hard to see.
0:26:11.880 --> 0:26:41.310 Nav Narayanan	You know, and unfortunately, we're sort of living in that era where that long term risk has been sort of neglected for quite some time and now, we're in this, you know, post antibiotic phase pretty much. So, you know it's really hard to deal with the real time stuff at the bedside and convincing people that everyone sort of has to chip away at this problem to prevent the long-term issues that we sort of are seeing and dealing with. So yeah, I think that what if is always a tough question to sort of to navigate.
0:26:42.450 --> 0:27:1.710 Jean Patel	This is a place where diagnostics could play a role, right? The issue of does a patient have an infection or do they not have an infection? Could we just deescalate antibiotics if the patient doesn't have an infection? But do you have the diagnostic tools you want today to make those kinds of decisions?
0:27:4.780 --> 0:27:36.670 Nav Narayanan	I guess I'll start by saying yes and no. I mean we have some tools, right? I mean, you know from a microbiology standpoint, you know that rapid diagnostics as sort of in my mind sort of been a revolution compared to what it's been conventionally for, I don't know, for 100 years. So, the fact that we're able to sort of cut the time to in certain infections, certain specimen types and all that cut the time to
0:27:36.750 --> 0:28:7.870 Nav Narayanan	hours instead of days of figuring out, you know what? What you're dealing with. I think that's really helpful. I mean, at our hospital, I think rapid diagnostics is sort of a core element for us locally as far as our stewardship program is. So, and it's from two different perspectives. One, we're able to get people off antibiotics days faster because we realized that the organism that we found and that we one added two blood culture, it's probably more likely contaminant and not compatible with sort of the clinical picture of an infection.
0:28:8.380 --> 0:28:38.350 Nav Narayanan	And then we are able to stop drugs like vancomycin earlier, which is something that we use in a lot of patients, probably more than we need to. And then on the other hand, we're able to actually find those resistant organisms or phenotypes a lot faster. And that's really important because you know, we've seen time and time again that time to effective antibiotic therapy is a big determinant. When we think about clinical outcomes. So, I think from those two perspectives we have that. But there's, there's still so much more I think.
0:28:38.810 --> 0:29:7.110 Nav Narayanan	In terms of a gap of understanding, is this patient actually infected? How you distinguish between contamination or colonization and infection, and even just, you know, panels these syndromic panels having specific targets versus sort of being sort of broad range, which is what we what we get even though it's slower from conventional sort of cultures where we try to culture out whatever is there. So anyway, that's sort of the yes and no from my view, yeah.
0:29:7.850 --> 0:29:38.280 Eric Myers	Yeah, I would totally agree with all of that. I think when it comes to taking a patient who's on antibiotics, identifying the organism quickly and getting some data to inform antibiotic optimization, we've come a really long way there. I think what the need is for us is really that try to differentiate that infection versus colonization. I think the question I get from our sites the most often and I'm not nearly as halved in the direct
0:29:38.420 --> 0:30:10.920 Eric Myers	clinical care as I used to be, but I do get questions off hours from some of our smaller facilities that don't have 24/7 ID services and it's almost always it's CRE in a urine culture and they're trying to see if you're using something like Ceftazidime-avibactam, if they're OK with approving that. And my question is always well, what the UTI symptoms did the patient report and it's typically some vague story where patient came in, altered, they didn't necessarily complain of any focal symptoms, but they're not sure if.
0:30:10.980 --> 0:30:25.110 Eric Myers	They just weren't able to because the altered mental status and that's tends to be really the scenario that we struggle with is how do we really differentiate colonization from infection in those types of situations.
0:30:26.40 --> 0:30:32.470 Nav Narayanan	And Eric, I think that makes me think of, you know, the other part of sort of antimicrobial stewardship that is.
0:30:33.270 --> 0:31:5.580 Nav Narayanan	You know is being discussed more and more, which is diagnostic stewardship, and you know sometimes the right answer isn't take to get a specimen in someone that might not actually really have an infection because then you might find something from microorganism standpoint and then it's really hard to sort of figure out what to what to do from there. So, I think even just knowing when to draw the cultures is an important aspect and we think about sort of the downstream effects of using antimicrobials unnecessarily because you can't differentiate between you know a contaminant or a colonization or true infection.
0:31:8.50 --> 0:31:34.460 Jean Patel, Nav Narayanan	So, I always think about a bacterial versus viral diagnostic as the Holy Grail of diagnostic tests that are needed in this space. But right, it really depends upon test performance. You have to have really high test performance in order to use a single test like that to make a yes or no decision for antibiotics. Like even to be honest, even years ago when we started
0:31:35.80 --> 0:32:4.910 Nav Narayanan	umm, when we started doing rapid diagnostics and our stewardship team became the one that would call physicians and other providers directly to let them know, you know, those gram-positive cocci in clusters from the blood culture. It came back as Staph aureus with no methicillin resistance detected and you know the question I would get is initially especially when this was a big change was, “can I trust that result - is it real? Should I just wait for the culture and…”
0:32:5.290 --> 0:32:37.160 Nav Narayanan	you know, I think trust in diagnostics and what they tell you, especially novel ones are really important for clinicians to sort of understand. I don't, I personally from my experience, you know clinicians aren't going to automatically sort of accept the results as sort of as gospel and that's going to be the truth in the universe with those results. So, I think that's another area where stewardship is an important factor is those sorts of intangibles of building understanding of diagnostics and what they mean and what their performance is and where they can and
0:32:37.250 --> 0:32:50.600 Nav Narayanan	can't be utilized and you know the context of it, so I agree, I mean that that Holy Grail I think would be a pretty great to have, but the performance matters a lot you know and how people use that information.
0:32:52.740 --> 0:33:28.190 Jean Patel	And so today we have rapid tests that can detect resistance mechanisms like you mentioned and the phenotypic susceptibility testing that has been the gold standard for data for prescribing antibiotics takes longer. Those are getting faster, but we haven't replaced conventional AST yet. Can you tell me a little bit about the difference between using this information about a resistance mechanism versus phenotypic testing and how you use those two different pieces of information?
0:33:29.490 --> 0:33:44.630 Nav Narayanan	Yeah, I think you've always heard is it that is the phenotype or the genotype and sort of that eternal battle that's going on and…we, so I'll just give an example. So, at our institution for
0:33:44.950 --> 0:34:7.470 Nav Narayanan	gram-negatives from blood cultures we use Accelerate Pheno, which is a rapid phenotypic assay and then for gram-positives and blood culture to use the Verigene instrument to be able to identify that quickly as well as those resistance mechanisms, and to be honest, I think there's
0:34:8.880 --> 0:34:19.80 Nav Narayanan	There's utility in in knowing both because I think actually Jean your presentation was excellent and it showed that, you know, CRE is not just sort of one sort of
0:34:19.550 --> 0:34:48.330 Nav Narayanan	monolith of resistance, it's sort of a cluster of different mechanisms and genes and from a therapeutic standpoint, those resistance mechanisms make a big difference to know. So, I think knowing the phenotype is important. And then when you get into really tough to treat resistant infections like CRE even knowing the genotype is important. I mean there's IDSA guidance -
0:34:49.170 --> 0:35:16.520 Nav Narayanan	the Infectious Disease Society of America. They have guidance, which is not, you know, the same thing as guidelines in terms of being high quality grading and sort of recommendations. But this guidance document is really meant to help sort of bedside clinicians in general just understand sort of how to navigate difficult to treat infections and they even break it down in there. It's not just CRE, this is what we recommend, it's saying CRE and then known resistance mechanisms and those
0:35:17.980 --> 0:35:46.910 Nav Narayanan	sort of, those therapeutic options vary across resistance mechanism, so for us I you know, I think we're honestly even in mid-discussions that are institution about trying to sort of also know that the genotypic profile of these difficult to treat gram negative resistance mechanism. So yeah, I know it sounds a little greedy, but I'd like both the phenotype and if I could live in a perfect cost-free world.
0:35:48.420 --> 0:36:10.880 Jean Patel	And then Doctor Myers, you're trying to take this complicated environment and implement antibiotic stewardship measures across multiple institutions. How do you do that? Do use data to do it? Is it education? Are you putting out guidelines for these institutions?
0:36:12.210 --> 0:36:13.910 Eric Myers	Yeah. So, all of the above.
0:36:15.70 --> 0:36:29.280 Eric Myers	We do have general, you know, empiric treatment guidelines and we've recently come out with some guidelines specific for some of these multidrug resistant organisms that are based on those IDSA guidance documents that that Nav mentioned.
0:36:29.860 --> 0:36:58.950 Eric Myers	And it is a little tricky from kind of a large system standpoint to come up with empiric antibiotic recommendations, since obviously that has to be tailored to the local sites resistance patterns and sometimes our resistance patterns can vary pretty significantly from one hospital to another. So, we tend to put out something more of a framework and then work with their local stewardship teams to kind of adjust it based on their own antibiograms.
0:36:59.750 --> 0:37:31.580 Eric Myers	That a lot of what I'm doing these days is around metrics and kind of trying to define appropriate antibiotic use, which is kind of the question that we've struggled with in the stewardship world for a long time. You know, going back five years ago, we would, we would all sort of measure the same thing as you'd have antibiotic days of therapy per thousand patient days, and it would just kind of be this number that you'd pitched to physicians, and it wouldn't really mean anything to them, and they wouldn't really know how to interpret that or if that really reflects appropriateness.
0:37:32.150 --> 0:38:4.600 Eric Myers	And so, we're really trying to kind of go one core disease state at a time. We're doing community acquired pneumonia, right now we've identified UTI as our big 2023 quality improvement project and we're basically just looking at within this disease state A what, what aspect of antibiotic use can we even measure accurately. And then in those, kind of, between those aspects, what based on the evidence is the most clinically meaningful that we can kind of get in front of physicians
0:38:4.680 --> 0:38:32.870 Eric Myers	and tell them you know how they're doing in a way that actually reflects antibiotic appropriateness. And so, what we really settled on for community acquired pneumonia was to focus on treatment duration, since there's several randomized control trials looking at five-day courses compared to longer, even three-day courses compared to longer now that really show no advantage to the longer course and actually increase risk of harm when they incorporate some of the antibiotic related adverse events.
0:38:33.530 --> 0:39:12.800 Eric Myers	And so, we're focusing on treatment duration. We're including inpatient discharge procedures as that's the best identified as an important piece where we on the inpatient side, we tend to do a really good job of stewardship of that as soon as the patients discharge, you know they might have an extra 7-day prescription of Augmentin that we didn't account for. So, we're essentially comparing our facilities and their median antibiotic durations for CAP and that now we're starting to get into potentially getting some provider level metrics and comparing one provider to another and they're their own specific treatment durations.
0:39:14.90 --> 0:39:15.460 Jean Patel	Wow, that's a great program.
0:39:16.650 --> 0:39:49.330 Nav Narayanan	Eric, that just makes me think of well, a couple things. One is just to emphasize how important data is and surveillance data in terms of antibiotic use, prescribing patterns and resistance patterns. Cuz it's hard to know what to do if you have no idea of what your resistance issues are in your hospital, it's hard to know sort of what to target in terms of overuse certain antibiotics. So, I mean, even in sort of large academic institutions, it's hard to get the type of granularity of the data that you need. So, I think.
0:39:49.490 --> 0:40:13.200 Nav Narayanan	I don't know. I think that's an important point to emphasize that you need sort of surveillance data and multiple fronts. And the other thing is it's a scary world outside that even outside the hospital, right cause I mean most antibiotics use is outside the hospital and it I think it really makes the point that you know we do all that we can especially because you know it's a high-risk environment and, in the hospital, but
0:40:14.140 --> 0:40:45.110 Nav Narayanan	you know, reaching out into the communities is, you know, the sort of the last frontier that that needs to be met. You know, when it comes to actually helping with rational antibiotic use, you know, we have a policy where anyone being discharged on parenteral antimicrobials needs an infectious disease consult. But, you know, there's still, there's still a whole array of world antibiotics that can do just as much damage from a resistance sort of standpoint that obviously there's a lack of oversight in so.
0:40:46.20 --> 0:40:58.990 Nav Narayanan, Jean Patel	Anyway, but I just made me think of those things, so I it's hard in the community. Yeah. You bring up an interesting question. What is the current state of Community antibiotic stewardship? Does that even exist?
0:41:0.960 --> 0:41:22.770 Eric Myers	I think it's it. It's starting to very early stages. I think there really is a huge disconnect between where most of the antibiotic usage is, which is outpatient in the community. I think it's as high as 75 to 80% of antibiotic use in humans. It's in the outpatient setting. Yet when you look at where really all of the antibiotic stewardship
0:41:23.480 --> 0:41:48.370 Eric Myers	efforts have been it's all been focused, impatient and I think that's just because that's where the resources have been. Hospitals have had more resources than they've had the capability to kind of take on that work. But really the bigger need in my opinion is in the Community and that's something that we're starting to look at. We're starting to evaluate metrics or how can we measure antibiotic use at some of our outpatient clinics.
0:41:49.30 --> 0:42:7.730 Eric Myers	And using an insurance payer data and you know how often antibiotic prescriptions resulted from encounters that probably shouldn't have resulted in antibiotics and like, you know, viral URIs and things. So, we're starting to look at that, but it really is a big unmet need at this point.
0:42:8.760 --> 0:42:39.750 Nav Narayanan	Yeah. And, you know, I had a relative in this sort of cold and viral season that had an upper respiratory infection and then, you know, I was told. Oh, but they got a pack of Azithromycin and you know, it just made me - it just gave me an instant sort of headache to think about it. You know, it's hard to even stop it with relatives, you know, because. So, I think that just brings up another point is it's not just engaging sort of outpatient providers but patients and just community members in general to be aware and understand that.
0:42:39.830 --> 0:43:11.970 Nav Narayanan	I think you know a lot of times when people go to the clinic or their doctor's office or whatever to get care, there's sort of in some folks and there might be an expectation of something to be given some prescription to be given to you, right? Some something to write this, this sickness that you're dealing with, you know, although and many cases like it's just sort of time and sort of you know, self-limiting illness and needs to sort of work out on its own. So, you know I think patients being aware that antibiotics aren't always the answer is sort of a big
0:43:12.180 --> 0:43:24.90 Nav Narayanan	a big part of this from our perspective and even though we're, you know, in the healthcare system from a hospital standpoint, I think it's sort of an impetus for us to sort of make sure we spread that awareness in the communities that we serve.
0:43:25.170 --> 0:43:29.140 Jean Patel	Yeah. Yeah. Patient education is going to be really important.
0:43:30.990 --> 0:44:3.730 Jean Patel	Asking each of you to think about the future a little bit. So, we just talked about increasing resistance, you know, scary types of resistance, but then the pipeline is slowing down quite a bit and how are those dynamics going to affect empiric treatment decisions? It just seems like those are going to become very, very hard in the future. Yeah. Any thoughts on where that's going to go and how to be managed?
0:44:4.890 --> 0:44:25.370 Eric Myers	Yeah, I read more than anything. I think it just really puts an excellent exclamation point on how important it is to preserve the efficacy of the antibiotics that we do have. You know these novel antibiotics work great right now, but we're already seeing resistance to them. So it's certainly not going to last forever.
0:44:26.710 --> 0:44:54.400 Eric Myers	And with the pipeline not looking so great looking, you know 10-20 years out. It's just really going to be critical to make sure that we're only reaching for these drugs when we really need them, which can be really difficult in the empiric settings because there are patients where even if you don't have a culture confirmed, Sierra are that you're looking at based on their micro history based on their antibiotic history, you could make an argument that they're at risk.
0:44:55.460 --> 0:45:3.190 Nav Narayanan	Yeah, just to piggyback off that that well, there's two things that I think about when that with that sort of.
0:45:4.300 --> 0:45:35.240 Nav Narayanan	Disconnect between sort of the supply of new antibiotics coming out to the market and then the resistance growing is one is you know we do need more diagnostics to help us move from empiric therapy to sort of more you know definitive targeted therapy, right. We sort of operate in this sort of nebulous world where we don't know exactly what we're treating and there's risks. And so, we have to treat with some of the bigger guns especially in vulnerable patients, immunocompromised patients where you can't go a day with sort of.
0:45:35.330 --> 0:45:49.610 Nav Narayanan	Missing the target on what they could have. So, I mean that's why I think diagnostics especially sort of you know in a time dependent manner where they're rapid and they're accurate and they cover the gamut of the sort of targets that you need.
0:45:50.490 --> 0:46:19.840 Nav Narayanan	You know that's extremely important. It's really hard to just kind of just keep operating in an empiric standpoint. And then the other aspect I think about is I mean sort of the antibiotic pipeline and this the structure and payment models and all those things are sort of sort of broken and you know in the United States at least you know there's sort of legislation that's just sort of waiting. So, the payment models are fixed. And I don't know, Eric, I'm, I'm sure you know like actually like to hear what you think at the system level of
0:46:19.950 --> 0:46:46.160 Nav Narayanan	What it is, what the cost because you know, everything gets lumped into sort of 1 DRG and you know it, it costs a lot and you know if you could use Ceftriaxone which is cheap and versus Ceftazidime-avibactam, I’m sure that you know keeps you up at night, maybe sometimes. But you know when patients need it, they need it and it shouldn't be that it is going to be cost restrictive, especially in sort of maybe smaller hospital settings or whatnot.
0:46:48.80 --> 0:47:14.720 Eric Myers	Yeah. Yeah, cost is definitely a big focus coming from administration. I feel like I'm constantly sort of caught between the C-Suite and the physicians. And I really try to avoid even discussing costs when we make these decisions and we meet with our, we have a system level antibiotic Stewardship Committee that essentially incorporates the stewardship leads from all of our facilities.
0:47:16.40 --> 0:47:30.50 Eric Myers	And we really try not to talk about cost unless we're dealing with a drug that really does not have significant efficacy or safety advantage over something else, in which case, you know, cost is sort of the obvious tiebreaker.
0:47:31.490 --> 0:47:56.510 Eric Myers	But it it's really hard not to. You know, the pressure is definitely there. We're in an environment now where if you're not cost conscious as a health system, you're going to struggle to keep the doors open. So, I mean, it's definitely something that we have to consider, but it really should never take the place of what is clinically necessary in a given situation.
0:47:57.190 --> 0:48:15.450 Nav Narayanan	Yeah, I feel like we've been spoiled. I mean it's, you know, it's sort of ironic because the antibiotic pipeline is sort of dried up over the decades. The things that have been around forever are now very cheap, relatively speaking and in, in many settings. And so people have just been used to antibiotics being, you know.
0:48:16.100 --> 0:48:39.850 Nav Narayanan	Dollars a few dollars. You know, for a day. And you know, we don't sort of blink twice and we see new sort of biologics or oncology related drugs and the cost associated with that and you know I mean these are life-saving drugs, these antibiotics in acute situations. So, I think there's sort of a perception issue too and so hopefully that that sort of cost payment model will get fixed at the same time.
0:48:41.420 --> 0:48:51.740 Jean Patel	So, thanks to both of you for sharing your expertise from the frontline. This has been invaluable. I think we have time for a few questions from our audience. So, let's see if we have some questions.
0:48:54.830 --> 0:49:18.590 Webinar Host	Yeah. Great. Thanks a lot for that interesting seminar, Jean, Navaneeth and Eric. Now let's move on to the question-and-answer session from the audience. Right. So, the first question we've got here from an attendee is why has AMR become a global threat? Maybe if you could each just give a short summary of the main factors you think are indicated in this
0:49:20.100 --> 0:49:38.10 Jean Patel	Well, let me jump in. I think you know I've spent a career watching the epidemiology of antimicrobial resistance and it just spreads easily. It can amplify within a patient and then it can spread from one patient to another. So now we have hard to treat infections all over the world.
0:49:40.640 --> 0:50:2.950 Eric Myers	I think a lot of it too is just travel at global travel is a lot more prevalent now than it used to be. So, when we get some of these novel resistance mechanisms that are able to be passed via plasmid and just because of the nature of global travel, today they're able to spread all over the place a lot more quickly versus maybe 40-50 years ago.
0:50:4.510 --> 0:50:31.260 Nav Narayanan	Yeah. The only thing I'll add is you know a lot of our antibiotics are derivatives of natural compounds and bacteria have been exposed to that for millions of years. So, they have a pretty, pretty good head start on developing resistance. And then you know, as Eric said it, the world is very globalized. So, you know, one thing on one part of the world is, you know, spread very quickly before we know it.
0:50:33.620 --> 0:50:52.630 Webinar Host	Great. Thank you all for that. The next question here is, because of the good effectiveness of Fosfomycin on some gram-negative bacteria such as CRE isolates from uncomplicated UTIs. And why do you not recommend this drug for CR Enterobactericeae treatment?
0:50:55.600 --> 0:51:5.630 Nav Narayanan	Yeah, it's a good question. I would be interested to hear what Jean has to chime in as well, because I know we've talked about this at some meetings we've been mutually at.
0:51:6.840 --> 0:51:23.400 Nav Narayanan	It is a good drug. I mean, there's sort of a discrepancy amongst the Enterobacteriaceae in terms of its effectiveness for E coli. I think there's good effectiveness. It is not as accessible in in some parts, at least in the United States. Not every formulary carries it
0:51:24.720 --> 0:51:58.360 Nav Narayanan	The dosing is sort of difficult to figure out depending on the type of your name, tract infection, you're dealing with and a lot of times you know you don't necessarily know the etiology when you're treating your urinary tract infection up front. It's sort of empiric and then you figure it out afterwards and you know unfortunately for Klebsiella species, it's not as reliable. And then even the testing is even sort of less reliable. So, it's hard to know if it is actually susceptible or not. So, I do think it is a good drug and in certain cases but in other cases it might not be as reliable as we would hope.
0:51:59.790 --> 0:52:29.500 Eric Myers	Yeah, I agree with that. I think this is susceptibility testing is a big limitation. When providers are dealing with an organism that's already very resistant. They want to make sure that the antibiotic they're using is going to be effective and we don't have fosfomycin on any of our automated susceptibility testing cards. So, they don't really know that. I do think it's a really good point though, about using agents that spare some of these newer antibiotics or even carbapenems for ESBL in UTI.
0:52:30.10 --> 0:52:48.930 Eric Myers	And we do try to promote Nitrofurantoin heavily for cystitis, but we also try to promote single dose aminoglycosides heavily for cystitis which a lot of people shy away from aminoglycosides because of the nephrotoxicity, but with the one-time dose you can tend to avoid a lot of that and still spare some of these novel antibiotics.
0:52:49.980 --> 0:53:23.350 Jean Patel	Yeah. I think this is compatibility testing has been a challenge for this organism. There's, you know, a difference of opinion about whether this drug is appropriate just for E. coli or for other species of Enterobacterales. And I think that difference has impacted different breakpoints around the world. There are differences between CLSI break points and EUCAST breakpoints and which breakpoints should occur on panels. Which ones are the right ones?
0:53:25.890 --> 0:53:36.630 Webinar Host	Great. Thanks all for that good insight there. The next question is, could someone address the intrinsic link between diagnostic stewardship and antimicrobial stewardship?
0:53:38.480 --> 0:54:2.60 Eric Myers	Yeah, that that's a super important question and I think diagnostic stewardship is one of those things that's historically I think antibiotic stewardship programs have not paid nearly enough attention to. I think that's thankfully changing today. We're starting to emphasize that a lot more, but you really cannot have an effective antibiotic stewardship program without diagnostic stewardship.
0:54:2.300 --> 0:54:35.810 Eric Myers	And so often providers will sort of reflexively treat a positive culture, and even if the patient doesn't necessarily have symptoms consistent with infection, once they're staring, that positive culture in the face it, it becomes almost impossible to convince them not to treat it, especially if it's a very resistant organism. Then the sort of fear level goes up. And so, the most effective way to prevent some of that is to just not get the culture to begin with. And we classically think of urine cultures in this treatment of asymptomatic bacteriuria, but
0:54:36.600 --> 0:54:53.0 Eric Myers	even other culture sites, sputum cultures, blood cultures are contaminated fairly often and that leads to more vancomycin use and so on. So, I think you know, being good stewards of our cultures and of our diagnostics is extremely important for antibiotics stewardship.
0:54:54.60 --> 0:55:24.270 Nav Narayanan	Yeah, I'll. I'll just add that it's one thing of either doing the test or not. And it's also of sort of getting the right specimens in general, you know is it a tissue specimen from you know, the operating room that actually might tell you something more about the pathogen or is it sort of a swab of the skin you know around the around the wound site where you going to pick up, you know a bunch of organisms that will be there, you know whether there's an infection or not and it might not help you, but it'll just cloud the picture so
0:55:24.570 --> 0:55:48.580 Nav Narayanan	you know, using diagnostics in the appropriate way and then on the flip side, making sure that you know, you try to access novel helpful diagnostics for the right patient populations, all of that, you know sort of fixes the issues more upstream versus, you know letting the issues sort of get out and then and then having to deal with it on the back end with trying to you know, limit how much antibiotics are being overused and inappropriate way.
0:55:50.460 --> 0:56:15.640 Jean Patel	I think there are some examples of healthcare settings where they have actually written treatment guidelines based upon the diagnostics used in their institution and so this can be very specific. They know what kind of results a doctor would get, and you can really teach factors to use the antibiotic based upon a very specific test result. I think those kind of treatment guidelines are really helpful.
0:56:16.450 --> 0:56:25.120 Nav Narayanan	Yeah, we've done that yet for some of our rapid diagnostics from blood cultures, you know, depending on the result, depending on the resistance that's found, you know, based on our formulary
0:56:25.700 --> 0:56:37.270 Nav Narayanan	you know what? What we would recommend in general and then we even provide sort of decision support as a stewardship team to help support those, those general guidelines that we provide. So yeah, no, that's a great point.
0:56:39.990 --> 0:56:55.210 Webinar Host	Great. Thank you a lot for that one. I think we have time for just one or two more questions. This next one I think is directed mostly at Eric and Navaneeth and it is, how important is subscription type payment models for antibiotics in your hospitals?
0:57:4.320 --> 0:57:17.790 Nav Narayanan, Eric Myers	I wonder if Eric - I'm not sure about subscription type models. I'm not as familiar with what that means. I'm not sure what is meant by subscription, subscription type payment models.
0:57:20.510 --> 0:57:35.390 Webinar Host	That's fine. We can move on to the next question. We can follow up with that one by e-mail after the webinar. So, the next question you got here is, how can you suppress antibiotics resistance in a patient?
0:57:38.740 --> 0:57:47.430 Eric Myers	That's a that's a tough one. I think. Sadly, the only way to completely prevent antibiotic resistance is not use antibiotics, obviously
0:57:48.130 --> 0:58:18.660 Eric Myers	we know that's not really an option because there are a lot of patients who need them. And so, we're sort of left with how can we minimize antibiotic resistance as much as possible? So essentially it comes down to using as little antibiotics as we possibly can. I think that the duration of therapy piece is probably the one that we're focusing on the most in in my institution, just because it can be very difficult for a stewardship team to kind of swoop in and
0:58:18.780 --> 0:58:42.260 Eric Myers	convince the physician that shouldn't be using antibiotics at all. But once they're at least come up with a diagnosis and have given an antibiotic, we can at least try to use the minimally effective duration. And there's a lot of good, good literature there showing that that's how that sort of reduces some of these antibiotic-associated adverse events without really impacting efficacy.
0:58:43.260 --> 0:59:0.340 Nav Narayanan	Yeah, and infection prevention, so just limiting the spread, you know, in healthcare facilities as well. So that's not an intrinsic thing, but it's an important thing to think about. And obviously there's a lot of overlap when we think about infection prevention and healthcare, epidemiology and antibiotic stewardship.
0:59:2.470 --> 0:59:32.740 Webinar Host	Great. Thank you all for that. I'm afraid we've run out of time, so I'm going to have to wrap it up there. But thank you again. Jean, Navaneeth and Eric, for today's informative discussion and presentation. Thank you to everyone joining us online and for your interesting questions. I hope you've all found this a worthwhile session and if you do have any other questions, please feel free to e-mail me at editor@selectscience.net and I'll follow up with your questions for our speakers. And remember, you can also download a certificate of attendance in the related Resources tab to the left of your screen.
0:59:33.280 --> 0:59:42.930 Webinar Host	And if you would like to listen again to today's webinar or invite a friend to listen, it will be available to watch on demand in a few days. Goodbye and thank you once again for joining us.
0:59:44.580 --> 0:59:45.870	Thank you. Thank you.

*Beckman Coulter Inc. is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. Program. These credits are recognized by the State of California. Most programs also provide State of Florida credits (with valid license number). At this time, we cannot issue continuing education credits for those who provide healthcare (or work for an institution that provides healthcare) in Massachusetts or Vermont.

Choose your country/region and language

Country or Region

Language

Antibiotic Prescribing Dilemmas in the Face of Increasing Resistance: How Do Diagnostics Help?