All right, hang on. We'll go ahead and get started. No, no departmental update today. So we'll dive right into medical grand rounds, which is good because it's a good one. And just as a reminder, for questions, if you don't mind just taking a microphone, just so everyone in the room in hear and that folks listening from afar can hear as well. And then there are some audience response kind of questions as part of the grand rounds. So those will be text-based. So text into UVAGME. That'll be up on the com. So either way, we're really excited to have Dr. Amy Mathers here today from the Division of Infectious Disease. I think we all know Dr. Mathers fairly well. But just in terms of some brief background, Dr. Mathers did some of her initial training through Maine Medical Center. She was a resident and a chief resident there before coming down to UVA as a fellow and then staying on as faculty. And here she's really kind of quickly become a leader within the division and the department, serving as the Medical Director of the Antimicrobial Stewardship Group, as well as the Associate Director of Clinical Microbiology. On the research side, she's really distinguished herself as well nationally. And that's been measured in a number of ways, notably earning the top 10 manuscripts from the American Society of Microbiology in several years of the past couple of years. And then she's also kind of easily become one of the most appreciated and respected attendings amongst residents and fellows. And so I think if you ask anybody, she's one of the most fun to work with and one of the ones we kind of learned the most from. So we really appreciate that, and I think that's been kind of evidenced as well by a number of teaching awards and honors over the years. And we're fortunate to have her here to talk about a obviously influential topic that we all deal with, and that's the issue of increasing antimicrobial resistance and how we're going to confront that as a group. So with that, please join me in welcoming Dr. Mathers. [APPLAUSE] All right, so can you guys hear me? Is that right? Can you hear me? Yeah, good. OK, so thank you for having me. I wanted to talk today about antibiotic resistance, which is near and dear to my heart. Kind of everything that I do, I ask, well, does it have something to do with antibiotic resistance. And that is my gauge for whether or not I say yes or no to a task. And so I think about it all the time. It's really important. And I thought, you know, I was trying to come up with how can we make this a little bit more interesting and fun. And you know, it's been roughly 80 years since penicillin came to market. So I thought it might be a good time to look back at sort of where did antibiotics start and give some homage to having antibiotics and effective antibiotics. And how are we going to keep them effective for the next 100 years or next 80 years at least? And so we'll talk a little bit about that. I do have some disclosures with both diagnostics and therapeutic companies. I'm not going to mention any of them by name. So where are we at with antibiotic resistance? At least every six months or so, you'll see some news report. This is one from last year actually of a superbug. This killed a woman in Nevada. And it made big news, and I'm not sure exactly why. This was a patient who'd had a hospitalization in India and then was transferred to a Las Vegas hospital and succumbed to an infection with a highly resistant Kleb pneumo. It was an NDM. And they said it was only susceptible to one antibiotic, which was fosfomycin, which wouldn't have worked anyway. So I think we are really-- the news is becoming aware. The public is aware of antibiotic resistance. However, locally, do we ever see cases like this in the news? And at UVA, this fall, we had a 52-year-old woman who was admitted for a meningioma resection. She did have multiple comorbidities, but had no travel outside the US ever. And after a prolonged hospitalization with iatrogenic complications and comorbidities, this is what grew in her sputum and, ultimately, in her blood. And it's the same, if not worse, than that Kleb pneumo that they described in this report that got so much news. It's a Providencia stuartii, which, unfortunately, is intrinsically resistant to a lot of antibiotics anyway, but then it's resistant to all the new agents that have come to market, mostly because it had a metallic carbapenemase indium. And so this isn't just a problem happening somewhere else. It's happening here at UVA, and it's happening to our patients. And so what are we going to do to try to protect folks? I'm going to give you a little bit of the sort of where we at globally and in the US about resistance and then talk a fair bit about what is antibiotic stewardship. And what are we doing here at UVA in terms of antibiotic stewardship? And what's our stewardship program look like? And then my mission is always to sort of to try to get you guys to all see yourselves as champions of antibiotic stewardship. And you're the stewards really. I mean, I don't prescribe that many antibiotics. So it's really your prescriptions that will make the difference. So I tried to kind of go back in history and then look forward. And of course, it's always easy and fun to look back at, you know, how long have humans had antibiotics. So I really like this slide. And it shows a timeline of human existence. So the top line is the pre-antibiotic era. Six billion years we think the planet has been going. And bacteria have been on the planet for a long, long time. That last little, tiny sliver that you probably can't see that's pink is as long as humans have been on Earth, 20 million years. And then that tiny, little sliver at the end of that is the antibiotic era. And so the last two bars down there are sort of when did antibiotics come into use. So sulfo was properly in use in 1937. And what you'll note is, on the bottom graph, there's sulfo resistance in 1942. And this is a common theme. And I'm sure you've all seen something very similar to this. Penicillin hits the market in '41. Erythromycin, which isn't in here, is '52 and so on, followed quickly behind with antibiotic resistance in clinically relevant bacteria. And so they're just better at this than we are. And what I would say is that humans have observed that antibiotic resistance-- how does this happen? Well, it does seem to happen when we use antibiotics. And so I again tried to find a lot of historic articles. We've known about antibiotic resistance and its relationship to use for a long time. There's a picture of a Chicago hospital. And they were noting a fair bit of Staph aureus, penicillin-resistant Staph aureus on the wards. As you can see, their percent Staph aureus resistant, so they were seeing 50% penicillin-resistant Staph aureus. So they made it so you couldn't use penicillin in that Chicago hospital-- it was Cook County-- because there was a new drug, erythromycin, on market. And so they made everybody who had a Staph aureus infection get treated with erythromycin, which I'm thankful this isn't our stewardship policy, but it is what happened. And you can see quickly erythromycin resistance skyrockets. So when you use a lot of antibiotics, you see resistance. It's a lot more complicated at a molecular level, particular bug, particular drug. So it's not just a one to one, but use does beget resistance. And how does that happen really? Well, you've got a mixed population. You expose it to antibiotics. You eliminate the bacteria that are susceptible to that, whether it be gut flora or anywhere else that antibiotics are used. And you leave behind a population of a lot of resistant organisms. Those are then the ones that can go on to cause infection or spread from patient to patient in the hospital. For bacteria, this can happen through gene sharing. It can happen through a mutation. It can just happen through selection. So how bad is it really? This is a report from Jim O'Neill out of the UK that was done in 2014. It cites 700,000 attributable deaths at that point based on roughly 2010 data. So we don't have great data of how bad it really is. From this report, they based on current projections that it will outstrip deaths from cancer by 2050. Just so you know, current figures are something like, just some of the stats that stand out in my mind, 58,000 babies a year are dying of drug-resistant pathogens in India alone in the first year of life. So how bad is it the US? Well, one important thing that I hope you carry away from this is the US doesn't have great data. So there's a whole host of reasons why that is. But we don't have good data. So this is a recent report based on 2015 data that came out of Europe. I thought it was sort of fair game in that we have similar access to antibiotics, similar diagnostics. So it's somewhat comparable. And from this report, things that are important, most of the infections are hospital-acquired. So 63% of the infections in this series were hospital-acquired. There's an increase from 2007 to 2015 in terms of resistance and roughly 33,000 attributable deaths to antimicrobial resistance. For this study, they really only looked at bloodstream isolates. And I guess I should have said things that they really focused on were-- how did they define it? EspLs, MRSA, VRE, and penicillin-resistant Strep pneumo and carbapenem-resistant organisms. So from that report, you can see down in the hashed-bar lines that more than 50% of the mortality and attributable problems from drug resistance are attributed to carbapenem-resistant organisms. And so there's some real problems going on in Europe and, potentially, elsewhere too if you start tracking it. From this report, the burden of infection, so the number of cases, attributable mortality, and disability-adjusted life years, are equivalent to those of influenza, tuberculosis, and HIV at this point. And so it's not going great. So let's take a look back again at sort of what do we think about in a world without antibiotics. And why do we need to protect them? So you don't have to make this up. You can just look back. So I liked this series because most of this series took place before antibiotics were widely used. It's 561 patients from a single center in 1933 to 1947. And these are all the patients that got TURPs. So I've never seen a patient die from a TURP. And in this series, they had a 3% mortality. 1% of that mortality was just sepsis in the setting of the TURP. So if you can't use perioperative antibiotics around a urologic procedure, people die about 1 out of 100. And so that's a really important use of the antibiotics. We also know that we probably wouldn't be able to do a lot of dialysis. And all the immunotherapy and immunosuppression that we now use that runs modern medicine is probably not going to work all that well or for very long if we don't have effective antibiotics. So we really need to preserve this from all sides. So what's the consequences of antibiotic resistance and/or antibiotic use? We know that there have been studies showing increased risk of hospitalization, length of stay, hospital costs, ICU stay, and increased risk of death. We also know a modern dilemma cropped up in the 21st century has been the scourge of C. diff. And there are a lot of great people here that work on C. diff. And it essentially is a sine qua non. It does not happen without antibiotic exposure, essentially. What I want all the house staff to realize is that there are studies that show that it is associated-- there have been studies that have shown every single dose counts. So the number of doses you got increases your risk of C. diff. The spectrum that you get, the duration that you give all increases your risk of C. diff. So every dose counts. So improving antibiotic use is a relatively new prospect for public health, but public health has stepped in and said we've got to deal with antibiotic resistance. However, most antibiotic resistance happens in a hospital, at least in the United States and the kind that I'm talking about today. And so this is somewhat new territory for public health systems to try to help hospitals. Hospitals in the US are capitalistic, and we don't really want to talk about our antibiotic resistance rates, nor do we have to publicly report any of that yet. And so this is all somewhat new and uncomfortable, but that's part of where the lack of data is. I think it's really important that public health does take a big role. As everybody knows, antibiotics are the only medication that, you know, they're less effective today than they were when they started in 1950, whereas hydrochlorothiazide works just as well as it did in 1950. If I take an antibiotic, if I take azithromycin, and then I give Bethany Keller a big hug, I've just transmitted macrolide-resistant Strep pneumo. And so how you use antibiotics in one patient affects all the other patients in that population. So it really does belong in public health, but hasn't traditionally lived there. So what's the US government doing? Well, the Obama administration realized this was a problem, partly because the World Health Organization prioritized this as one of the major threats and required that all countries have a antibiotic resistance strategy or plan. And so this is sort of what the government's response was, the Antibiotic Resistance Solutions Initiative and so, you know, that we need to detect and track antibiotic resistance patterns, as well as share some of that data on how we're doing that, respond to outbreaks of antibiotic resistance, prevent transmission, and then discover new antibiotics and new diagnostic tests. Of course, this isn't happening at the rate that we'd like to see it, especially with new antibiotics. And there's a lot of real big problems that I'm not going to talk too much about today. But new antibiotics are probably not going to carry the day for a whole host of reasons, at least in the foreseeable future. Most of the Antibiotic Resistance Solution Initiative talks about stewardship. How can we protect the antibiotics we have in hand now? And so there are a lot of national guidelines coming down saying you've got to really take care, both inpatient and outpatient, of how you're using antibiotics to keep them effective. These are stats most of you have seen. Some of them are slightly outdated, but I like this slide. 60% of hospitalized adults get one dose. Some more recent quotes say maybe it's closer to 50% of hospitalized adults get at least a dose of antibiotics. 40% to 50% of this is inappropriate. And then it costs the health care system a lot of money. So the government is now going to be tracking you. And so one of the issues that I wanted to highlight to you guys is, for those who are aware of the SAAR, in terms of the standardized ratio for line infections or CAUTI or a lot of what infection control has been talking about for a long time, we now have the SAAR. And that is the Standardized Antimicrobial Administration Ratio. So how are we using antibiotics compared to like hospitals? And what was surprising to me is we really I felt like pushed really hard to get through lots of work with our IT partners to get this reported to CDC. And so we are sort of early in the game for reporting, partly because I didn't want our SAAR to be when it was mandated, and we found out that we were way over every other hospital. And we want to know where we sit. And so we pushed to get this through. We got our first report, which I'll share with you in just a moment. But what's also interesting about it is all these checkboxes that are quickly coming. Public reporting is up next and then quickly followed by payment program and accreditation, as well as professional recognition. So this is all going to be affecting you guys in the next five years. Whether you like antibiotic stewardship or not, it's coming. So I'm going to share with you are some of our SAAR data. For the adult SAARs, its medical-surgical ICUs, medical-surgical wards, step-down units, and then hem-onc. And you can see the categories there are BSHO is Broad-Spectrum Hospital Onset, so a lot of antipseudomonal agents, broad-spectrum community onset, gram positive, things like linezolid, dapto, vanco, narrow-spectrum beta-lactam use, fungal, C. diff, high-risk agents, and then all antibiotics. And you can see the different ways they're going to compare university hospitals and other things. So they're trying to make it very comparable. So this is where we're at for the last year at UVA. We're right at average, which is I'm happy. That's great. [LAUGHTER] I wasn't sure where we would be to be honest, but I think that's pretty good. There's 700 hospitals we're being compared to, and more will be folding in. I think this is going to be a requirement very soon. But let's look at a little bit of general medicine comparison. So just remember I've put the wards there of how we're doing. MICUs, STICU is what goes into our adult ICUs. Adult onc, adult med-surg all listed there. So those get piled together. And then these I thought C. diff because C. diff is also important to all of us. There's the C. diff antibiotics. That's what the CDC considers high risk. I think this is debatable, but that's what they did. And here's where we sit. So our ICUs were quite a bit above other ICUs, adult onc, for those agents, not too bad in most months. And then adult med-surg, we look pretty darn good, or we're at average I guess is what we would say. And so there is sort of the breakout of the ICUs. And as people would predict, the MICU is using more antibiotics, and appropriately so, than the SICU. But that high average is probably driven by the MICU. And so is this an area we want to focus on? I don't know. But we'll be sharing this type of data. There's so many different categories to talk about and what to do with them. And we're open to ideas that people have because, this data, we don't know exactly how to use this. So let's look a little bit more. So also, in getting all of that data built, we worked with the data warehouse to get our antibiotic usage data so that we could take it and build reports and share it with individual wards and individual practitioners. So this is all sort of fresh off the press too. So for gen-med words, this is how we used antibiotics for the last 12 months. Ceftriaxone is number one. We at UVA decided not to completely adopt the CDC's definition of high risk. We think cefazolin is also a potentially high-risk antibiotic for C. diff. And we use a lot of ceftriaxone and vancomycin IV are our number two antibiotics on the gen-med wards, which probably isn't surprising to anybody. Again, it could be worse. [LAUGHTER] So what is the antibiotic stewardship? And how are we going to take this data and make sure that we all are doing what we need to do to protect antibiotics? It is not the antibiotic police. It's not other words associated with antibiotic blank that we're trying to take away your effective therapy. We just want you to use the best therapy for a patient that needs it at the right time for the minimum amount of duration. So we just want to, you know, minimize the collateral damage from antibiotic use when it's appropriate. We know, with antibiotic stewardship, there's data showing that it increases patient-- you get better patient outcomes when there's a stewardship program in place, and you listen to them, saving money, and it's better patient care. So the six D's of antimicrobial stewardship, I kind of like this concept. It's not mine. I stole it from somebody else, but it all comes down to really just knowing your patient and knowing what infection they have and how to treat it, so making the right Diagnosis, Draining infection when it needs to be drained, and no amount of antibiotics are going to work, getting the right Drug and the right Dose for the right Duration going, and then Deescalating whenever possible, getting rid of spectrum you don't need for the infection you're treating. I will say that, near and dear to my heart, good clinical micro is central to most of these issues. So how can you minimize collateral damage from antibiotic use? So fewer unnecessary antimicrobial days, meaning I'm going to talk a little bit about shortened courses. When can we do that? Stop empiric antimicrobials when cultures are negative. You've got to know what exactly that means. When cultures are negative, can you rely on them to say there is or is not an infection? Being able to interpret your clinical micro results-- so knowing that, if you have Candida or enterococcus in a sputum, you shouldn't treat enterococcal pneumonia because that's not a pathogen for the lung typically and so understanding that. And then not using antibiotics as a physician anxiolytic, so trying not to just-- so my patient has a fever, and they're tachycardic. And I know they haven't had positive cultures for days, but they seem like they're infected, even though everything is telling you not, just really going back. All of these things, I think the central piece is just being a really good doctor, and knowing your patient is probably the most effective thing you can do for antibiotic usage. When you get culture data back, target your therapy. Know who is at risk for multidrug-resistant organisms. You know, I'm going to talk a little bit about how we can improve figuring out who's at risk and understanding the guidelines on who actually needs a carbapenem and who doesn't. So I had promised people, because C. diff is so near and dear to everybody's heart, and it's in the big six, that we would talk a little bit about C. diff. So we review on stewardship-- Jae Shin's been doing it this year-- review all nosocomial C. diff cases, which is just a definition of a positive PCR within 72 hours of admission. So that's the definition. That's what's reported. That's what ends up on the dashboard. So for medical subspecialties, there's been 28 cases. A lot of cases have no opportunities for improvement. There's just we don't see anything in our review that could have been done differently to prevent this patient from getting C. diff. A lot of them have more than one. So that 18 is not 18 different, unique cases. And we see antimicrobial optimization from all of those things. Alternate explanation for the diarrhea is still the number one opportunity for improvement that we see in medical subspecialties. And the tests not being indicated is still happening. So my first question-- 75-year-old female comes in with nausea, abdominal pain, has a small bowel obstruction, while on the floor, ends up with emesis and a witnessed aspiration on the floor. Soon after, she has a fever, a faint infiltrate on chest X-ray, does not have a new O2 requirement, and she remains stable for the floor. What should you do? Initiate amp/sulbactam for aspiration pneumonia. Initiate ceftriaxone or metronidazole for aspiration pneumonia. Monitor signs and symptoms without antimicrobials to assess for the development of pneumonia. Or initiate amp/sulbactam to prevent the development of aspiration pneumonia. Or obtain a sputum culture. So I'll have you guys all-- I think you text in to UVAGME, all caps. Text UVAGME, to 22333. And then put in your answer response. And the reason I bring this case up is because this was one of our OFIs from a case of a C. diff review where antibiotics were used when I'm not sure-- well, you guys can tell me what we should have done. Oh, look at that. It's probably one answer. [LAUGHTER] Right. All right, so it looks like most people would hold off on treating. And some people would get a sputum culture. Maybe it's because they know that I want to make sure everybody gets good cultures, but I don't think that's necessarily the right answer. You should just hold off and monitor your paper. And so again, this goes to know the guidelines that we have. And these are the University of Virginia HAP/VAP guidelines. Here if you have a witness aspiration event on the floor, it's that fever and even that infiltrate are likely chemical pneumonitis, especially in the first 48 hours. Hold off on antibiotics. They may develop a pneumonia, unfortunately, but really you want to monitor your patient and not start antibiotics. There's a recent nice study that came out in CID in the last year showing that, you know, if you give patients antibiotics to try to prevent the development of pneumonia, it doesn't work. What you then do is you increase the number of mean antibiotic days. And when they do get pneumonia, which is actually what happened with this particular case, they then had to escalate to a different therapy. And so people get more broad-spectrum antibiotics. You select for more resistant organisms, whether they're going to get pneumonia or not. It's a bummer, but they might get pneumonia. And you giving antibiotics at the bedside in that moment, hard not to do because an infiltrate, a fever, and an old lady are like oh, but really you're better off holding off. So what about another situation where we could kind of conserve antibiotics? So going back, Heather Cox found this series that was the first 500 cases of penicillin. It was a multi-center use. It was a description of the first 500 cases of penicillin used in the United States. And this was their description of how they used penicillin for the pneumococcus infection. They gave 100,000 units over two to three days, which is just incredible. I've never given less than millions of units. And I don't recommend we lower our penicillin dosing, but they gave it for two to three days. And then if they were still sick, they gave it another day. And then somewhere when antibiotics were abundant and rampant, we sort of moved everything to this football score thing where we did 7 days or 14 days or 21 days. And it's great because now there's a lot of literature coming out that we could probably get away with shortened courses. So for CAP, HAP/VAP, our recommendation is five days, seven days, intra-abdominal infection, [INAUDIBLE] four days, urinary tract infection, seven days, three days potentially and, for CLABSI, as few as five days for coag-negative staph and seven days for enterococcus and gram negative rods. What I will say about all of this data, this is great. You should be adhering to these guidelines. However, you need to know your patients. There are a lot of patients who get excluded from a lot of these studies, and three days may not be the right amount of time. For example, if you have an empyema, please do not treat your CAP for five days. If you have a parapneumonic effusion-- you know, so just know your patient, and know when the shortened course applies. And use that shorten course. Antibiotics work great, and you don't need them for very long. So what about diagnostics? How far have we come? And so I just put up-- I knew everybody was going to be here. So I feel like everybody else has had a lot of technology come their way, and ID has been left a little behind. So in the 1940s, we had urine glucose for diabetes to see when you were spilling glucose into the urine. And now we have, you know, continuous personalized monitoring. The stethoscope for cards, and now we have cardiac MRI and a whole bunch of other stuff. And then bacterial infection, we still have bacterial culture. So most of what we do is still driven by bacterial culture. And the World Health Organization has really identified this as a gap that could help antibiotic resistance a lot. And so this quote is from the director of the World Health Organization, talking about we need-- "Antibiotics are rarely prescribed on a definitive diagnosis." We sort of antibiotic empiricism, ballpark it, get cultures maybe, maybe not, come up with a duration, and then may not even respond. There's a paper showing 40% of clin micro results actually never get looked at. So you know, having rapid, low-cost, readily available diagnostics so that you can really target your therapy is what we need. This is also on the heels of making sure that people don't die of sepsis. As we see increasing numbers of drug-resistant pathogens, we know that, no matter what the species, if you do not have active therapy in the throes of sepsis, your patient is going to do worse. And active therapy usually has something to do with resistance. So if you see a lot of MRSA bacteremia coming into your hospital, you have to have vanc on board. And that's why we do that in the patients that are at risk. We know that if you don't get adequate therapy going quickly-- this is a study of 800 patients basically where they looked at adequate versus inadequate therapy. And the mortality was much higher in inadequate therapy. But what was interesting is, if you did not get to definitive therapy within 48 hours, you did worse as well. And so you really need to-- you can show a difference. Getting patients on the right drugs sooner saves lives. Also, the sicker the patient at the beginning, the worse they're going to do if you don't have appropriate therapy. And so this is again a bloodstream infection mortality risk score. The sicker the patient they are when they walk in the door, if they don't get on the right drug right away, they're not going to do well. And so I think I'm going to close with some rapid diagnostic stuff that we've been doing in stewardship and clin micro to try to minimize and close this gap between when we decide for empiric antibiotics versus when we decide definitive antibiotics. This is going to be really, really important as antibiotic resistance emerges. I don't want everybody to just use carbapenems on everybody that walks in the door. And so we've got to get-- we've got to shorten that empiric therapy. So this is our own data that we looked at trying to roll out a rapid diagnostic with gram negative susceptibility testing available. And in the orange lines, the dotted orange line is the time that it takes from the time of the gram stain on a blood culture to the time you have susceptibility results available. And then we've got a rapid diagnostic that has susceptibility results available in about eight hours. So it's a difference of almost 30 hours between the two susceptibility testing platforms and about 24 hours in between ID. And so when this rapid diagnostic became FDA cleared and available, we thought it might be helpful for our patients. So we launched it July. This is a workflow, as of July 2018. So and this again is in line with what we saw with the VERIGENE that has molecular target for gram positives, which can give you definitive therapy. But for gram negatives, you really need susceptibility data to come up with definitive therapy. The way it works, we take a blood culture. It goes in an incubator. When we see monomicrobial gram negative rods, we put it on. It works like PNA FISH and real-time microscopy. Then we get a predicted susceptibility test, and that gets emailed to the antimicrobial stewardship team. One of us then takes a look at it, decides what to do with it, and really almost always calls you guys. So when we call you with these results, we usually have really relevant information for you. So answer our page. And we then call the micro lab and tell them sort of what to do with it. Some of these don't work very well. So we don't report them. And that's part of why we're sort of handholding them through the process and not just releasing them straight from the micro lab. We know that, from the first 77 patients, comparing to a prior group of 77 patients, we have susceptibility data 28 hours sooner from the time of gram stain on blood cultures. And so I'm going to finish with just one last case or two last cases around the empiric and definitive therapy. So 77-year-old, diabetes, comes in with weakness, dysuria, hasn't been peeing much for the last three days, and decreased PO intake. She's febrile. She's got some suprapubic tenderness. She's got a leukocytosis, some AKI, and her UA is very positive. Blood cultures get sent from the ED. She get started on cefepime and sent to the MICU for the treatment of DKA. So her blood cultures go positive about 15 hours later, which is pretty typical. Call that to the MICU resident, which is still our standard. Then we get the results to our antimicrobial stewardship program email in real time at 11:00 AM. And then around that exact same time, the MICU note says let's just do seven days of cefepime. So this is what comes back. So easy question, so what do you select for definitive therapy on that? Ampicillin, amp/sulbactam, cefazolin, ceftriaxone, cefepime, or cipro. Take a good look at it because I'm going to take away the susceptibility because it has to go to this. So it's an E. coli susceptible to things that were on that panel. Nobody likes the MICU plan. [LAUGHTER] So yeah, so basically, we've got a lot of calls for cefazolin, a lot of calls for amp/sulbactam, and a few for-- I think ceftriaxone was also on there if I recall, cipro, ceftriaxone. So good, everything but cefepime. So I would argue that what I would want to see that patient transition to cipro would be fine I think. Amp/sulbactam would be fine. And cefazolin would be fine. The problem is, the next morning, ampicillin came back as susceptible. And so really, what I'd want to see you do is change it at that point to ampicillin. Unfortunately, ampicillin is not on our rapid diagnostic. And so we cannot tell you to change it to ampicillin. So this is one of the things that we've learned from our first 77 cases. We are not getting people on ampicillin when we could. And so we're getting there faster, but not quite all the way. And so in terms of how I view the world-- this is controversial. I'd love feedback from ID clinicians, but this is sort of how I view the world in terms of spectrum of beta-lactams, carbapenems, pip/tazo, cefepime, ceftriaxone, cefazolin, amp/sulbactam, or ampicillin. And we want to get rid of spectrum that we don't need. So again, not significant from the first 77 patients compared to 77 beforehand, but what is really important is we are getting-- it is happening sooner. We're seeing patients getting to ideal or institution-preferred therapy, as we've called it, narrowest-spectrum beta-lactam, sooner. But also, what's really important-- and this is the last case I'm going to finish with is that 22 patients and 21 patients in the post/pre groups were not on active therapy at the time this result came back. And we are getting people on active therapy sooner. So that's a really big deal. So even if we haven't changed spectrum quite as much as I would want-- and we're working on it-- we are getting patients on active therapy sooner. And we know probably from the data that's going to end up saving lives. So last case, 72-year-old with a renal transplant-- and it's been slightly complicated since the time of transplant with two urinary tract infections-- comes in with altered mental status, hematuria, fever. She wasn't febrile there, but she had reported a fever at home. She's leukopenic. Blood cultures get sent. She also has a positive UA and suprapubic tenderness. She gets admitted to 3 West. So what do you select for this patient? She's come to you from the ED. What do you want to put her on? Wow. All right, this is really good because I think this is probably one of the most important questions, actually, now that I look at the results. This is a patient that's had exposure to two courses of antibiotics in the last 90 days, is complicated, immunocompromised, and has a complicated GU tract. I would want, if that patient came to my gen med service, I'd put them on meropenem. And that's what they needed. And that's not-- and so that's what happened. They got put on cefepime, which is OK, probably would work. And it does say cefepime susceptible. But for definitive therapy in an immunocompromised with ceftriaxone non-susceptible, aztreonam non-susceptible isolate, which is what she grew, I'd probably prefer a carbapenem until the dust settles. And so that's what we called and recommended. And I'll leave you with just remembering-- because we're seeing this a fair bit-- people are not starting carbapenems when they need to. And just remember your risk factors. Who needs a carbapenem? Who's at risk for an ESBL? E. coli, and it's complicated GU tract. Any antibiotics-- a recent paper came out, the more antibiotic courses you have in the last 90 days, the more likely you are to have one. If you've had a prior ESBL, that also puts you at high risk. If you're coming from outside country where there's higher rates of ESBL, all of these things you want to remember are potential risks. ESBLs vary across the country in terms of is this is Pyelo causing E. coli, complicated and uncomplicated, and the rates vary across the country. So it's somewhat local. And here's our data. And unfortunately, in 2018, it looks like we are losing ground on ceftriaxone in E. coli showed there on the right. Remembering that amp and E. coli, amp is still good for half of our E. coli, which isn't great. You can't use it for empiric therapy. Don't use amp for empiric therapy, please. But if you know that amp is susceptible, you should use it. And let's not leave people on ceftriaxone for things like it's convenient, might as well. They've only got three days left of therapy. Or I don't know. There's a lot of reasons why people say, but I just-- let's not. And so that's what I'll finish with. Antibiotic resistance is a threat to modern medicine. And I think it's really going to be your job to combat it. I think you can all be good stewards by just being good doctors, knowing your patients, get good cultures, believe your culture results, and narrow when possible. And please, please call us whenever you have questions. We love your calls. We're happy to talk about cases. Page me personally. I'm happy to-- I'd love to chat about it. And just for an update, this is our stewardship team. And so we've got several new PharmDs that have started with us-- Meghan Shaw, Lindsay Donohue, Heather Cox, myself and Lindsey Buscemi and Brandon Hill, Zach Elliott, Jae Shin, and Patrick Jackson are all members of the team. So call us if you need any help. Thank you so much. [APPLAUSE] If we're allowed to have questions, questions, I'd like to ask a question. OK. [INAUDIBLE] Yeah, would you mind using this. Yeah, sure. Thank you. On SBP prophylaxis, for a long time, we would treat just cipro once weekly if indicated. Then it got switched to daily. Recently, there was a study from Korea that showed weekly was as effective and cheaper. What are your thoughts on that in terms especially of breeding resistance or not? That's been the concern. That's right. [LAUGHTER] So the question-- well, you heard the question. SBP prophylaxis, how much? Again, it does come back to less is probably more. You know, we know that some of the prophylaxis and fluoroquinolone resistance has really crossed hairs. I mean, cipro used to be effective for prophylaxis in the setting of GU procedures. It is no longer. At least in our community, just with a 30% resistance rate, it's just not reliable for E. coli. And there's been increases in prosthetic abscesses or infectious complications from surgeries when you use that as a prophylaxis. So we've had to switch to ceftriaxone for our urology procedures. So I think, you know, patient selection-- who really needs SBP prophylaxis? Who is your high risk patient? Making sure that decision gets made thoughtfully, and use it wisely if it's working well in your patient population once a week. I haven't looked at our local data or-- There's no big advantage? In terms of-- [INAUDIBLE] was that [INAUDIBLE] To cause resistance? Yeah, we've seen [INAUDIBLE] seems better. Yeah. I would agree with that. I mean-- I don't know if anybody else has an opinion on that. It's an infectious disease. I don't-- I think it's a wash in terms of resistance selection. Thinking about fluoroquinolone resistance and how that gets selected for, I would think it'd be a wash. Can you comment on the use of fluoroquinolones, such as cipro, given the recent associations with elastic tissues and the development of aneurysms? Yeah, with the [INAUDIBLE] black box warning on the fluoroquinolones, it's hard. It's really hard to prescribe in your-- you know, there's a it's like there's a support group online. I forget. Heather knows what it is. But it's like that have you been a victim of fluoroquinolone, you know, poisoning. They're good drugs. It's the only oral antipseudomonal option. You know, but there's a lot of toxicities. And I think you really have to counsel. I counsel patients extensively. And if they get nervous about it, then we come up with a different regimen. And I try to do just sort of patient information. It probably does do some selection for C. diff. Although, I'm not sure, now that NAP1 strain is down a bit, how much that is cephalosporin versus a fluoroquinolone, a bit of a wash. So it's not a very good answer to your question, but I think it's a real issue. It's a real patient perception issue. And I think you have to be sober about those. My concern is is there might be missing black box warnings on some of the other antimicrobials. Right? So like if you decide I'm not going to do a fluoroquinolone because of potential tendon rupture, and you're into an aminoglycoside, there's just no black box warning that's been put out lately because people aren't using that drug because it's so horrible and ineffective. Like you know? So I think you have to be really sober about it and just kind and thoughtful about how you're doing. But I usually talk through with patients about what the risk is. [INAUDIBLE] Yes, yeah. Even more inappropriate is not-- [INAUDIBLE] And there's also [INAUDIBLE] It's a class of drugs that should virtually never be used. Yeah. So [INAUDIBLE] Yeah, I would agree with that. And in Australia, they've banned it for any outpatient use. You have to get an exception. In the UK, they've banned it and seen a real decrease in C. diff and a whole bunch of other issues. I agree with that. It's a really handy drug when you know what you're treating, and you're between that and a PICC line. I have a hard time saying cipro is inferior. If I have to decide between a fluoroquinolone and a PICC line, I usually favor the fluoroquinolone. But that's true that [INAUDIBLE]. [LAUGHTER] So what about the use of procalcitonin in the ER setting for evaluating whether you should put somebody on an antibiotic? I know there was a recent study trial in an ER setting that did not show an impact of procalcitonin, except I think in whether or not they prescribed antibiotics for the final diagnosis of bronchitis. But is there a role? I know we don't use it. So I'm glad you ask. [LAUGHTER] I-- [LAUGHTER] I get asked about procalcitonin quite a bit because it could be a really helpful stewardship tool. And some people come to be like, oh, the hospital was I was at, it was just awesome. The data is plus minus. What I would say is I'm a fan of procalcitonin if we use it correctly. What I don't want to have is that we add in sort of George Hoke approach to, you know, like the diagnostic. We just start testing a lot more people, and then we don't actually act on any of those results because my patient is too sick to actually believe the procalcitonin. And so if we rolled it out really thoughtfully and in a way that we had some real guidance around how we would use it, I think it could be helpful. I have personally thought, from a stewardship program, that we had higher priorities that were going to give us more juice for the squeeze, if you will, then procalcitonin, but I'm not opposed to it. If somebody wants to do that, we would help them write said guidelines and help support that. What I don't want to see happen is every single person that gets admitted through the ER gets a procalcitonin. And they weren't even coming in complaining of an infectious condition. And then you have to deal with that issue. Thanks. Unrelated, are there any public health campaigns to reduce public pressure on physicians to prescribe antibiotics? Yep. So I do a little bit of research and work in the UK. And they have done some awesome stuff raising public awareness around antibiotics. And across surveys in the mind of the average UK citizen, it is in the top five most threatening issues facing the world today is antibiotic resistance. That is not true of the US. [LAUGHTER] And so it can be really effective. They have been trained. And the CDC is trying to get the word out with, you know, Get Smart and lots of deployed public health information. And that campaign is still ongoing in the outpatient settings with the Get Smart campaign. But I would say that the CDC has put a lot of resources into a lot of the stuff that I talked about, potentially to sort of-- you know, there's only so many resources to go around, but it's still a big campaign of theirs. But a lot of resources are going to hospital Get Smart campaigns, if you will. The EMR has made it too easy to know that someone in the past, you know, 40 years had an ESBL. What is your advice about empiric treatment when a patient has a history? Like how long or how recent does that need to be to make you reach for that first? Is it more about how sick they are if that comes up a lot on the wards? It does come up a lot. It comes up for me on stewardship too. Like you know, what's the sort of cut off? So there's data that supports 12 months. There's data that supports 90 days in some of the studies, as a closer cutoff. The issue I have around the 12 months or the hard fast is, whatever problem they had going on that brought them to have the ESBL infection in the first place, was that issue then resolved, and now they're kind of in a different risk group. Because I find that patients that have had an ESBL in the past-- I could think of some patient names that come through a fair bit. They actually haven't had an ESBL in the last, but they've been admitted four times the last year for a UTI. They just didn't happen to have an ESBL. So I kind of go off those risk factors. 12 months is not the wrong thing to carry around, especially if that risk factor has been mitigated, is what I'd say. Yeah? So as an historian, I'll take you even before the pre-antibiotics. And we had asepsis and the emergence of asepsis as a concept in the 19th century where you actually sterilized your operative knives between patients, which leads me to my question. How are we doing with handwashing? And what happens-- I think I saw a photo of someone doing a project where they covered the lids of toilets as a way to prevent the spread. Yeah. So how are we doing with those kinds of preventive measures? So that is also in line with my other job of like I just always say yes to resistance. So the hopper lid, so we know that-- so let me go back. Hand hygiene is paramount. If you're in the hospital, in terms of drug resistance, transmission of resistant organisms, there is no reason to believe, and there's data to support that good hand hygiene is critical to not spreading drug-resistant pathogens. I'm a fan of alcohol gel. It's been shown to be equivalent. It's a lot quicker when I'm in the hospital. My hands like end up with that film, and then I try to wash. We do know, just from my other job or my research and stuff is on sort highly drug-resistant pathogens in the wastewater of the hospital. And so we did find that putting a lid on the hopper, where we had a lot of drug-resistant pathogens that were sort of probably spraying when we were flushing, did cut our acquisition of carbapenem-resistant Enterobacteriaceae in half. And it is a palpable difference. We don't have-- we have half the cases that we had in prior years. And I would say we're on track to have that be a quarter of cases of clinical infections this next year. And so it has really made a difference. So infection control is paramount to be hand in hand with antibiotic stewardship, or none of it's going to work. And so yeah, that's a great question. Thanks. More questions over here. Oh, yeah. 2/3 of antibiotic use in the United States is done in animals that we eat. Yeah. How does that affect us in the hospital? So we don't know for sure how it affects us, but I am a firm believer-- and I don't want to get all crazy conspiracy theory. But you're absolutely right. The amount of antibiotics used in North Carolina in a single year in animals was equivalent to all the human use in the same year. So the tonnage, the numbers are just astronomical. I mean virginiamycin, named after our great state, is animal husbandry antibiotic. It doesn't jump quite as much as we would think and in ways that we think. But what I work on my molecular resistance stuff that a bunch of the people that work with me work on, I think that we have changed the fabric of E. coli permanently through antibiotic use. And I don't think a lot of that has been in humans. I think they're carrying more genes of drug resistance on mobile elements in a way that they probably weren't historically. And so they can pick up additional resistance elements quicker. We have some data showing that some resistant organisms that start in a human at time of, you know, when we're looking at these people over time that have the same resistant organism, and we have whole genome sequenced it over time, we can see that resistant bug picking up additional resistance mechanisms as it goes. There's no reason to believe that that stuff is not happening in animal feed and animal husbandry all the time. And so we really need a one health solution is what it's dubbed. The problem is is health care is not very involved in the one health solution. None of us know-- I don't even know a livestock farmer personally, but we're supposed to be at the table working with the animal groups, trying to get a handle on antibiotic use in that industry. So it's problematic. [INAUDIBLE] more questions. So thank you for the plug for infection prevention. So the answer to the question, as far as how we're doing with hand hygiene-- not good enough. And so we're measuring about in the high 70%, which is not great. And what I'll tell you is the measurement is not as robust as it needs to be. So we have these secret shoppers who go out and do x amount of observations, but really the n is not high enough to give us a robust look at what's really happening through all of our shifts and our weekends and that sort of thing. So what we're hoping to do at some point is to move to an electronic real-time monitoring with like smart rooms and such. And that'll really give us a good idea of how bad we're doing. And then we have to do something about it. So one of the things we're doing is we're putting in some more of those hand sanitizer stations that Any was talking about because the rules changed. And they're allowing us to utilize more in health care, which is a great thing. So you'll see that. But at some point, we have to have some accountability. So if you're not doing well, and you're consistently not doing well, what are we as an institution going to do about it? The other thing I wanted to comment on is I know you were super excited about your SAAR because you were at 1, and that's awesome. And so that's your observed over your expected. But as you will find, as this becomes a metric that gets reported to CMS and others, 1 isn't good enough. So some of them are 0.7 they're expecting. Leapfrog for CLABSIs is 0.49. So we won't get the money from CMS if we're at 1. So as Amy is professing, please continue to work hard to decrease that use of antimicrobials. Excellent. I think we're in the difference between the SIR and the SAAR that I will say, though, is we don't know how to-- like you need antibiotics to practice modern medicine unlike you don't need a CLABSI to practice modern medicine. [LAUGHTER] And so how the CDC is going to come up with the rules of the road, I'm hoping, you know, that we can come up with and be kind of leading in on, and UVA writ large, on how should we use this data. How should CDC enforce CMS? What does bad practice look like? What does good practice look like? So thank you guys so much for your time. [APPLAUSE]