 titled, “Outsmarting Resistant Bacterial Infections.” Multidrug-resistant infections are placing a considerable burden on hospitals in the United States and are associated with significant morbidity and mortality. Fortunately, several new antibiotics have been approved in recent years that are effective against these difficult-to-treat infections. This 

 panel of experts in infectious disease will discuss the role of these newer therapies in hospital settings. We will also discuss the importance of antimicrobial stewardship in the battle against resistance.

I’m Dr. Peter Salgo. I’m a professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons and an associate director of Surgical Intensive Care at New York-Presbyterian Hospital. Joining me for this panel discussion are Dr. Sandy J. Estrada, an infectious disease clinical pharmacist from Lee Memorial Health System of Fort Myers, Florida; Dr. Debra Goff, an associate professor and infectious disease specialist from The Ohio State University Wexner Medical Center in Columbus, Ohio; Dr. Jason Pogue, an infectious diseases clinical pharmacist at Sinai-Grace Hospital of Detroit Medical Center and clinical assistant professor of medicine at Wayne State University School of Medicine, in Detroit, Michigan; and Dr. Andrew Shorr, section head, Pulmonary and Critical Care Medicine, MedStar Washington Hospital Center and professor of medicine at Georgetown University in Washington, DC. Thank you all for joining us here today. Why don’t we get started?

I think the best thing to do is take a look at how big a problem this is to begin with. What is the prevalence of multidrug-resistant bacterial infection in the United States?

 Well, according to the CDC, they estimate about 2 million patients a year are infected with a multidrug-resistant pathogen. Of that, about 23,000 patients die. But that might be actually a little bit of an underestimate.

 Well, not every hospital reports their data and not every death certificate lists the infection as the cause of death. Andy would know that.

 I was an intensivist who filled out a lot of death certificates.

 Oh, OK. That’s an astounding number. Let us assume for a moment that it’s 23,000 deaths, how many 747s? I can’t do the math in my head. If we had that many plane crashes a year, people would sit up and take notice.

 Absolutely, but they don’t. It’s a number that outside of health care doesn’t generate a lot of discussion unless you frame it as a 747 going down. So, it’s really a challenge.

 And I think the thing to think about, too, when you’re talking about the impact that drug-resistant infections have on our patients is that that number is increasing. Pick your favorite organism. For the most part, if you look at resistant versions of that bug, the numbers are going up over time and that’s why it’s an urgent threat for us.

 You know what I hear? I hear it’s my fill-in-the-blank. Mom, grandmother, friend’s mother was in the hospital, she had pneumonia, they gave her antibiotics and they didn’t work and she died. Shouldn’t antibiotics work? Do you hear that? I hear it all the time.

Sandy J. Estrada Lopez, PharmD, BCPS (AQID):

 I think we do. From time to time, we hear cases where antibiotics had to be switched so perhaps we had to try 2 things, 3 things, 4 things, and then they did eventually work. So, the cases of not working at all are still fairly rare but becoming more common. But the cases where there’s extended length of stay, extended cost, need to stay in the hospital, or have repeat visits are becoming more and more common.

 I think another way to conceive of it is if you look at crude mortality rates for some, particularly in highly resistant gram-negative organisms, with what are our best available therapies up until what has recently been approved, the outcomes arrival mortality rate is seen in the pre-antibiotic era, particularly with pneumonia. So, it’s as if we’re back to placebo.

 I think it’s really important to just focus on that for a minute. All medical students and residents that I know give them an antibiotic and say, “Let’s go home.” But we’re facing a real crisis here. Our antibiotics are becoming less effective and we’ve got diseases that we’re having a lot of trouble treating.

 Right. And the prevalence, as Jason pointed out, of these infections is going to go up, not only because of the aging of the population, not only because of the epidemiologies of these pathogens, but also because we’re being more and more aggressive with immunosuppression across the board for nearly every disease state. And people are living longer and they’re not dying of their heart failure, they’re not dying of their renal disease. And as Osler said over 100 years ago, “Pneumonia was the captain of death,” and it is for a reason; because you’ve got to die of something. And so, this is not going away, and I think we’ve all lamented it. I think the problem now is we’ve got to figure out how to solve it.

An Overview of Multidrug-Resistant Bacterial Infections

 My point was not, is it a big problem and are you hearing about this in the hospital, is there a drum beat? My point is it’s actually beginning to percolate into the population. People are beginning to understand that not every antibiotic works, not every infection can be cured with what we’ve got. And to some degree, I’m not sure they have the sense that it’s our fault. But it is, isn’t it, to some degree?

 It’s not necessarily our fault. It is, to some degree, because the simple answer is yes, but even appropriate use of antibiotics is going to lead to resistance development. Sure, we could mitigate it a little bit by more appropriate use, limiting unnecessary antibiotic use. And I would say that infection control plays a big piece of that story as well. But it’s natural selection, right? We would expect this to occur. And as Andy pointed out—and I think it’s an important thing to keep in mind&mdash;we keep people alive longer now for things that they used to not be able to survive. And they end up becoming the poster children for getting these drug-resistant infections.

 I’m going to disagree with you a little bit, Jason.

 It’s fascinating. But to bastardize Shakespeare, I disagree. I think the fault does lie with ourselves and not with the stars. This is not something where we should have stepped back and said, “This was inevitable. There was nothing we could do.” This has been like watching a slow-motion car crash for a generation, and we’re still playing catch-up. We’ve created the problem, we have to fix the problem. And each one of us in our roles as clinicians, whether they’re in the SICU, the MICU, ER, on the floors, as a PharmD, we have all contributed to this, and it is incumbent upon us to figure out how to solve the problem, period!

 I think getting back to the question about more information in the community, with the increase in 

 and they are starting to be aware that it’s associated with overuse of antibiotics. So, this is starting to very slowly be a topic that’s discussed outside of hospital settings. But while we’ve worked on antimicrobial stewardship a lot over the last decade in the inpatient setting, it’s really just starting to even be discussed as a need in the outpatient setting.

 This gets back to what I was saying. This is a lot of deaths, 23,000.

 It’s a lot, and I think I have to piggyback on Andy’s comment when he said we’re to blame. It has been occurring over decades. But there’s a bigger issue called One Health. About 70% of antibiotics in the United States are actually prescribed to animals, and so when you look at the animal-to-human transmission of resistance, there’s a big component right now of who’s to blame. So, yes, health care providers are part of it, but responsible use in the animal sector is another part. And it’s becoming a blame game, which we’ll never solve. It’s a responsibility amongst all of us.

 How about we just accept the fact that there’s enough blame to go around.

 And we’re all in the same boat. Let’s take a look at the impact. Yes, it’s beginning to percolate and the point is, if everybody realized that was a lot of 747s crashing, maybe there would be some outcry here. Until that happens, people have to understand the impact. First of all, what are the clinical and the economic impacts here on the hospitals, per se?

 I think the clinical impact is best described on the patient. Again, pick your favorite resistant organism and look at outcomes in patients who have an infection due to the resistant form compared to the susceptible form. What you’re going to find across the board are twice as worse outcomes: mortality rate doubles, and if the patient survives, length of stay is double, as is the need for extra care afterwards. And again, from the hospital standpoint, there’s a cost associated with every single one of those things.

 How many of these resistant bugs are hospital acquired? How many out in the community?

 I don’t know. In my opinion or based off of what we see, the majority of them are some exposure to the health care industry. But there are certain versions of these that have transmitted out into the community. MRSA is a good example of that. You can certainly see patients with purulent skin infections from the community that’s community-acquired MRSA. We can see it in community-acquired pneumonia from time to time as well. And even in the gram-negative space we’ve started to see that occur, and ESBLs are the real example there. That was a traditionally nosocomial pathogen, and as the epidemiology changed, you saw this push out into otherwise healthy individuals.

 You know, Jason, a good example of that is young women who acquire their first urinary tract infection and everybody thinks, “Oh, no big deal. You give a couple days of Cipro and call it a day,” except when it doesn’t work. And so, we’re seeing patients who have never had health care exposure acquire their first E. coli UTI, multidrug resistant. I think the best example is a 23-year-old model from Brazil who was exactly that scenario, got her first UTI, got 3-day course of Cipro, except it was resistant to everything and she ended up dying. And that put it on. She was the face in Brazil for that statement of, “We’re in a crisis,” and so that’s a big problem.

Understanding the Causes and Impact of MDR Infections

 If we’re in a crisis, why don’t we tease it apart just a little bit? The most common types of these. By the way, how would you define a nosocomial infection? How would you define it, a nosocomial infection?

 I’m not sure that language is necessarily valuable anymore.

 Because we used to categorize infections classically as community onset of nosocomial because that gave us information about the pathogens that the patient was at risk for. And although that used to be particularly specific, I’m not sure it’s very sensitive anymore. And by that, I mean 

 remains the number 1 pathogen in community-acquired pneumonia if you have pure community-acquired pneumonia. But if you look at patients who present in the emergency room with pneumonia and then you start dissecting the pathogens, 

 isn’t number 1 anymore if you work in a hospital like mine where 50% of our admissions to the ER with pneumonia come from nursing homes. The number 1 pathogen is now staph (

) or some gram negatives. And so, where you sit determines where you stand, as I like to say. Your perspective on answering that question is only valuable if nosocomial really works to segregate the at-risk patient from the non—at-risk patient.

 It makes sense because as the sociology and organization of health care delivery is changed, the pathogens have followed the pathways out of the hospital that we provided them.

 I asked that for a specific reason because I want to begin to drill down on hospital-acquired infections first and with the understanding that some of these pathogens are out in the real world. Let’s use the word “nosocomial” and use it specifically to say hospital-acquired or health care—facility-acquired infections and leave it at that. What are the most common types?

 So, by far and away, the number 1 hospital-acquired infection, in terms of just prevalence, is pneumonia. Part of that reflects that people will hallucinate pneumonia wherever they see an infiltrate and shortness of breath, and it may be heart failure or it may be something I call Lasix-responsive pneumonia. It may be aspiration phenomenon and the patient has had a CVA and it clears up in 2 days and they don’t need antibiotics; they need a pat on the back and maybe a swallow evaluation. But pneumonia, if you look at all the data sets, whether it’s the old National Nosocomial Surveillance System, the CDC data, everybody reports pneumonia as number 1 in terms of just crude numbers because every patient in the hospital is at risk for pneumonia, followed by things like urinary tract infections, surgical-site infections, occasionally hospital-acquired intra-ab, which tends to be secondary, or tertiary peritonitis. It’s really a failure of initial surgery that’s super infected, it’s not really hospital acquired. And then there are bacteremias, whether they’re catheter-associated or secondary to some other process like pneumonia or the skin infection itself.

 But to be fair, the UTI is the second most common, which I agree with if you look at any data. It suffers from those same limitations as any catheterized patient. If you get a urine culture positive and if you have one nonspecific infection sign or symptom that you can’t attribute to something else, you’ve now met the definition for CAUTI, right? And so, it’s the same problem. The diagnostics really blur the lines on these numbers.

 And just for the record, I can’t believe I’m going to be nice to my surgical colleagues, but I will. An infection in a hot belly postop is not necessarily a surgical failure.

 Right. It could be surgical failure. It could be that it just happens. It could be lack of source control. It could be ischemic bowel that had nothing to do with the primary surgery. There are lots of reasons.

 So, we have a lot of MDR pathogens, but we have some new therapies. Why don’t we just list, if you will, some of the MDR pathogens for which we have new, effective therapies or newer effective therapies?

 The good thing is I think with more focus on resistant organisms and resistant infections, there has really been a focus, nationally as well as internationally, on the development of new antibiotics over the last 10 years. And so, we have seen more development of antibiotics than we were seeing before. There has been a lot of excitement around that. Unfortunately, if you look at it, a lot of them really have been developed to treat MRSA infections. And so, most of the new antibiotics that we’ve seen up until the last couple of years were targeted in a gram-positive arena. Meanwhile, we are continuing to see increases with gram-negative multidrug resistance. However, in the last 2 to 3 years, we have had 3 new agents developed for the treatment of multidrug-resistant 

 as well as carbapenem-resistant Enterobacteriaceae. So, we are now starting to see more excitement on the gram-negative side of things as well.

 You actually pronounced Enterobacteriaceae. I love that.

 And one of the things that I’d highlight, too, that I found pretty exciting regarding new antimicrobials or new therapies, in general, is that some stuff has come out in the 

 It’s not here, per se, an MDR pathogen, but that is a disease state that we’ve had 1 or maybe 2 therapies for the longest time. And we had some new agents there, too.

 And we’ve got some new evidence from new drugs for MRSA, too, right?

 But the question is, with all of these novel agents, not one of them is a cure-all? And in fact, I think it’s spurious to believe that we would find a cure-all, right? Because I don’t want someone to create for me the antibiotic that’s going to kill everything up front so I can be decerebrate in my antibiotic prescribing because that’s how we got into this mess in the first place. I think the important thing to realize is particularly among the newer agents for the gram-negatives―whether it’s Zerbaxa, Vabomere, Avycaz―they all have unique strengths and weaknesses. They all have trade-offs that have to be contemplated. They all have different spectrums of activity, and not one of them is going to be the right answer for every hospital. You have to be thoughtful in looking at these agents and decide, do they offer me a benefit? Is there a role for it at my hospital? Does it fit with my concept of antibiotic microbial stewardship? And it may be no, they don’t, and it may be yes, they do. Maybe some do and some don’t. But it’s one of these issues where you actually have to do a lot of thinking and cognition to decide how you’re going to utilize these on your formulary, if at all.

 But don’t you think that that decision is no longer at the individual physician level? It’s managed by a stewardship program.

And we’re going to get to that, too. Since you bring it up, I think it is worth at least touching on this right now. There is the ancient catch, if you will, the catch-22. I’m sitting in front of a patient, that patient has this bug, this drug is great, kills everything. I want to give my patient the bug juice that works, but then I say, “But wait, I’ve got this responsibility to society as well.” There’s got to be a way to reconcile these 2, right?

 So, it’s a societal problem, but most of the time you’re prescribing in the moment. You’re not thinking about the impact on society.

 And so, it’s really hard. It’s called the behavior change of antimicrobial stewardship. How do you change behavior of what we’ve done for decades? That, to me, is the biggest challenge of a stewardship program, understanding how to change behavior because that is the million-dollar problem.

 Well, no, no, I’m not going to change my behavior.

 All those other doctors can change theirs because I’m going to do what I like to do or at least that’s what you hear, right?

And I think we’ll get into this a little bit later more, but I think that the different perspectives are a huge thing to appreciate because that’s why your stewardship program has to have all of these key players on it. It can’t just be ID and pharmacy that’s making these decisions or these rules.

MDR Infections: Current Pathogen and Treatment Paradigm

 Let’s go piece by piece. Why don’t we start by focusing on gram-negatives? I don’t know; we could have started with gram-positives. But we’ll start with gram-negatives, and we’ll use nosocomial specifically to imply health care facility—acquired infections. What are the risk factors for an MDR health care-acquired infection, gram-negative to start with?

 So, the risk factors for an MDR gram-negative are diverse, and they basically include a number of issues related to the patient and their underlying immune system status, whether they’re frankly immunosuppressed, they’ve had a stem cell or a solid organ transplant, or they’re on corticosteroids because someone hallucinated a reason to give them corticosteroids.

 There’s a lot of hallucination at your hospital.

 I think there’s a lot of hallucination in medicine. We do a lot of treating ourselves because of a lot of cognitive biases about loss aversion. So, there are things we do to the patient, there are things the patient brings with them: their diabetes, their renal failure, their chronic comorbidities. There’s the severity of illness. If you’re on a ventilator and you’re sick, you’re at high risk for these things. And critical illness itself turns out to be immune suppressant, especially given the literature where we’re learning about reactivation of CMV disease in that population. And then there are other things that we do to the patient that violate their mucosal barriers. I’m putting in tubes and lines in places that allow biofilm to grow, which is basically a fertile ground for bacteria to overwhelm. And I’m injecting pus into the body some way. The point is all of these essentially also are markers for antibiotic exposure. And prior antibiotics consistently, there have been meta-analyses over and over again that indicate that it is the antibiotic exposure that selects out for a resistant pathogen. And the tonnage of antibiotics used in the patient is literally linearly correlated with that risk.

And so, that’s really crucial because, in addition, I can’t fix how sick they are when they show up, can’t fix their immune system. I occasionally have some role and control over getting lines out but I may not be able to. But I certainly can control what they’re seeing and what they’re getting. And the problem, though, is these risk factors are heterogeneous, but they’re also nonspecific. It’s not like this group of risk factors means you’re only at risk for CRE. This group of risk factors only means you’re at risk for MDR pseudomonas. The list of these overlap substantially, and often you need to think about what’s the epidemiology in your hospital. If you don’t have CRE, the patient is not at risk for CRE, but it would also be helpful to know sometimes what the patient has been colonized with or infected with in the process.

 OK. Clearly, I think what you implied is if a patient had an MDR infection in the past, guess what, you’ve got it again or at least it has to be in your differential.

 Tell me about nursing home long-term care, SNF care, all of these environments that are not in the patient’s home and where they’re in contact with lots of other patients and the health care community.

 I think the literature convincingly showed that those places breed resistance because they’re the last Wild West where there’s no focus necessarily on good infection prevention and there’s very little focus on antibiotic prescribing. And so, there’s a lot of, for lack of a better term, drive-by medicine and people run in and run out, and no one is taking ownership of the system. And those patients bounce back and forth to the hospital, especially given how we’ve designed some reimbursement schemes in this country. And so, they bring back with them the problem that we may have started but was finished out there and then all of a sudden comes back to bite us.

 I was going to say, to be fair though, whatever your view of the drive-by medicine is, we send a lot of folks who’ve had a ton of antibiotics over to an LTACH, and they just sit there sharing bugs, right?

 Yes. Largely everything Andy talked about as a risk factor, those are those patients. They’re poster children from that standpoint. So, yes, it’s fair to say that they get some of that antibiotic exposure from us. They get some of that resistant epidemiology of the hospital, but I think everything is kind of on steroids when you look at what’s going on in that long-term care facility.

 That’s an interesting area. Let me lay this out this way. We send in a whole bunch of people who have had a lot of antibiotics in the acute care facility, they go to an LTACH, now they get sick, and the doctor is confronted with this patient who had resistant bugs in the hospital. I can’t get all the cultures every day. This is an LTACH. I’m just going to blast away. Now, I understand that. And to some degree, the logic isn’t all that wrong, is it?

 Oh actually, I think it’s fundamentally wrong.

 What we see is that those patients never have cultures taken in the LTACH. I have no qualms with anyone starting broad spectrum antibiotics so long as they’re making the commitment to figure out a pathway off that ramp. I know that as an intensivist, I’m sure you, as an intensivist, feel the need to have access to the antimicrobials that you feel are going to guarantee appropriate therapy. Because other than fluid resuscitation, that’s pretty much all that saves lives for a severe infection. However, as I tell my house staff, if you start an antibiotic without having a way to get it stopped, then you’re doing a disservice to the patient. And what we see is, when we ask the referring providers who are sending us patients from the LTACH, “Well, when they got sick 3 days ago, did you get a culture?” and there’s just silence on the phone. And it’s often because they actually don’t have access to microbe facilities there at all.

 I was going to point out, it’s easy to be hard on these people, but sometimes they’re at a severe disadvantage.

 Right, and I understand that, but the point is, now what am I treating? And there’s also a resistance more so I think in those facilities than in the institution. And again, I understand why, because of the lack of monitoring, to never stop the antibiotics if they found an alternate diagnosis. And again, my favorite is the chest X-ray’s hazy, there may be some left lower lobe atelectasis, the secretions are yucky. I’m going to treat them for pneumonia, but then you gave them 80 mg of Lasix and the infiltrate is gone tomorrow. It’s not a bacterial infection. We stop those antibiotics in the hospital, but I think in those facilities, because you can’t get the monitoring as closely, you’re afraid that if you stop too soon there might be a consequence. I understand it, but that’s the health care system we’ve designed and we’ve got to deal with it.

 It happens on the other end, too. Patients going from the hospital to the LTACH, go on antibiotics. Maybe they’ve already been on antibiotics for 12 days, they need 2 more days, 3 more days, and for whatever reason, that stop date gets lost in translation when they leave the hospital. And 2 weeks later I get a call from a pharmacist at the LTACH, “Are you sure why they’re on these antibiotics?” or “How long they should be on them?” And so, that’s a big point…

 Is every patient in an LTACH guaranteed to see a physician every day? Often not in my experience, no?

I think it varies from state to state. I know in the DC area they have physicians who are dedicated to seeing them every day in the LTACH. I know in other states where there are less. There aren’t separate ventilator—facility kind–of LTACHs. It varies.

 But don’t you think one of the biggest problems is there’s no communication between the 2 health care systems?

 We’re doing everything we can to just stay above water with the hospitalized patients, but at some point, we have to marry each other because we’re never going to solve this problem. And there’s a social responsibility to doing it right, and so this is the blame game like, they created it, gave it to us, we send it back. There’s no continuity of care.

 It’s that gosh-darn LTACH and that gosh-darn hospital.

 And it’s on both of us, and I think that’s the key thing. And I think that transition of care is one of the big areas for advancement and it goes both ways. The problem is you need someone. Again, if you’re talking about it from a stewardship standpoint, you need someone to give that information to which may or may not be there, and you need to have someone who will give that information back to you.

Gram-Negative Nosocomial Infections: Systemic Risk

Now that we sort of set the landscape here, I don’t think anybody is really that ignorant of what’s going on in terms of where patients go, what they get, and how they get treated. You get a patient. What are the important patient and disease factors that you consider when you’re deciding on a treatment?

 This is key. We mentioned earlier that you get a student or resident, and they think, “OK, infection. I want to give an antibiotic.” And so, they come to an ID rotation perhaps wanting to be told, “OK, this infection, this antibiotic, get the little checklist, and get it right.” But unfortunately, as I’ve heard my colleagues and I say recently, the answer to every question in ID depends, and it’s very much because of all of this.

 It is true because every patient is different. And so those patient factors, as Andy already mentioned, immunocompromised, these types of things are important to other risk factors that the patient may have. Have they been in the hospital recently? Did they just come from an LTACH (long-term acute care hospital), or are they a previously healthy person? Do we suspect a bug? Do we have a high suspicion, based on what we know about the patient, of a bug, or even better yet, do we actually have a culture and susceptibility?

 OK, well, that implies something. Let me stop you right there because I know he mentioned in passing it means somebody sent a culture, right?

 So, one of the things you’re going to do is get a culture. That would be useful, right?

 You’re going to consider the pathogen.

 You’re going to consider, as you pointed out, the institutional history. What do we see in this hospital. Is that what you’re talking about?

 Right. If I’ve never seen a CRE (carbapenem-resistant enterobacteriaceae) before then, yes, I’m aware of it, but I’m not probably going to say, “Oh, I really think we should empirically cover for it until I do start seeing it.”

 What about source control in the sense of where is this bug coming from. Does that make a difference?

 Absolutely. If my source is urine, then it’s very different empiric coverage than if it is pneumonia or something else.

 And does it matter how sick the patient is? In other words, if you suspect this is from here with this bug, and you’re going to give this drug because you’re convinced that probably is a good idea, does it matter whether the patient is a little bit sick or making lactate like there’s no tomorrow and there may be no tomorrow?

 You know, that’s the “It depends.”

 Oh, thank you so much. You were right, you know that?

 But I think when you see a 23-year-old bone marrow transplant patient, your threshold to pull out the big guns—one of the newer agents&mdash;you know you’ve got 1 shot to get it right. And if you don’t have rapid diagnostic tests in your hospital to tell you immediately what the organism is, you can’t blow that 1 shot. So, my trigger to allow a newer agent to be used in that patient absolutely is a little different from the 90-year-old nursing home patient who the family is already contemplating whether this is a DNR do not resuscitate and we are calling it a day. They are different patients, even though they might have an equal risk for multidrug-resistant gram-negative infection. How we would approach might actually be different.

 And I think the severity-of-illness piece comes into that same story, as well, right? So if they’re going right to Andy in the ICU and they’re hemodynamically unstable, they’re getting dumped with fluids, the patient is at the same risk for drug resistance. But my threshold for needing to cover is much larger than a patient who’s coming from the nursing home with “mental status” changes because they’re dehydrated. And, sure, 40% of the time, that urine, if they culture it, it’s going to have an ESBL (extended spectrum β-lactamase) in it, but that doesn’t mean a) the patient has an infection and b) that I have to be crazy up front from that standpoint.

 Two other issues, I think, that are important to consider are focusing on what is the clinical evidence supporting the molecule. There are some drugs where we actually have head-to-head trials and we can argue about, say, the linezolid versus vancomycin literature in nosocomial pneumonia. But there are some cases where we have in vitro active options and we look at the clinical data to guide us. For some of the newer agents, some of them have clinical data in certain disease states or certain syndromes and don’t in others. Now, the absence of proof isn’t proof of an absence, but I think we all prefer to go where there are actual clinical trial data than when there are not, or at least some guidance on how to dose some of these drugs. Because the history of drug development is littered with pneumonia failures where it looked great in the urine or looked great in skin, and they studied it in pneumonia and, lo and behold, it didn’t work because it was inactivated by surfactant—which, last I checked, happens to be in the lung&mdash;or, for example, it’s underdosed because of lung penetration.

All those things matter, and at the same time, I think another thing that’s important to consider is the patient’s renal function. And those are issues that I consider in terms of not only the dosing of the drug but how nephrotoxic might the drug be, what are the issues with nephrotoxicity. I think that relates a lot to the recent literature on the interaction between piperacillin/tazobactam and vancomycin because I think vancomycin is given like water, and piperacillin/tazobactam is abused considerably. And everybody thinks, “Well, there’s no harm,” and then we look, and it’s like, “Ew.” The interaction might be something here that we never consider. This might be dangerous because of what this kind of penicillin is doing with this kind of glycopeptide. And so, I think all those things need to go into consideration.

 But I would kind of counter a little bit that absolutely you want to see clinical trial data, but when you’re talking about using one of the new agents for an XDR (extremely drug resistant) or 

 or CRE, the chances of having good robust data in that population are poor. But your point is really well taken that, is there surfactant? So, if the right preclinical work is done, you can predict that you have a pretty good likelihood of having a good outcome in that situation. I would disagree to a degree that I need robust clinical data in this exact disease state.

 Right, especially when you’re all trying to use colistin. The concept of robust data is nonexistent. And so, again, it’s a trade-off question. It’s a risk versus benefit, and this is why it’s 2 to 3 years of training to figure out how to do this, because it’s a complicated calculus. And that’s why all these things need to be considered.

Factors in Choosing Therapy for Gram-Negative NIs

 Run down some things you’d like. What are the tests that you want to confirm the pathogen and the tests that you then want to decide on treatment?

 Well, there are several out there. They are game-changing in the management of infectious diseases.

 What are they? Define them for everybody.

 One of the first that came to the market was an instrument by Cepheid that is a PCR-based and could tell you for bacteremic patients if you had MRSA (methicillin-resistant 

. Now, we implemented that at Ohio State. It was game-changing in the management of 

 bacteremia. We could get patients on appropriate 

 therapy faster, and we actually had a trend toward a lower mortality. Because, gee, guess what, if you treat them with the right antibiotic sooner, they get better faster.

 Not really surprising. But it’s nice to have evidence, and that was back in 2010. There have been a plethora of studies, by everybody here on the panel, that have confirmed that. Rapid diagnostic tests; Sandy has done work with a rapid fungal diagnostic test. So, imagine direct from blood. For some of the rapid diagnostic tests, you have to have growth and a blood culture. There’s 24 hours, and then you could do the test. But in one of the new T2 tests, it’s direct from blood, meaning, in case you’re not aware of this test, you draw the blood and you send it to the lab, and in 2 to 3 hours, you know 

. That’s game-changing for an intensivist to know which antifungal actually will work instead of the paradigm we used for decades, which was “Let me start with my best guess, and in 3 to 4 days, I’ll know whether I was right.” How crazy is that?

 If you have that intra-abdominal infection after 2 weeks in the hospital and an antifungal is being considered, these patients stay on them for 2 weeks because there might be something there and the cultures didn’t grow anything. These are areas where we are able to start. Getting back to your original point: Start anything you want to as long as you have a path to figure out where you’re going with it. And so some of these rapid diagnostics help us get on that path much faster.

 I think one of the big issues with the rapid diagnostics, at least in my opinion, is there are actually 2 main ones. First, it requires bacteremia or concern for fungi or whatever it is in that situation, and we need to get beyond that from that sample. But the second thing is I think that people—and I know this because I’ve spoken with people, and I even know how we rolled it out at our institution&mdash;do a poor job of telling people what that information is that’s popping up in the chart. If you look at Verigene or any of the ones that give you information, like you can get gram-negative rod, it will tell you the bug, it will tell you certain resistance genes; there are like 4 paragraphs of information that pop up. And it’s hard to even know what is positive when you’re looking at that. So, there’s a huge education piece that&mdash;

 So, you understand this? Can we give everybody your cell phone so that they can call you? My point is, yes, it was a joke, but in fact, somebody’s got to distill this.

 Well, first you have to get the information to someone. You lose all the benefit of a rapid diagnostic if the test result comes at 9:30 and you rounded at 8:30 and you’re not going to look in the chart again until the next day. Now you’ve lost 23 hours versus those rapid results. We learned, when we implemented PNA FISH 10 years ago, they were coming to a fax on my desk. So, if I wasn’t at my desk, then they were not acted on unless someone else happened to see the information.

 I did. I did. Now they come to an electronic in-basket that all pharmacists do 24 hours a day in our hospital. And so a provider will be called if there is an actionable result.

 I think although the rapid diagnostics have lost the promise and there are lots of issues that still need to be sorted with them, there are simple first-order issues that need to come well before that. And that certainly comes down with just knowing your antibiogram.

 I was going to say, isn’t it at least one of the ABCs, the bedrocks, here: Know what bugs you get, know what bugs your hospital is prone to, the antibiograms?

 Right, because the antibiogram, you can break it out by ICU versus floor versus different ICUs, your stem cell unit versus whatever, and you can see what your problem bugs are. So, you can actually create, and it doesn’t take a lot of math to sit there and ask, “Well, if I want to make sure that I’m getting 90% coverage empirically right from my gram-negatives, what’s that combination? What X-versus-Y combination gets me there?” And that’s the way you’re going to get to that. Because, again, for a lot of these MDR pathogens, MDR 

cases, and about 20% of all my gram-negatives are 

. So, 20% of 20% is now 4. That’s 4 in 100, maybe 1 

, so now we’re talking about 5 or 6 of these super ugly pathogens in 100 patients. That’s not a rate at which most people are going to start empirically treating for all those things. So, I need to still come up with what’s going to get me to 90%, and then I’m going to worry about that 5% that I’m never going to figure out until my rapid diagnostic, the patient’s failure to respond to therapy, or the eventual cultural insensitivity to guide me to figure out what’s going on.

 But your thought process that you just described is not done in the majority of hospitals. At most hospitals, if you walk around and ask a physician, “Can you name your top 5 pathogens in your hospital?” “Um, no.”

 And 2 of them are not hospital administrators.

 Right. And so, most people do not even know how to access their antibiogram. We’ve been preaching this for decades, and you’re absolutely right in your thought process, but I just don’t see it being done in the majority of hospitals unless someone takes ownership of doing it. And in the microlab, there are fewer and fewer microbiologists and microtechs. They’re getting short staffed. We’re seeing pharmacists doing antibiograms. I just don’t think that’s right. That’s not our training. Sure, we can learn it, but you know what, it’s like if you want the data, you’ve got to do it yourself. People just don’t take the time, but it’s important.

 We’ve required our unit directors, whether they’re ICUs or intermediate care units or floor unit directors, to actually take ownership of understanding and disseminating the people who practice there what their local specific antibiogram is.

 If I may, we have been rounding in our ICUs with PharmDs who know the antibiograms and know the antibiotics and know the bugs in the hospital. It has been a game changer.

Diagnostic Tests for Gram-Negative Nosocomial Infections

 Let’s talk about some pharmacy. Let’s talk about some new antibiotics. There was a 2017 approval of meropenem/vaborbactam. That’s Vabomere, right? What are the key findings from this study, TANGO II?

 TANGO II is an interesting study because it’s the first real study that was trying to do a pathogen-directed study. So, when you see new drugs come to market, if it’s a gram-negative drug, it’s going to be studied in UTI and it’s going to be studied in intra-abdominal infections because that’s where gram-negatives cause problems.

But to Andy’s point from earlier, as much as it pains me to say it, people want to see data in the actual infections that they’re going to use the drug for. When you talk about a drug like meropenem/vaborbactam, it’s a hell of a CRE drug. It’s a great KPC (

 carbapenem)-active agent from that standpoint. So, people want to see how it fares in that situation. And so, what they did was a pragmatic study of patients who had either suspected or documented CRE infections. As you can imagine, that makes a mess of a clinical trial. There’s a reason people do UTI studies and intra-abdominal infection studies, because patients who have CRE, Andy listed all the risk factors for us. There’s a lot going on in that scenario. So, the numbers are very small, and the comparator group was actually kind of practical, where it was just the treating physician could ask, “What do I think the best antibiotics are? If they don’t get this new antibiotic, what’s my favorite cocktail to give them anyway?” And so, the numbers are very small, but even in that small cohort, you saw signals that it improved outcomes. You saw clinical care go up 30% to 35%; you saw suggestions of mortality decrease. And so, it’s a really cool type of trial, although they are extremely messy data to sift through.

 I think the points about TANGO II that are also important to realize are it is a remarkably sick population. The mortality rate in that study is actually relatively high compared with what you see historically in the randomized, even nonblinded, trials in this disease state or in this space because most clinical trials exclude the sickest of the sick. And so this is fascinating because there are actually some real-world pragmatic data that the antimicrobial is effective in sick people. And in fact, if I’m remembering it correctly, TANGO II was terminated early because of benefit.

 Again, to my recollection, never has a data safety monitoring board in antibiotic stopped a trial early for benefit. Now, I think there is another trial that’s done looking in kind of the same paradigm, the CARE study, with plazomicin. That’s about 28 patients, I think. TANGO II is a little bit bigger, with a 2:1 randomization. But the point is I think we’re finally beginning to see data emerge where they’re actually taking the drugs that are designed for specific pathogens and doing studies in populations and disease states that prove the drug doesn’t kill anybody, the drug does what it’s supposed to do, and then saying, “But no one is going to ever use this for empiric therapy in UTI, nor should they. And everybody would agree, so let’s go and prove to the doctor that this is going to work against the pathogen, in most cases in the blood, that we’re worried about.”

Gram-Negative NIs: Vabomere and the TANGO II Study

 There are 3 newer cephalosporin/β-lactamase—inhibiting drugs. There’s Vabomere (meropenem and vaborbactam), Avycaz (ceftazidime and avibactam), and Zerbaxa (ceftolozane and tazobactam). So, why don’t you start us off. Let’s run through these things and just tease them out. When do you use them? What are they good for in gram-negative infections? How do you use them? You’re up. They all volunteered you.

 So, they’re very targeted agents. They’re not the catchall. Give me the gorillacillin that covers everything.

 That’s new. I like that phrase. I like that. That approaches his brain-dead approach to antibiotics, gorillacillin?

 Yes. So, you have to know where they’re best utilized. Even though they have a diverse spectrum of activity, I really see them in that order. CRE is the targeting of meropenem—vaborbactam.

 Yes. And that’s where it’s best used. Ceftazidime/avibactam, CRE. Those are the agents.

 Right. And then ceftolozane/tazobactam we would target for 

, and that’s a very simplistic bug—drug matching, which is sort of how I put that.

 Because I know the comments coming from the other side.

 No, no, no. So, that was a good overview, and I agree with that overview. I think there are a couple of key pieces to know, and one is that, again, this is not a class. These are 3 new drugs, and I pick 1 of them, and I’m going to use that for my gross-resistant organisms. They each have their particular niches. And I agree. I just know that your own institution might favor one of these versus one of the other ones. And so, understanding how these perform and your local microbiology becomes crucial to making that decision.

 And they also all have other attributes. Although your paradigm, I think, is straightforward and to the point. With meropenem/vaborbactam, giving the dose of meropenem, you’re giving in the extended infusion to optimize pharmacokinetics. It picks up a lot of ugly-looking 

 cases that you wouldn’t pick up necessarily. It has nothing to do with the β-lactamase inhibitor. It’s all because of the dosing of the carbapenem, but it’s optimizing these 2 concepts. Ceftolozane/tazobactam has some ESBL activity. That’s why it’s paired with the β-lactamase inhibitor. It’s not the world’s super-reliable ESBL activity, but it kills some of them. And, again, Avycaz, on the other hand, still will pick up some extra 

 cases you might have missed, particularly ceftazidime-resistant 

 where the susceptibility is now restored. So, there are other pieces to this complex puzzle, but I think all those attributes are really secondary. And Deb’s point is correct about where we really need to be targeting them because we don’t want them abused just because they can do something else.

 What about safety issues? Are they all safe? 

 is a relative term. Like, wait a minute, I get to say it—it depends. Can I be an ID specialist now?

 I’m getting there. But what about the safety issues of these drugs? What do we know about them?

 I’ll chime in again. We’re limited at this point by clinical trial data. We’re limited by sometimes small numbers from that standpoint, but they’re β-lactams. Ceftazidime is the same ceftazidime that you give by itself and you’re adding avibactam, and there’s no real safety signals that have come up from that standpoint. Meropenem is meropenem, and ceftolozane, to date, has been, at least I can speak to my own experience, very well tolerated in patients. And I say that so when people ask whether they have side effects, they behave like cephalosporins, they behave like carbapenems, from that standpoint.

 There’s a confidence that we don’t have with colistin, polymyxin B, even aminoglycosides from that standpoint. So, when you think about the alternatives, then you feel even better about the safety.

 And you can even see that in some of, to Sandy’s point, the small retrospective case series that have come out with ceftazidime/avibactam. For example, you see not only improved outcomes, but you also see significantly decreased toxicity when you compare it with the polymyxins, which are poison.

 But in that same vain, I think for all these agents, there is the risk for emergence of resistance on therapy or the risk for creating emergence, particularly as we’ve seen with Avycaz and the Pittsburgh experience. If you use that drug over and over again in the same patient, you will create, in the patient, a clone that is causing infection that is Avycaz resistant. These are not tools that engineer us out of the entire problem. They still need to be used smartly, and I think Brad Spellberg’s editorial, that one with the Pittsburgh papers kind of describing their experience, was quoting from 

: “We need a bigger boat.” So, I don’t think you could use these willy-nilly and they’re going to solve the problems. The principles of stewardship, that I know we’ll talk about in a minute and that my colleagues all live every day and really enforce, become even that much more important and that much more crucial if you’re going to bring one of these drugs into your hospital.

 So, to that point, I just want to elaborate or add a couple of things on to there.

 So, again, obviously resistance, and I think you’ve seen it a lot with ceftazidime/avibactam in the published stuff, and a lot of that comes from the fact that it has borderline activity to begin with. Some of those MICs to begin with are 4 or 8, and if I had ceftazidime at a 4 or an 8, I’d expect certain things to occur in that scenario. And I think that when people are actually comparing it—as Deb said, CRE, CRE, 

—I think one of the most notable differences between the 2 new agents is potency. Again, meropenem is often active against KPC on its own, and so now you’re adding a β-lactamase inhibitor to that instead of ceftazidime. And I think that that thought process should go into your choice between the 2 because they’ve actually done some data that suggest that because they pharmacodynamically optimize meropenem and because they give 6 g of a β-lactamase inhibitor, it seems to have less of a propensity to have that situation occur.

Gram-Negative NIs: Cephalosporin/&#946;-Lactamase Inhibitors

 You know what we’re going to do, we’re going to shift gears slightly. We’re going to go from the gram-negatives over to the gram-positives because we already do the gram-negatives. That’s why we’re going to do the gram-positives. And although it is tempting to say we want to talk about community-acquired gram-positive infections in hospitalized patients, as you pointed out, it’s a gray area. The community-acquired infections and the hospital-acquired infections, they’re all sort of mushing together. So, why don’t we start with, are there differences between community-acquired bacterial infections versus hospital health care—acquired infections, in the emergency department, for example, specifically with regard to gram-positives?

 Yes. I think that this is another situation where it becomes syndromic in nature and with what disease state you’re presenting with. Again, we talk a lot about community-acquired MRSA with regards to skin infections, for example. But it’s a certain type of skin infection. It’s purulent, it’s an abscess. So, knowing those types of presenting factors. Like I mentioned earlier, people talk about community-acquired MRSA as it relates to things like community-acquired pneumonia. And while it’s absolutely true that it’s a very infrequent pathogen in community-acquired pneumonia, when it does occur, it’s a nasty bug. And so, when patients present with severe necrotizing pneumonia, it has to be in your differential. So, what I would say, I guess, is more knowing. It’s crucial that we know the patients who are at risk for it and how they present, and that’s when we know we have to cover for it.

 But wait. If you say you have to know the patients who are at risk for it who come into the emergency room, how can you know that if, in fact, the MDR pathogens are out there in the community? Is it safe? I think it used to be safe to say, “Oh, this patient is coming in from home with a skin infection; it’s not going to be an MDR bug.” Is that a safe assumption anymore? I’m sensing it’s not.

 I wouldn’t say it’s a safe assumption. Without getting into that health care—associated piece of the story, because, again, are they actually coming from home or are they coming from some other…

 Let’s take that piece out of the story and just say they’re coming from home. Is it safe to say it’s not this? And I think the answer is no in certain disease states. Like I said, there are particular ways when you see MRSA present in a community-acquired infection, there are flags that kind of allude that to you. But even when you talk about pneumococcus—again, drug-resistant pneumococcus is an issue&mdash;you’ll see the same things that play true. Are you in a community that has high rates of it? Has your patient gotten macrolides in the past? It’s the same kind of concept. It’s just being applied now out to the community.

 But are you implying—and I seem to have heard this, and I want to be very clear&mdash;that MRSA, in terms of its clinical presentation, without regard to its antibiotic resistance, it’s a 

? Does it present differently than ordinary 

 You can see an association because, again, there’s a blurry line between MRSA and MSSA.

 It depends, yes. But the simple answer is, yes, it can present differently because the strains of community-acquired MRSA have been associated with a bunch of different virulence factors. But now that has kind of been portrayed in some of our MSSA as well, which really muddies that water. But it’s notorious in a skin infection, again, to see purulence, to see an abscess. Those are the types of things you see with MRSA, and again, you don’t really see it with MSSA to the same degree, although you can. But you know that MRSA has a higher likelihood of being a player in that scenario.

 Because that, to me, is a real change. Because I was always taught that 

simply means you’ve got to treat it differently. But it’s a bad bug, when you get it in your blood. Like dogs and cats sleeping together, mass hysteria, 

. And you’re telling me that MRSA is a bad 

 And I’m not saying that MSSA is a good 

 I would say that, again, we’re talking specifically in patients presenting from the community with certain disease states. And what you’ll find in the hospital is a lot of those virulence factors that I talked about now exist in MSSA as well. So, you see the same types of things. I think the biggest difference, at least in my opinion, is we have better drugs to treat MSSA than we do with MRSA.

 Right. I was going to say part of the badness is because we have basically 1 drug to treat them with parenterally that we’re still arguing how to dose it 3 decades later.

 Yes, that would be correct. And so, that created some of the challenges. You have a drug that probably if it came to clinical trials today, I’m not sure where it would be. And it probably wouldn’t be in the position that it is in most hospitals now. So, that creates some of the badness with 

 Let me nail this if I can. We’re talking about a really bad actor here. We’re talking about MRSA out in the community. Do we have a number? What is the prevalence of MRSA out there in the real world? Does anybody know really?

 In terms of infections brought into the hospital, what proportion are MRSA?

 Yes. What is the prevalence of a MRSA from the community to come into your ER?

 So, the guys at UCLA have probably done the best study on this. They have a multi-ER surveillance system across the country, and they say that about 30% to 40% of the 

and these data are old, so it’s probably higher now—coming into emergency departments in community-onset kinds of infections are MRSA. And that’s a miss of USA400 and USA300, these kinds of toxin and nontoxin-producing strains. And so, again, it’s a mess because it’s a very promiscuous bug and these plasmids move back and forth, left and right.

 My daughter, who is 13 years old, if she heard those numbers would probably text, “OMG, 40%.” We are really blurring the line. The whole sense of, “Oh, it’s a community-acquired bug, a little vancomycin, go home, have a nice life.” Not so much anymore, yes? This sounds icky. How’s that?

Understanding Gram-Positive Nosocomial Infections

What about the newer long-acting lipoglycopeptides to treat MDR gram-positive infections? What are they? How long have they been out there? What do they do? Who wants to jump in on this to start?

 I’ll start that one. So, the new lipoglycopeptide is kind of like the rapid diagnostics have been game changing, as was referred to earlier. They can be game changing in the treatment of skin infections with MRSA—really because we’ve talked about the risk of health care exposure&mdash;to potentially provide an option for a patient who needs an IV antibiotic for a MRSA skin infection to remain in the outpatient setting, so admission avoidance or possibly early discharge. So, these agents are oritavancin and dalbavancin. They were both approved in 2014, so we have about 3 years of experience now. And the key thing is they require 1 dose to get about 7 to 10 days of active therapy.

 Nifty. How do you use them? When would you use them? How do you pick one versus the other? What are the nuts and bolts?

 The focus is the outpatient setting for a few reasons. There is a tremendous cost associated with these antibiotics. And so, if you compare that cost to the cost of a hospitalization, then all of a sudden that cost is not at all high. But if you compare that cost to a few days of a different antibiotic, then the cost would appear high. So, it’s how you’re framing it. Really, the target is that patient who needs an IV antibiotic either due to severity of infection, having failed previous oral antibiotics, resistance to oral antibiotics, or perhaps the patient where there’s significant concerns for adherence. So, we’ve had patients like that where even we did try to keep them out of the hospital but bring them in for IV infusion every day for vancomycin/daptomycin. They come for 2 days, they don’t show up anymore. So, there’s a big cost associated with that, right, if they get readmitted a week later, and now maybe we don’t want to give them that antibiotic again when moving further down the line.

 What are the differences between these 2 drugs? How do you pick one versus the other?

 As far as efficacy, they both work. They have similar mechanisms of action. They are both lipoglycopeptides. They both have activity at the cell wall. Oritavancin has additional activity at the cell membrane. Coverage is very similar, gram-positive organisms only. So, really it gets into some practicalities with regards to how to use them. They both do now have a 1-dose strategy, although dalbavancin also has a 2-dose strategy. So, from all of those standpoints, they’re the same. Many times, it’s going to come down to cost. Insurance coverage can come into play. Dalbavancin has a 30-minute infusion, oritavancin has a 3-hour infusion. So, on occasion, that can come into play as far as convenience for the patients.

 You’re going to be in the doctor’s office, or in the emergency room somewhere, and you’re going to make the diagnosis and you’re going to give this 1 dose and say see ya in a week?

 Most facilities are doing this in the emergency department—again, as a means of avoiding an admission for that patient. In some cases, such as in our facility, we primarily administer it in the infusion center. So, that patient may perhaps come to the emergency room, get 1 dose of IV vancomycin or something like that, and then they’re referred to the outpatient infusion center. We could also get referrals directly from the ID clinic or other places where, again, previously they may have been sent from the clinic to the emergency department. Now they can go directly to infusion.

 I want to add one patient population that’s a little different than what you described. So, I’d agree with you that outpatient is usually where we think of this, until the opioid crisis has plagued many states, including the state of Ohio. And it has caused us to rethink some of these drug abusers that have bacteremia, and 

 is primarily what they’re coming in with. As a health care provider, you want to treat their bacteremia correctly, not just a couple days’ worth and they’re going to leave. And so, this has been a very complicated discussion, but sometimes sending a drug abuser out with a PICC line is just a different discussion. So, giving an IV drug in the hospital that you know is going to assure 1 more week of coverage is sometimes a good option. It’s a very unique role, and people have very different opinions on it, but it’s an area where I’ve started to see clinicians doing that.

 We’ve had that population as well, and actually that was what we thought would be our biggest population. When we started using oritavancin, it was for the IV drug users for the reasons that you mentioned. We can keep them out of the hospital. We don’t need to put in a PICC line if they don’t come back. So, these weren’t necessarily patients that we knew were bacteremic but still focusing on that skin infection, although we have gone over into some of those other scenarios as well. But as time has gone on, in addition to those patients, we have a lot of elderly patients who travel a lot. And so, there’s a lot of logistical convenience considerations with those. And so, if they are saying, “I’m getting on a plane in 3 days, I can’t come for these infusions, I definitely don’t want to be in the hospital,” we want to treat them with something that’s one-and-done, so to speak. And so, that has been really good in that scenario.

 It sounds great, right? Who on earth wants to admit an IV drug user with a MRSA endocarditis? Let’s talk about disaster here. But something occurred to me, too. If this drug is on board for a week and there’s more bacteria being introduced because of the lifestyle, is that a good thing? Does it kill those bugs, too?

 Well, we haven’t been able to enroll them in a study, so I can’t really answer that. But, no, that’s the patient population you’re very uncomfortable with. And I think that’s where you engage a group of experts to decide what makes the most sense for this case right in front of us. And each one, it depends on the scenario. But it is very individualized because sometimes it’s almost an emotional decision of how you want to approach that young drug addict and what is the home scenario. It’s very complex. So, there’re pros and cons of each decision. It’s just an area that some are choosing to use some of these agents in patient populations.

 Did you actually give us the doses? Can you do that?

 I can, yes. Oritavancin is a 1200 mg dose, so it’s that 1-time infusion over 3 hours, and dalbavancin is a 1500 mg dose, also a 1-time infusion.

 It’s probably on the label, but I just thought we’d get this out.

Outsmarting Resistant Infections

An Overview of Multidrug-Resistant Bacterial Infections

Understanding the Causes and Impact of MDR Infections

MDR Infections: Current Pathogen and Treatment Paradigm

Gram-Negative Nosocomial Infections: Systemic Risk

Factors in Choosing Therapy for Gram-Negative NIs

Diagnostic Tests for Gram-Negative Nosocomial Infections

Gram-Negative NIs: Vabomere and the TANGO II Study

Gram-Negative NIs: Cephalosporin/β-Lactamase Inhibitors

Understanding Gram-Positive Nosocomial Infections

Selecting Lipoglycopeptide Therapy for Gram-Positive NIs

Gram-Positive NIs: Nuancing Lipoglycopeptide Therapy

Gram-Positive NIs: Costs of Lipoglycopeptide Therapy

MDR Infections: Overview of Antimicrobial Stewardships

Importance of Technology & Data Within Antibiotic Stewardship Programs

Antimicrobial Stewardship Programs: Goals and Challenges

Multidrug-Resistant Bacterial Infections: Key Messages