MDR Infections: Current Pathogen and Treatment Paradigm

Peter L. Salgo, MD: 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?

Andrew Shorr, MD: I’m not sure that language is necessarily valuable anymore.

Peter L. Salgo, MD: Why not?

Andrew Shorr, MD: 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 pneumococcus 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, pneumococcus 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 (Staphylococcus aureus) 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.

Peter L. Salgo, MD: So, we’re blurring this entire thing.

Andrew Shorr, MD: 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.

Peter L. Salgo, MD: 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?

Andrew Shorr, MD: 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.

Jason Pogue, PharmD, BCPS-AQID: 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.

Peter L. Salgo, MD: 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.

Andrew Shorr, MD: No, not at all.

Peter L. Salgo, MD: Sometimes that just happens, right?

Andrew Shorr, MD: 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.

Peter L. Salgo, MD: 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?

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): 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 Pseudomonas as well as carbapenem-resistant Enterobacteriaceae. So, we are now starting to see more excitement on the gram-negative side of things as well.

Peter L. Salgo, MD: You actually pronounced Enterobacteriaceae. I love that.

Jason Pogue, PharmD, BCPS-AQID: 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 C. diff space as well.

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): That’s true.

Jason Pogue, PharmD, BCPS-AQID: 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.

Peter L. Salgo, MD: And we’ve got some new evidence from new drugs for MRSA, too, right?

Jason Pogue, PharmD, BCPS-AQID: Yes.

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

Peter L. Salgo, MD: So it’s not all hopeless.

Andrew Shorr, MD: 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.

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

Peter L. Salgo, MD: 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?

Debra Goff, PharmD, FCCP: 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.

Peter L. Salgo, MD: Well, that’s my point.

Debra Goff, PharmD, FCCP: 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.

Peter L. Salgo, MD: Well, no, no, I’m not going to change my behavior.

Debra Goff, PharmD, FCCP: We’re going to try.

Peter L. Salgo, MD: 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?

Debra Goff, PharmD, FCCP: Right.

Jason Pogue, PharmD, BCPS-AQID: 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.