Peter L. Salgo, MD: How do patients with resistant Pseudomonas infections differ from other patients? Are they more expensive? Do they do better? Do they do worse?
Jason Pogue, PharmD, BCPS-AQID: I think that’s our biggest challenge. They don’t have a sign that tells us they have Pseudomonas compared with some other resistant gram-negative organism. If you look at risk factors, studies, or scoring systems, everything overlaps. It gets back to the same concept that we’ve been talking about so far: understanding your local epidemiology and knowing your patient-specific microbiology history. What are they? Get surveillance cultures, those types of things, or previous antibiotic exposures. That’s going to drive it because they’re completely overlapping risk factors. Pick your favorite drug or just an organism; they have the exact same risk factors.
Peter L. Salgo, MD: Not to put a grenade on the table, but we have a fair number of leukopenic patients who come in with only the fairest wisps of hints that something’s going on. They’re developing pus, they’re not getting big infiltrates until their white cell count comes back, and they need antibiotics. How do you do that? This is all a challenge, isn’t it?
Marin Hristos Kollef, MD: I do think there’s something unique about Pseudomonas. I say that because we did a study where we looked at patients who had bacteremic pneumonia at Barnes-Jewish Hospital in St. Louis. What we found was that the patients who had bacteremic pneumonia due to Enterobacteriaceae were more likely to get treated with an antibiotic that didn’t cover the bug. But the mortality was highest in those who had pseudomonal infection. And so, there’s something about the host—bug interaction in that setting that’s really key. It really makes me pay more attention to patients who I think are at risk for having a Pseudomonas infection.
Peter L. Salgo, MD: I think that’s where we started, which is not only that Pseudomonas is a nasty bug but also that the patients who get it tend to be the most vulnerable. And so, they’re more likely to die of all causes. Pseudomonas is maybe what tips them over, but it’s a nasty combination.
Yoav Golan, MD: But there’s still a lot to achieve with adequate therapies.
Peter L. Salgo, MD: Well, yes.
Yoav Golan, MD: They are the ones who lose the most from inadequate early therapy.
Peter L. Salgo, MD: They have the most to gain and the most to lose. Nobody is sitting back and saying, “Oh, look at Mr. Jones. He’s so old; he’s so immunocompromised; he’s so sick; leave him alone and let him die.” No, that’s the fun part, treating him. Right? Making him better.
Marin Hristos Kollef, MD: But it’s not just Mr. Jones. Without getting into specific details, we recently had a couple of patients—they both had cystic fibrosis—in our intensive care unit, and both had multidrug resistances. In fact, it was extremely drug-resistant Pseudomonas that led to fatalities in both cases because we couldn’t treat the organism. So, it’s not just older patients who really have nothing left. These are younger people who potentially have years or decades of life ahead of them.
Peter L. Salgo, MD: We have to go on and discuss the treatment options that we’ve got because nobody wants to let these people die if we can at all help it. So, what’s out there? What are the antibiotic classes? What are the agents we’ve got that are effective against resistant Pseudomonas aeruginosa? Why don’t we just run through some of the advantages and disadvantages. Do you want to start us off?
Marin Hristos Kollef, MD: I would have to go with our own experience, and I would have to say that carbapenems are really the backbone. We’ve gotten to a situation now—and this is even true among our house staff—where for anyone who comes in with any type of a risk factor, we tend to go to a carbapenem. Now, in our institution, we have other agents that also may be effective, but the carbapenems seem to have the greatest overall activity, at least locally. We’ve become more of a carbapenem-driven hospital. I’ll let some of the other people comment on other things.
Jason Pogue, PharmD, BCPS-AQID: I would just emphasize here that it will be institution specific. You need to know what you’re looking at because we’ve actually flipped our institution’s carbapenems. Cefepime, piperacillin/tazobactam, and meropenem are the least likely to be active against Pseudomonas empirically, and it’s just because of the complexity of resistance mechanisms.
Marin Hristos Kollef, MD: Yes, but I’m talking about in the ICU.
Jason Pogue, PharmD, BCPS-AQID: Yes, in their ICU as well.
Andrew Shorr, MD: We have the same thing in our ICU. About 20% of our Pseudomonas infections are carbapenem resistant. Piperacillin/tazobactam continues to have the highest activity, and we don’t actually have an ESBL problem in our institution. We’re very fortunate thus far. And so when we do the game and the numbers, we say that theoretically, I want to get to a 95% empiric hit rate from the gram-negatives I might encounter. What do I need to start with? We generally start with piperacillin and tazobactam plus aminoglycoside.
Peter L. Salgo, MD: I was going to say, am I hearing this right? You’re using monotherapy against Pseudomonas?
Andrew Shorr, MD: There’s a difference. There’s monotherapy against Pseudomonas when you know the pathogen and you know the susceptibilities, which I think we would all call the de-escalation phase or the definitive therapy phase, versus multidrug therapy as an initial pathway to ensure that the patient’s getting at least 1 drug that’s in vitro active against the culprit pathogen. That’s an important paradigm and an important lesson that I just realized: What you start with ought not actually be what you finish with.
Peter L. Salgo, MD: Fair enough. Sorry, you wanted to say something?
Jason Pogue, PharmD, BCPS-AQID: Just to build on that a little bit too. It’s not just Pseudomonas. Andy suggested that before. But if you happen to have a lot of carbapenem-resistant Acinetobacter in your ICU, that all has to go into that empiric therapy decision. So, you’re looking at that cocktail, that combination, that gives you the best ability to give it up front.
Peter L. Salgo, MD: Now you see, I anger all my colleagues. Maybe not anger, but I make them uneasy. When I see somebody who I really suspect has resistant Pseudomonas, I take the grenade, I pull the pin, and I throw everything I’ve got against the wall. I’m perfectly happy to calm down later when we get the culture results. But our antibiogram is that these are bad bugs, and we often need 2 or 3 drugs. The aminoglycosides are always part of it, no?
Yoav Golan, MD: Well, every patient and every infection is different, and I think that always being very aggressive or never being very aggressive is probably not the way to go. The patient tells you how aggressive it is to be. If the patient tells you, “Look at me and how sick I am; look at me and how quickly I deteriorate.” The patient tells you that you only have 1 chance. In those circumstances, you want to be very aggressive. If the patient tells you, “Listen, I may have a UTI; I may have pneumonia or not; I’m relatively stable; I’m not that sick to begin with,” maybe you’ll take a different approach. Remember that the antibiotics sound like any other medication.
To use overuse them, use too many of them, will affect your ability to treat your patient. You have to balance them. When you talk about the antibiograms, when you talk about personalizing risk factors, I think it’s important to do that. I think that’s the infectious disease doctor’s approach. Very often you say, “I want to do everything because my prospective patient is everything I have on my table right now.” That’s an OK approach, as well, but I think that you have to balance it.
We talk about antibiograms as guidance for treatment. In hospitals that have a lot of those ESBL-producing bacteria, the physician uses a lot of carbapenems. Hospitals that use a lot of carbapenems push their Pseudomonas to become resistant. Hospitals that have less of that may have more susceptible Pseudomonas. So, the antibiogram gives you some guidance, just knowing the type of infections treated in your ICU.