Classes and Agents Available to Treat <i>Pseudomonas</i> Infections

Peter L. Salgo, MD: I haven’t heard 2 classes of bug juice at this table. I haven’t heard anybody really talking about the fluoroquinolones. What about—here’s a really old drug&mdash;polymyxin? Do they have a role here? Does anybody want to step up on this one?

Andrew Shorr, MD: I’ll take on fluoroquinolones. There’s no role.

Peter Salgo, MD: That’s fine. Done.

Andrew Shorr, MD: That’s pretty easy. In our hospital, fewer than 30% of our Pseudomonas infections are susceptible to fluoroquinolones. Beyond the fact that most people don’t know how to dose the fluoroquinolones properly if they’re going to use them, there are all the issues associated with fluoroquinolone safety, particularly Clostridium difficile for us. We’re really trying to take fluoroquinolones out of our institution completely. So, they’re not really an option.

As for colistin polymyxin and all those agents, this is an area where we’re actually clearly getting into strong opinions because we don’t have strong data. That’s the nature of medicine: The stronger the opinion, the weaker the data. I think all of us would agree that colistin is probably a laundry detergent masquerading as an antibiotic. Is it sometimes the only choice we have? Yes. Is it ever our first choice? In the United States, no. In other parts of the world, yes, because they’re dealing with a higher prevalence concurrently of Pseudomonas, CRE (carbapenem-resistant enterobacteriaceae), and Acinetobacter. And 50% are infections, so they have to start with colistin. But nobody knows how to dose it properly, especially in critically ill patients with changing renal function.

Do I use it sometimes? Yes. Do I use it for MDR Pseudomonas? Pretty much no because I have other choices before I get there, including not only different classes of antibiotics but also different dosing paradigms for the antibiotics we currently have. One of the lessons that I’ve learned from my ID and pharmacy colleagues, and why I think it’s important to realize this is a multidisciplinary group, is that pharmacokinetics matters. Just because I have an MIC in a test tube doesn’t mean I can’t figure out how to be smarter than the resistance by giving more of the drug over a longer period of time and optimizing these pharmacokinetic principles that we forgot about from 20 years ago.

Jason Pogue, PharmD, BCPS-AQID: I’ll build on both of those things. First with fluoroquinolones, I do think they have a role. First off, in our institution, our susceptibilities have come back a good bit because we restrict them. I think the bigger issue with fluoroquinolones is that the MIC break point might be wrong. To your point, the way that we dose them is probably suboptimal in a lot of those patients. I’m not saying that I like them empirically; I’m not saying they’re my go-to; but they’re potentially a step-down option to these patients. I do think they have a role.

With regards to the polymyxins, yes, they have issues. As Andy said, we have some other agents that we can use. Since you’re talking about Pseudomonas, you’re often talking about lung infections. Then there’s an emerging body of evidence that suggests those drugs maybe don’t work in the lung, so they would be a suboptimal choice.

Marin Hristos Kollef, MD: Just to add to that—and correct me if I’m wrong, Jason&mdash;my experience has been that over the past couple of decades, one of the most common combinations of empiric therapy has been Peptazol (pantoprazole) and levofloxacin to cover gram-negatives. And yes, you have to use institution-specific antibiograms, but at our place and at most others that I can find, I can’t find any evidence that there’s any additive effect of combining those 2 drugs. What you end up getting is the side effect of levofloxacin&mdash;Clostridium difficile, etc—when in fact what that patient should get is an aminoglycoside.

Jason Pogue, PharmD, BCPS-AQID: I agree wholeheartedly, and I think that brings us into the combination antibiogram piece of the story. If you’re going to choose a second drug, you want that second drug to be active against those that are resistant to the first drug. When you have β-lactam resistance, you often have fluoroquinolone resistance, as well, which makes the aminoglycoside that much of a better empiric drug. I completely agree with that. That said, I can tell you that we’ve long restricted fluoroquinolones at my institution. To Andy’s point, we rarely use them, to be honest with you. We have seen rebounding and susceptibility to a degree, and I think they have a role if used correctly as step-down therapy to complete therapy from an overall standpoint.

Peter L. Salgo, MD: Can we just put something on the table? I hear this every day. Are aminoglycosides safe to use in patients with renal failure?

Andrew Shorr, MD: Everybody would say that 1 dose of aminoglycoside while you are waiting for culture results to come back is fine. It’s the extended duration, and certainly the duration of exposure, associated with the interaction with the current kidney injury and fluid staph infections to the patient that matters. I think none of us use aminoglycosides as our monotherapy definitively for Pseudomonas, particularly in the lung. In my institution, it’s usually that they’re on something plus amikacin because that’s our best aminoglycoside, for 2 days. If we know what the bug is, we drop to the agent that’s going to kill it. If we have an isolated gram-negative, then it’s gone.