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Pseudomonas Infections: Secondary Approach to Treatment

JUN 19, 2018 | PANELISTS: PETER L. SALGO, MD; MARIN HRISTOS KOLLEF, MD; JASON POGUE, PHARMD, BCPS-AQID; YOAV GOLAN, MD; AND ANDREW SHORR, MD
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Peter L. Salgo, MD; Yoav Golan, MD; and Andrew Shorr, MD, discuss their personal approaches to treating Pseudomonas infections when an earlier strategy has failed, taking into consideration past treatments, a patient’s sepsis status, and timely decision making.

Peter L. Salgo, MD: Suppose you start with your standard cocktail in a patient who’s bacteremic, septic, hypoxic, hypotensive, high lactates, and you guess wrong. You’re giving these antibiotics, and you’ve done your best, but how quickly do these patients turn to stool?

Yoav Golan, MD: If you have an antibiotic that can save your patient’s life in your right pocket and you use an antibiotic from the left pocket, you may lose the patient. You may lose the patient very quickly, and it all depends on how sick the patient is and how anemic the patient is. Because as we know, within a day or 2 or 3 the patient may die if not treated adequately. On the other hand, there are patients who are stable and in whom you don’t have to take such an aggressive approach. But the duration from infection has not changed, and particularly Pseudomonas and some of those very virulent bacteria can kill people very, very quickly.

Andrew Shorr, MD: We’re talking about drug-resistant pathogens, but we all still see people dead within 48 hours of pneumococcus.

Peter L. Salgo, MD: We do.

Andrew Shorr, MD: We still see people dead within 48 hours of MSSA [methicillin-susceptible Staphylococcus aureus] endocarditis. We’re talking about gram-negatives, but rapidly deteriorative patients with infection exist for all of us and not only with ugly gram-negatives. I think the other thing we’re missing in this conversation is source control. We’re talking about only 1 piece of the toolkit for taking care of these patients. No matter how many antibiotics you throw over someone, if you think they’ve got pus in the belly…

Peter L. Salgo, MD: Go for the belly.

Andrew Shorr, MD: Right, you’ve got to put a needle in and you’ve got to get your surgical colleagues involved. Source control is crucial. If you’ve got a catheter that’s infected and you’re leaving it in, and you think you’re going to treat through that biofilm that we’ve talked about, forget it. That’s true particularly for Candida, for gram-positives, and even for gram-negatives. People fail not only because we give the wrong antibiotics: There’s host failure, but there’s also source control failure.

Yoav Golan, MD: Just to be practical, because we came with a lot of doubt and we expressed a lot of opinions asking why are things complicated, why is it difficult, and why can’t you get it right every time, even if you use rapid diagnostics with the coming of rapid diagnosis in the future? I think that it is important to note at the end of the day, you need to treat the patient, and you need a practical a priori. I think that it is important to know that one can put together a practical paradigm that will help clinicians.

Peter L. Salgo, MD: All right, let me ask you, how do you do that?

Yoav Golan, MD: All right, so this is how I would do that.

Peter L. Salgo, MD: He’s going to tell us how he does that.

Yoav Golan, MD: That’s my practical paradigm. I start with the patient and ask myself how sick the patient is or, in other words: What will happen if the patient is not getting treated adequately? You would be surprised. In most patients the answer is that not much is going to happen in the next day or two. That gives you a lot of time, and you don’t need to be very aggressive and you can preserve antibiotics. This is the bulk of our practice, but this is the most important question.

Then the second question I would ask is, What do I think the source of the infection is? As Marin said, sometimes you have no clue. Sometimes, you know exactly. The patient had an observed aspiration episode, and you talk about the ICU. The patient had those recurrent urinary tract infections. Sometimes you have a very good sense and ask yourself, What kind of bacteria causes this type of infection? What do I have to cover? This will give you a clue. Then you ask yourself, What did the patient show in the past in terms of infection and colonization? This is always helpful. You want to cover that even though you know it’s not necessarily going to be the previous bug. And then you ask about the classic risk factors for resistance.

What was the exposure of the patient to the antibiotic or their exposure to health care? We talk about Pseudomonas, but Pseudomonas is unlikely in the first day or 2 or 3 of hospitalization for someone who hasn’t seen health care. If someone came to surgery and the surgery got complicated, but he came from the street, he’s less likely to have Pseudomonas in the first day or 2 and far more likely to have it on day 7. So it’s exposure to health care, exposure to antibiotics, and patient health factors, as you mentioned: being immunocompromised and so forth.

Peter L. Salgo, MD: It’s funny, you mentioned something that I think is important. I had a resident the other day saying, “This patient is septic, but he’s a happy septic patient.” And I said, “How do you define happy sepsis?” He said, “He’s sitting up in bed, he’s smiling, and he’s not intubated, yet his blood cultures are positive and his lactate’s going up. But he’s not septic, near deadly sick.” They come in different flavors, so I guess that’s what you’re implying.

Andrew Shorr, MD: But the other point that’s crucial is you’re never going to show a mortality risk for inappropriate antibiotic therapy in patients with low risk for death. When you look at the literature that all of us have contributed to, there may not be a mortality penalty in some of the patients that Yoav is describing. There is clearly a morbidity penalty for getting it wrong, and that morbidity penalty is measured in subsequent escalation of care and in length of stay at the hospital.

I think it gets to a principle that we danced around, especially as it relates to any of the newer antimicrobials, which is cost. The most expensive antibiotic is the one that’s used inappropriately or in a delayed fashion. The point is, yes, you look at this patient and you think you have time to get it right. Yes, you have time to get it right if your endpoint is mortality. If you think about it from the perspective of, “Well, I’d like to get this patient out of the hospital as quickly as possible and with as few complications as possible,” the clock is always ticking. It’s not like you can sit there and intellectualize the process. You still have to make a decision, which is why with my residents, I pull their badge and I say, “It says MD after your name. Make a decision.”

Yoav Golan, MD: Here is the clash between the intensivist and the infectious disease doctor.

Peter L. Salgo, MD: I’m liking what I’m hearing over there.

Yoav Golan, MD: We both have the same interest, of course. But I guess what Andy is saying is that it’s always important to get it right early, but what you don’t say is, “I’ll always use my first-line antibiotics.”

Andrew Shorr, MD: No, I’m not saying that at all. I’m not saying I have a hammer and everything is a nail and I treat them all the same. But I’m saying that you can’t fall into the trap of thinking, Oh, there’s no consequence for taking my time on this decision.

Peter L. Salgo, MD: Because the cheap, common antibiotic, if it gives you an extra week in the hospital, is very expensive. That’s what you’re saying.

Andrew Shorr, MD: Correct.

Yoav Golan, MD: But you also have to realize that some of the antibiotics we consider to be old and cheap and not very active...

Andrew Shorr, MD: They work pretty well.

Yoav Golan, MD: They are the best antibiotics that we have. Of course, the best examples are from the gram-positive arena, where we use a little vancomycin as a super antibiotic, but all those cheap—not very cheap sometimes—drugs such as cefazolin and so forth are much better than vancomycin. So there is something to gain, there is something to lose, but I think the patient should guide you, and I think that’s the principle.
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