Gram-Negative Nosocomial Infections: Systemic Risk

Peter L. Salgo, MD: 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?

Andrew Shorr, MD: 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.

Peter L. Salgo, MD: There’s a lot of hallucination at your hospital.

Andrew Shorr, MD: 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.

Peter L. Salgo, MD: 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.

Andrew Shorr, MD: Absolutely.

Peter L. Salgo, MD: 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.

Andrew Shorr, MD: 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.

Peter L. Salgo, MD: 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?

Jason Pogue, PharmD, BCPS-AQID: 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.

Peter L. Salgo, MD: 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?

Andrew Shorr, MD: Oh actually, I think it’s fundamentally wrong.

Peter L. Salgo, MD: I picked him for a reason.

Andrew Shorr, MD: 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.

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

Andrew Shorr, MD: 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.

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

Peter L. Salgo, MD: Is every patient in an LTACH guaranteed to see a physician every day? Often not in my experience, no?

Andrew Shorr, MD: 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.

Peter L. Salgo, MD: Right.

Debra Goff, PharmD, FCCP: But don’t you think one of the biggest problems is there’s no communication between the 2 health care systems?

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

Peter L. Salgo, MD: You think?

Debra Goff, PharmD, FCCP: 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.

Peter L. Salgo, MD: It’s that gosh-darn LTACH and that gosh-darn hospital.

Jason Pogue, PharmD, BCPS-AQID: 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.