Outsmarting Resistant Infections - Episode 11

Gram-Positive NIs: Nuancing Lipoglycopeptide Therapy

Peter L. Salgo, MD: What are the downsides? What is the risk of these drugs?

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): I think the downsides are that some of these complex patients—let’s say that perhaps the patient is bacteremic and we didn’t realize that because they came into the ER—they looked like they just had an abscess, we drained it, but it was significant. We felt like they needed antibiotics, 7 days should be plenty. But on day 3 their culture comes back positive and we can’t find the patient. So, yes, they still have 7 days of antibiotics on board but maybe now we’re thinking, “Oh, they need 14 days or we need repeat blood cultures and we don’t have that patient in front of us.” Now, that goes back to the types of patients we’re talking about. They were going to leave anyways, but at least we know we gave them 7 days, so we still feel like that’s a pro. But in some other scenarios, we need to bring them back in, and now we have some decisions to make. Would we consider that antibiotic active for 7 days and then give another dose, which would be off-label, and switch to another antibiotic? At what point would you add another gram-positive agent that perhaps has a similar mechanism of action when this one is still active? And so, there’s a lot of uncharted territory because we don’t have the clinical work to tell us.

Peter L. Salgo, MD: If you had somebody that you knew was bacteremic with a gram-positive organism, would you use these drugs or would you use different drugs?

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): We would use different drugs unless we were in a unique scenario where we could not.

Peter L. Salgo, MD: So, that’s the point. In other words, you see somebody with a Staph abscess, you give this, and we hope the abscess is going to go away after you drain it. Because you can’t really cure these things, where the absence of evidence is not the presence of an abscess, something like that.

Jason Pogue, PharmD, BCPS-AQID: So close.

Peter L. Salgo, MD: But if they come back and now they’re bacteremic, this is another kettle of fish and these drugs are not designed for that, we don’t think.

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): They haven’t been studied well.

Andrew Shorr, MD: It depends on the bacteremia.

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): Exactly. There is a lot of “it depends.” They may well be designed for that, but we’re not quite there yet.

Debra Goff, PharmD, FCCP: So, it kind of reminds me of the old Z-Pak days where when azithromycin was the first game-changing antibiotic, that was a 5-day course of therapy. You discharge a patient on it, and they’d go, “There’s not enough pills here.” And it really took a lot to teach people. But what we started observing is people would start giving a second Z-Pak, and pretty soon. And so, you don’t want to go down that path again.

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): A colleague of mine says you have to have the intestinal fortitude to not give another for a week no matter what.

Debra Goff, PharmD, FCCP: Right. Patients expected to get better overnight with this new short-acting drug, and it sometimes just doesn’t happen.

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): That’s a good point. Patient education is very important. And we found that out when we first started infusing this that just because you’re only going to get 1 dose does not mean you’re going to wake up tomorrow and if your leg has been red for the last week, it’s not going to be completely not red tomorrow. So, setting appropriate expectations that you should start to see improvement in 48 to 72 hours. You won’t see a total improvement for 7 days or even more.

Peter L. Salgo, MD: I do remember several people coming to me with older therapies, which were known to be effective. They said, “I had XYZ, I took my antibiotics, and I’m still sick.” And I would ask, “Well, when did you take the therapy?” “Oh, this morning. Why am I not cured?” So, it’s both. It seems to be practitioners and people getting the therapy, right?

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

Andrew Shorr, MD: But I think Sandy raises a good point. The novel long-acting glycopeptides are not better than the currently available therapies. They have a different profile that may or may not offer a benefit to your patient or your institution, but they’re not better in vitro, they’re not better in clinical trials. They’re not better, they’re just different. And you have to decide if that distinction is a difference that matters to you or not. In addition, just for the sake of balance, we also have now a new oral fluoroquinolone that has anti-MRSA activity that has recently been approved, and it’s unique in that it also has gram-negative covered. So, now we have an anti-MRSA fluoroquinolone. Again, whether that’s good or bad in terms of spectrum of coverage, there are some patients where you’re actually worried about gram-negatives as a co-infector or the only pathogen in their skin and skin structure infection, and there are some where you’re not. So, again, you need to individualize and think about these things. And you can’t say, “Well, this is always going to be the right choice or this is never going to be the right choice.” And I think around this class of drugs, these long-acting agents, the reimbursement scheme we have in this country for who pays for what really complicates the decision-making process about how to apply them. Because if you’re admitted, it’s going to be covered by a DRG (diagnosis-related group), and then my pharmacy director never wants to pay out of his silo budget for a week’s worth of antibiotics if the hospital stay is supposed to be 2-and-a-half days and the outpatient payer should be covering the tail. And same way in the ER. They’re never going to let the ER spend that much money on an antibiotic without some other authorization.