Challenging Gram Negative Pathogens and Oral Carbapenems: MAD-ID Updates With Jason Pogue, PharmD

How to manage infections caused by extended spectrum beta-lactamase (ESBL)-producing bacteria, what pathogens to be on alert for, and how to approach oral carbapenems were all hot topics in 2 presentations at the Making a Difference in Infectious Disease (MAD-ID) 2022 annual meeting, held May 18-21, 2022, in Orlando, Florida, by Jason Pogue, PharmD, BCPS, BCIDP, clinical professor of pharmacy at University of Michigan College of Pharmacy.

Pogue joined Contagion® for a video interview to discuss his talks and share key takeaways for infectious diseases clinicians.

This transcript has been edited for clarity and length.

Contagion®: Can you summarize the key points from your presentation, "Treatment of Challenging Gram Negative Infections"?

Pogue: For the first session at MAD-ID, we'll be focusing on 3 particular problematic gram negatives. The first one we're going to talk about is managing ESBL infections. There's a clinical controversy surrounding whether or not you can use piperacillin-tazobactam or if you have to start with the carbapenems, or if that's the preferred therapy in that situation, and so we'll be [taking] a deep dive into the literature support. And hopefully, by the end of the talk, I'll convince you that if you have a patient with an invasive ESBL infection, they should get a carbapenem.

The second thing that we're going to talk about is focusing on AMPc-producing organisms. We're going to try to myth bust a little bit in that presentation. Hopefully, by the end of that, the SPACE acronym [Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter] will be out of your mind. And you'll be thinking HECK YES [Hafnia alvei, Enterobacter cloacae, Citrobacter freundii, Klebsiella aerogenes, Yersinia enterocolitica], and Sam Aitken will be in your mind instead.

Then the last part we're going to touch on is really the most problematic organism, which is carbapenem-resistant Acinetobacter, a challenging pathogen, very difficult to treat with our current options. We're going to focus on probably the 2 most popular current options and deep dive into the data for ampicillin/sulbactam and for the tetracyclines. I'm going to get to leave [you on] a positive note though, because there is a new agent coming in the Acinetobacter baumannii space, sulbactam-durlobactam. I'm going to present a little bit of the data that was presented at ECCMID last month.

Contagion®: What is the main takeaway for infectious diseases clinicians?

Pogue: Bottom line, takeaway No. 1 is to use carbapenems over piperacillin-tazobactam for ESBL. Please, I beg of thee.

Second, when you're thinking about AMPc situations where you should really want to avoid a drug like ceftriaxone, the organisms you should really be focused on there are Enterobacter cloacae, Klebsiella aerogenes, and Citrobacter freundii. The other ones like Serratia, you're probably okay to use drugs like ceftriaxone. And then for Acinetobacter, good luck, in a lot of ways. But really, what's really important to note is that for amp-sulbactam, we’ve got to be pretty aggressive in our dosing. We're going to want to be giving extended infusions as the standard of care. But then, in addition to that, with regards to tetracyclines, know that there's more that goes into it than just the S for susceptible. A lot of those breakpoints are actually too high, and you probably have to pay a little bit closer attention before you choose which tetracycline to use.

Contagion®: Can you describe the basis for your second talk, "Oral Carbapenems Are Coming: Are You Excited or Anxious?"

Pogue: The oral coverage, that's going to be a fun one. That's a fun talk. So one of my former residents and I, Katie Barber, will be debating, are we excited or anxious about oral carbapenems? I will be taking the anxious side, and not just because I'm an anxious guy, which I am, [but] that's just a coincidence in this situation. It's a little bit of a funny—funny is a bad word choice—it's a little bit of an interesting topic to be had now, since a week or 2 ago, the oral carbapenem that we were really focused on discussing was kind of rejected by the FDA or they had to go back and do additional stuff. So the “they are coming part” is a little bit less soon that we're going to see that. But I'll be focusing on the con and I will be honest, I do have anxieties about [oral carbapenems]. There's a reason we don't currently have one, and that main reason is that the compounds have very poor oral bioavailability and so your exposures are very borderline. When you start to go through the [pharmacokinetics/pharmacodynamics], you look at the clinical data, there are a lot of warning signs that come out. I'm hopeful, I'd love to have oral carbapenems for my patients, but there's a reason to be anxious, there're definitely some issues there and some red flags.

Contagion®: And the bottom-line takeaway for clinicians there?

Pogue: The main takeaway that I would have is that, unfortunately, it's not going to be an issue in the near future, because it's going to be a while again before we see an oral carbapenem. But what's really key is…let's just use, for example, had tebipenem made it, because it would have been available probably within the next month or so or it would have been available in the very near future. It's really important that, even for an oral antibiotic, we do all the appropriate preclinical work to make sure that the dose is right that we can achieve our PK/PD targets and that the clinical data support that, because like I said, if you look at those data, there's a lot of things that pop out at you.