Unmet Needs in Treatment of CABP

In this podcast, Frank LoVecchio, MD, speaks about the unmet needs in the treatment of community-acquired bacterial pneumonia, and potential alternatives to the standard treatment regimen. This podcast is part 3 of a 3-part series on the unmet needs of treatment for CABP.

Additional Resources:

For more information on community-acquired bacterial pneumonia, visit our CABP Resource Center.

Frank LoVecchio, MD, is the principal investigator for the Infectious Disease Network (IDNet) studies, and the medical director of clinical and community translational research at Arizona State University, in Phoenix, Arizona.

TRANSCRIPT:

Leigh Precopio:  Hello everyone, and welcome to another installment of Podcasts360, your go‑to resource for medical news and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360.

The treatment of patients with community‑acquired bacterial pneumonia, or CABP, continues to be a challenge. Factors such as changing epidemiology, point of care decisions, and antibiotic resistance contribute to making CABP a difficult respiratory illness to treat.

Here with us today, to further discuss the unmet needs in the treatment of CABP is Frank LoVecchio, MD. Dr LoVecchio is the medical director of Clinical and Community Translational Research at Arizona State University, and the principal investigator for the Infectious Disease Network (IDNet) studies.

Thank you for agreeing to answer my questions today, Dr LoVecchio. What are the unmet needs and treatment, and what are some alternative or new regimens when common regimens cannot be used?

Frank LoVecchio:  The unmet needs include, you know, there's more and more resistance out there with organisms. We have done very well with antibiotic development. As of late, we've made a lot of new antimicrobial agents.

They aren't fully adapted. We should consider them, especially in patients who are more likely to have resistance. More likely to have resistance because they've been on antibiotics in the past, or they have multiple comorbidities, where they live. Are they exposed to the healthcare industry at large? Are they dialysis patients? Are they nursing home patients? Have they been in and out of hospital for other reasons? In those patients, you should strongly consider changing up the regimen or maybe using one of the newer agents.

Leigh Precopio:  To dive a bit deeper, could you briefly discuss how factors such as allergies, antibiotic resistance, inadequate penetration in lung tissues, and undesirable adverse effects, impact the treatment regimens you prescribe your patients with CABP?

Frank LoVecchio:  Some of these points are the most important. If they're allergic to something, obviously don't give it. If you know that there's high antibiotic resistance in your community, or even in that patient to, for example, a macrolide, obviously you can't give that.

With regard to inadequate penetration of lung tissues, not all these agents are created equal. Obviously, the lung is where you want it, but we always pay attention to side effects. Almost all antibiotics will cause nausea, vomiting, diarrhea. Many of them will cause C. diff. C. diff is almost universal in all antibiotics, but it appears to be caused less in tetracycline group.

Sometimes with patients who've had a history of C. diff, which is debilitating in some patients, I tend to offer more tetracycline class because as a class, it's much, much less. There are some newer agents out in the tetracycline space that seem to be pretty safe. The newer agents are a little bit more expensive, but sometimes they're a little bit more convenient.

Leigh Precopio:  Among which type of patients would you prescribe delafloxacin (fluoroquinolone), omadacycline (aminomethylcycline), or lefamulin (pleumomutilin)?

Frank LoVecchio:  With these agents I think it's worth giving a brief review. Lefamulin is first in class. It's been used in animals before, but it's a pleuromutilin antibiotic. And it came out for the treatment of community acquired pneumonia, in cases of Strep pneumo. Also, it covers MSSA, Haemophilus, Legionella, Mycoplasma and Chlamydia pneumoniae. It's pretty amazing that it covers all of the organisms that we really want in community‑acquired pneumonia. It doesn't have the approval for MRSA pneumonia, but there probably weren't enough patients in those clinical trials.

The omadacyline is somewhat unique. It attacks this ribosomal bacterial unit, the subunit. The reason why having a mechanism that's unique is it's probably less likely to cause resistance. It can be given IV, or oral - 150 milligrams IV every 12 hours, or 600 PO every 12 hours.

You do have to play with the dose sometimes. It may prolong your QT, so you should avoid it in patients who are on medication for QT prolongation or have a baseline for prolonged QT. It does cause some drug‑drug interactions and should be avoided in using drugs that are Cytochrome P450 inducers or P‑glycoprotein inducers.

I said a lot of negative things about this, but the important thing to remember is that this is a newer agent, is less likely to cause resistance. The bioavailability if you take PO, you know, is quite well. It's too soon to tell if you can use it in someone who's pregnant, and it's strongly discouraged at this point.

When delafloxacin came out - delafloxacin is a newer fluoroquinolone, and the fluoroquinolones are good for Strep pneumo, for atypical. People like them because it's one agent for the typicals and the atypicals.

But delafloxacin is also good for MSSA. Staph aureus pneumonia, we’re always worried about it. Particularly in certain susceptible population. Maybe somebody who's had influenza in the past can develop Staph aureus pneumonia. Maybe somebody who uses drugs can have Staph aureus pneumonia. This gives comfort because it will cover MSSA pneumonia. It can be given IV or orally, 300 IV or 450 oral. It’s an over 12 hour drug.

Unfortunately, it does have some of the same warnings as the other fluoroquinolones, particularly if there’s tendon issues, drug‑drug interactions, etc.,  But the advantage of course is that it does cover MSSA. It is one agent, made a little bit differently so there’s potential that it has less resistance. I don't know if that's panned out in the clinical trials yet.

The other drug that's relatively new is omadacycline. Omadacycline sounds like it's just another tetracycline, but it's actually different in the sense that it is a first in class aminomethylcycline antibiotic. So it’s just like a tetracycline, but it works a little bit different, and go with the understanding that tetracyclines can cause some resistance. What we're going to do here is change where this omadacycline works. By doing that, we're less likely to get resistance.

Though it also has efficacy against MRSA and multi-drug resistant Strep pneumo. It also has efficacy against vancomycin-resistant enterococci. It covers gram negative, Legionella, Chlamydia. So it's pretty exciting, and the bioavailability, orally and IV,  is pretty good. You could take it orally, and the only reason you are admitting the patient for many of these agents. If they’ve been taking them orally, and are already well - Many of them are once a day or twice a day, and by doing that you could be more likely to send the patient home.

With borderline patients, we look at PORT scores of 2 and 3, you might consider in those patients. Some people even push the envelope and the only reason they're admitting the patient for a PORT score of 4, and if they have good follow up, they might get one of these newer agents. Even though they might be a little bit more expensive, the advantage would be they save them a hospital bed. They're made with permission because they were needing IV antibiotics.

Leigh Precopio:  How do these 3 treatment options compare? When would using one be better than another in terms of disease presentations and outcomes?

Frank LoVecchio:  These 3 agents are pretty exciting. It's always nice to have newer agents. When you have a newer agent, it helps you if there's antimicrobial resistance. Many times they're not resistant to the newer agents. The bugs haven't seen them yet.

When you compare all 3 agents, they're not all the same. Some of them are given once a day, some are given twice a day. The advantages are with, for example, omadacycline, the advantage would be that it's a newer tetracycline class, a tetracycline-like antibiotic. It has a different mechanism. There's less likely to be resistance to organisms that were resistant to tetracycline in the past. I would think about that, and I'd also remember that the incidence of C. diff is much less in patients who have been using tetracycline, etc. Think about it. If a patient does have history of C. diff, you might want to use an agent that's less likely to cause it.

For delafloxacin, the advantage with that compared to other fluoroquinolones is that it does cover Staph aureus pneumonia and the lot. That's a huge advantage. Again, unfortunately, it does have all the side effects of fluoroquinolone. Most drugs do have side effects, but fluoroquinolones are pretty well defined.

Lefamulin is also attractive because it's got a newer mechanism. A newer mechanism is less likely to have resistance for some of these organisms that are typically resistant to other antibiotics. With lefamulin, it's a newer class, it's one agent for community acquired pneumonia and Staph aureus pneumonia. So it's very important to think about that, and IV and oral, the transition is pretty clean. The fact that it has an IV and oral formulation makes it easier to switch somebody if they are responding well to the IV.

So as far as when you do 1 or the other, the advantage of these 3 newer agents is less likely to be resistant. You have to be aware of if they've had C. diff in the past or at risk for it, maybe might err more towards the omadacycline. If they had tendon issues in the past or QTc issues in the past, we have to pay attention to delafloxacin and any issues with QT.

A lot of our time is spent on antibiotics and talking about the best antibiotic etc. What this last year has taught us is that a lot of the basics are very, very important. Good hand hygiene, covering your face when you cough, cough etiquette. I also think vaccines. There's good vaccines for pneumococcal pneumonia, etc. You should really, really consider it in your patients. Of course, if they smoke, smoking cessation would do much better in most cases than just telling them to take an antibiotic. Think about that. Think about warning people of the comorbidities, what got them there. If they're at such high risk because of their general activities, where they live, what they do, are they overdoing antibiotics for things that would not have required antibiotics.

I know some patients are very persistent with physicians, and providers many times give in, the more often you give antibiotics when it's not necessary. We have to have those conversations. We need to have this conversation before we actually get pneumonia. Not everything requires antibiotic, i.e. viruses, but I think that’s come to light more.

Leigh Precopio:  Thank you for answering all my questions today.

Frank LoVecchio:  Thank you.

 

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