Thomas File, MD, MSc, MACP, on the LEAP Trial Results

In this podcast, Thomas M. File, Jr, MD, MSc, MACP, talks about his session at CHEST 2021, during which he discussed the results of the LEAP 1 and 2 trials that evaluated the efficacy and safety of lefamulin for treating community-acquired pneumonia.

Additional Resource:

• File T, Mariano D, Gelone S, Moran D, Waterer G, Sandrock C. Lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia: pooled analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 trials in patients with multilobar or unilobar pneumonia. Paper presented at: CHEST 2021; October 17-20, 2021; Virtual. https://journal.chestnet.org/article/S0012-3692(21)01961-9/fulltext

Thomas File, MD, MSc, MACP, is a professor of internal medicine at Northeast Ohio Medical University; chair of the Infectious Disease Division at Summa Health System in Akron, Ohio; and a recent past president of the Infectious Diseases Society of America.

TRANSCRIPT:

Amanda Balbi: Hello, and welcome to another installment of Podcasts360. I’m your moderator Amanda Balbi, with Consultant360.

Today we’re speaking with Thomas File, MD, MSc, who is a professor of internal medicine at Northeast Ohio Medical University; chair of the Infectious Disease Division at Summa Health System in Akron, Ohio; and a recent past president of the Infectious Diseases Society of America.

He recently presented findings from a study on lefamulin at CHEST 2021.

Let’s listen in as he answers our burning questions.

Thank you for joining us today, Dr File. To start, can you give us an overview of the study on the efficacy of lefamulin?

Tom File: Yeah, I’d be happy to do that. The purpose of our study was to investigate the efficacy and safety of this novel antimicrobial agent, lefamulin, in patients with community-acquired pneumonia based on the presence of multilobar infiltrates, since we know the evidence suggests that multilobar pneumonia can be associated with decreased clinical outcomes. So, we did a post-hoc analysis of 2 randomized clinical trials comparing lefamulin with moxifloxacin. One was an IV-to-oral study, and the other was just oral. 

We found that one-third of the patients had multilobar pneumonia. These patients were more likely to be older, have a history of lung disease, were in more-severe infection as scored by the PORT Score than patients who just had unilobar pneumonia.

The bottom line, we found that lefamulin efficacy was high for patients with unilobar or multilobar pneumonia and comparable to that with moxifloxacin and had a similar side effect profile.

Amanda Balbi: Thank you, so how can these key take-home messages—the findings from your study—be implemented in clinical practice?

Tom File: Lefamulin is FDA-approved for community-acquired bacterial pneumonia. Lefamulin is a novel antimicrobial agent that has a different mechanism of action than other antimicrobial agents used to treat pneumonia, and therefore, it's active against the many resistant organisms associated with community-acquired pneumonia.

It belongs to what we call the pleuromutilin class and works by binding to the peptidyl transferase center of the 50S ribosome, which then inhibits bacterial protein synthesis, and therefore, the probability of cross resistance to other antibiotics, such as β-lactams, macrolides, tetracycline, and even the fluoroquinolones, is very low. 

It has a potent activity against all the key pathogens associated with community-acquired pneumonia, such as new Pneumococcus, Haemophilus, Morexella, and the atypical pathogens, but interestingly, it has low activity against Enterobacteriaceae such as the gram-negative bacilli that are in the gut flora and anaerobes, and therefore, it's likely to have minimal effect on the gut microbiome and that can be helpful as well. 

So, lefamulin provides an additional option to treat community-acquired pneumonia. It's a nice IV-to-oral class of a drug that provides targeted antimicrobial activity as I just said and, therefore, provides an additional option for therapy, particularly in patients who may not tolerate or be able to be treated with the usual antibiotics, such as macrolides, β-lactams, or even fluoroquinolones.

Amanda Balbi: Absolutely. So then, what is the next step in your research regarding lefamulin or treatments for CAP?

Tom File: Right, I think there are several new research studies that are going on with the treatment of community-acquired pneumonia. That's going to be very helpful in the future, and let me just focus on a few, Amanda.

One is that right now we're going through what I’m going to call an “increased logarithmic, new advances in molecular diagnostic methods,” and this is going to allow us, I think, more rapidly to identify pathogens associated with community-acquired pneumonia and perhaps give more-specific therapy when we evaluate these patients initially.

Also, we're becoming more aware of the significance of what I'm going to call the “lung microbiome.” I mean, we used to think that the lung area was devoid of bacteria, but now we know that there are bacteria that are part of the lung microbiome. When we disrupt that that could be inflammation, which can be associated with symptoms such as pneumonia, so this is going to be very important going forward for new research.

And then the other, I think, very important aspect will be research going on concerning the host response and how we can potentially modify the host response and maybe using coadjuvants such as steroids and other adjuvants that may be helpful in addressing the host response and maybe they use some biomarkers, such as procalcitonin and pro-adrenal medulla, which is a peptide that can be associated with increased assessment of patients, but by virtue of their host response. Therefore, this can be helpful in our future treatment and how we monitor patients with community-acquired pneumonia.

Amanda Balbi: Great, thanks so much for joining us today, Dr File. And for our listeners, you can click the links below for more content on community-acquired pneumonia. Thank you for listening!