Clinicians’ Concerns for the Future of CABP

In this podcast, Christian Sandrock, MD, MPH, talks about how the current burden of community-acquired bacterial pneumonia (CABP) has impacted clinicians' concerns about the future, the increasing burden of treatment-resistant bacteria, and the resulting treatment limitations. This is part 3 of 3 podcasts on CABP from Dr Sandrock.

Additional Resources:

• Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. https://doi.org/10.1164/rccm.201908-1581st
• More CABP podcasts here: https://consultant360.com/specialty/consultant360/cabp
• Listen to part 1 here.
• Listen to part 2 here.

Christian Sandrock, MD, MPH, is a pulmonary, critical care, and infectious disease physician and professor of medicine at the University of California Davis in Sacramento, California.

TRANSCRIPTION:

Amanda Balbi: Hello everyone, and welcome to another installment of Podcasts360, your go-to resource for medical news and clinical updates. I’m your moderator, Amanda Balbi with Consultant360. 

Our guest today is Dr Christian Sandrock, who is a pulmonary, critical care, and infectious disease physician and professor of medicine at the University of California Davis in Sacramento, California. Today he joins us to share his thoughts on clinicians’ main concerns about community-acquired bacterial pneumonia (or CABP) for the future. Let’s listen in.

As more bacteria become treatment-resistant, more treatment limitations will be realized. What are clinicians’ concerns for the future of treating CABP?

Christian Sandrock: This is always a real great question. What are some of our future concerns? I think what we've really seen—and there are lots of antimicrobial resistance among organisms—the ones in community-acquired bacterial pneumonia that concern us are predominantly the macrolides, so it's azithromycin and clarithromycin.

And then obviously the tetracycline class, so in this case tetracycline and doxycycline, and to a lesser extent then is the fluoroquinolones. In general, because of some of the limitations of the fluroquinolones, many of us like to lean on the macrolides and/or doxycycline as first-line therapy. When we look at monotherapy, however, in parts of our country, we certainly have high resistance rates. In general, macrolide resistance for pneumococcus, for example, is above 25% throughout the country. That then means that's an agent you're generally not going to want to use for monotherapy when those rates hit 25% or higher, based on what the guidelines say.

Doxycycline might be higher than 25% in some regions on the east coast. It's about 15% here in California where I live. So, having that ability to have a good, adequate monotherapy when you have this resistance becomes a concern. This is really where these newer agents are trying to make their mark.

Okay, we want to get away with monotherapy, we want that monotherapy not to be a fluroquinolone or, for example, the patient may have a beta lactam allergy. In those cases, having these newer agents are really going to play a role, whether it's omadacycline or lefamulin.

And I think the little bit that the guidelines mentioned is newer agents are always hard when you have guidelines. Guidelines want to have long-term, established data, and if you have a newer agent, it's a little harder to throw them in at a high ranking, which the guidelines acknowledged. They basically said, “Hey, we need more data, but these may be real reasonable options.” I think this idea of the future of resistance is where these newer agents are going to make their mark.

Amanda Balbi: Other treatment limitations might include medication allergies, inadequate penetration in lung tissues, and undesirable adverse effects. How might these challenges be overcome via new treatment options?

Christian Sandrock: That's a great question. Our patients are never straightforward, right? So, they often will have a beta lactam allergy, a cephalosporin allergy, and might have a contraindication of fluroquinolone, whether they've had a prior C diff infection. They may be worried about tendon rupture. They might have diabetes and you're worried about hypoglycemia or history of aortic dissection. Whatever the reason may be, that then makes things a bit harder for us. 

Again, you can imagine, if you look at the guidelines for a patient who has comorbidities, as we talked about before, and say, for example, they have a beta lactam allergy, and they can't tolerate a beta lactam, so that leaves amoxicillin clavulanate out.

And because of whatever reason—maybe they have diabetes or they were recently hospitalized and had a C diff infection—you want to avoid the fluroquinolones. I will tell you here at UC Davis, we're very fluroquinolone avoiding. Like many places, that's a big cornerstone of our stewardship is to limit fluroquinolone use. I mean if we have to use them, we do, but we really try not to.

Again, if you're not going to use a fluroquinolone, and you're not going to use a beta lactam, that doesn't leave you a whole lot of options. That then leaves you monotherapy initially with his azithromycin or doxycycline. And when you have comorbidities, and you have resistance rates as high as they are, those are not great options. 

The guidelines really do a nice job of mentioning that in patients with comorbidities monotherapy with azithromycin or monotherapy with doxycycline really may not be a good choice. We don't have a lot of data in those cases, and I think that's where these new treatment options will come in. 

They spent a lot of time in the clinical trials for these newer agents—omadacycline and lefamulin, as an example—really focusing on patients with comorbidities, looking at monotherapy comparing that monotherapy to fluroquinolone and showing that at least their outcomes were no different in phase 3 clinical trials.

That's really where these new treatment options may have that niche is where you don't want to use a fluroquinolone for whatever reason and you can't use a beta lactam, which are the really the standard therapies in the guidelines. These will then have a nice place.

Amanda Balbi: What are clinicians’ concerns about treating atypical pathogens?

Christian Sandrock: Atypical pathogens play a role, usually if we're looking at admitted patients and inpatients, whether it's ICU or non-ICU. Again, the atypical pathogens are not as common unless you're talking about Legionella.

But on the outpatient side, atypical pathogens have a much more of a presence, particularly in the middle-aged to younger individuals, whether it's mycoplasma or chlamydia. I think we have some concerns about those atypicals. When we see our patients, particularly if they're that middle-age younger group, we have no idea per se whether this is mycoplasma or chlamydia, or if it's going to be pneumococcus.

Again, the guidelines don't recommend hunting these down very aggressively. So, in those cases, we're going to treat and cover both agents. If you're going to do monotherapy with doxycycline or macrolides, you're covering atypicals. Same thing if it's a fluroquinolone. If you're doing dual therapy, you're going to start with amoxicillin, we have to add in that atypical coverage.

Again, that's reserved for middle-age and younger individuals who are nonhospitalized. Whether we're talking about mycoplasma, chlamydia, legionella, it’s a different story. If they're hospitalized or older, that's going to play a bigger role. I think there's some concern, but I wouldn't say it's as concerning as pneumococcus or H influenzae coverage that's appropriate.

Amanda Balbi: What financial concerns surround the future of CABP treatment and/or management?

Christian Sandrock: The financial concerns are always a bit tricky. What we want, and one of the cornerstones of treating any infection honestly, is that our patients have access to the antimicrobial that we want to use, particularly if it's on the outpatient side.

We want them to have access to the antimicrobial. That antimicrobial should be administered as soon as possible and has to have a good half-life, good penetration, be available to our patients, and not be onerous for them to have it, again whether it's IV or oral.

Now, the thing that's great is when we look at things like amoxicillin clavulanate or, even to a degree, doxycycline and azithromycin, they're generally generic. Some of the fluroquinolones are generic as well, so they tend to be less expensive for our patients and are often covered by insurance, if they are insured.

The problem is that those agents may not be the ones we chose and what we wanted to use as well, so these newer agents are great. They're fitting some of the holes in areas where we normally didn't want to use a fluroquinolone as monotherapy, for example, and then developing a role.

When you have newer agents, they are priced a little bit differently. They may or may not be covered by insurance. So, I think making sure that we have access to these agents and our patients can get them quickly I think is really key. I think that that's really the important point.

Streamline an avenue where if we choose not to use, for example, an amoxicillin base because of a beta lactam allergy, and we don't want to use fluroquinolone, we just have to make sure that we have easy access to these alternative agents and that our insurance companies, for example, will allow us to do that without having to fill out a tar over multiple days. 

Once you start stretching that antimicrobial out over a few days, now the patient is noncompliant, doesn't have access. That leads to admissions, that leads to failures in therapy, that leads to excess cost, all the stuff we talked about in podcast 1.

I think that's really where the future of our concerns are—just making it easy for our patients to get access to these newer treatments.

Amanda Balbi: In your opinion, what are your concerns (or hopes) for the future of CABP treatment?

Christian Sandrock: A lot of my concerns/hopes—I think they're the same—is that the guidelines are great. The guidelines didn't change a ton between 2007 and 2019. The beautiful thing is that the length of therapy is 5 days. The other beautiful thing is that most of the recommended therapies are largely unchanged, so that's a good thing, and I think that's a really great hope.

I think what lies in the concern there is that the guidelines don't cover every patient we see. And there are certain patients who are going to fall outside of the guidelines. I think my hope for the future is that we make sure we have options readily and easily available for to cover those patients who fall outside of the guidelines. Basically fill that donut hole overall.

I think that's really probably the biggest key. For the most part, our diagnostic options, our length of therapy, recognition of complicated community-acquired pneumonia that needs further workup and prolonged treatment, those of all actually gone really well and work well.

Right now, it's just really around the treatment options of making sure that all of our patients in our clinic and that we see in our practice have access to all of the agents that we want to be able to use. That's always a challenge for all infections that we have, but I think my hope is that we're going to have a nice adequate options that's really going to make our job a lot easier and hopefully at least reduce the burden overall of community-acquired pneumonia.

Amanda Balbi: So, I'm not sure if there are any in development now, but in your opinion, do you feel that the development of new antibiotics could potentially reduce the burden of CABP or any infection?

Christian Sandrock: This is always a great question. If you come up with a newer antimicrobial, is there a way to decrease the burden of that particular disease? The answer to a degree is “yes,” but it depends on what you mean by burden.

If we have a newer antimicrobial, the diagnosis of community-acquired pneumonia may not change. However, if we look at using these agents and they’re oral options, they cover patients with comorbidities, that we have easy access to them, that may make us as physicians and providers feel a little bit more comfortable not admitting a patient or discharging them early, that then decreases the burden, overall. 

I think when we look at the future of decreasing the burden of community-acquired pneumonia, it's again around preventing an admission or sending someone home early from their admission and reducing that access to health care, which we kind of talked about in podcast 1, but it's probably the area where we're going to need a lot of help in reducing that burden.

So, it's really not so much in reducing the amount of cases; that's more around vaccination and prevention. But once we have these newer options, they could really provide us an approved treatment at home on that short course therapy.

Amanda Balbi: Thank you so much for joining us today, Dr Sandrock. And for our listeners, you can find more resources on CABP on Consultant360 and on the page below. Thank you for listening!