Frank LoVecchio, MD, On Outpatient Treatment of CABP

In this podcast, Frank LoVecchio, MD, discusses how treatment of community-acquired bacterial pneumonia is managed in the outpatient setting, and the challenges that come with outpatient management of these patients. This podcast is part 2 of a 3-part series on unmet needs in treatment of 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.



Leigh Precopio:  Hello everyone, and welcome to another installment of Podcast360, your go‑to resource for medical news and clinical updates. I'm your moderator, Leigh Precopio with Consultant360.

Patients with community‑acquired bacterial pneumonia, or CABP, are often treated empirically. Illness severity and mortality prediction scores are utilized to help health care practitioners determine the appropriate site of treatment for each patient. While treatment in the outpatient setting is favorable to requiring hospitalization, outpatient management has challenges of its own. Today we are joined by Frank LoVecchio, MD, to further discuss the treatment of CABP in the outpatient setting.

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 joining me today, Dr LoVecchio. How is treatment managed in the outpatient setting and what are specific challenges in this setting?

Frank LoVecchio, MD:  Treatment in the outpatient setting is always evolving. There's many newer antibiotics out. But if we go with the guidelines, it's a good place to start and you can kind of add on.

One of the things you can ask yourself with your patient that's going to be okay for outpatient therapy. That's based upon maybe your clinical result, their social situation. Maybe you've gone through CURB‑65 or PSI. You should think about the regimens you can give them. Think about the guidelines, they often recommend amoxicillin. I find a lot of us ‑‑ when I say "us" I mean clinicians ‑‑ don't really use amoxicillin. It is more common in other countries, but we usually recommend amoxicillin 1 gram, 3 times a day. The argument that a lot of us say in America is, "Well, we're going to miss atypical pneumonia."

It's true. Amoxicillin won't cover things like Legionella, or Mycoplasm, or Chlamydia pneumoniae. It seems like it's less likely to cause significant harm, with the exception of Legionella. Legionella is more likely to kill you but those patients typically look ill. There's a worry of that, so we usually tend to give something like doxycycline, doxycycline 100, twice a day. There’s a recommendation for it, but it wasn't a strong recommendation because there aren't as many trials with doxycycline. I tend to use doxycycline, but I'm always worried about patients taking it and taking it with calcium product or magnesium product at the same time. So I'm always cautious as to how they take it. I'm also cautious, and I caution them, "You can't go out in the sun”, et cetera. It's going to cause a pretty significant sunburn.

The thing that we often give is macrolides. Many times, people give patients azithromycin. I'm always telling people, or physicians, "Just be aware of what your pneumococcal resistance strain is," because there's a lot of macrolide pneumococcal resistance.

If you do have somebody who's going home and they have comorbidity, you have to crank up the volume a little bit. You could do mono therapy with the respiratory fluoroquinolone. There's only a few left out there ‑‑ levoflaxocin, moxifloxacin, or gemiflaxocin.

Personally, I tend not to use fluoroquinolones if I can avoid it. The reason why is if you have other agents, they might be considered safer. As we've heard and known, fluoroquinolones are commonly associated with QTC prolongation, many drug‑drug interactions, tendon rupture, et cetera. If they have comorbidities, you can use a fluoroquinolone but as 1 agent.

Think about it in the sense that, did I have alternatives? Why am I giving those? Because there is potential for harm there.

Another option for comorbidities is combination therapy with something like amoxicillin, hyaluronic acid and a macrolide. You should add on the cephalosporin and a macrolide, or andoxy.

The way I like to think of it as is you have to give 2 agents. One to cover Strep pneumo really well and one to cover atypical really well. And if you’re not using the mono therapy or fluoroquinolones I'd say think about augmentin and a macrolide, or think about a cephalosporin and a macrolide, or a cephalosporin and doxycycline.

If you ask me what I personally do is I usually give a respiratory fluoroquinolone if the patient can afford it. They're relatively safe. These are oral third generation. And many times I'll give a macrolide with it. For me, that seems like an easier regimen, somewhat cheaper.

If my macrolide resistance is really high, hopefully cephalosporin will help overcome that and will assist in killing the Strep pneumo.

Doxycycline, even though it's generic, it is still someone cost‑prohibitive. Ask people to look and see. The drug prices still might be in the hundreds of dollars.

Leigh Precopio:  Could you discuss the latest updates to the IDSA/ATS guidelines on outpatient management?

Dr LoVecchio:  Ask yourself one question, "Did this patient fall into the category of outpatient pneumonia?" Maybe it's your clinical result, the PSI index, your CURB‑65 and ask yourself, "Are they at risk for MRSA or pseudomonas?"

If they are at risk of 1 of those 2, you’ve got to add on different regimens. We extend the regimens many times for amoxicillin, doxycycline or a macrolide. Of course, paying attention to the fact that you're getting lots of pneumococcal resistance to macrolides and just be aware of that. In general we don't like to use macrolides unless the resistance rate in your community for pneumococcus is less than 25%.

If they have comorbidities, which many patients do, you should do combination therapy with augmentin or cephalosporin and a macrolide or doxycycline. Or you could do mono therapy with a respiratory fluoroquinolone.

There's pros and cons to all the regimens. Personally, I try to avoid the fluoroquinolones if I have an alternative because of some of those side effects of the fluoroquinolones.

Leigh Precopio:  What are some common empiric treatment regimens that health care providers often utilize in the management of CABP?

Dr LoVecchio:  When you treat somebody empirically which often you have to because you don't have cultures back. Even if you do get cultures, sometimes they're not that helpful. You have to think about how severe the patient is. In many cases you should think about if the patient is not severe and going inpatient, many people usually give a beta‑lactam and a macrolide.

Beta-lactam includes things like for example ceftriaxone. Macrolides many times include things like azithromycin.

You don't have to use those regimens but those have become the standard. They're pretty common place. Or they use a respiratory fluoroquinolone. You have to ask yourself, "Do I have to add MRSA coverage?" None of those agents cover MRSA, or certainly not all that well. You also have to ask yourself, "Do I have to add pseudomonas coverage?" If any of those are true, you have to change your antibiotics a little bit to increase the coverage.

When thinking about severe inpatient, again, you probably are with the beta‑lactam and macrolide, or you might give a beta‑lactam and fluoroquinolone. That gets a little bit more into severe category. That gets a little bit more into the person that's going to the ICU or pretty close to the intensive care unit or looking like they might need that.

You think about adding MRSA coverage. For MRSA coverage many people give vancomycin for example. There are some other agents that work well and might be easier later on, that don’t give you trops, et cetera. Don't have the renal issues, et cetera. Agents such as linezolid for example. Ceftaroline for example, which is a respiratory cephalosporin that also covers MSSA.

You should think about adding coverage for a pseudomonas, empirically if they are at risk for that and look relatively ill. Things that you might add, depending on your situation, you might add things like cephalothin for example. You should think about being more aggressive about culturing these folks.

A third option for patients who have contraindications to macrolides or fluoroquinolones, and sometimes combination therapy with beta‑lactam, ampicillin sulbactam, cephalexin, cefazolin, cephalothin, and doxycycline. Remember doxycycline doesn't have as many robust clinical trials, but I think the clinical experience is pretty strong with doxycycline, and we will be using it a lot more.

Leigh Precopio:  Could you discuss patient factors that influence which treatment option is used in the outpatient setting, and for how long?

Dr. LoVecchio:  Obviously, if the patient has been allergic to an agent, you’'re not going to use it. If they bad reaction to a medication in the past, you're not going to use it. The other thing you should realize is if the patient is older, the older you are and the more steroids that you're on, the more likely you are to get a reaction to a fluoroquinolone.

If they're older and they are on fluoroquinolone, they are more likely to develop tendon issues, other issues that may come up. The data is not great but there are some retinal detachment issues, or some precornic issues that have been associated with fluoroquinolone.

I know that the data goes back and forth on those 2, but most people don't argue that fluoroquinolones do have a lot of drug interaction and are associated with tendinopathy, one of the ligament issues.

I also think about all the other agents. If I'm going to give them something like doxycycline, am I worried about the reaction, or the binding with the calcium? Is this patient able to stay away from their regimen of food, et cetera, and calcium so they don't have to take it at the same time with magnesium? Usually, you can accomplish that just with some basic education.

There are some things that I look for. I look for my resistance in the community. Resistance in the community is tough to define because the patients who get cultured and have cultures for community-acquired pneumonia are usually the sicker patients, the ones that get bronchoscopy or in the intensive care unit. It is somewhat of a bias. You're not generally profiling people in the outpatient who are relatively stable unless you're doing it for study purposes. In fact, the guidelines tell you not to do that. Don't culture people in the outpatient.

Leigh Precopio:  Could you briefly discuss how you may have to modify a treatment regimen because of a patient's antibiotic allergy, potential drug interactions, specific exposures, or other patient‑specific factors?

Dr LoVecchio:  When you hear of a patient’s antibiotic allergies there's almost always another choice that you can go with to avoid their allergies. You always want to ask if it's a true allergy or not. We're always worried that if they’re allergic to penicillin, which many people are really not even though they say they are, is there a cross allergy with cephalosporin? That is extremely, extremely low. Unfortunately, a lot of people would avoid the cephalosporin. I think they should not unless it's a true known allergy of cephalosporin.

When you think about potential drug interactions, et cetera. Of the drugs that we mentioned, the main drugs that cause drug interactions are fluoroquinolone, that interacted with cytochrome p450, doxycycline or tetracycline interactions with medications et cetera. that have potassium, or magnesium, calcium, et cetera, where they bind it.

Cephalosporins really are relatively safe with regard to drug‑drug interactions. There aren't many that they have. Sometimes we give linezolid. I think we mentioned that earlier for MRSA or MSSA pneumonia. If you're taking an SSRI or something that increases your net serotonin, perhaps for depression, there is a small potential you can get serotonin syndrome when you add linezolid.

When you think about patient‑specific factors that influence your care ‑‑ travel, age, are all important factors to think about. The older you are, and if you've had multiple vaccines for pneumococcal pneumonia. You still can get pneumococcal pneumonia as there tends to be different strains of it. If throughout their exposures, have they been on an antibiotic in the past? If they've been on an antibiotic, certainly the last 30 days, they are at risk for resistant organ. You should think about increasing the coverage or changing from what they've been on prior.

Leigh Precopio:  Great. We appreciate you taking the time to answer our questions today.

Dr LoVecchio:  All right. Thank you.