Michael Smith, MD (Host): This is Expert Insights with the Carle Foundation Hospital. I'm your host, Dr. Mike. Today, I'm with Dr. Aline Azar. She's the Medical Director of Infectious Disease. We are discussing cellulitis today. Dr. Azar, let's start off with a nice definition of what cellulitis is and why do you think it's important we're talking about this?

Aline Azar, MD: Yeah, for sure. Good morning. So, cellulitis is a common bacterial skin infection that affects the deep dermis and surrounding subcutaneous tissue. It's a very common disease, so it's very important to highlight a few key points. It's reported that over 14 million cases occur annually in the United States.

Personally, I do believe that might be an overestimate because I think physicians do diagnose cellulitis at times lightly. Nevertheless, there is an article published in JAMA back in 2016, that showed that cellulitis accounts for around $3.7 billion in ambulatory care costs and more than 600,000 hospitalizations annually.

So, yes, it's a very common disease and I do believe physicians should be very familiar at diagnosing it and treating it. So thank you for bringing it up today.

Host: Oh, absolutely. I'm glad we're talking about this too. Let's talk about risk factors. Who's at risk for cellulitis? Are some of these risk factors, I guess we could say modifiable, so we could help right there, maybe prevent cellulitis from ever happening?

Aline Azar, MD: Right., right and maybe we can get to that at the end, but I like that question a lot because in an infectious disease world, we always talk about treatment. In cellulits, prevention is a big part of it. So, and also when I'm talking about risk factor, I like to talk about two main thing in cellulitis.

Obviously, we all know the skin serves as a protective barrier preventing the normal skin flora and other pathogens from reaching the subcutaneous tissue and lymphatic system. So when a break in the skin occurs, it allows those normal skin flora and other bacteria to enter into the dermis and subcutaneous tissue, and the introduction of these bacteria would lead to the acute superficial infection called cellulitis.

So any skin break will put the patient at risk of having cellulitis, however, the other comorbidity that comes with that, will put the patient at higher risk of developing the cellulitis. In other words, any breakdown in the skin, you have a skin injury, surgical incision, IV drug user, fissure between toes, athlete foot, bites, other skin conditions like eczema and psoriasis will put the patient at risk of having skin cuts or skin break that will introduce the bacteria down into the dermis and the lymphatic system. But that by itself, if in a young immunocompetent patient, can get rid of the bacteria and develop a good immune response. But unfortunately, when we have comorbidities like poorly controlled diabetes, venous insufficiency, peripheral arterial disease, lymphedema; those will put the patient at higher risk of that simple skin break leading to a simple bacteria sneaking down into real developing a full blown cellulitis.

So, and lymphedema, you see that all the time and you read about it. It's the stagnation of lymph that would prevent a good immune response and limit the clearance of bacteria. So back to your question, when we're talking about risk factor and preventing cellulitis, we're talking about preventing those two big events, the skin breakdown and those comorbidities.

So taking care of your skin, you have bad psoriasis or eczema, skin cuts, abrasion between the toes; taking care of the skin, keeping it clean and moist, is very important. And then furthermore, what's even more important is to address those comorbidities. Well-controlled diabetes, your lymphedema is controlled, the swelling is controlled, the peripheral arterial disease, we can address that. So working on all those points will prevent the cellulitis from happening.

Host: Great information there. I want to move into the role that culturing the wound plays in your workup of a patient with potential cellulitis and also imaging as well. How often are you culturing these wounds and imaging these wounds?

Aline Azar, MD: So not all the cellulitis are related to wound infection. If you do have a wound that can get super infected and develop cellulitis around it, yes, culturing the wound would help.

If you have blisters, yes, culturing those blisters would help, but that's not the majority. The majorities of cellulitis are just simple skin inflammation and infection with no wounds or blisters to culture. So wound culture will not play a major role there. And the same thing applies for blood cultures. Blood cultures are positive in less than 10 percent of the cases of cellulitis.

So in general, you don't really need blood culture when you're diagnosing or treating cellulitis. Unless you're dealing with a severe infection, patient's in septic shock in the ICU, the initial antibiotic therapy that you had picked had failed. This is when we say, okay, maybe we need blood culture to determine if the patient has bacteremia.

Is it an atypical pathogen that we're dealing with? So in general, blood cultures are not always indicated in cellulitis. Cellulitis is a clinical diagnosis. In other words, when you see a unilateral leg that's swollen, red, warm, tender, that's cellulitis.

Do we need imaging to diagnose cellulitis? No. We do imaging like a CT scan or an MRI mainly to rule out other complications that can come with cellulitis. In other words, we want to rule out osteomyelitis or abcess. I'll give you an example. A diabetic foot infection, that with surrounding cellulitis, we do MRI and CT not to diagnose the cellulitis, but to rule out any underlying bone infection or abscess that needs surgical intervention. So imaging per se is not needed to diagnose cellulitis. We do it to rule out other associated underlying problems.

Host: So when you mention that cellulitis is a clinical diagnosis, just for the audience, what you're really saying is you're making the diagnosis off the physical exam and the appearance of the leg for instance, right?

Aline Azar, MD: Correct.

Host: Let's talk about the difference then between dermatitis or maybe some chronic skin changes that people deal with versus cellulitis. How are you determining the difference there?

Aline Azar, MD: Yeah and unfortunately this is a talk so we're not showing a lot of pictures, but I think looking at different patients and pictures will help the most in those cases. But also very good point, because a lot of physicians unfortunately mislabel chronic skin changes and stasis dermatitis with cellulitis.

So the first key point is, when you see someone with both legs being involved, think it's less likely cellulitis. In other words, cellulitis is more a unilateral where one leg is affected instead of two legs. Can we see cellulitis in both legs? Yes, but rarely. It happens in patients with chronic wounds on both legs and they come in sick with superimposed cellulitis on both legs. Yes, it can happen. But, usually it's unilateral. Usually the leg is very red, warm, tender, and swollen.

In stasis dermatitis, it's clearly chronic skin changes where the patient has had the same changes forever, for months and years. The leg is not necessarily tender, nor erythematous. It might be a little bit swollen, might be a little bit warm, but that does not mean it's cellulitis.

So I encourage doctors to just really look up different pictures of what stasis dermatitis looks like and what cellulitis is. That would help the most.

Host: So when we talk about then what's causing it, specifically the microbiology, what bacteria is most consistent with causing cellulitis?

Aline Azar, MD: So cellulitis is most commonly result from infection with group A Strep, group A beta hemolytic Strep, like what we call Strep pyogenes, group A Strep, and, Staph, Staphylococcus aureus. Whether it's the MSSA, the susceptible Staph aureus or the MRSA, the resistant Staph aureus. Those are usually the most common pathogens, what we call gram-positive infection.

That being said, you can have cellulitis secondary to a gram negative bacteria when we're dealing with a wound infection. Diabetic patients with wound, they can be colonized with different bacteria including Staph, Strep, and other gram negative. I'll give you example like E. coli, Pseudomonas. So those are not commonly associated with cellulitis, but in patients with chronic wounds, that can be the case.

But when we're talking about cellulitis, we always think about Strep and Staph. Atypical organism sure can cause cellulitis in specific situation. For instance, patients who have cellulitis after a dog or cat bite. You think about a pathogen called Pasturella, the cellulite is caused after an exposure to water, such, I'll give you an example, like a cut from an oyster shell. Now we're thinking about Vibrio, a different pathogen. I mentioned the gram negative like Pseudomonas in diabetic and immunocompromised patients. So those are specific rare cases, but in general, it's Strep and Staph related.

Host: So let's talk a little bit about the MRSA or MRSA, the methicillin resistant Staph aureus. How often do you see that and how do you specifically diagnose that in a patient?

Aline Azar, MD: Well, unfortunately MRSA prevalence has increased over the years. We think about more MRSA cellulitis in specific risk factor, like we know they're colonized with MRSA. We know that they went in the hospital or at a nursing home for a prolonged period of time recently.

Immunocompromised patient. Those patients we would like to cover for MRSA. Now, if cultures are not available, in other words, I don't have a wound to culture. I don't have a positive blood culture. I don't have blisters to culture. The studies show that there is a good evidence that when we swab the nose and we get the nasal MRSA PCR, the negative predictive value is really high and very helpful.

In other words, you have a patient, you swab their nose with a PCR test to check if they are colonized with MRSA or not. If the PCR is negative, there is a high likelihood that you don't need to cover for MRSA. In other words, there is low risk that this cellulitis is related to MRSA, and you can safely cover with antibiotics targeting the regular Strep and the susceptible Staph aureus, MSSA.

Host: So you've made the diagnosis, as you mentioned, it's a clinical diagnosis, right? Cellulitis is what you're diagnosing in this patient. What are then the best treatment practices that you are directing at the Carle Foundation Hospital?

Aline Azar, MD: Let's say you're a family physician and you see patients with cellulitis, the antibiotics that you would like to go with is targeting Streptococcus species and MSSA, unless you believe the patient do have risk factor for MRSA.

You know they've had MRSA before, you know they've been at a nursing home, they've had recent hospitalization. You would want to cover for MRSA. So, antibiotics wise, if you want to cover for the Strep and regular MSSA, cephalexin, which is the Keflex, 500mg, 4 times a day, would be the drug of choice. The other alternative is called Cefadroxil.

I like it because it's more twice a day, so patients are more compliant with taking, obviously, twice a day antibiotics over 4 times a day. So that would be my drug of choice. If you want a cover for MRSA, a physician can add Bactrim or doxycycline. Interestingly, more studies showed recently that Bactrim and Doxycycline by itself are even good alternative for both the Strep, MSSA, and MRSA. In other words, you don't really need to add Cefadroxil plus Bactrim or Doxy. You can just use Bactrim or Doxy by itself to cover for Staph, including MRSA and Strep.

I do want to highlight one important point. Clindamycin is an antibiotic that's widely used or widely been used for cellulitis and other skin and soft tissue infection. Personally, as an infectious disease expert, I don't recommend using clindamycin for different reasons. One, we all know about the different risk factors, including C. diff from the clindamycin, but what's even more important to highlight is our MRSA, MRSA susceptibility to clindamycin has decreased tremendously over the years, part of it because we've used it so much.

So it's not going to work as good anymore for MRSA. And that's why I want to encourage physician to go away from clindamycin and use more the Bactrim and Doxy, plus or minus Cefadroxil if they need to. Now inpatient, you know, it's technically the same. The only addition that we can use inpatient is that swabbing.

It's easily available. We can get the patient, swab the nose swab and get the nasal MRSA PCR. And if it's negative, we can easily drop the MRSA coverage. So what I encourage my physician here to do is you have a patient coming in with cellulitis, they don't have wound, you're not worried about gram negative infection, you want to target mainly a gram positive.

So you can start with vancomycin if you're worried about MRSA, and that would cover the Strep and the MSSA. Get a nasal MRSA PCR, and if that's negative, you can de-escalate your antibiotics to Cefazolin, which is a first generation cephalosporin, targeting mainly MSSA and Strep and not necessarily needing MRSA coverage.

If you do have wounds, obviously culture that. If you did blood cultures on admission in the ER, and they end up growing MRSA, please cover that MRSA, obviously. But if you don't have any culture data, use the nasal PCR as a good negative predictive value whether you need MRSA coverage or not.

Host: In case somebody is listening to this podcast, Dr. Azar, and they've been diagnosed with cellulitis, maybe let's say they're doing it outpatient, they got the antibiotics, they got that going. How long of a course of treatment are we talking about? Can you give that kind of person some guidance there of how long this is going to take to kill off the infection and really begin to see healing?

Aline Azar, MD: So, it's a misleading, when we say cellulitis gets better overnight, because it does not. And I want the patients and physician to know that it will take days for a cellulitis to improve/resolve, especially if we're dealing with patients with underlying comorbidity like morbidly obese or they have severe lymphedema; cellulitis will take longer than expected. But an immunocompetent patient who is not morbidly obese, who does not have severe lymphedema, on an outpatient basis, develop a simple cellulitis secondary to cut or skin injury; then I would say five days is an average of treatment course. And within 48 to 72 hours, they should see significant improvement on an outpatient basis.

And if that does not happen, this is when we need to take a step back and say, okay, are we really treating cellulitis? Are we treating the right pathogens? Do we need more testing or changing antibiotic scores?

Host: So, to wrap this up, great information, Dr. Azar. I really appreciate this. I know this is going to be helpful to the listening audience. What's your let's just say take home message about cellulitis that you would like people to know?

Aline Azar, MD: I have a lot of take home messages. So one, differentiate cellulitis from stasis dermatitis and chronic skin changes. It's a very, very important. I really want physician to just Google, put pictures, review pictures, because I don't want to over treat stasis dermatitis. I'm an infectious disease doctor. I know we're here to treat and give antibiotics, but I always like to tell patients and physicians that I'm here even more to direct when antibiotics are really needed and avoid them when they're not needed, to avoid all the risk factors that they come with. So one is differentiate stasis dermatitis from cellulitis.

Two, you know, we talked about the antibiotics and when you need MRSA coverage outpatient. Three, use the nasal MRSA PCR for your inpatient. It has a high negative predictive value. Four, you know, recurrence of cellulitis is high. It's been reported in around 14 percent of cases within one year and up to 45 percent within three years.

So tell your patients, once you get cellulitis, you're at high risk of getting it again. Part of it is obviously the comorbidity and the anatomy that we're talking about. And, if I want to emphasize the most, I want to emphasize on prevention. Treatment is, great and you get better, yes, with antibiotics, but if you have those comorbidities, your risk of getting recurrent cellulitis is high, and working on prevention is the most important point here.

If you have dry skin, work on that. If you have bad eczema, work on that. Work on the underlying lymphedema and swelling. If you feel like your patient needs to be referred to a lymphedema clinic or a vascular surgeon to address the underlying venous stasis or peripheral artery disease, please do so.

Obviously controlling the diabetes is very important. We all know the importance of that. So working on prevention is a key. The other take home point that we can address is obviously prophylactic or suppressive antibiotics. I have physicians asking me that.

If you do have someone with recurrent cellulitis that usually improve with simple penicillin or Keflex, which means it's been caused by regular Strep or MSSA, then using suppressive penicillin might be helpful. If you have a patient who develops cellulitis more than three times a year, you know it's Staph or Strep, not really MRSA, then using low dose of penicillin will help.

If you have someone with recurrent MRSA cellulitis, unfortunately, simply prophylactic or suppressive antibiotics is not indicated, but more we talk about decolonization. But yeah, prevention is a key.

And

Host: Gotcha. Listen, this is information. Dr. Azar, thank you so much for coming on the show today. For more information and to get connected with one of our providers, please visit carle.org or for a listing of Carle providers and to view Carle sponsored educational activities, head on over to our website at carleconnect.com. And that wraps up this episode of Expert Insights with the Carle Foundation Hospital. I'm Dr. Mike. Thanks for listening.