Management of Skin and Soft-Tissue Infections: Application of Antimicrobial Stewardship Principles

(upbeat music) – We’re gonna talk about skin soft-tissue infections I have worked with a few companies, although none related to skin soft-tissue infections These are the objectives We wanna describe the opportunities We wanna talk about pathogens And, really the way I’m gonna talk about this, you know, when we talk about skin soft-tissue infections there are things we look at Right? What does it look like? Well, it looks like this What causes that is a really important thing to understand because if we know what it is, or we know what we think it is, and we know what bug it is, we can usually pick the right antibiotics And, then we’re gonna finish off at the end with a bunch of like interesting, weird stuff, and mimics because I’ve been fooled a bunch of times by what I thought were infections which were not This is just some data showing that skin soft-tissue infections are increasing and exceedingly common It’s about three to 5% of all ED visits are due to skin soft-tissue infections There’s a, as you get older, you develop more skin soft-tissue infections And, interestingly, during the summer there are more skin soft-tissue infections The approach we’re gonna take is really gonna be to work our way in from the superficial to the deep Were gonna focus on the microbial epidemiology because if you can sort out the microbial epidemiology you can like look up the drugs, right? I think it’s Strep What covers Strep? Oh, it’s green in the checkbox there I can use that And, then we’re gonna talk about some uncommon things And, then we’re gonna talk about mimics so, there is a real opportunity here This is a study done at Denver General which is a big county hospital in Denver where they looked at about 300 skin soft-tissue infections The culture shows Staph or Strep in 97% in the cultures What I would highlight here is that antimicrobial use covered gram-negative 60 to 80% of the time, and anaerobe 70 to 80% of the time Only a third of people, at best, got gram-positive therapy only Over half got three or more antibiotics And, the median duration of therapy was 10 to 14 days And, when they looked at another set of patients, in an outpatient setting, about half of patients got totally unnecessary antibiotic exposures And, so I think this shows that there’s some real opportunity in skin soft-tissue infections The other thing I really liked about this study was they looked at not only skin soft-tissue infection antibiotic use, but they looked at imaging And, when I’m on service, I see a lot of imaging for skin soft-tissue infections The thing I would point out here is that the overall yield for imaging in skin soft-tissue infection was 4% Which means that we don’t find a lot You know, imaging, it makes sense maybe to do an x-ray If you find something in the x-ray it’s usually a big deal, but most of these other imaging, there’s really not a big role in most patients I see ultrasounds ordered all the time I would say about .3% is about right for ultrasound yield in skin soft-tissue infection It’s pretty much useless And, so I think there’s real opportunities, not only for antibiotics One of the things I often talk about is syndromic antibiotic stewardship Antibiotic stewardship focused around an infectious syndrome, which is kinda what we’re talking about here today And, that’s where there’s a lot of opportunity, not just to improve antibiotic use, but Dr. Roab talked about prevention We can talk about imaging, diagnostic use There’s just a lot of opportunities around not just antibiotic use This is a study from the dermatologists who, you know, I think one wanted to show their value, but two also wanted to show you the problem that we have with diagnosing cellulitis They looked at 260 cases of cellulitis, and a third of them weren’t cellulitis A lot of vascular disorders, other inflammatory things, and what they found was that about half of those people who didn’t have cellulitis, didn’t even need to be admitted to the hospital And, when they extrapolated that out for cost, they found it’s probably about 50 to 130 unnecessary hospitalizations per year in the US, with lots of extra money, and lots of extra nosocomial infections caused by admitting all those people to the hospital, and giving them antibiotics when they don’t need it And, so these are sort of my principles of skin soft-tissue infection treatment And, these are important to think through when you’re looking at a skin soft-tissue infection And, these are kinda how I think through things Being a good steward is really about being a good clinician So, the first question is, is it an infection? And, you might say well that’s really easy I’ve been fooled many times It’s actually not that easy to look at something Sometimes it’s really easy I saw a guy with cellulitis yesterday It was really obvious he had cellulitis But, I’ve seen a lot of skin ulcers, and wounds that I’ve looked at and said, ahhh, I don’t know Is that infected? But, it’s a really important question because if it’s not an infection, giving antibiotics clearly aren’t going to make it better Next, based on the appearance, what sort of skin soft-tissue infection is it?

Rather than classifying as community onset, hospital onset, you know, COPD exacerbation We look at a skin infection and say it looks like an abcess, it looks like a cellulitis Then, we have to say based on what I see, what bacteria do I expect? Based on what it looks like, we can usually make a pretty good guess as to the microbial etiology But, we need to factor in a few things like Dr. Rupp talked about Are there exposures that might suggest an unusual pathogen? Something has happened that makes me think it might be some other bug than the typical ones Or, what’s the immune status, or something with the patient that makes me think it might be a different pathogen I’m gonna show you a few examples at the end And, then last, how bad is it? Right? Is it like so bad you’re like why did you come to clinic even to show this to me, or is it like call the surgeon right now, we have to do something And, that again, is gonna influence our antibiotic decisions So, let’s work through some of these pathogens First, impetigo You’ve probably, a lot of you have seen impetigo, Staph and Strep, it starts as a macule, then progresses to a pustule, but eventually ends up in the honey colored crust here, which is usually what we see It’s painless You use topical therapy to cover Staph Mupirocin, Retapamulin If people aren’t getting better, or it’s really severe, like this bullous impetigo which I’m showing you here in this larger picture, then you’re gonna wanna use oral antibiotics again targeting Staph and Strep, to as a concern for MRSA you might use Clinda, or maybe add some Doxy or Bactrim If it’s this bad, you might think about doing a culture as well, but usually you don’t need to do cultures in these Folliculitis You’ve all see inflamed hair follicles These are often bacterial, although if you were to culture them, it would grow something like skin floras, which our lab will tell you, rarely they’d say Staph aureus There is something called hot tub folliculitis, so it’s hot tub use It’s caused by Pseudomonas, it’s self-limited, it goes away Usually you don’t need to do much with these Some warm compresses Maybe some topical antibiotics If they aren’t getting better you might think about culturing them because occasionally dermatophytes can cause them, although there are a lot of things that can cause folliculitis as well Erysipelas You know, in infectious disease, you get infections that you kinda think are fun I kinda think erysipelas is kinda cool Has a very characteristic, clinical appearance It’s an infection to the upper dermis and the lymphatics It’s well demarcated, and that’s the thing that really sets it apart You can see, and you can literally feel the edge of the infection In this gentleman’s face, you can feel the step off where the infection ended As opposed to cellulitis, we’ll look at it’s sort of vague and indistinct where the infection ends People with erysipelas are usually systemically ill They often are young or old It’s often in people who have lymphedema And, this is almost exclusively caused by beta-hemolytic Strep And, when we have beta-hemolytic Strep we know they’re susceptible to beta-lactams, and we can use penicillins, and early generation cephalosporins to treat them And, five to seven days is really about all you need Skin abscesses You’ve probably all seen skin abscesses So, I do have to warn you there are some gross pictures at the end You couldn’t do a skin soft-tissue infection talk without some gross pictures So, they usually start in areas where there’s hair follicles, there’s inflammation, this develops and turns into an abscess in the subcutaneous tissue If you have one it’s called a furuncle If you have multiple it’s called a carbuncle They’re typically in areas where there’s hair and friction So, neck, buttocks, face, axillae There’s perioral straining This is a pathologic picture where there’s a lot of inflammatory cells sort of inside this capsule Multiple ones in the back of the neck This is a carbuncle with numerous draining sinus tracts What do you need to do with these? Well, you need to drain them But, you also need to think about the epidemiology You know? And, so this is pus Right? And, so when I see pus, I think Staph aureus And, that’s what you should think Now, when you see pus and think Staph aureus, you have to think is it MRSA or MSSA? This is some older literature, but I think it still holds to These are perioral and skin lesions cultures in the ED 60% of them were MRSA Almost 20% of them were MSSA Meaning that about 80% of all the pus in skin lesions in the ED is due to Staph aureus And, a lot of that is MRSA And, so knowing that, that adjusts how we think about therapy These are painful, they’re tender Obesity, steroids, diabetes are risk factors We talked about MRSA My opinion on cultures is usually you don’t need them If they’re so bad they’re coming in the hospital, I think it’s reasonable to get a culture If it’s a weird place, you know, perirectal, other places like that, you might think about other pathogens The key treatment for these, incision and drainage Right? It’s not even antibiotics The most important thing you’re gonna do is incise and drain these If they’re very small, you might get away with some moist heat Carbuncles you’ll never get away with that, you have to surgically debride them What is the role of antibiotics? I’ll tell you this is an area where my practice has changed in the last couple of years

As have our guidelines So, three years ago I used to have this slide in my talk Three randomized trials, looking at the use of antibiotics in skin abscesses, showing no improvement in clinical cure with antibiotics Although I’ll tell you this, KEFLEX study was basically double placebo study because it was about 80% MRSA There was maybe a suggestion of decreased recurrence of Bactrim And, so there are actually two large trials funded to look at the use of antibiotics in skin soft-tissue infections And, what they found is actually both of them showed improved clinical cure with use of antibiotics The first trial was in people over 12 They had to have a lesion of at least two centimeters, and they got other placebo They all got drainage, and then they got placebo or Bactrim Increased clinical cure And, actually decreased subsequent infections Decreased infections in household members in people who got antibiotics This other trial randomized people, the placebo Bactrim or Clindamycin, and they saw basically increased clinical cure with either antibiotic A little better decrease in subsequent infections with Clinda, but way more diarrhea with Clinda, about twice the rate of diarrhea And, so my take from this, and our guidelines changed, to say boy, you know, if you have a skin abscess you probably do benefit from antibiotics And, so while incision and drainage is the primary therapy, most people are gonna benefit from antibiotics, particularly when there’s multiple lesions, anything over two centimeters If it’s smaller it’s sort of risk versus benefit What’s the patient? Immunocompromised Anything in a sensitive area Anything that’s getting worse And, when you pick an agent, you need to pick something that’s active against MRSA, unless you know it’s not MRSA And, so to me, that means Bactrim, doxycycline, minocycline, you certainly could use linezolid, it’s more expensive, or tedizolid, or, you know, delafloxacin which is way more expensive which we’re not gonna talk about, but I’m not sure why you would But, that’s just a personal opinion We’ll talk about the role of clinda here in a little bit And, if it’s really bad you’re gonna use your IV anti-MRSA agents And, again, five to seven days is all that you really need What about clindamycin? I’m just gonna show you are antibiograms susceptibility in Staph aureus to clindamycin? You know, it’s in the low 80’s I think these last two years we’ve changed our methods, it’s a little lower, but it’s not above 80% And, so there is increasing resistance to clindamycin, and so that’s why having those antibiograms is very useful But, know that Staph aureus has increasing resistance to clindamycin The other thing you should know about clindamycin, there’s a lot more diarrhea Probably two to three times the rate of any other antibiotic you’re gonna give, and the rate of C. diff is higher And, so I’m not a big personal fan, but that’s just an opinion All right Cellulitis Very common It involves the deeper dermis and subcutaneous tissues Painful, tender, swelling It’s not elevated The borders are very indistinct You often have systemic symptoms You may have this lymphangitis streaking, pretty characteristic from Streptococci And, the etiology of this infection is almost exclusively Streptococcal But, it’s really hard to know the etiology of cellulitis because we get blood cultures, and they’re positive in like one to 2% of people And, people have tried lots of different ways to diagnose this Be it, you know, biopsies, eluting culture aspirates, and skin swabs, and there was a study of PCR, all of which have been really unfruitful And, so I do wanna show you one study that looked at this This is a prospective study of nonculturable cellulitis No pus present And, what they did was they wanted to find out what percent were due to beta-hemolytic Strep And, they found using Strep serologies and blood cultures, that about 73% were clearly beta-hemolytic Strep The problem with Streptococcal serology is you gotta like do them when they present, and do them four weeks later, and so that’s not very useful as a clinician, right? But, as somebody who wants to sort of sort out on the back end what percent were due to Strep, it’s somewhat useful They treated most of the patients with beta-lactam, and had a 96% response rate to beta-lactams And, in those patients who tested negative for Strep, they had a 91% response rate to beta-lactams, that being Ancef, cefazolin, narrow spectrum beta-lactam And, so their conclusion was, boy cellulitis, non purulent cellulitis, it’s due to beta-hemolytic Strep There’s a second study from Scandinavia that replicated that very similar And, so the recommendation is for cellulitis we use first generation cephalosporins, or anti-Staphylococcal penicillins, either IV or oral The guidelines would recommend five to seven days If people don’t respond, well you could treat them, but I’ll tell you this paper from 2016 is a really interesting paper The factors that influence response to treatment had nothing to do with antibiotics They were all patient factors And, so their lack of response at day one or day three, didn’t have anything to do with whether you picked the right antibiotic or not, it was really if whether they had lymphedema, how long they’d had symptoms,

what their sex was, what their BMI was Couple questions about cellulitis Should we add anti-MRSA therapy for cellulitis? Should we add Bactrim to our beta-lactam? Our guidelines used to recommend that They do not anymore There have been two randomized trials looking at the addition of Bactrim to a beta-lactam in cellulitis Both of which showed no improvement in clinical cure rate Absolutely none Actually, no difference in adverse events either So, we’re not really hurting, but boy we really aren’t helping And, so I would not add an anti-MRSA agent to a beta-lactam for cellulitis What about clindamycin? There have been some studies suggested maybe including clindamycin helps you get better faster This was a randomized trial that looked at this where they had beta-lactam plus clindamycin in nonculturable cellulitis, and their outcome was improvement at day five because that’s a thought as maybe clindamycin makes people better faster The answer was in this study, which was randomized, it did not It did improve diarrhea, though You want more diarrhea? Again, clindamycin, more diarrhea So, again, I don’t add clindamycin In typical cellulitis cases, doesn’t look like it has benefits So, to summarize, non-purulent cellulitis we treat for Strep using a beta-lactam In our very large patients, or lots of lymphedema patients, it’s reasonable to go with very high doses because it is hard to get the drugs into the tissue If they have an abscess, you must drain it, but most people need antibiotics, and generally you’re gonna treat for MRSA, which means Bactrim, or doxy/minocycline, maybe clindamycin, it will work but it has some downsides, and then for severe you got your Vancos Complicated infections which I’m not gonna talk a lot about, burns, wounds, et cetera, generally we treat those like purulent infections because Staph aureus is a common cause of those complicated infections So, in that whole talk, I’ve not mentioned a single gram-negative, or a single anaerobe, and I will tell you I see lots of people admitted to my hospital who get vanco and cefepime, or vanco and Zosyn, for their cellulitis with sepsis When should we cover with gram-negatives? There are situations where we should use anti-gram-negative therapy One of them is diabetic foot infection, but not all diabetic foot infections Generally, from mild to moderate diabetic foot infections it’s Staph and Strep For our severe, you know, my toe is black and necrotic, okay that’s where we need gram-negative therapy, that’s where we need anti-anaerobic therapy We can often use oral therapy in these patients once we’ve sort of sorted through this disaster How long we treat really depends on a host of factors like what debridement did we do, was there underlying osteo, how is the foot doing? I’ll just point out some data that one of our fellows collected He looked at diabetic foot infections at our institution, and looked at the culture data 30% of our diabetic foot infections had a surface swab which is actually recommended not to be done in the guidelines But, they say don’t do a swab because it will grow a whole bunch of bacteria that don’t bear any relation to what’s actually causing the infection Only about 57% actually had a surgical debridement with tissue cultures, but when we did that, this is what we found Beta-hemolytic Strep, MSSA, Strep viridans, only 10% MRSA, and only 2% Pseudomonas And, so we looked at what percent got anti-MRSA therapy, it was 90%, and 80% got anti-pseudomonal therapy related to the percent who actually had those pathogens Very out of proportion there And, so we revised our diabetic foot infection guidelines to sort of help people figure out what’s mild, moderate, and severe And, so for mild we’re recommending anti-Staphylococcal and Streptococcal therapy, and if they have a history of MRSA you might wanna cover for MRSA That’s sort of our rule If you’ve had MRSA before in your foot it’s probably reasonable to treat for MRSA in your foot I point out in our severe recommendation with therapy is ceftriaxone plus metronidazole It’s not Zosyn, although I wouldn’t say that’s a terrible choice, but it’s not generally Zosyn, it’s not, you know, cefepime, unless you have sort of water exposure, or a history of Pseudomonas And, so it’s just not a very common pathogen And, so we’ve really tried to change our guidelines We changed our order sets Here’s another situation you might use anti-gram-negative therapy, necrotizing fasciitis, right? Can be mixed, or monomicrobial by Strep pyogenes, could be clostridial These are infections where when you see them you want broad spectrum covering MRSA, covering gram-negatives, covering anaerobes until you know differently Surgical debridement, again, is the key you need to go from here to here when there’s lots of infection and then narrow it down These adjunctive therapies I think are not very useful Surgical site infection This actually our most costly nosocomial infection because there are a lot of surgeries that go on

even though it’s only a small percent that get infected Pretty obvious there’s pain, swelling, drainage at the wound site How do you treat these? Often opening the wound is all that’s needed for the mild ones Open the wound, pack it, it’ll often get better on its own The guidelines recommend if people have fever, significant surrounding erythema, signs of systemic infection, then you should use an antibiotic, and I think if you’re gonna use an antibiotic, in this case it’s reasonable to get a culture The antibiotic you use depends on what the surgery was If it’s a clean site, trunk, head, neck, something like that, Staph and Strep are your bug, and so you’re gonna use antibiotics for that If it’s a contaminated site, GI site, female genital tract, oropharynx, then you wanna cover gram-positive, gram-negatives, anaerobes those are the bacteria that are encountered at the surgical wound All right, we’ll finish off with about five minutes of fun stuff So, which animal bite is most likely to get infected? Is it a dog, a cat, a human, a zombie, or a chupacabra? So, right, I think most people would say zombie It’s like 100% of people bitten by zombies turn into zombies, there is no prophylaxis If you were to look at actual animals that exist it’s actually human followed by cat followed by dog which is way down there Human bites are the most likely to get infected There’s a whole host of bacteria in our mouths Strep, Staph, anaerobes We always prophylax human bites, or human mouth wounds for three to five days with Augmentin For animals, cats much more likely to get infected I just saw a guy who was admitted to the hospital with a cat bite yesterday Pasteurella is the bacteria you always think about, but there’s Staph and Strep and other things When do you need prophylaxis? Anything deep That’s why cats often need it because they have very sharp teeth that are small that can puncture deep Anything that is bad on the hand or genitals, something sensitive, or immunocompromised patient But, again it’s easy, it’s amox/clav Easy to remember All right Some final fun things This is where we talk about unusual exposures So, a 56 year-old guy, chronic Hep C, severe cellulitis of his left leg, and septic shock He just came back from the Gulf Coast where he scraped his leg on the sea wall while swimming So, what’s he got? It’s a classic medicine board question So, he’s got Vibrio vulnificus which causes severe necrotizing infections associated with salt water 44 year old guy presents with infection of left knee laceration, he cut it while swimming in a local Iowa lake, is infection’s really bad, and progressing rapidly The last one you probably wouldn’t see This guy I have seen This is not his knee, but I did see this So, it’s a water associated bacteria, this is Aeromonas So, also associated with leech therapy You probably don’t see a lot of that This is a gal I saw in clinic 28 year-old female from Mexico She had progressive skin lesions over the last three to six months They were non-tender, she said maybe my dad had something similar in Mexico, she had these nodules in her arms, you could also, on her legs, you could also feel them on her arms, her face, she otherwise looked pretty well She hadn’t been visiting any nail salons to give you a hint So this is a mycobacterial infection, she had a skin biopsy which was swimming with acid-fast bacilli, and she had lepromatous leprosy Which is a skin infection, right? Showed up in my clinic here So, this is 28 year-old guy, who recently came back from Iraq, he has multiple skin lesions like this, he’s gotten a bunch of antibiotics, they aren’t getting better He’s not really sick, they’re not really tender Saw this guy in my VA clinic So, he has, this is what the biopsy would show He has cutaneous leishmaniasis, right? And, so again, we talked about a good history Well, I spent the last four months in Iraq Oh, well, hmmmm Maybe this isn’t a bacterial infection So, this was another patient I saw 37 year-old non-breastfeeding female She presented with bilateral breast infections that weren’t getting better despite antibiotics to treat Staph So, again, we took a little bit of history, and she admitted to injecting IV drugs into her breast veins, and so she had a Mycobacterium fortuitum infection This gentleman was up in our bone marrow unit, had been neutropenic for 23 days, and developed this progressive black lesion on his forearm So, progressive black lesions, in people who don’t have neutrophils are always bad, so he had mucormycosis, and had to have a big wide tissue debridement All right Finish off with a mimic This won’t take long Patient admitted two days ago for community acquired pneumonia Now we’re called to see her for left deltoid cellulitis She has a painful, red, hot, swollen left deltoid I asked one question and made the diagnosis Did you get a flu shot? And, she said oh yeah, they gave that to me yesterday Okay, well this is not deltoid cellulitis, it’s a flu vaccine reaction But, they had her on antibiotics for cellulitis This was a patient with chronic liver and kidney disease She came in

These lesions had been progressive over the last three weeks She otherwise looked okay, but these are pretty tender and sore They were very firm, very hard So, she has calciphylaxis due to renal failure Also doesn’t get better with antibiotics This patient had a high white count, a high fever, left shift, high eosinophil, they had this blanching rash This is a drug reaction due to allopurinol This patient had pain, swelling, redness at a peripheral IV Thrombophlebitis, right? This patient has a right leg that’s swollen after coming back from a trip They have a DVT This patient was referred for recalcitrant cellulitis that nobody could make better He looked all right It was kinda painful, kinda red, didn’t have a fever, CRP was normal That’s his leg I lifted it up above his heart, and it suddenly went away This is dependent rubor This is probably a quarter of the patients I see for refractory cellulitis Bilateral cellulitis? Venous stasis, right? And, then this last one, patient with a rash, he’d had lots of antibiotics, super painful, indurated and tender, didn’t get better with elevation He had something I’d never heard of Lipodermatosclerosis Which is a fibrosing panniculitis due to chronic venous stasis that looks like cellulitis, but ain’t So, it’s a dermatologic condition There are lots of other things that can cause and look like infections, but aren’t And, so I’d encourage you to be familiar with those as well So, these are my conclusions We make a lot of misdiagnoses We can improve our antibiotics You guys can see what we should do with our antibiotics Think about patient factors, and then mimics when you’re looking at these With that I will stop (audience applauding) (upbeat music)