 Good morning. Welcome to Grand Rounds. Thanks for coming. I see some new faces. I know we have some visiting medical students and some of the new path fellows are here. But a great presentation this morning by Dr. Jim Bell. He's one of the interns and currently on rotation with us at the VA. He's done a fantastic job. It's a job that goes, it's kind of a thankless job. It's invaluable to us as chiefs. Absolutely invaluable. He does so much and he does a really good job at it. He comes from us from, I'm going to say this wrong, Louisville or Louisville. You have to ask him to say it. It's pretty how he says it. He's going to be talking to us today about orbital cellulitis and the topic title is a stagnant diagnosis or an evolving disease. Thanks, Snow. I actually, on my drive in this morning, I heard she thinks my track is sexy on the radio and it made me think of high school dances. So anyway, I am the intern on the service right now at the VA and one of the jobs of the intern over there is to help with all the consults at the VA and to help with all of the buddy call with residents on Friday afternoon or Friday evening and then Saturday during the day and one of the common consults that we got seemed pretty common to me was to help rule in or out orbital cellulitis and also to help come up with a treatment regimen if it was ruled in. So I thought it was an appropriate disease to talk a little bit about today and I thought we'd start with a case that we saw early on. So one Saturday when we were over at primary Children's, we got called about a patient who was in the emergency department and he was a five year old boy came in with periorvital swelling in erythema, ocular pain, all of this on the right eye. He had a red eye as well. Weeks before he came in, he'd wrecked his bike and ended up with a black eye, but it had resolved before his presentation. It was back to normal, at least in appearance before he ended up with this new swelling and he didn't have any other significant past medical or ocular history other than this black eye. He was a pretty healthy little boy. So his vital signs when he first came in were a blood pressure of 106 over 53, heart rate 118, respiratory rate 26, and he had a fever of 40.4 degrees Celsius. Physical exam also all on the right. He had an injected conge pain with ocular movements, erythematous and endometous lids, and he had a few labs that were important. He had a leukocytosis, a white count of 15.7, and a CRP when he first came in was 5.9. It increased to 7.1 by the following morning. Blood cultures were drawn. They didn't actually end up growing any organisms at any point in time. And a CT of his orbit showed tissue swelling within his orbits along with Aaron, the orbits on the right. So as you can probably guess from the title of my talk, he was diagnosed with orbital cellulitis. And this was all prior to when we actually met the patient. He was admitted to the hospital, started on some antibiotics, which were changed around and he ended up on seftriaxone and clindamycin. He then developed an allergic, what was thought to be an allergic reaction because he had throat swelling and a rash that developed. And he was switched to urtipenem, according to the infectious disease team's wrecks. And he got better and was discharged to home with urtipenem via a pick line. And that's not the end of his story. I'll leave you with a cliffhanger because we actually met him later on, but we'll come back to that later. So a couple of definitions most in this room are probably familiar with preceptile cellulitis is the inflammation of the tissue anterior to the orbital septum. And orbital cellulitis is inflammation of the fatty tissue and muscles within the orbit. And there's a whole spectrum of severity with these diseases. On initial presentation, they can look really similar. And even some forms of conjunctivitis can look similar as well. But it's really important to distinguish them early on because the consequences of these diseases and the treatment regimens are really different. So right from the start, it's good to have a strong idea of what you're dealing with. And further, further physical exam and imaging help make this possible. So the origin of the infections is different. Usually preceptile cellulitis occurs because of a break in the skin barrier and then orbital cellulitis often is associated with some form of sinusitis. And out of the perinazle sinuses, the ethmoid sinuses are the most commonly involved. Orbital cellulitis can come from lots of other associated infections as well, erycephalus, sympathigo, adontogenic infections, septic thrombophlebitis, penetrating trauma to cross the stylus, and then retrograde flow through orbital veins or some of them more common than a lot of others. It has a lot to do with the anatomy of the area involved. The lamina paparacea is the most thin portion of the medial wall of the orbit. It's also the lateral border of the ethmoid air cells. So it would make sense that ethmoid sinusitis is the most common form of sinusitis associated with orbital cellulitis that's got lots of natural bony defects. So debris can just go back and forth between those two spaces. Orbital veins are also important and interesting because they actually don't have any valves. So it's easy for an infection to spread in either direction along those veins. And unfortunately, they kind of act as a highway to the cavernous sinus. So that's an important aspect of this disease as well. Jane and Rubin wrote a series of papers where they sort of classified a spectrum of orbital cellulitis and within that spectrum, they included preceptile cellulitis is sort of the least severe form they also bumped up to orbital cellulitis with or without intracranial complications and then orbital abscess with or without intracranial complications and that can be subdivided into a subperiosteal abscess or a true orbital abscess. So to start with, they're least severe form of the disease, preceptile cellulitis, the patient can present with edema, erythema, pain, leukocytosis. And so this can be really scary for the patient, as you can see in that picture can have quite a devastating look to it. But if you press a little further, the patient should be able to move their eyes without any extra pain, they shouldn't have any proptosis and their vision shouldn't be affected by this disease. If any of those are present, it should raise some red flags. But if they're if all those findings are absent, those are all good signs. The infection isn't limited to the orbit, so it's fairly easy for it to extend along the skin of the face, get to areas such as the cheeks, other things to consider are adenoviral conjunctivitis and things like contact dermatitis. But this is not a life threatening disease. It's really scary for the patient, like I mentioned, it's often caused by strep pneumo or staph aureus, which would make sense because it's associated with breaks in the skin barrier a lot of the time. And because it's often caused by those common organisms and not often life threatening, it can usually be treated on an out patient basis with oral antibiotics like a moxosome clavulinator. And the recovery is usually quick and dramatic. And by that, I mean, within a couple days, the patient should notice a difference in how they feel on their appearance. And if they don't, then it might be time to rethink things. Orbital cellulitis, on the other hand, is quite different. It can lead to blindness, cavernous sinus, thrombosis, meningitis, epidural, subdural abscess and brain abscess and any of those, or some of those can lead to death even. So it's not something that you want to get mixed up right off the bat. It's good to distinguish between the two diseases right away. Unfortunately, like preceptile cellulitis, orbital cellulitis presents with a lot of the same things. The patient can come in with the edema, hyperemia, pain, leukocytosis, and the appearance, as you can see in this picture, it's not necessarily on initial exam. More severe looking than the preceptile cellulitis. They can look pretty similar right off the bat. But if you press a little further, if the patient does have any of the things we talked about before, like proptosis, if they can't move their eye in a certain direction, if they have extra pain with eye movement, or if their vision is compromised, or they have an APD, again, those are red flags to be raised because something else may be going on. So just to go through a typical presentation of a patient with orbital cellulitis, there was this 68 year old gentleman, history of prostate cancer and hypertension, otherwise a really healthy patient came in with a day of right upper lid edema and right eye pain and proptosis, and restricted lateral gaze with his right eye. So so far, seems pretty much like orbital cellulitis. We'll talk a little bit more about imaging for diagnosis of this disease later, but a CT of his orbits showed a preceptile inflammation with a sub periosteal collection over the right lateral orbital wall. So the arrows kind of pointed out here. So a pretty large collection there. So they thought it was an abscess and he was admitted and started on broad spectrum antibiotics, which should have been adequate to cover whatever was causing this infection, but he didn't actually improve in 48 hours. So they took him to the operating room. This collection was drained. And it actually didn't show anything growing, but it did show metastatic prostate cancer. So that just sort of throws out the key point that even though it looks and smells like orbital cellulitis, that might not actually be what the patient has. And it's important to keep a good differential on board like it is with all diseases. They pressed a little further with the history and got in touch with this oncologist and found out that he'd had a prostatectomy and received chemotherapy years prior and had been in remission. But unfortunately, it obviously recurred. So he was started on oral corticosteroids, which helped his ocular symptoms resolve. And he was discharged, followed up with his oncologist and unfortunately passed away eight months later. So it is important to remember that other diseases could be causing these same symptoms. Examples of this are things like sarcoidosis tumors like leukemia, lymphoma and retinoblastoma, thyroid disease and also trauma. So if a patient's on what you would consider proper treatment coverage, and they're not getting any better, it might be time to rethink what might actually be going on. So labs can be helpful with this disease as well. A CBC like our patient had can show leukocytosis, but it's not necessary. It's more common in orbital cellulitis than it is in preceptile cellulitis, but it doesn't rule in or out either disease. Blood cultures can be real helpful. But unfortunately, most of the time they're not. They don't come back positive. One large study I read showed that they're positive in about a third of children less than four years old. This number seemed pretty high compared to a lot of the other smaller chart reviews that I was reading. But those reviews also included older patients. So I think that had an effect on their numbers. Just 5% of adults with orbital cellulitis will actually have a positive blood culture though. So it's not positive often, but when it is positive, it's helpful in determining a treatment regimen. Cerebral spinal fluid analysis can also be helpful, but it's not typically a lab that you would order on these patients. Usually you would just get it if the patient has bilateral disease or central nervous system involvement. Otherwise, it's usually not not a good lab to get. Imaging is one of the mainstay mainstays of diagnosis for this disease. CT with contrast is the test of choice. It's best for determining the presence of an associated sinusitis that can help distinguish between preceptal and orbital cellulitis. It can also help classify and determine if an abscess is present and also if there's any central nervous system involvement. So CT is the test of choice. Interestingly, ultrasound actually has a higher resolution. It just doesn't give you any idea of what's going on in the posterior third of the orbit, which is why it's not the first choice of tests. In MRIs, it's generally thought to be more helpful for cavernous sinus thrombosis than it is for orbital cellulitis. Imaging, so this is just an example of a CT with an abscess. I thought it was a cool picture. But it's a fungal subperiosteal abscess that's sort of eaten through the wall of the medial orbit or the medial wall of the left or the right of the left orbit. So pathogens that are commonly involved with orbital cellulitis include strep pneumo and staph aureus, but not far behind them are other species of strep, non-typeable H flu, and non-spoir forming anaerobes. Unfortunately, you cannot really predict the organism based on the symptoms of the patient. They can all present with the symptoms we talked about earlier. But you can make a guess and the older the patient is, the more likely it is that they're going to be more than one organism involved. And also, the more likely anaerobes are going to be involved as well. So one of the things I wanted to talk a little bit about today was how this disease, its management, its diagnosis might be changing now as compared to before. And I'll talk a little bit more about more recent changes later on, but sort of a big seismic shift from what I understood in the literature was that before 1985, H flu was actually pretty common as a culprit for this disease. And so this wonderful vaccination came out and changed all that. A lot of people at one point in time considered that lumbar punctures were something that should be gotten if you were concerned about orbital cellulitis. As I mentioned earlier, now they're more often just gotten if there's actually central nervous system involvement. But before it was really part of the mainstay of diagnosis. So this vaccination really changed the way this disease was approached. Orbital cellulitis treatment should be started before the organisms identified. As I mentioned earlier, the chances of a blood culture coming back positive are not good. So it's better to just start broad spectrum antibiotics early on. The antibiotics should cover strep pneumo, staph aureus, and other strep species. So the big ones that I mentioned, but it can also cover gram negative organisms and anaerobes, if you think the patient has a high likelihood of having those involved in the infection. And it should be IV for at least three days or until the symptoms are improving. For seven days of bacteremia was actually present. So more specifically, naphthalene is good for covering gram positives. It was recommended. Clindamycin for anaerobes and sephataxine for gram negatives and resistant gram positives. Some authors argue that seftriaxone was usually sufficient for patients under nine years old. But a lot of times, clindamycin is included, especially if the patient's older than nine, because then you have a bigger chance of anaerobic involvement and seftriaxone won't be sufficient in those cases. Fankamycin is suggested if the patient has a penicillin allergy. And then tyrosilin, clavulane, ampicillin, solbactam, and pipericillin, tazobactam, or commonly is just because they cover so many different organisms. Nasal decongestants are often thrown in as well because they can help the patient train their sinuses if there is an associated sinusitis with the orbital cellulitis. So I've talked about the medical management of this disease, but there's a big surgical component as well. But the patients don't always need surgery. So there are specific indications for taking a patient to the operating room. One of them is if there's optic nerve or renal compromise due to a mass effect. Sometimes in these cases, cantholysis or canthotomy are needed right away. But even if those are performed, the patient is probably still going to need to be taken to the operating room for actual drainage of the abscess. Severe pain to the abscess is also a possible indication for surgery. And then worsening of vision or extraocular motility after 48 hours of antibiotics. We saw this in the patient that I talked about earlier. He was on what was considered proper treatment, but he didn't get any better and it turned out he didn't even have orbital cellulitis. Other ways that this could possibly be helpful is if the antibiotics you have the patient on are not adequately covering the organism involved and if there's an abscess that the antibiotics just aren't penetrating. So any of those is a good reason to take the patient to the operating room. It has been found that serial CTs over the first one or two days really aren't very helpful. The patient might be improving clinically, but the images won't show much of a difference. So if you do want repeat imaging, it usually won't show too much of a difference unless you wait more than a couple days. So I mentioned that not every patient always needs to be taken to the OR. Some authors actually argue that that's true, but most seem to believe that like all surgeries, abscess drainage has its inherent risks and some patients will get better without needing the operating room, so it's best to let them improve with just antibiotics. There are risks with the surgery like seeding of infection elsewhere, start starting a new infection that wasn't there to begin with. It is a general role younger patients tend to respond better to just antibiotics without surgical intervention. But the BCSC provides sort of a list of criteria for at least strongly considering the operating room. So if a patient has any of the following, if they're older than nine years old, if they have frontal sinusitis, a non-medial location in the abscess, a large abscess, anaerobic infection or dental infection as well, which are related, or evidence that chronic sinusitis or optic nerve were compromised. Those are all strong reasons to consider taking the patient to the operating room. So I'm going to switch gears here a little bit and talk a little more about how this disease might be changing now. You hear a lot about MRSA in the news but also in the medical literature. The infectious disease doctors at the university actually have made an argument that it should be considered a separate organism all together from MSSA because it's gotten to where it's not only resistant to different antibiotics but it behaves in a different fashion, especially the community acquired version of the disease. It's much more aggressive and even with proper antibiotic coverage, it might take a few operating room trips for abscess drainage for infections other than orbital cellulitis before the disease is finally controlled. So I was wondering how it was affecting these particular diseases preceptile and orbital cellulitis and if there were any new recommendations for how these patients should be treated and how they should be monitored. So there weren't any real large studies on this but there were a number of case series and retrospective chart reviews concerning how MRSA may be affecting this disease. One of them was a case series published in 2009 that looked at 11 cases of MRSA preceptile cellulitis and these authors noticed that these cases seem to be more aggressive which is why they decided to write it up. There were sort of two different groups of patients, one of them was teenagers and they seem to have these focal abscesses that the authors described as easy to drain and they did well with outpatient antibiotic treatment. So this seemed to behave a lot more like your typical preceptile cellulitis that could be monitored on an outpatient basis. However, the other group was the adults. They had infections that spread rapidly along different tissue planes with multiple abscesses even once the patient was already on an antibiotic that should have been covering MRSA. They needed hospitalization, IB treatment, multiple surgeries and some of them the authors believed that steroids helped them get over the infection. So I think they were really making the argument that you know sometimes if MRSA is involved it can be a much more aggressive infection and require a different approach. This is radically different than what I was talking about earlier which is sort of the the status quo for treatment of preceptile cellulitis which is that you know it's not a terribly dangerous disease and it can be treated outpatient but all of a sudden these patients are needing multiple surgeries and multiple days of in-house antibiotics. So it could be changing the way this is approached but I don't think the authors were arguing that it's common enough that all patients need to be monitored for this. I think the idea was that basically if a patient's not improving the way you would anticipate them to improve or if they come in with a description of a disease that came on way faster and way more aggressively then you would expect a typical preceptile cellulitis that maybe it would be good to consider that this particular organism might be involved. So I like this cartoon. So MRSA and orbital cellulitis was sort of the bigger one that I wanted to look at and there was a retrospective chart review at Texas Children's Hospital in Houston where they looked at diseases orbital cellulitis associated with sinusitis that was their main inclusion criteria for these cases from 2001 to 2005. Out of the cases that they ended up looking at nine out of nine orbital aspirates 13 out of 16 sinus aspirates and two out of 27 blood cultures ended up actually being positive and out of those positive blood culture or out of those positive cultures in general the most common organism they encountered was staph aureus with the most common subtype being MRSA. All of the MRSA that they identified was sensitive to clindamycin or vancomycin or both and from what I gathered from this review all these patients ended up doing well. They didn't really focus on how the course of the patient may have differed depending on the organism involved. They were mostly looking at what type of organism was involved. There were a few shortcomings with this particular study just inherent to the nature of the disease itself. One of them was that basically if you break it down almost all of these positive cultures came from surgical specimens so essentially it still doesn't give a great idea as to how many of the cases in the larger group that didn't have an abscess drainage were actually MRSA. You really just get a better idea of what the surgical patients actually had infecting them. But I think the authors really kind of wanted to point out that it might be good to at least consider MRSA in these patients. I don't think that they were arguing and I don't think that you can take it from this paper since it's a relatively small number of cases that empiric treatment should include covers for MRSA because we just don't have huge numbers for that kind of projection. Interestingly they only had one case of strep pneumo out of these cases. They thought that maybe that was due to the expansion of the vaccine to infants but that was just speculation. They also made the recommendation not to obtain blood cultures based on the low yield they got. I actually disagree with that recommendation. It is a low yield certainly in this case and in other studies that I looked at but if that blood culture does come back positive it can provide invaluable information as to what type of antibiotic you need to be using to treat the patients. There were more smaller studies for MRSA involved in orbital cellulitis. A number of studies involving infants. I'll just use one as an example here but many of them were similar. There was a two-month old boy with MRSA associated orbital cellulitis to make a long story short. He had bacteremia and multiple abscesses. He was on vancomycin and meropenem and in spite of this he kept developing abscesses and kept needing drainage in the operating room. Eventually he got over the hump and he did quite well after he was discharged but this and other cases led to the argument that MRSA may be more commonly associated with bacteremia than other organisms and it may lead to more abscesses even when they're on proper antibiotic coverage. So these authors were kind of making that same argument that the authors of the preceptile cellulitis study made which is that this type of infection is much more aggressive even when you're on top of things they might still develop abscesses so it needs a higher level of care and more aggressive treatment than other organisms. And it seemed like when they mentioned it it was more often the community acquired version of the disease than the nosocomial version of the disease. They argued for initial treatment with vancomycin or even clindamycin and including trimethyprinselphomethoxazole and these patients regimens when they're discharged from the hospital. I think that's reasonable if you know that you're dealing with MRSA but I don't think that you can really project their results to the general patient population which is I think what they may have been doing because it is such small numbers it doesn't really give an idea of the incidence of the disease it just gives the idea that when it is present it can be quite aggressive. So again if the patient's not improving the way you would anticipate them to improve MRSA may be an organism to consider as the reason for that. There were a couple of large studies. One of them was done in Houston. They looked at positive, they looked at infections anywhere in the body that ended up being positive for MRSA from 2000 to 2004. They looked at over 3600 cases and out of all those cases only 49 of them actually involved the eye and out of those 49 cases involving the eye the most common type of infection was preceptile cellulitis. Aside from preceptile cellulitis there was a spectrum of other disorders. It wasn't just orbital cellulitis they included things like corneal ulcer and ophthalmitis but the only trend they noticed in their study was that as the years went on community acquired MRSA was increasing but the nosocomial subtype was not but at the same time you know it's a fairly small number of cases to make any huge conjecture from. So this is kind of the way I feel by this point in the talk and I thought it would be good to kind of play devil's advocate with myself. So there's another chart review for pediatric cases at a children's hospital in Aurora Colorado from 2004 to 2009. Their inclusion criteria were that these cases had to be confirmed by CT exams but had to be present on imaging. They had a number of exclusion criteria though. No patients with malignancy any type of immunodeficiency and anatomic abnormality trauma or previous surgery or a preceptile infection could be included. So they rolled out quite a number of types of patients. In the end similar to the last chart review they ended up with only 4% of their blood cultures but 81% of their surgical specimens coming back with positive positive results and out of 94 patients in the study only 9% actually had staph aureus as the primary organism and out of that 9% only one patient actually had MRSA. So not all these studies agree with each other. Yet in spite of these results as the years went on it increased but depending on the year 14 to 57% of these patients were receiving vancomycin as part of their antibiotic regimen. So some some clinicians certainly are using vancomycin more often presumably not because the patient had any type of allergy but because they were concerned about MRSA being involved in the infection. And I think these authors were just kind of trying to make the point that it may not be necessary at this point in time to include that in part of an empiric regimen. It may only be necessary if you find that that's what the patient actually has. And again these studies are kind of limited in one fashion because the results that we're getting that we're using are for the most part from abscess drainage. So it might be that a different type of organisms involved when no abscess form they might behave differently in those situations. It's kind of hard to speculate in that sense. Interestingly as a side note strep anginosis was the most identified organism for these patients and actually had to look that up. I think that qualifies as part of the other strep species but it's normal floor of the GIGU in respiratory tracts. So conveniently in the April issue of the Journal of Emergency Medicine there was a study published from our own department of pharmacy at University Hospital where they looked at patients who came into the ER at University Hospital with some sort of soft tissue or skin infection with MRSA. And they just looked at what antibiotics these MRSA subtypes were susceptible to. So if you're wondering what antibiotic in our own community to use 58 out of 58 were susceptible to vancomycin or some other antibiotic on this list. 57 out of 58 were susceptible to Bactrim. 50 were susceptible to tetracycline and only 47 were susceptible to clindamycin. So the strange in this community seemed to be more susceptible to vancomycin and Bactrim than they are to clindamycin at least at University Hospital. So back to our original case the cliffhanger. Within 24 hours of discharge really more like within half a day this patient came back to the ER and that was where we met on that Saturday. And his parents were saying that he couldn't any longer look up with his right eye and his right eye had become more red. Exams showed that he wasn't febrile this time around but like his parents said he did have limited up gaze on the right. And a CT showed a newly formed multiloculated abscess including a large portion against the orbital roof. So with the criteria we talked about before he has three of them at least to go to the OR. One was that he wasn't improving on a proper antibiotic regimen. He had a large abscess and it wasn't medial in location. So he was taken to the OR and it was drained and it grew it grew based on it. So not all these cases are MRSA involving. Sometimes common things are common. He was continued after his drainage on erudipenem and discharged to home and he did really well. So just a little overview of how the disease might be changing with MRSA evolving as a more common organism. And I can take any questions that anybody has. I'd been reading that one of the ones I was coming across was Linazolid. Is that I was reading that a Linazolid is a lot of times the first line if the MRSA is resistant to vancomycin. I don't know if that's what other people have come across but at the University Hospital in Louisville you actually had to get infectious disease approval before you could give anyone Linazolid but it's kind of a drop in the bucket if that's going on in the poultry industry and I think that would do too much good. That's interesting. The argument was bilateral disease only but I came across that once. So it was bilateral disease only but I haven't heard of that personally in my brief time with exposure to ophthalmology but that was their argument.