Episode 100
100: StAR: Periprosthetic joint infections
This StAR episode features the CID State-of-the-Art Review on periprosthetic joint infections.
Our guest stars this episode are:
Sandra Nelson (ID physician at Massachusetts General Hospital)
Jodian Pinkney (ID physician at Massachusetts General Hospital)
Antonia Chen (Orthopedic surgeon at Brigham and Women’s Hospital)
Aaron Tande (ID physician at Mayo Clinic)
Journal article link: Nelson SB, Pinkney JA, Chen AF, Tande AJ. Periprosthetic Joint Infection: Current Clinical Challenges. Clin Infect Dis. 2023;77(7):e34-e45. doi:10.1093/cid/ciad360
Journal companion article - Executive summary link: https://academic.oup.com/cid/article/77/7/939/7289507
From Clinical Infectious Diseases
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Febrile is produced with support from the Infectious Diseases Society of America (IDSA)
Transcript
Hi everyone, welcome to Febrile, a cultured podcast about all things infectious disease.
Sara Dong:We use consult questions to dive into ID clinical reasoning, diagnostics, and antimicrobial management.
Sara Dong:I'm Sara Dong, your host and a MedPeds ID doc.
Sara Dong:Welcome to our next Febrile StAR episode.
Sara Dong:Again, these are featuring topics and authors from the CID Journal State of the Art Reviews.
Sara Dong:I encourage you to listen to episode number 97 to get a quick introduction from the editors.
Sara Dong:And this is now our third of four straight weeks of STAR episodes to kick off the series.
Sara Dong:So, I'll introduce our guest stars today.
Sara Dong:Dr.
Sara Dong:Sandra "Sandy" Nelson is an ID physician at Massachusetts General Hospital and an assistant professor at Harvard Medical School in Boston, Massachusetts.
Sara Dong:She serves as the Associate Clinical Director of the Division of ID and oversees the ID inpatient service and OPAT program.
Sara Dong:Her academic interest is in the care of patients with musculoskeletal infections.
Sara Dong:At MGH, she directs the Program in Musculoskeletal Infectious Diseases, which is actively engaged in clinical care, educational efforts, and research.
Sandy Nelson:Hi, I'm Sandy Nelson.
Sara Dong:Dr.
Sara Dong:Jodian "Jodi" Pinkney is an ID physician at Massachusetts General Hospital in Boston.
Sara Dong:She is interested in health equity and maternal health and is wholeheartedly dedicated to eliminating maternal deaths related to vaccine preventable diseases.
Sara Dong:She is currently enrolled in the MPH program in health policy with a concentration in maternal and child health at the Harvard T.
Sara Dong:H.
Sara Dong:Chan School of Public Health.
Sara Dong:and is a fellow in the Commonwealth Fund Fellowship in Minority Health Policy.
Jodi Pinkney:Hi, I'm Jodi Pinkney.
Sara Dong:Dr.
Sara Dong:Antonia Chen is the Chief of Arthroplasty and Joint Reconstruction at Brigham and Women's Hospital and an Associate Professor of Orthopedic Surgery at Harvard Medical School.
Sara Dong:She specializes in hip and knee replacements, as well as in the care of complex patients who may require revision procedures for their previous hip and knee replacements.
Antonia Chen:Hi, I'm Antonia Chen.
Sara Dong:Dr.
Sara Dong:Aaron Tande is an infectious diseases consultant and professor of medicine at the Mayo Clinic in Rochester, Minnesota.
Sara Dong:He also serves as the associate division chair for outpatient practice, the chair of the orthopedic ID focus group, and physician co chair of antimicrobial stewardship.
Aaron Tande:Hi, I'm Aaron Tande.
Sara Dong:Awesome.
Sara Dong:Well, thank you guys for joining.
Sara Dong:Before we talk about your article, we're going to start with the general Febrile introduction.
Sara Dong:As everyone's favorite cultured podcast, we like to ask our guests to share a little piece of culture, really just something non medical that brings you joy.
Antonia Chen:My favorite thing is my four pound Yorkie.
Antonia Chen:She brings me a lot of joy and she's a lot of fun.
Jodi Pinkney:I am a huge fan of reggae music and the new Bob Marley movie that just came out, because my dad is a reggae guitarist who played with Bob Marley back in the 70s.
Aaron Tande:I've always been a fan of music and I'm excited this weekend I'm going to go see Jason Isbell.
Aaron Tande:If anybody knows who he is, he's probably the best songwriter alive today.
Sandy Nelson:I'm going to share that this year I started making my own kombucha, which is a piece of culture in more ways than one.
Sara Dong:It's like the perfect piece of culture.
Sandy Nelson:It is such the perfect hobby for the nerdy ID doc.
Sandy Nelson:And you get your fermented foods and a yummy drink all in one.
Sandy Nelson:It's really, really pretty cool.
Antonia Chen:And it's good for your gut.
Sandy Nelson:That's right.
Sandy Nelson:Yeah.
Sara Dong:Well, I am so excited to have you guys here.
Sara Dong:We are partnering with CID to talk about these state of the art reviews, and you all authored a paper about periprosthetic joint infection current clinical challenges.
Sara Dong:I have a couple cases today for us to try and tackle.
Sara Dong:I may have added a few additional questions to get your thoughts.
Sara Dong:So I'll start with our first patient.
Sara Dong:He is a 70 year old male, has a history of hypertension and diabetes, and he had a left knee arthroplasty for severe arthritis two years ago.
Sara Dong:He comes in with left knee pain and stiffness over the past two to three months.
Sara Dong:He says he has no fevers at home, he hasn't really noticed any redness, any obvious swelling of that knee.
Sara Dong:He's really just generally feeling okay otherwise.
Sara Dong:On his labs, his CBC, ESR, and CRP are normal.
Sara Dong:And he undergoes a left knee arthrocentesis, which results with cloudy fluid with a white blood cell count of 2, 500, and the differential on that had 75 percent neutrophils.
Sara Dong:The gram stain and culture is negative.
Sara Dong:And so I want to pause here for a second because most of our Febrile audience are likely ID fellows or ID physicians, or at least medicine trained folks, and Antonia, we're really excited to have you here.
Sara Dong:Can you tell us a little bit about the surgical perspective at this moment?
Sara Dong:You know, what is the spectrum of options we have available for someone that we're wondering if they have suspected prosthetic joint infection?
Antonia Chen:So, first of all, thanks for having me on here.
Antonia Chen:I know that there's definitely contention between ID docs and orthopedic surgeons, so we appreciate you guys a lot, and we know we cause you guys a lot of stress, so thank you for having me here.
Antonia Chen:That's the first thing.
Antonia Chen:And this is the type of patient that we all typically see way too often in clinic, right?
Antonia Chen:It's that in between gray zone that's the hardest person.
Antonia Chen:So, the patient obviously has comorbidities like diabetes, which places an increased risk of infection.
Antonia Chen:The surgery was two years ago, which is definitely considered chronic, you know, people debate if it's chronic is four weeks or three months, but two years puts past that timeframe, but the pain and stiffness is over the past two or three months.
Antonia Chen:So that's a longer timeframe than most of us are comfortable with most of the time.
Antonia Chen:So we consider it as probably pretty chronic at this point in time.
Antonia Chen:You know, things like ESR and CRP, whenever I see a patient who comes in with a joint replacement, I always run that first.
Antonia Chen:And typically that's elevated, when they're normal, that says, okay, now what do I do?
Antonia Chen:If the patient still has persistent pain, especially swelling, I will likely take an arthrocentesis like this patient had.
Antonia Chen:The cloudy fluid always makes me a little bit concerned, but you do have to worry about other things that can cause cloudiness to the fluid.
Antonia Chen:And the cutoffs that are typically used in a diagnostic criteria are 3, 000 and then 65 percent neutrophils.
Antonia Chen:So the problem is you're in this gray zone where it's a little bit below the white blood cell count, but a little bit above the neutrophils.
Antonia Chen:So from a surgical perspective, it's one of those things, the gram stain and the culture are negative.
Antonia Chen:This is not Sorry, not from a surgical perspective yet, from a diagnostic perspective, I would potentially consider doing something like next generation sequencing.
Antonia Chen:And this is where I would call on my ID colleagues to say, is this something worthwhile doing or not?
Antonia Chen:And then on top of it, adding things like other markers.
Antonia Chen:So alpha defensin, leukocyte esterase, these are other things I would look at to try to see if we arrive at the same diagnosis of infection.
Antonia Chen:So from a surgery perspective, I'm not jumping into surgery at this point.
Antonia Chen:I think it's too premature, and I would consult my wonderful ID friends to see what they would say before undergoing any surgical management.
Sara Dong:Perfect.
Sara Dong:And we can step away from that case for a second.
Sara Dong:And I would love as an ID doctor to hear how you sort of think about what is the spectrum of interventions that are available, because I think that sometimes just understanding exactly what's happening in the OR for patients that you do end up taking to the OR is helpful.
Sara Dong:Do you mind telling us a little bit about that?
Antonia Chen:It's always a special in between and this is a constant source of debate between orthopedic surgeons, ID docs, and generally people because there's no hard and straight answer.
Antonia Chen:Typically when a patient has an acute infection, so typically defined as let's say within four weeks of the index surgery or four weeks of symptoms, we could do something called DAIR, which is debridement, antibiotics, and implant retention.
Antonia Chen:And when I was in training, it used to be irrigation, debridement, and polyethylene exchange.
Antonia Chen:In theory, it's the same thing.
Antonia Chen:You're taking out what we call the modular components.
Antonia Chen:So typically for a hip replacement, typically for a knee replacement, what we're doing is we're putting in a plastic component in there, and we can take it out, and by taking out this plastic component, we have more access to either the joint or to other surfaces.
Antonia Chen:So this group knows better than I do that bacterial organisms have a higher affinity towards metal, right?
Antonia Chen:Or towards foreign objects.
Antonia Chen:So the more foreign objects you can remove, the better it is, but you wanna be as least invasive as possible.
Antonia Chen:So if an acute setting, if you can get away with it, a DAIR is nice because you take out the modular parts and you clean back.
Antonia Chen:If you're doing the knee replacement, the idea of taking the modular part allows you get to the back of the knee or the posterior capsule.
Antonia Chen:And for the hip replacement, if you take the plastic part out, you can get to the acetabulum or to the metal component there.
Antonia Chen:But you can't get down the canal because it's already filled with a metal piece.
Antonia Chen:So that's the first option.
Antonia Chen:The next thing that has changed actually over time is this thing called a, people call it a destination spacer, a 1.
Antonia Chen:5 stage spacer.
Antonia Chen:It's kind of when you take everything out of the joint.
Antonia Chen:So you're removing all the potential bio burden, right?
Antonia Chen:You're taking the metal, you're taking the plastic, you're taking everything out of the joint, whether it be a hip or a knee or a shoulder or wherever you're taking it.
Antonia Chen:And you're putting in something in the interim.
Antonia Chen:When I was in training, the interim part was a spacer, and that spacer could take multiple different forms.
Antonia Chen:The first spacer type would be what we call a static spacer, meaning it didn't move.
Antonia Chen:So if you're on a knee, you'd be stuck straight.
Antonia Chen:If you're on a hip, you'd be stuck in one spot as well too.
Antonia Chen:And as you can imagine from a functional perspective, it's not great.
Antonia Chen:But it eludes antibiotics, it delivers antibiotics, and you do go back in and you replace it with a new joint.
Antonia Chen:That said, more and more patients don't want to go back under surgery, which I understand.
Antonia Chen:If your infection is, for lack of a better term, suppressed or at least treated, and you don't need to go back from a surgical perspective, why not put in an implant and actually serve as a regular implant?
Antonia Chen:And that's where this 1.
Antonia Chen:5 stage spacer comes in.
Antonia Chen:So for a knee replacement, for example, my algorithm is to put a metal femur and put in all poly tibia, and then I put dowels up and down the femur and the tibia.
Antonia Chen:So it allows for antibiotic cement delivery in the canals and on the prosthesis itself, but it's a brand new implant.
Antonia Chen:You can walk on it, you can do everything you want to.
Antonia Chen:It's put in with antibiotic cement, which has less strength.
Antonia Chen:So if you have to go back in to take it out, it's easier to take out.
Antonia Chen:So it's not as robust or not as good as a real revision implant, but for especially a low demand patient or patients who say, I want to put off surgery for as long as possible, it's not a bad option.
Antonia Chen:And then for the hip, what you do is you can put, you can cement an all poly liner in there.
Antonia Chen:and put a stem that's coated in antibiotic cement.
Antonia Chen:And again, it's not as good as the real thing, but it gives you an articulating surface that you can walk on and function with.
Antonia Chen:And some people, I have them live them for life.
Antonia Chen:They really don't want to go back for surgery as long as their infection doesn't come back and things like that.
Antonia Chen:And then from a surgical perspective that you do have to come back, that's one thing you can do.
Antonia Chen:And then the one stage is something else you can think of.
Antonia Chen:So the reason it's called 1.
Antonia Chen:5 stages, the two stage procedures, you take everything out, you put it in a spacer, and you have to go back in with a new implant.
Antonia Chen:The one stage is, at the same time you take everything out, you remove everything, clean everything up, you put a whole new setup and you put all the brand new prosthesis at that time.
Antonia Chen:So from a patient perspective, that's wonderful because it's only one surgery.
Antonia Chen:From a morbidity perspective, it's a long procedure, right?
Antonia Chen:It's twice as long as the other cases.
Antonia Chen:For some, some patients can't sustain that, so you can't offer that to them.
Antonia Chen:And it typically is with certain sites that do them more commonly than others.
Antonia Chen:It's something that can be done, but a lot of surgeons don't necessarily offer that.
Antonia Chen:So that's the gamut of different treatment options, and obviously it can go into a lot of depth of all of them at any point in time.
Sara Dong:Thanks so much.
Sara Dong:So, you know, we're making up this scenario a little bit, but let's just say, you know, this patient was taken to the operating room.
Sara Dong:We have some operative culture results, and Sandy, you get called and are told that one of five of the cultures from the OR obtained are positive for Cutibacterium acnes.
Sara Dong:So, you know, ID is called in to see how do we address this C.
Sara Dong:acnes in just a single positive culture?
Sara Dong:Is this PJI?
Sandy Nelson:So, I think that there's really two questions there.
Sandy Nelson:And one of the questions is, is this a prosthetic joint infection?
Sandy Nelson:And we now have a better potential chance of answering that question because the data that we get from the surgical procedure is much more complete than what can be obtained preoperatively.
Sandy Nelson:And then the second question is, is this infection secondary to it?
Sandy Nelson:And to the first question, I think that Antonia addressed this, the one addition that I would say is that while there are these thresholds that are used in the diagnostic criteria, and there is a threshold of around 3, 000 for synovial fluid white cells, that's really not a hard and fast number.
Sandy Nelson:Many individuals will have infections with lower cell counts than 3, 000.
Sandy Nelson:That's particularly true in knees, in which some other studies suggest that the, that the optimal cell count threshold is actually lower.
Sandy Nelson:While you'd say that they don't actually meet criteria, it's also not the same as saying that they don't.
Sandy Nelson:And so in this individual, we have normal inflammatory markers, but borderline cell counts, a pretty concerning percent neutrophil, and now we have one positive culture.
Sandy Nelson:And this isn't going to be a confirmed diagnosis, because a single positive culture with several minor criteria, it does not confirm.
Sandy Nelson:But you've really met the criteria for possible or probable prosthetic joint infection.
Sandy Nelson:And then when we think about how to treat it, we also think about what are the stakes and what has been done.
Sandy Nelson:And so this is an individual that's had a surgery.
Sandy Nelson:We didn't discuss which particular surgery.
Sandy Nelson:And in that case, I'm likely going to say, you know, we've gone to great lengths already for this patient.
Sandy Nelson:And I think the safest option is probably to presume that there is a prosthetic joint infection.
Sandy Nelson:Cutibacterium is particularly tough.
Sandy Nelson:It's particularly tough in the shoulders, but we do see it sometimes in hips and knees.
Sandy Nelson:With one out of five positive cultures, as a general rule, we're going to discount that as a contaminant.
Sandy Nelson:I think that's a little bit of a harder judgment to make in the shoulder setting, in which it really can go either way with true infection or contamination.
Sandy Nelson:But in the knee or hip with one out of five studies, I'm not going to put all of my eggs in the Cutibacterium basket, and I'm gonna treat more broadly as if this is a culture negative infection, and this is the time that you might think about doing some of those advanced diagnostics for, you know, molecular identification of pathogens.
Sara Dong:Of course, as you both were mentioning, the antibiotic strategies and the surgical approaches are entwined, and we really have to understand if there's residual undebrided infection left, is there retention of hardware, and that helps us select and construct an antibiotic plan.
Sara Dong:And maybe trying to think more broadly, Aaron, I was hoping you could talk a little bit about how you approach antibiotic selection and how you think about duration of therapy, and that could be thinking about these example cases, but really just more generally in your practice.
Aaron Tande:No, I think that that's the right place to start.
Aaron Tande:And that's one of the values of working closely with our colleagues in orthopedic surgery.
Aaron Tande:You really have to go back to and say, you know, I'm not in the OR.
Aaron Tande:You don't want me in the OR.
Aaron Tande:I don't know what I'm doing in there.
Aaron Tande:But I want to know what Antonia saw in the OR.
Aaron Tande:I want to know, what was debrided, how confident she is in the adequacy of debridement.
Aaron Tande:And that doesn't get to a surgical skill.
Aaron Tande:It gets to what's available to the surgeon at the time of debridement.
Aaron Tande:So you want to have an idea of what was debrided, what's left after the debridement, what was done with the implants, and we mean all the implants.
Aaron Tande:Was the metalwork revised?
Aaron Tande:Is there a cerclage wire there to fix a extended trochanteric osteotomy or some other defect that had to be left behind, because that is going to play into the treatment decisions.
Aaron Tande:In general, we sort of approach this thinking about was everything resected and we have fresh either just cement or implants there, and was it done in a completely clean way, and if that's the case, then you're going to be looking at trying to go for a cure where you're going to be treating and stopping.
Aaron Tande:And the duration of, of treatment, we're getting more and more data, uh, over time about what is that optimal duration of treatment.
Aaron Tande:We had this really nice DATIPO study that I'm sure your listeners have probably read, um, looking at 12 versus 6 weeks.
Aaron Tande:You have to be careful when you're interpreting that.
Aaron Tande:But what I took away from that is that there's no difference for, uh, carefully done one stage exchange between 12 and 6 weeks, although a lot of times we will use 12 weeks for one stage exchange.
Aaron Tande:For two stage exchange, there seemed to be a difference, but I think when we interpret that study, you have to look at who got the two stage exchange in that European center, and it was probably those higher risk patients.
Aaron Tande:In our practice, and I think the totality of data says that, after a complete resection without re implantation at that time, six weeks is probably sufficient for the vast majority of patients.
Aaron Tande:We typically stop there.
Aaron Tande:For those patients, either with what I would call an unintentional one stage exchange, and what I mean by that, and again, it's really important to talk to your surgeon, was it that they did a direct revision to new components there, but they didn't re drape or re set up, as Antonia said, they didn't use new instruments, and it was sort of like, oh.
Aaron Tande:We're surprised with multiple positive cultures.
Aaron Tande:Then I think you're looking more along the 12 week line of therapy.
Aaron Tande:And then debridement and implant retention, that is something that we are still learning more and more about.
Aaron Tande:My approach and the way I think about that, again, incorporating the DATIPO study and other data is, I typically say 12 weeks is where we start.
Aaron Tande:And then from there, you really have to individualize it after that.
Aaron Tande:And you have to take into account all the different factors that weigh into the art of medicine.
Sandy Nelson:Erin really stated the way that many of us or most of us practice and the majority of the literature really is pretty limited when we think about it.
Sandy Nelson:We are learning a lot more and we're beginning to dial it down, but there are some features that certainly would support longer treatment and the knee as opposed to the hip is one of those scenarios because knee prosthetic joint infections actually don't do as well and there is some data to support longer treatment for knees.
Sandy Nelson:There is also more data about Staph aureus than other pathogens.
Sandy Nelson:You know, Staph aureus, especially the severe infections, would make us want to think about a longer treatment course.
Sandy Nelson:But otherwise, we don't have a test of cure, and these are really, really difficult decisions.
Sara Dong:Two other management questions that come up a lot that I wanted to make sure we didn't skip, even though I think it sort of takes us in a step away from the example case.
Sara Dong:But say we had someone who had acute Staph PJI, and the question about rifampin comes up.
Sara Dong:I would love to hear insight on how you think about rifampin and incorporating it into your regimens.
Sandy Nelson:If you talk about Cutibacterium as sort of the bane of my existence, rifampin is in some ways the antibiotic, the most challenging drug that we use in musculoskeletal infectious disease, simply because there is a lot of controversy around its role.
Sandy Nelson:And if it were easy to use, and if it didn't have toxicities and side effects and drug interactions, it would probably be a little bit less of an issue.
Sandy Nelson:This is one, again, where we have to look at the totality of the evidence.
Sandy Nelson:There are really two small randomized control trials that have looked at the role of rifampin in orthopedic device infections, one specific to PJI.
Sandy Nelson:And both of the studies have really pretty significant limitations that make it hard to draw significant conclusions.
Sandy Nelson:But when you look at the totality of data, which includes retrospective human data and animal data and some vitro data.
Sandy Nelson:There really is increasing support for the use of rifampin and the data is the greatest when the infection is due to Staph with retained hardware.
Sandy Nelson:And then as you move away from staph towards different gram positive organisms or towards removal or exchange of hardware, the data is a little bit less clear.
Sandy Nelson:And so, because rifampin is not easy to use, I think we work the hardest to use it when the indications are clearest.
Sandy Nelson:And so, the patient with a Staph infection with retained hardware, that's someone who we're going to really try to use rifampin.
Sandy Nelson:But when we talk about other organisms, Cutibacterium, Strep, Enterococcus, all of which have some support, low quality support, I would say, for the addition of rifampin.
Sandy Nelson:We may not push as hard in those individuals or if hardware has been removed, particularly if there are some drug interactions.
Sandy Nelson:In this case, the one that you highlighted, I would call this culture negative infection.
Sandy Nelson:I personally don't add rifampin in culture negative infection because it really does add to toxicity and you usually have to use a little bit more breadth of a regimen and in a lower burden infection, which presumably culture negative infections are, I don't think we actually have the data to support it, but that would be my own practice.
Aaron Tande:Yeah, I would, I would agree with you, Sandy.
Aaron Tande:I wouldn't use it in culture negative infection and I really do, you know, you have to be very thoughtful about it.
Aaron Tande:And this is where medicine becomes a team sport and we involve other team members, our pharmacy colleagues with their expertise in drug drug interaction Internal medicine specialists or family medicine specialists that are primarily caring for this patient and looking at those drug interactions.
Aaron Tande:So, um, yeah, I, I probably wouldn't use it in this case, but I do really try and make an effort to use it for Staphylococcal PJI with implant retention.
Sara Dong:Great.
Sara Dong:And the other question, uh, is how do you decide who does or does not need long term antibiotic suppression?
Sara Dong:You have a really nice Table 3 in your article that shares some of the considerations for suppressive therapy.
Sara Dong:I was wondering if you could walk us through that.
Aaron Tande:Yeah, I'll take a jump at that.
Aaron Tande:And I think, again, it gets back to what do I love about OrthoID, and I do love it.
Aaron Tande:I love working with my colleagues in surgery and the decision about suppression really has to go back to that partnership and understanding, how does the surgical management depend on success or failure?
Aaron Tande:And it starts with a good discussion with the surgeon about what are the options and what are the risk factors that they see for failure for this individual patient?
Aaron Tande:And then if failure occurs, what are the consequences?
Aaron Tande:Because I think those are the two key things that help us decide whether or not to give suppression.
Aaron Tande:So as far as risk factors for failure, I usually just start by looking at the infection when it occurred, and were they inappropriate?
Aaron Tande:Again, if we're talking about debridement implant retention, which is the most common indication for suppression, were they a good DAIR candidate, or debridement implant retention candidate in the first place, or was this a salvage DAIR?
Aaron Tande:If it was a chronic infection and the outcome of performing more radical surgical approach such as reconstruction would be too morbid and that's why DAIR was chosen.
Aaron Tande:Those patients typically do benefit, in my opinion, from suppression because we're really trying to do everything we can to keep this patient functional and avoid a very morbid procedure.
Aaron Tande:So that's where I start.
Aaron Tande:And then if the patient did have an appropriately timed performed DAIR, then I look at what is my estimate, both currently and as well as at the time of infection, of their risk of failure.
Aaron Tande:So, did they only require one debridement?
Aaron Tande:Did they have that debridement performed in a timely manner?
Aaron Tande:Was polyethylene exchanged or the modular components exchanged?
Aaron Tande:If there was Staph aureus or Staphylococcal PGI, did they get rifampin?
Aaron Tande:Was it a late acute infection which seems to have a higher rate of failure versus early postoperative, which has a lower rate of failure?
Aaron Tande:Was it a knee versus a hip?
Aaron Tande:Like Sandy mentioned, knees have higher rate of failure.
Aaron Tande:I look at all these things and I talk to the surgeon and we sort of come up with a plan about whether to offer suppression and the key thing too is I think that we have to reassess as data points accrue.
Aaron Tande:So, if a patient is offered suppression, they're put on suppression and then they're tolerating it very poorly, look at the risk benefit approach.
Aaron Tande:And maybe then those risks are now starting to outweigh the benefits.
Aaron Tande:And, but again, this is an ongoing discussion with our colleagues in surgery, as well as with the patient and their decision makers.
Sandy Nelson:You know, especially historically, we use suppression more than we are now.
Sandy Nelson:We're seeing a little bit more of the harms of long term suppression.
Sandy Nelson:And in addition, we are beginning to have some more fine tuned data that not everybody needs suppression.
Sandy Nelson:And then you're stuck with patients who've been on suppression for some period of time.
Sandy Nelson:And putting somebody on suppression is, in some ways, is an easier decision than making the decision to stop suppression down the road.
Sandy Nelson:And those are very challenging, but can be done.
Sandy Nelson:And over time, as I've stopped more and more of my chronic suppression patients, the vast majority of them have, reassuringly, done well.
Sandy Nelson:But these are really, I think, scary, for the patients, uh, for us and, and probably for the surgeon as well.
Aaron Tande:Yeah, you know, you want to sort of start those discussions early and then pick a time that works for everybody involved.
Aaron Tande:If you are going to stop suppression, which I totally agree, we, we are probably giving too much suppression, pick a time that works with the patient, with the surgeon, where you're going to carefully stop that suppression in a controlled manner.
Sara Dong:Okay.
Sara Dong:We're going to go to a second case.
Sara Dong:This time we have a 50 year old male.
Sara Dong:He has a history of CKD, obesity, and diabetes, and underwent a right total hip arthroplasty for osteoarthritis about five years ago before coming in.
Sara Dong:He comes in now with right hip and thigh pain, and he reports that he initially was doing okay, but really, it's just been over these past couple weeks that he's noticed these symptoms.
Sara Dong:Other than the pain, he has not had drainage from an incision.
Sara Dong:He's had no fevers or overlying skin changes, no obvious sinus tracks.
Sara Dong:We have some initial labs that show that his white blood cell count is 11 with a normal differential.
Sara Dong:His platelets were 275.
Sara Dong:And his chemistry is normal with the exception of his creatinine of 1.3, which is his baseline.
Sara Dong:We have a CRP of 10, which is slightly elevated.
Sara Dong:The normal is less than 1.
Sara Dong:And then the ESR is 40, and the normal range for that is 0 to 30.
Sara Dong:So he has an initial joint aspiration that has 25, 000 white blood cells and 90 percent neutrophils.
Sara Dong:So, Antonia, I wanted to get a sense of what you're thinking about for this case.
Antonia Chen:These are the tough ones.
Antonia Chen:You kind of look at this and I think immediately people will think and scream, Oh, this has to be infected, right?
Antonia Chen:The white blood cell count is a little bit elevated.
Antonia Chen:Patients have some symptoms.
Antonia Chen:ESR and CRP are on the cusp of elevation, right?
Antonia Chen:I used 10.
Antonia Chen:I guess the mark of the use here is normal of 1.
Antonia Chen:But it depends on your units.
Antonia Chen:You have to pay good attention to your CRP units.
Antonia Chen:In your ESR 40, our 30s are cut off.
Antonia Chen:And we just had a good conversation about white blood cell counts, but when you get 25, 000 in a joint that has been there for a long time, five years, then you become a little bit more concerned about infection.
Antonia Chen:That said, these are the type of patients that you look at and you say, well, you know, we want to make sure that we see the type of hip there is.
Antonia Chen:And this is where having our ortho with ID colleague collaboration is really useful.
Antonia Chen:And one of the things that really became a problem was actually metal on metal implants.
Antonia Chen:And metal on metal implants are not being used as frequently now as they were in the past, but patients are obviously living with a bunch of them.
Antonia Chen:And there've been a bunch of recalled metal on metal hip implants.
Antonia Chen:And what this means is for hip implants, you have a metal cup, you have a metal stem, and they're typically made of titanium, and then you put a ball on that, and you have a neck.
Antonia Chen:So the neck trunnion is made of titanium, and the head is typically made of cobalt chromium.
Antonia Chen:And by doing so, you have dissimilar metals, and by doing those dissimilar metals, it can actually cause what is called an adverse local tissue reaction.
Antonia Chen:It can cause metal debris, essentially, and if there's a little bit of metal debris, your body will clear it, but as it accumulates over time, which happens with use of the hip, that becomes problematic.
Antonia Chen:It is normally measured by cobalt and chromium levels.
Antonia Chen:Now there's two ways that you can have metal issues.
Antonia Chen:You can have metal issues from the cup itself to the ball, because it's one metal articulation, or you can have trunnionosis, where is that stem to the ball, right?
Antonia Chen:So the one that's at typically higher levels are the one that's the cup.
Antonia Chen:and the ball because it's cobalt chromium rubbing against each other.
Antonia Chen:So those are typical lab values that I'll check on patients.
Antonia Chen:A lot of these patients are asymptomatic.
Antonia Chen:They don't have any symptoms, they don't hurt, but they have this implant.
Antonia Chen:So typically what I do for these patients is every year I check these lab values and if they start creeping up, that's something concerning.
Antonia Chen:This patient had an aspirate done.
Antonia Chen:And you can see it here that the numbers out there.
Antonia Chen:If your facility has it, our facility doesn't have it, but you can potentially ask for a manual cell count.
Antonia Chen:When you have to take the fluid out, they can actually count it and that actually really helps determine what the fluid levels are there with regards to inflammatory factors.
Antonia Chen:And if you want to look at it from an imaging perspective, you can get what we call a MARS MRI or a Metal Artifact Reduction Sequence MRI.
Antonia Chen:So it suppresses the metal there and you see if there's any sort of soft tissue out there.
Antonia Chen:The worst case scenarios are patients who've had this for a long time, really high cobalt and chromium.
Antonia Chen:It can affect cardiac issues.
Antonia Chen:It can be neurologic issues.
Antonia Chen:It can have other sequelae as well.
Antonia Chen:That's problematic.
Antonia Chen:And we obviously don't want that for our patients, but this is what you can look for in these types of patients, the problem is there's inflammation around the joint and called pseudotumor can be produced there.
Antonia Chen:So if you're looking at this inflammatory level, don't just jump to infection right away with a 25k white blood cell and a 90 percent polymorphonucleocytes.
Antonia Chen:Still culture, you know, still do the routine stuff and think of it also, you can have a metal on metal reaction and have infection at the same time.
Antonia Chen:So be sure to cover all bases with these patients but this is something I think about in these total hip patients as well.
Sara Dong:That's so helpful.
Sara Dong:If we say, in this case, we have negative cultures, we're having that question of, is a culture negative PJI here, we mentioned briefly earlier about some of the non culture based tools that we have for PJI, and so I do think there is some variable use of those tests in
Sara Dong:different centers as far as alpha defensin or synovial CRP, and I was just wondering if we could pause for a second to talk about those.
Sara Dong:Like how, how are those tests used in PJI?
Sara Dong:Sort of what is your perspective?
Aaron Tande:Yeah, no, I think that that's a great question.
Aaron Tande:And this is the exact kind of case, much like the previous case too, where you've got some discrepant test results, you may or may not have infection.
Aaron Tande:And so that's when you want to start to look at that.
Aaron Tande:And the, the non culture based diagnostics looking synovial fluid fall into two categories.
Aaron Tande:The first is, is there infection or not?
Aaron Tande:And the second is, okay, we think there's infection, but we can't culture anything.
Aaron Tande:And so how can we sort of make a microbiologic diagnosis?
Aaron Tande:So the first question of the, is there infection or not?
Aaron Tande:Yeah, there, there are a number of different options out there.
Aaron Tande:I think that the one with probably the most data thus far is alpha defensin.
Aaron Tande:And the data does suggest this is probably a good test.
Aaron Tande:However, to me, I remain to be convinced that it is superior to the much more widely available and cheaper cell count and differential.
Aaron Tande:I think it should be reserved for use in cases like this where you may need an additional piece of data because, say, your cell count may be artificially changed based on adverse local tissue reaction.
Aaron Tande:I think alpha defensin, synovial fluid CRP, if they're available to you, they're good in situations where you're on the border between infection versus not, and that's going to affect your initial surgical management strategy.
Aaron Tande:To get to the second question of, okay, I think there's infection, but we can't grow anything, you know, there are, again, now a few different options available, and these molecular diagnostics, they're sort of in two flavors.
Aaron Tande:The first is using a broad based approach, such as a 16S PCR, and that can be followed by either Sanger sequencing or a targeted metagenomic sequencing.
Aaron Tande:The advantage there is that you can identify novel pathogens that are not common causes of PJI.
Aaron Tande:You know, there's a lot of case reports about that.
Aaron Tande:And I think that that, uh, does seem to show some benefit, again, in those unique circumstances where you need to make a culture based, culture negative diagnosis.
Aaron Tande:The other category are sort of multiplex PCR assays.
Aaron Tande:And there's one that's commercially available.
Aaron Tande:The chief advantage there, again, it may be less influenced by antimicrobials previously.
Aaron Tande:It also typically has a rapid turnaround time, but the huge limitation of that test is it didn't include some key pathogens such as Cutibacterium acnes or Staph epi.
Aaron Tande:And so there's a couple different options.
Aaron Tande:Each probably has a role.
Aaron Tande:Each is a tool in trying to get to that answer of what is the pathogen here that can help you with your management.
Sara Dong:Aaron talked a little bit about duration of therapy earlier and in your article, you talk about how we sometimes think about the treatment courses and stages with IV therapy and oral phase and then whether or not that patient also then gets oral suppression.
Sara Dong:I want to make sure that we give a little bit of time to talk about that sort of oral therapy options and that phase.
Sara Dong:Sandy, maybe you can tell us a little bit.
Sandy Nelson:So, we have a patient who has a confirmed or suspected PJI and we're planning on treatment.
Sandy Nelson:The standard is usually to start with IV antibiotics in the perioperative window and that's generally for a couple of reasons and, you know, one is simply logistics that the patient may not be able to tolerate oral medications very well early on, but there's also this idea that we can have enhanced drug delivery with higher level dosing that can be achieved through the intravenous route.
Sandy Nelson:There is very strong emerging data in support of oral therapy for many bone and joint infections.
Sandy Nelson:You know, our pharmacists like to say that the bug doesn't really care.
Sandy Nelson:The bacteria don't really care whether the antibiotic was ingested or injected.
Sandy Nelson:It's going to get there, and as long as the drug gets there, it doesn't really matter.
Sandy Nelson:My focus has shifted a little bit away from using intravenous antibiotics to using oral antibiotics that have a very good bioavailability.
Sandy Nelson:And it seems to be that the bioavailability is the relevant factor.
Sandy Nelson:I think there are some important cautions and, you know, number one is most of the studies in support of oral therapy don't start oral therapy on day one.
Sandy Nelson:There is usually a window of time where patients are receiving IV therapy and that ranges in the various studies from, you know, a day or two up to five days or up to nine days depending on the study.
Sandy Nelson:So it's not a right away, do we start oral therapy?
Sandy Nelson:But once they're able to tolerate oral antibiotics, and if there is a good, highly bioavailable oral option for that particular organism, then it is reasonable to discuss and reasonable to consider.
Sandy Nelson:You know, this individual has culture negative infection, or, You know, assuming that we didn't identify an organism through some of these advanced diagnostics.
Sandy Nelson:I think that we have to use a little bit more caution with culture negative infections simply because there is a greater chance that we're going to potentially miss the pathogen.
Sandy Nelson:I think there are some other considerations.
Sandy Nelson:We need a, you know, a functioning GI tract.
Sandy Nelson:We have to really consider those drug drug interactions because if a medication has excellent bioavailability but not if it's taken with some other medications that the patient's on.
Sandy Nelson:then that becomes a barrier as well.
Sandy Nelson:We don't have good data in support of its use in patients who are obese, simply from the standpoint of pharmacokinetics and drug distribution.
Sandy Nelson:I personally avoid oral therapy if an infection is life threatening or limb threatening.
Sandy Nelson:We don't have data to say that you can't use oral therapy in those settings, but I feel less comfortable in those settings that We really want to give these patients the absolute best tool in those situations.
Sandy Nelson:And, and the final point around oral therapy, which I don't think I appreciated until I started using more oral therapy.
Sandy Nelson:With IV therapy, we've, you know, many of our hospitals have developed these infrastructures to support patients after they leave the hospital.
Sandy Nelson:And those, we haven't really developed the same infrastructure to support patients who leave the hospital on oral therapy, but may actually still have significant toxicity, significant intolerances.
Sandy Nelson:And making sure that we have equal paths for bi directional communication with the patients so that we are ensuring that they're tolerating, adhering, and succeeding with that therapy has been one of the barriers that I didn't think about before I started doing it.
Sara Dong:I want to thank you all for emphasizing a lot of important points, but especially this collaborative and multidisciplinary approach to these infections.
Sara Dong:Another key theme in a lot of these CID reviews is thinking about ID topics through the lens of health equity.
Sara Dong:And Jodi, I know you've been leading some work and thinking about how racial disparities may affect PJI, and I'd love to hear a little bit more about that.
Jodi Pinkney:Thanks, Sara.
Jodi Pinkney:Yeah, we actually did a follow up study to this afterwards looking at racial disparities in PJI incidents and found that non Hispanic Black patients were twice as likely to develop prosthetic joint infections compared to their white counterparts.
Jodi Pinkney:And so really trying to understand why that is, at the end we realized that comorbidities played a huge role in this disparity, accounting for 26 percent of the difference between And so, thinking as a clinician, what are some of the health related social needs that may be acting as barriers for our patients going forward?
Jodi Pinkney:We've mentioned that this is management is extremely complicated and collaborative.
Jodi Pinkney:We have a lot of questions about diabetes, and we have been working with surgeons and infectious disease specialists, but also considering their primary care physicians.
Jodi Pinkney:You know, a lot of them have obesity that needs to be managed, diabetes, chronic kidney disease, and so are we also opening the channel for communication with their primary care providers?
Jodi Pinkney:You know, does their insurance cover their primary care visit?
Jodi Pinkney:Does it cover the medications that they need to be adequately treated for these other contributing comorbidities that can really affect their outcomes.
Jodi Pinkney:From the health equity lens, we usually need to take a step back and think of the multiple layers or structures.
Jodi Pinkney:One great framework to do this is the socio ecological model.
Jodi Pinkney:That looks at individual patient factors, which may include like comorbidities and, you know, level of trust, establishing trust, especially because this is such a stressful and overwhelming diagnosis for many patients that are now unable to do their day to day activities.
Jodi Pinkney:Walking the dog in the park is hard.
Jodi Pinkney:Going upstairs is hard.
Jodi Pinkney:Going to work is hard.
Jodi Pinkney:So, understanding what factors is.
Jodi Pinkney:um, are driving their decisions on an individual level, but also understanding what factors are driving their decisions on, um, the social level, you know, are we being flexible in the care that we can provide?
Jodi Pinkney:Maybe they can't come in during the week because they have, um, You know, they're an essential worker, they're working 9 to 5, so do you have flexible office hours?
Jodi Pinkney:Do you have language congruent information about what to do if you are having pain?
Jodi Pinkney:Is everyone on your healthcare team aware of the different ways that people perceive pain or communicate that they're having pain?
Jodi Pinkney:are open to that across all, all racial groups because there has been discrimination in that arm for just over a long time in the U.
Jodi Pinkney:S.
Jodi Pinkney:healthcare system.
Jodi Pinkney:So really, I think thinking about individual factors, social factors, health policy factors, including things like that you don't normally think about.
Jodi Pinkney:Hey, does this person patient of mine that I'm really invested in, I really want to see them get better, does they have access to a dentist?
Jodi Pinkney:You know, dental care is really important in terms of being a risk factor for transient bacteremia and seeding of your prosthetic joint.
Jodi Pinkney:But hey, a lot of our insurance plans don't cover this.
Jodi Pinkney:Private insurance is not, you know, easily accessible.
Jodi Pinkney:So thinking about maybe I need to connect my patient with my social worker or a free medical clinic or a mobile clinic that's dental led is something we really need to start taking into account as physicians, particularly now given the increased emphasis on social determinants of health screening that has now become mandatory as
Jodi Pinkney:of January this year, where hospitals accreditation will depend on the fact that they're screening and mitigating these social risk factors for patients, so I think just zooming out a bit and not just, you know, realizing that our patients have individual concerns, but also that broader policies and social needs are at play.
Sara Dong:At the, at the end of these, I like to leave it open in case there's things that you want to highlight or take home point.
Sara Dong:So I'll open it up and see if there's anything else you guys want to make sure that we add.
Sandy Nelson:I'll just like to thank you, Sara, for having us, but also a particular shout out to my co authors on this because, you know, it really was a collaborative team approach.
Sandy Nelson:And I just wanted to highlight that as an ID physician who specializes in musculoskeletal infections I think one of the most rewarding things that we really get to do is work collaboratively with our colleagues, not only our orthopedic surgeons, but our musculoskeletal radiologists and the pharmacists and plastic surgeons and others, and,
Sandy Nelson:and really working together to brainstorm ideas for really difficult or challenging problems has been a surprising source of a tremendous amount of joy in my practice.
Sandy Nelson:And so just wanted to express that and hope that those that listen can share in that joy.
Antonia Chen:I'll let go that from the orthopedic standpoint that it's wonderful that you guys actually listen to us.
Antonia Chen:I'm heartened by that because a lot of times I think these stereotypes in medicine are probably true when it comes to orthopedics.
Antonia Chen:We really don't think about things as deeply as you guys.
Antonia Chen:So we're thankful for you guys and we're thankful that you guys listen to us and we really all do this to make our patients better.
Sara Dong:A huge thank you to our guests, Sandy, Jodi, Aaron, and Antonia for joining Febrile today.
Sara Dong:You can find their article at State of the Art Review, Periprosthetic Joint Infection, Current Clinical Challenges from CID, linked in the episode information and on the Consult Notes.
Sara Dong:We'll be back next week with another STAR episode.
Sara Dong:Don't forget to check out the website, febrilepodcast.
Sara Dong:com, where you can find the Consult Notes, our library of infographics, merch store.
Sara Dong:Febrile is produced with support from the Infectious Diseases Society of America, IDSA.
Sara Dong:Editing and mixing is provided by Bentley Brown.
Sara Dong:Please reach out if you have any suggestions for future shows or want to be more involved with Febrile.
Sara Dong:Thanks for listening.
Sara Dong:Stay safe and I'll see you next time.
