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So, infection is common after combat injuries and this is particularly after blast injuries, traumatic amputations, uh increasing severity of injury and soft tissue and muscle disruption. And there is a high rate of recurrence of such infections. So, bone infection is usually a problem because it is it can be difficult to diagnose and difficult to treat. So we will discuss diagnosis first. Uh So on the first picture, you can see that uh this is clearly an infected wound. But on the second picture, you can see that the incision is a little bit red. Uh It may be infected metal work underneath, it may be a superficial infection and it can be difficult to tell. So we, we would say that we always assume that there is an infection. If there's underlying metal work when it comes to diagnosing, we often do a common laboratory tests like white cell count, neutrophil esr crp. But in chronic infection which is associated with implants, uh these may all be normal and they often are on all normal. Uh W I don't know if you want to add anything at this point. Other than to say when you're looking at at implant. If you ever have a sinus there, it's always infection. That's quite important. Yeah. So what about imaging? So there are many different ways to image a place with infection. There are anatomical scans like a CT or an MRI which only show you a static image. There are functional scams like isotope bone scan or labeled white cell scam which shows you a bit about the metabolism. And there are combination scans like spect or pet which show you a combination of the anatomy and the metabolism, but none of the scans are entirely 100% conclusive. So when we are trying to diagnose a chronic infection, then it is usually accumulation of all the evidence. So the clinical evidence and the uh laboratory tests and the imaging um rather than one thing which will tell you definitely whether it is infected or not apart from if as Deborah has said there is a sinus or discharge, then that is usually infected. So, microbiology, um we prefer not to take swabs from the surface because they're usually contaminated. So if we want to make a diagnosis about the microbiology, we prefer to take tissue samples and these are usually taken with clean instruments. So we normally take five or seven samples with a clean set of instruments for each sample, taking care not to touch the skin because this will give you a contamination with skin organisms. Uh The other way to do it is with a clean image guided biopsy. Once the samples are taken, it is important that they are processed and as soon as possible to prevent the risk of contamination, just a thought about taking samples when the patient's on antibiotics. So, bone infection is a chronic problem. Um It's been there for a very long time. So when the patient first presents and you think there's bone infection, there shouldn't really be any need to use antibiotics straight away. Samples of antibiotics are much better, but there will be some patient's who a presentation have got a very florid soft tissue infection. The bone has pussed out and you've got a hot red soft tissues in those patients', we would treat, settle the soft tissue infection down with a week to two weeks. Antibiotics, then leave it and then carry on with our diagnostic sampling or surgical management. Uh I think that's a very important point because the other advantage of giving antibiotics for a soft tissue flare up is that when it's the soft tissues have settled, it means that you don't need such a big soft tissue reconstruction. I think whenever we use antibiotics in managing bone infection, we need to be very clear what the goal of antibiotic treatment is. Is it to settle soft tissues short term or is it along with surgery? Your infection? But we need to be very clear that without surgery, antibiotics alone will never cure bone infection. Uh So just as we were saying it is impossible to have uh optimal antibiotic therapy without proper diagnostic microbiology. That's really important because as Deborah was saying, it's really important to understand the goal of treatment with antibiotics and to know what you're targeting. Yes, deeper. And I will have conversations about what treatment to put the patient on, to follow on from surgery. I can use very broad spectrum antibiotics as a best guess. But actually for the patient, what we need to do is find a regime, preferably an oral regime which is easy for them to take at home. But we can specifically target the organisms that are there. So some thoughts about what you might do if you don't have good diagnostic microbiology, we're very lucky in our practice, but we're able to do that. So I think you need to make a decision about if you do not have diagnostic microbiology, should you really be managing bone infection? I would suggest you shouldn't because if it doesn't work, you might well have limited your further surgical options. So it's going to be a risk benefit um of subsequent surgical reconstruction. And the only time when I would probably use a lyrical therapy is in the patient who has an acute soft tissue flare where you can't, well, you sometimes cannot get good diagnostic sample because you're not going to take the patient to theater. And I would work on the basis that is most likely to be staph aureus causing that. And I would choose antibiotics to target staph aureus. And my choice will be based on my understanding of local epidemiology. So if you have a lot of MRSA, you would need to target MRR SESSION. Uh So as we were saying, it's necessary to isolate the organism, but isolating the organism depends on really two things, how good we are taking the samples and how we process them. So it's necessary to be quite meticulous in how the samples are taken and equally in how they're processed. So that's talking about the diagnosis. Now, if we come to the management, uh generally speaking, when you see a patient with established bone infection, you have four options. So first of all, you can do nothing if you have a patient who is a poor host. So let's say a patient with multiple comorbidities who will not be able to withstand prolonged complex surgery and who is not very uh disabled by their infection or troubled by the infection. You can do nothing. The second option would be to just treat the infection with suppressive therapy. But if you're going to suppress it, then we lead to know what we're suppressing. So that means that you have to get samples so that you can target uh your antibiotic therapy. The third option is the option which we probably most involved in which is trying to eradicate the infection. So, limb salvage and then the final option is an amputation Uh So the decision between limb salvage and amputation depends on uh quite a complex relationship between many different factors. So there are factors related to the patient and batters related to the injury. So, for example, for the patient, it's a question of their wishes and expectations, their general fitness and all their other comorbidities for the injury. It is about uh the uh degree of bone loss, subsidy loss, whether the joints are affected or whether there's any vascular impairment. Uh It's quite complex decision making and we usually advocate that it must be done by at least two senior surgeons usually more. So the things that make bone infection difficult to treat our uh because usually implants or dead bone are covered by a biofilm. The biofilm is where microorganisms can exist in a very low metabolic state. So they're not accessible to antibiotics. Bone infection is also associated with instability of bone. With the problem of having a dead space once you have divided and a lack of vascular soft tissues to provide a good soft tissue envelope. That's we should also add that there will be some microorganisms that are difficult to treat because of their antimicrobial resistance that will be particularly relevant. The gram negatives, we might be left with antibiotics that have a lot of toxic side effects. Um And depending on the age of the patient and the co morbidities that may make treatment which is likely to extend for six weeks that might make that very difficult indeed. So we will focus on a limb salvage because this is the majority of the work that we do. Um And the principles of treatment consists of optimizing the patient first. Because if you don't optimize the patient, then uh the outcome of treatment will be poor. Are following that. We treat the injection by removing the biofilm, filling the dead space and using targeted antibiotics. And then we encourage fracture healing. If there is a non union uh by providing stabilization to the bone, to the soft tissues and providing good vascular soft tissue cover, perhaps we should add optimizing the patient that we would be very strict about making sure they're not smoking, particularly if we're going to have to use a plastics reconstruction for soft tissue and making sure that diabetes is well controlled and other comorbidities. Yes. So exactly, as Deborah has said, we tend to be quite strict about smoking because we know that in smokers, they have three times the incidence of infection and nonunion compared to nonsmokers. And then as we have said, we try to treat all the court morbid conditions before we start. So regarding the biofilm, as I was saying, it's, it is uh to be found on the surface of implants or dead bones. Uh it is uh it exists yearly on the surface and it contains organisms that are in a low metabolic state, which means that they are not replicating So they're usually inaccessible to most antibiotics. I will let ever speak about the antibiotics which can penetrate the biofilm. But because they are in the low metabolic state, they're usually undetected by the hosts mechanisms. So they, they don't really cause a big inflammatory reaction. Um And unless you remove the biofilm completely, the risk of recurrence of infection is high. I think I, all I would add here is that this really explains why antibiotics alone will not cure it. So you need to be very clear that managing bone infection and curing, it always involves surgery. Uh So radical surgical debridement, as we have said, is the only way to remove the biofilm. And it's important to remember that the entire net print of the implant has to be removed. So on that photograph, you can see that there was an infected plate and screws and the whole surface of the bone and where there's the screws, holes were, the whole thing has to be debrided. Uh If it was an intra medullary nail, then you would have to re mount the canal. So every part of the bone that has been in contact with the implant has to be divided. And good surgery is the main principle, as we have said in managing bone infection, we wouldn't normally give antibiotics as a prophylaxis, we would normally treat an infection as it occurs. So, if we have done a thorough divide mint, um uh presume for when you say a gunshot wound. Naturally, we're talking about a complex open fracture. So we would manage that in the initial phase by using antibiotics for either 72 hours or until the soft tissues have been closed, whichever is the smaller amount of time. But we wouldn't then continue the antibiotics prophylactically until an infection had occurred. As we said before, we would normally use antibiotics for six weeks after the surgery. Um, that seems to work, but arguably it may be more than we lead if you've done really adequate surgery or our practice is do you six weeks? Um I think there is an interesting discussion to be had about how much of that would normally be intravenous and then change to oral. And as time and experience has gone on, we tend to switch to oral therapy earlier. Obviously, that depends on the organism. Your, there are some instances, for example, if you're doing, um if you are using an antibiotic, cement, adding antibiotics to the cement does affect the mechanical properties of the cement. Um usually in bone infection, we are not using it as a structural material. It's usually just to fill a cavity um to recreate a funeral head or something like that when you, you wanted to be able to withstand weight bearing or something like that, when you might worry about the concentration of antibiotics. So my choice of antibiotics would be Vancomycin in cement, the staph aureus, which will also cover MRSA and on a minor glycoside, which will depend on your local sensitivity pattern. Regarding the concentration, you have to decide whether the cement needs to be structural or not. But my understanding is if it's not going to be structural, you can put as much in as you like, choice of antibiotics will depend on the sensitivity test from the laboratory because we're challenged with polymicrobial resistant organisms. We don't use bacteriophage therapy in the UK. But I'm aware there's a long tradition um in, in eastern Europe of doing that. Um And in the old Soviet bloc, but it is an area of research interest. As Debbie says, there is research going on with material finish therapy that we in the UK don't use. But I know that the consensus group on fracture related infection. Um They, they have discussed it and um there is some research going on uh from Andrey Trump who's who is obviously the bone infection guru in Berlin. So we'll talk about dead space. So if you have a soft tissue abscess and you uh in size and drain the abscess, then you can usually find a way for the cavity, the abscess cavity to collapse upon itself either by the drain in or something of that kind. But in bone infection, the wars of the abscess cavity are rigid so they can't collapse. What that means is that when you have done a thorough debridement, you get bleeding and you will then get a hematoma or a collection of blood within the dead space. Now, blood excellent culture medium. And so what we try to do as much as possible is to prevent that he returned from forming because the risk of recurrence of infection is high if we don't deal with the dead space. So we try to either fill it or eliminate it and we use mostly antibiotic carriers to fill the dead space. Usually bone infection is associated with either bone loss or instability. Because once you have done a thorough divide mint, you may end up with bone loss. So we find that using a circular frames or external fixation is the best way to deal with this. Uh because a circular frame is versatile, it allows you to get stable fixation to correct the for mitty and to recreate lost bone using destruction osteogenesis. So in in almost all cases, um I use external fixation because uh the surface area of an external fixator that is available to form a biofilm is less. So um we looked at recurrences and we found that we normally get a slightly higher risk of recurrence with into internal fixation. So we prefer to use external fixation because the risk of recurrence is less. But as I said, there are certain areas like the proximal femur which is difficult to manage with external fixation, at least in the UK. And so we use internal fixation for those areas that some areas of the body are not amenable to external fixation. So for example, if you have infection in the proximal femur, it is very difficult to control with a circular frame. So in those circumstances, we would normally exchange the implant uh simply to reduce, allow us to do a proper divide mint and to reduce the bacterial load. Although I know that there are many surgeons who are capable of putting circular frames in such a difficult anatomical position. But in the UK, we tend not to use it for such uh areas. And we are very fortunate in the UK because we work very closely with our plastic surgery colleagues and really their input is invaluable when it comes to treating these complex injuries. So we, we prefer to have vascular soft tissue cover when we're dealing with infection. And there's many reasons for that. Not only does it cover the bone, but it improves the vascularity of the area. Improved vascularity means that the antibiotic delivery is better because antibiotics will only go as far as the blood will take them. So if you have an area that is a vascular, then no amount of antibiotics will reach that area. So increasing the vascularity also increases the antibiotic delivery. And then finally, there is research that suggests that substitute, provide undifferentiated stem cells which participate in the bone healing process. So we remove the implant, do a third, a bride mint and cover it in the same sitting because if you do a third, a bride mint, um you will have bleeding bone and if bleeding bone is exposed, then it is likely to become colonized again. Uh We've recently uh looked at our own results of treating bone infection. We looked at the ones which we did a single stage and the ones which we did two stage and the results of the ones with the single stage are actually slightly better. So we tried to do it all in the single stage so that we don't leave any exposed bone. If we are doing it in stages, maybe where we can't get the substitute closure, then we would use negative pressure wound therapy. But that is only a temporary measure. It's not really used to treat infection because as I said in, in the UK, we are lucky, we work closely with the plastic surgeons. So we would always plan the cases with the plastic surgeons. So we wouldn't normally use negative pressure wound therapy if we have the plastic surgeons to help us to cover the soft tissues. If anyone is interested in reading more about infection related to fractures, then um in Europe, there is a consensus group on diagnosing and treating fracture related infection. And they have produced uh several papers on the diagnosis and management and other aspects of treating fracture related infection.