Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Of you who don't know me. My name is Emma Nickerson, I'm an infectious diseases consultant, um working at Ain Brooks Hospital. Um and I have a special interest in bone and joint infection and today's topic is uh fracture related infection. Um So I have no conflicts of interest to declare. Um So amazingly, there was no um working definition of fracture related infection um until 2017. Um So it's an area that there hasn't been um a huge amount of kind of consistent, er, work on, er, because we were lacking a definition. So, um there's been a great move to actually make a consensus definition um and the flow chart on that definition, um I'm just going to walk you through over the next two slides. Um So you, you've got obviously the suspicion of a fracture related infection and then you take the history and sort of clinical exam and then from that, you may have um er, suggestive criteria uh or um sort of confirmatory criteria. So obviously, if you've got a sinus or a wound breakdown or you've got perent discharge coming out of the surgical wound, then that's clear cut. But the sort of suggestive things would be uh local signs of redness around, um, a surgical wound or systemic so such as fever or kind of loss of appetite. Um, and then radiological and your joint effusion and blood tests as nonspecific as those are, um, and then persistent or increasing um, kind of wound drainage. Um, and then really you're going on to what's, um, these two arrows point down to surgery, which we'll go on to. Um, but you're then looking for the point of surgery to try and see if you can then confirm um, the diagnosis. Ok. Um So that's heading to this part of the chart and surgical exploration. So if you had from the history and exam, er, confirmation, then the arrow just points down here and you've made the diagnosis, if you can see pus coming out of the wound or you've got a directly down to metal, then that just confirms you've got a fracture related infection. Um, but say you've either got um, suggestive features or, um, then, or confirmatory features, you'll then go, when you go on to surgery, then you've got a further opportunity to try and prove this. Um, and this then comes down to the cultures. Um So the confirmatory criteria are going to be er, that you have two cultures with the same organism and the same antibiograms, that's the breakdown of resistances or sensitivities. Um, or you see the microorganisms on histology. Um, and then suggestive if you have just a single or um tissue sample that er grows organisms um that again adds to the suggestive. Um And then you would see how many suggestive criteria you have to see whether you think that makes the diagnosis. Um Yeah, and sometimes it's really obvious. So, um here are some examples from patients um of, you know, er, discharge from the wound, redness and discharge. Yeah, sort of wound breakdown and, and discharge. Um er, this is a wound and you can see the metal here. I quite like this, like googly eyes um in the bottom of that wound. Um or I mean, similar to this picture would then be er, the mirror signs where you actually see your own face reflected in the metal um visible at the bottom of the wound. Um Or if you're familiar with working at Edinburgh's, we have these, er, an epic, these fever charts. So this um the top is temperature, then you've got white blood cells and C RP. Um and er, these, you know, show high C RP, high spiking fevers. So it's really obvious there's infection but sometimes it's not nearly so obvious. So you've got no fever, the bloods are essentially normal. Um And you might have some very slight pinkness but it's difficult to know. Um or again, a sort of wound here, possibly it hasn't healed there little bit. This photograph hasn't taken as well but it's just slightly pink around the wound. Um but it's not totally clear cut. Um And it's difficult to know whether this is just some redness that you would expect postoperatively or whether this is actually indicative of an evolving infection. So sometimes it's really not obvious at all. Um whether there is going to be an infection or not. Yes. So you've got the suggestive criteria for pain, um er, that's increasing or new onset, local redness, local swelling and increased in the local temperature and then also fever. Um and then looking at the blood tests, you can do. So we all know that the odds are as part of your management, you're probably going to go to theater. Um And obviously, the infection markers change with doing an operation. So this is a paper that looked at what are the changes in white count? C RP and E sr if you don't have an infection, just the process of having an operation. Um And the C RP tends to peak at day two or three postoperatively and then is normalized by sort of day 7 to 10 postoperatively. Similarly, with the white count, it peaks day two or three postoperatively, but normalizes a little bit quicker. So usually by day five and the E sr, so that is um the erythrocyte sedimentation rate. So that's how long a tube of red blood cells sinks to the bottom. And essentially the idea is that when you've got inflammation or infection, you've got additional proteins particularly fibrinogen, which weighs down the red blood cells and so they sink faster. Um And that is, and this is a marker that generally moves more slowly. So you tend to get a peak um five days postoperatively um and it stays elevated for longer. So it's, it's still not back to normal even by day 14. Um and the normal range adjusts with age. And this, we find quite certainly, I find ES RSA very useful in bone infection because it does shift more slowly. So, in certainly some of the long treatment regimens, your um the CRP will normalize relatively early. And then the ESR gives you something to track more late later down the line in terms of your um antibiotic management. So those are just to give you an idea of what you'd expect it just as a result of having the operation. Thank you. And then so yeah, the suggestive criteria are that you either have um a secondary rise or you have a rise after the operation and then it rises again or it stays elevated over a period of time. The problem is none of these are specific to bone and joint infection. And therefore it could be um these could rise for other reasons and that's always something you need to be mindful of. Ok. Blood cultures are an essential part of the workup if you're thinking about infection um and should be collected regardless of fever. And because there, it doesn't always, um, tally that you'll, they'll only be positive when there is a fever. So, if you're thinking about infection, then they should be part of the work up. Ideally, multiple sets, at least two. Um, and that's to help try and work out, er, particularly with these sort of more skin related organisms as whether this is, represents skin contamination or is a true pathogen, particularly if there's metalwork um in ti because it sort of coagulates negative staph, which may be highly relevant with metalwork in place, could also reflect skin contamination when the blood cultures are taken. So two sets helps to try and um resolve that. Um And then you also need to think about prolonged culture. So particularly with the kind of more indolent low virulent presentation, um prolonged culture may be important for some of those less virulent organisms to give them time to grow. So, osteomyelitis is a progressive infection of bone that results in inflammatory destruction, followed by new bone formation and normal bone is highly resistant to infection. So, osteomyelitis arises when either there's a large um inoculation of organisms, trauma leading to damage of the bone or the presence of foreign material. And often with fracture related infection, you're gonna have all three of those, in fact. No. Um So normally, um outside of the sort of fracture related er context, the sources of osteomyelitis are either the bacteria introduced by hematogenous seeding. So that may include intravenous drug use contiguous spread. So you've got a pressure wound that then, er, goes deep to bone trauma, obviously rather dramatic example of a, an open fracture. Um, and then surgery with or without prosthetic material. Um And so any of these may be relevant in the context of a fracture related infection. Yes. And so the pathophysiology of um osteomyelitis. So, the bacteria enter the bone either directly because it's an open fracture, um or the more common scenario, um er is that they spread hematogenously um and then they a they adhere to the bone. Um and sort of set up, you get this acute inflammatory reaction in the medullary canal. Um and that er inflammation spreads kind of from the blood system to the aversan system into the bone and you get a very strong in um infiltration of neutrophils to fight that in that um er infection and you get the formation of subperiosteal abscesses right there. Um and also um you get a suppurative injury and also ischemic injury. So, with the inflammation, you block off some of the smaller blood vessels and that leads. So you get pus that can then build up under pressure um and burst through, that creates your sinus. Um And you also because of um the inflammatory damage and, and er ischemic damage that from the inflammatory kind of blocking of smaller blood vessels, you then get areas of sequestrum, so dead bone because of the loss of blood supply um uh so you get um that build up and then um the as a reaction to the um compromised blood supply and the bone trying to repair itself, you then get this sort of sheath of new bone trying to grow over the top, which is the involucrum. Um and essentially um acute osteomyelitis is infection in the bone prior to the development of the sequestra. So these areas of dead bone before they develop, that counts as acute osteomyelitis. And then once you've got sequestra, it will be considered chronic osteomyelitis. The problem is you can't see what's going on on the inside of the bone um clinically. Um And the reason this matters is because in acute osteomyelitis because you haven't got sequestrum, antibiotics alone may be sufficient to treat it because you've still got an adequate blood supply. So the area where the infection is, you can still get antibiotic delivery. But once you've got sequestra, you've got pocket, it's a dead bone, dead bone, no blood supply, no antibiotic delivery. And then you, that's why debridement surgery becomes essential as well as antibiotics. So, what's difficult is in many situations, you're not sure the time frame of when acute changes to chronic. Um And so we unless it's a very obviously acute infection, we tend to go for the debridement and antibiotics in case there is any um sequester involved. Yes, this slide is just to remind um you that different parts of the body are colonized with different bacteria. Um, and, er, it varies also person to person. So particular infections are more likely to arise in different places but the bugs don't always stick to the rules. So you can get um, ultimately any bacteria in any location, but just that it does vary over the body. And then another really important concept is the immunity of colonization. So, um, when you've got your normal flora, you've got kind of bacteria that are um usually rather nicer um covering the surface of your skin. But with, when you take antibiotics, um that reduces your colonizing flora. And so there's kind of opportunity for other um bacteria to set up home. And so you then get new colonizers which are more likely to be kind of hospital acquired and drug resistant. Um taking up the opportunity of where the normal flora has been lost with antibiotics. Yes. And so just thinking about that, that over time your bacteria, the flora will change. Um So this is a paper um from both ST data from Stanmore and Oxford. So eight year period, 2011 to 20 1906 patients in these two UK specialist centers. Um and we had, there were 74 patients who went uh underwent repeat, total knee replacement and 32 who underwent repeat, total hip replacements. Um And over this is the microbiology um kind of over time. So you can um if we take table one a one first. Um this is looking at which organisms but then in revision, 1234 and even five for some poor patients. Um And you can see that staph, aureus and coagulase negative staph are the most common initially. But then progressively over time, you're more likely to get the gram negatives and fungi. So, you know, it generally gets more difficult because your colonizing flora has changed over time. Um And then yes, it tends to change increasingly more. So this is looking at the n the how many times the organisms have changed or whether you get no growth. Um And er this one, I was gonna say the problem is my screen is teeny. Um And I can't seem to uh so I'm struggling to see my own slides. Um And yeah, so no growth is more common. Um sort of in the relatively early stages um less. So later on. Mhm. So um as an example of this, this um er is from a case, er so a lady 81 year old lady relatively co morbid. Um So she had, she was on Warfarin for atrial fibrillation. She was a type two diabetic, she had replaced aortic and mitral valves. She was hypothyroid and overweight and she was involved in a road traffic accident in July 2017. And on this nice reconstructed um er imaging, you can see that she's had an acetabular fracture. Um So the decision was to give her a fix and replace. Um so to fix the acetabular fracture and give her a hip replacement all in one go. She had various other um kind of injuries as well. And then it also transpired that she had a tibial plateau fracture as well. So she ended up having a series of operations. So she had her initial fix and replace operation. Didn't, no samples were taken at that moment and she just had standard prophylaxis um with flucloxacillin. Um she should really have had a dose of gent and I don't think that was given um or anyway, um uh and then that unfortunately became infected. So she had a wash out. And at this point, we've got developed some gram negative bacteria. So, e Coli and klebsiella pneumonia and her antibiotics were empirically changed after the operation to Vancomycin and Tazocin. Um And then in light of the sensitivities of these gram negatives, then she was switched to Coamoxiclav. So we could downgrade a little bit. Then um the infection didn't settle and she then under formally went, underwent a debridement and implant retention of that hip replacement and acetabular um fixation. And at this point, she grows Serratia marcescens, which is a more difficult gram negative bacteria. And we had to escalate her therapy to meropenem. And then unfortunately, um there was a hematoma and because of the worry that the hematoma would mean that was very easy for bacteria further bacterial infection. She then um underwent a further a repeat um debridement and implant retention this time with the femoral head exchange. Um And at this point, we grew pseudomonas aigos and enterococcus facium. That was a VR. So we ended up having to change her antibiotics to ciprofloxacin and linezolid. So these bacteria are much more difficult. So over time, you can see she's become colonized and infected with ever more difficult bacteria. Um So, ideally, you don't want to be having to do serial operations. So what makes a bad bacteria? So, there's several factors that we will go through. So there's severe sepsis, biofilm formation, drug resistance, misidentification because the bacteria are difficult to grow and limited antibiotic options. So, sepsis, certain bacteria are more likely to give you a kind of life threatening infection that results in severe sepsis or septic shock. Um and the kind of big hitting bacteria that we particularly think of uh staph aureus including MRSA group, a streptococcus also known as streptococcus pyogenes, Streptococcus pneumoniae, which is pneumococcus and Neisseria, Meningitidis, Meningococcus. Um So those are your kind of big big hitting gram positive but severe infection. Um and they're also likely to have a risen or seed to other places. So, certainly Staphylococcus aureus, um endo infective endocarditis is the other major concern. Um As a further metastatic site of infection, osteomyelitis is also a common location for a staph aureus bacteremia. Um So just being aware of where else the infection may be ripae strep obviously can cause necrotizing fasciitis. You can get a very severe infection. Um, and certainly all staph and streps can produce a variety of toxins that can help the bacteria move through the tissues or er, cause other problems. And so sometimes with your antibiotics, you need to be thinking about um antibiotics that particularly target toxin, er, production biofilm. Um So organisms that produce biofilm are much more likely to lead to a persistent infection and can make the infection very hard to eradicate. And the organisms we're particularly thinking of related to biofilm. Staphylococcus aureus, again, and the coagulase negative staphylococci. So, staph epidermidis or capitis hominis, those types of bacteria and putteri acne. So this was previously known as propionibacterium acnes. Um pseudomonas origins is also good at biofilm formation. And although streptococci weren't particularly originally thought of as causing um biofilm, I think there's probably increasing evidence that they do. So, they're another um group that we need to consider. So what is biofilm? So this is where you've got your free floating planctonic bacteria that encounter a surface in the fracture infection. This is going to be the metalwork put in to fix the fracture um and they can within minutes become attached to that surface, they then to produce this sort of slimy substances, sort of glycocalyx um matrix um that and colonize the surface and they are able to then um er are kind of protected within that um matrix. So that they're less susceptible to the immune system that, um, and this kind of, er, matrix um, can develop within hours and then the bacteria go into um, er, a more dormant state, which means, and given most antibiotics work when bacteria are replicating, that's hugely problematic and they're protected in this matrix and then, um, they can convert to be planctonic again, er, and set up a new, um, area of biofilm so they can keep propagating and there's sort of special, er, er, thought to be different signaling pathways within a biofilm that they, the bacteria can communicate um and spread out to colonize the whole er, surface and they take on unique roles within this biofilm to evade the immune system. Um, and antibiotics. Um, and particularly if they enter a dormant state, um, they are then really difficult to target with antibiotics because antibiotics generally work when bacteria are replicating. Um, and they don't need to be in, um, they can be in a dormant state once they're in the matrix because they're protected within it. And so there are estimates that bacteria are perhaps 1000 times more resistant to antibiotics in this state because of that difficulty, then drug resistance. So some bacteria um have acquired resistance genes. Um, and that makes them much more difficult, er, to treat cos you've got less antibiotic options. Um, and the antibiotics may be more toxic. Um, and therefore you're more likely to have morbidity from the antibiotic treatment. Um So just to make sure that you're kind of aware of all these acronyms. So MRSA is methicillin resistant staph aureus. You've got Vancomycin resistant Enterococci, which can be either enterococcus facium or faecalis. Um You've got the resistant gram negative. So you've got your extended spectrum beta lactamases, your ampicillin producing um gene c er resistance genes um and your carbapenemase um producing inac ac. So those are your kind of gram negative collection. And then some bacteria if you um are have what this inducible resistance. So certainly bacteria like Enterobacter cloacae and Serratia marcescens, they test in the lab are susceptible to beta like oh beta lactams. But in reality, if you treat with beta lactams, then they induce their own resistance. So they will, those antibiotics won't um be effective. And it's important because that isn't always appreciated. And sometimes you can get um misinformation um from the lab because they test technically test it up a sensitive. But in reality, it, they won't be effective treatment. Some bacteria are just difficult to grow. You either need special media or very particular culture um um conditions for them to grow and anaerobes are always more difficult to grow. So something like folia magna needs time. Um it won't grow in a sort of standard culture of three or four days. It won't grow in that, in that kind of time frame. Um So it's important that you are thinking about the more difficult bacteria so that your cultures are set up to capture these um brucella, you would need particular media and mycobacterial infections. Again, you need different media um to be able to grow them. So you need to have thought about it otherwise you'll miss them. Um Some antibiotics, there are just very limited options. Um So you may well be aware that pseudomonas, aeruginosa, there's only one oral antibiotic that works against pseudomonas. Um And that's Ciprofloxacin enterococcus faecium, the only oral antibiotic possible is Linezolid. Um So they're just, you know, you, you've particularly if you're trying to give oral therapy, there's very limited um options and then sometimes you're in the situation. So you may or may not know. And essentially, when the lab determine whether a bacteria tests up as sensitive or resistant to a particular antibiotic on the susceptibility testing, there are these huge charts um kind of set up European wide that determine what the cut off between sensitive and resistant is, they're called the UCAS breakpoints. Um And some bacteria just there's limited data. So there aren't set breakpoints. So it's hard to interpret exactly what, at what point the bacteria will be either sensitive or resistant to certain bacteria and that can limit your antibiotic choices because it's not always clear what they will be. Um And then the other aspect is just because you've grown a bacteria isn't necessarily actually causing infection. Um So whether the bacteria are just colonizing the area or whether they're truly infecting and that's where the really critical part of proper sampling comes in. And then also just really careful. So you in the operation may be very certain where your sample was taken exactly at what level or which part of the tissue. But unless the sample is labeled really carefully, that critical information will be lost. So ensuring that you're a sampling in a, in a an accurate technique and then also really carefully labeling the samples is so so important for making sure you get the best information possible. Um And that's, you know, as the infection doctor, we are entirely reliant on the information that you can obtain for us. So really good sampling so that we can then optimize the treatment for you. Um because we need to know what the organisms are, what their sensitivities are so that we can choose um an antibiotic regimen that's going to um cover the bacteria that are causing the infection and minimize the morbidity from them. Um And that's where it's a real partnership between the surgeons and the infection doctors to make sure that that um the the samples and then the interpretation is as optimized as possible. And for that, um we really need plenty of samples by plenty, we mean at least five tissue samples from different areas, not just one big bit chopped up into five pieces. So five separate samples, each sample should be taken with separate instruments and a separate pot. Um You need to think about what samples you're going to do to get prolonged culture to things like sonication or um palatini. So, additional sampling techniques um to maximize the chance of identifying infection. Um Any fluid thinking about both universal tubes and blood culture bottles and swabs are a total waste of time. If you remember nothing else from today, just don't send swabs. We want t actual tissue or pus or bone not interested in swabs at all. Um So Oxford, um the bone infection unit at Oxford have um er, designed this sort of protocol which er, to really optimize the sampling. But given how important this information is. So in an ideal world you would be, have be off antibiotics for two weeks. Um beforehand, obviously in the trauma setting that may not um er, be possible. But yes, you're ideally wanting er, a period of antibiotics before um you take the samples before you give the prophylactic antibiotics. Um at least five samples and I'll show the data as to why that five samples comes about. It needs to be separate instruments and a separate sterile pot for each sample taken from a different location. They need to be different and predetermined locations. Um A and ideally um histology as well. And it's important to take the samples at the beginning of the operation because if you do it, once you have kind of irrigated, then the bacteria have washed everywhere. It's not helpful. You want to know exactly what is, where um so doing it early in the operation um is important. So this um is the data that er explains why er, or how, how they came to five s five or six samples as the optimum. So this line here um is showing if you have one sample positive and you've taken either 1234 or five or six or seven samples. If only one is positive, if it's one from one, then um so this is er on your um y axis, you've got the true positive rate and er the X axis is the false positive rate. So the further you are into this top left hand corner is the more the greater accuracy um of your sampling. So if you, if you only have one sample positive and you've taken sort of 234 or five samples and only one is positive, you're increasing the false positive rate. So only one out of five or six samples is, may not be a true infection. Whereas um if you look at the triangle, so that's where you have two samples taken from either 23456 or seven samples. So if you have two from five, that's showing a pretty accurate um determination of infection. And um the diamonds here are, if you have three samples from 3456 samples. So this is where the kind of two or more positive cultures from five or more samples comes from. So it's just trying to, the result that gets you closest to this top corner. So that's where the, the, the sort of data that determined why it's, we take it um a positive as two separate cultures from five or six samples. Um So the option, kind of the options having taken your samples, gram staining. So it's not infrequent um for people to say, oh, we aspirated a joint and, er, there were no organisms there so it isn't infected. Um, I don't know if people want to put in the chat. What you think the percentage of positives on an aspirate? So, a gram stain being positive on an aspirate. What's the percentage you put your answers in the chat? Yeah. So we've got 10% and 20%. It's rising over time. Ok. Um, so the answer is, um, 40% but still it's worse than tossing a coin. Um, and so, uh, you know, it's a complete bonus if it's positive but it, it doesn't move you forward at all if it's not. Um, so certainly you can't exclude an infection just from the gram result. Um, culture. I'll come on to, er, sort of, er, my next slides, got some pictures of, kind of how we culture. Um, so I'll cover that a bit more in detail in terms of um, P CRS. So if you don't grow anything, there's still a chance to find out um the information that of what could be causing the infection. So, the 16 S um is the ribosomal er um part of the er ribosome of bacteria that's highly conserved. Um So the 16 S can, you can identify um many bacterial species from that and 18 S is the similar equivalent for fungi. Um and those tests get sent off to Great Ormond Street Hospital. Um and there are also some specific PCR S that are done. So generally the kind of major infections. So, staph aureus, um er the group, a strep some other er streps, er pneumococcus, they all have er, specific PCR S that are run as well if you, so if you request a 16 S PCR, those specific um P CRS will also be done as well um in terms of histology. Um So, er, in Cambridge, we're classically not very good. We were outliers on the Aviva trial um for not taking enough histology samples, but ideally you should be taking um histology and really it's a kind of bimodal um information. So if you have five or more neutrophils per high powered field, then the positive predictive value for an infected non union is 100%. Um and if you have no neutrophils per high powered field, then the positive predictive value for this being an aseptic non union is 98. Obviously, it's tricky if you get somewhere between those two. So 1 to 4 is difficult to determine, but if you've got none or five or more then you've kind of got, you've got your answer essentially. And next generation sequencing um, is being used in some fields but orthopedic infection that, that hasn't really been um progressed as far. So, a very much under investigation and research tool at the moment. So, in terms of culture, um it's really important um for, er, you as the surgeons to understand what happens in the lab and to have a good working relationship with either your microblog or infection doctors to understand what is what we need from you in terms of your sampling and for you to understand what we do with those samples, er, to make sure that we're optimizing um the patient care. So most things are plated out on solid agar plates. Um This is an example of a bati um tube. So this is a sterile tube with sterile glass beads in um it has some sterile water in as well. Um And the idea is you put your tissue into that, it gets vortex. Um and that the glass beads bash into the kind of bone or tissue and help release bacteria and then they get cultured for a week and, and that we have certainly found in Cambridge that really increases the sensitivity of your cultures. Er, so that you're more likely to find the anaerobes, the, the kind of low virulent organisms because it's cultured for longer. Um And the er, you've kind of allowed, you've helped the er, tissue to release the bacteria um that may be present, even if they're only in low numbers, you can also do liquid cultures. So this is particularly important um for, if you're considering mycobacteria and they're generally done in liquid culture um and then also fluid into blood culture bottles. Um So blood culture bottles have some kind of extra media, um make it easier for particularly some of the bacteria that are more, less easy to grow, um are more likely to come up in those. Also blood culture bottles are in a machine that flags instantaneously. So you're not waiting for someone to check it several days down the line, you're gonna get a much quicker result if it flags in the blood culture bottles and then these two pictures are just to make sure that you understand in terms of susceptibility testing. So this is um if you're doing it on zone size. So this is a, um you've plated out the bacteria and then you put down these white discs are the anti different antibiotics and then the zone around it um determines, er, you is measured and then the UAs breakpoints tell you whether that's sensitive or resistant. Um And that's a little bit cruder because you're just measuring the zone size. This is where you're doing it, an E test. So this is a um a strip of antibiotic that's graduated in terms of concentration. So um down here is if is a much lower concentration, um up here is a much higher concentration. So you, it, the you read off on the marker um as to er an exact minimum inhibitory concentration. So this is a more accurate way of doing it but more expensive. Um So certain antibiotics are done like this. Um or if there's doubt from the zone sizes, if there's ambiguity, then you go on to do what's called an E test. So these um inhibitory concentration marking levels, sonication. So this um er er was a kind of the brainchild of er, Andre tramps. Um So he er this is where you take um your prosthesis, put it in a sterile container and then vortex it and then take the an aliquot of the liquid um and, and culture it. Um And in his original New England paper, um it, the sonicate fluid increased the sensitivity and specificity compared to routine tissue culture. Um And 14 cases um were identified only by the sonicate fluid. They were all the other tissue cultures were negative. Um And at the time, it was seen as a kind of massive breakthrough in terms of how you were going to identify some of the kind of low virulence um prosthetic joint, particularly associated or metalwork associated um infections. Um And, but it really depends essentially what your other sampling technique is like. Um So this er shows essentially this line here is, if you've got um tissue alone, the triangles is sonication alone and the circles is cultures plus sonication. So, doing your normal um and this is the number of samples. Um And so sonication adds a bit, but if you're already doing five samples, sonication doesn't add very much in terms of how many organisms you're going to um add. So if you're, if you are a center which has a, you're already doing very limited culturing, then sonication may make a bigger difference. But actually, if you're a center that's already doing five or six tissue samples, then sonication doesn't make necessarily a big difference. Um And certainly, um it's gonna be more accurate to do a combination of tissue and sonication rather than relying on just sonication. And some of that relates to the potential contamination through the process. So, thinking back to our flow sheet of the fracture related um infection. So, the confirmatory criteria is that you have phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue implants, um including sonication fluid if you need specimens taken during um er the operation. Um And this is saying that you should take, you know, at least three, samples separately um and not including um a sort of sinus tract or, or superficial swabs. Um And that if you see microorganisms on their histopathology, then obviously that also confirms the diagnosis. And then the suggestive criteria is if you only get a pathogenic organism identified from a single culture. So just uh yes, it's not quite as certain and for the reasons we've been through and then thinking about um what are you gonna be considering then in terms of your antibiotic treatment? So, having cultured and done the sensitivities, um er of the organisms. So then what are you gonna do with that information? So initially having, where after you've taken the samples and before you get those culture results, you're thinking about empirical broad spectrum cover. So hedging your bets until you've got the culture information and really important that you think about both gram positive and gram negative bacteria to cover once you've got your culture results and you're thinking about targeted therapy. And then the other things that you need to be thinking about are biofilm activity. Um So have you got retained metalwork, do you need that bone penetration? Are your antibiotics actually gonna get to where you need them to be? Are you gonna be giving intravenous or oral therapy side effects and tolerability? And then we'll also touch on local antibiotics as well. Um But the really important bit is that antibiotics alone are rarely enough. So, antibiotics that we talked about can't penetrate, sequestrum, sequestrum is dead bone, it has no active blood supply. The antibiotics are not gonna be delivered there. Antibiotics that we've already discussed don't penetrate biofilm. Well, um they don't, can't act on bacteria that are in a biofilm and dormant. Some antibiotics just don't get into bone well. So, flucloxacillin orally is pretty hopeless at getting into bone. Not a great option. Intravenously is fine. And also, um, antibiotics depend on the bacterial replication. So in chronic osteomyelitis, they're more likely to be in a chro a dormant state and therefore more difficult to treat. And it's a numbers game, you know, the antibiotics, it's limited what they can achieve. And so really the role of the surgeon in terms of source control and debriding adequately to remove as much of the infected material is critically important because otherwise the antibiotics haven't got a chance thinking about just your empirical antibiotics, thinking about um just giving you a clue about which bacteria are covered um by which er antibiotics. Um So the likes of Vancomycin and Tiopronin, they're the glycopeptides, they're gonna cover your gram positives, um Linezolid and then its newer version tees um Dalbavancin is a very long acting version of a glycopeptide to like Vancomycin. Um those that have got good gram positive and gram negative cover. So the likes of meropenem, Tazocin, Ceftrixone for certain limited bacteria and then uh cotrimoxazole or Sceptrin, um which is highly bioavailable, so good as an oral option. Um your anaerobes are gonna particularly be covered by metroNIDAZOLE um as well as meropenem and then gram negative cover, only likes of ciprofloxacin and ceftazidine. Um And then thinking about, you know, we always worry about that resistance has become a bigger issue over time. So um the Oxford Bone Infection Unit, er did this paper. So, looking at the microbiology of chronic Osteomyelitis changes over 10 years. Um and er interestingly, so the M RSA rate was lower in the period 2013 to 2017 compared to 2001 to 2004. So it went from um 30.8% in the earlier period to 11.4 in this later period. So, statistically significant drop. Um but the multidrug resistance, so your non M RSA drug resistance, this is particularly gram negative was kind of similar over time. Um So 15.2% in the later group versus 17.2 in the um earlier group. So perhaps against what we might think um overall, actually resistance is not a getting, necessarily w is not getting worse in terms of the resistant organisms, think about which antibiotics are good at biofilm. So over and above everything else. Rifampicin is undoubtedly the best. Um, absolutely fabulous. Um biofilm activity for Staphylococci, probably Streptococci um and er put bacterium as well. Um And the, the issue is that it, there isn't a high barrier to resistance. So you just have to be careful on the timing of the Rifampicin ciprofloxacin. Um I'll show you some data for that, but that's very good for gram negatives, including pseudomonas and then Daptomycin um as an interven intravenous agent. Um also has some er biofilm activity um and that's active against gram positives. So, rifampicin, um, the best evidence er, is for Staphylococci, um it's generally better given after five days. And although this sort of, there's this kind of way up cos obviously, as we talked about, you know, biofilm can start within hours of planktonic bacteria settling on, er, a, a prosthetic um surface so that your nice shiny new metal. Um but it's because it has such a low barrier to resistance. If you've still got an open wound or you've got a vac dressing, the problem is you've got bacteria on the surface that then can come in and if they become resistant um with the usage of rifampicin, you're going to contaminate your metal and or wound with resistant bacteria that are on the evolving flora on your colonizing kind of skin surface. So that's why there's this slight delay um as a kind of balance between acting quickly before your bacteria get too established on the metalwork versus the, the possibility that the bacteria will be able to become resistant. It's best in combination with um ciprofloxacin. Um and there's no association with dose which is interesting cos often people worry about being able to dose it high enough. Um Rifampicin is def the side effects are definitely dose related. So actually 300 mg twice a day is enough. Um and you don't need to go higher on the dosing. Um er particularly this, all this data comes from this fabulous paper called if when and how to use rifampicin. I would highly recommend it. Um, it gives you really great data on um, er, its usage. And then this is the paper um, for the, the sort of evidence for um, ciprofloxacin. So this was looking at gram negative prosthetic joint infections, managed with a dare. So you're leaving um, the implant in and therefore you're worrying about biofilm on that, um, er, implanted metal work. Um And this is taking what any gram negative infection and it's using ciprofloxacin or not. So this is the curve sort of um if you use er ciprofloxacin and this is if you're ciprofloxacin resistant or you don't use it for whatever reason, either an in an allergy or it's not tolerated. Uh All the bacteria is resistant, whatever the option is, but the survival curve is way better if you can use ciprofloxacin than if you can't. Um But obviously you will, you may well be aware that um the medicines, er regulatory body suddenly came out with this kind of warning about ciprofloxacin. Um And it was an interesting that they did in that there was no new data um that had emerged. Um But they just decided get more excited about the data that was there before. So the things they were particularly worrying about is that you can get tendonitis or tendon rupture myalgias or arthralgias, per peripheral neuropathy, anxiety and depression. And there have been people who've committed suicide um after starting Ciprofloxacin. Um And so the, the particular concerns are those who are over 60 in AK I A transplant recipient or on concomitant steroids. So those are a group that to be particularly sort of aware if you're clocking up a number of those factors. And so now, formally, you have to document that you have warned people and given them the information leaflet if you're going to use ciprofloxacin. Oh, but on the basis that it does make a substantially significant difference in the outcome, that's the reason that we think that the risk benefit favors its usage in um gram negative metalwork um er infections. So, fracture related infections that involve metalwork. Um for a long time, there's been a kind of debate about intravenous versus oral antibiotics. So, um and I guess, you know, why give IV antibiotics? So it might be um that you're thinking person can't swallow or they can't absorb and you haven't got microbiological kind of, you haven't got oral options as part of your um susceptibilities. Um in terms of thinking about penetration to different body compartments or the need for rapid activity. If someone's profoundly septic and some of it is ideological, people have just always believed that intravenous antibiotics are stronger or the kind of gold standard. Uh but that's not necessarily true. Um But one and very important aspect is the bioavailability and bone penetration. So, particularly with fracture related infection, you've got to be thinking about these, so some antibiotics, um, er, just don't get into bone very well. So there's your flucloxacillin, 10% bone versus serum concentrations. Um, whereas something like profin 100% so, um, the quinolones, er, are pretty good. The, so ciprofloxacin you may be worried about, it's 48% you dose it higher. So when you give it intravenously, you give 400 mg when you dose it orally, you give 750. So that's how you get round. Um, er, that drop there. Um But yeah, so Doxycycline 86%. So some, there's just a big variation um in penetration. So there was a Cochrane review in 2013 which included eight sort of randomized controlled trials or quality randomized controlled trials, four of which assessed oral versus intravenous antibiotics. They were all quite small. Staph forus was the most common pathogen and it didn't find that there was any significant difference in treatment outcomes, um er, or in moderate or severe adverse events. So this was then the trigger um to um what hopefully you've heard of is the Aviva trial. So the oral versus intravenous antibiotics for bone and joint infection trial that was published in the New England journal. Um and however, you analyze it basically, there's no difference. Um So this was um er, a trial of just over 1000 patients. There were 26 UK sites. Um Aden Brooks was one of the recruiting centers. Um, it was for adults. So those patients 18 years and older, um, and essentially, once you'd got informed consent, they were randomized and it was after you'd had seven days of intravenous antibiotics, you were then randomized to either continue intravenous or switch to oral. Um, and the inferiority margin was set at 7.5%. Um, look at the demographics. There were um, no significant differences between, um, er, the two groups but important to note that native joint septic arthritis because it's generally m may only require four weeks rather than um, six weeks of antibiotics wasn't included. Those with septic shock weren't included and those with a staph or bacteremia. So, bone and joint infection as well as a staph bacteremia were excluded on the basis that staphylus bacteremia should be treated with IV therapy. Um, as I guess you would expect Staph ari and then coagulase negative staphylococci were the most common um, species then followed by gram negatives. Uh And about 15% 16% were culture negative. Um And er, yes, however, you analyzed it, the outcomes were the same. Um but the there was a significantly shorter length of stay if you were on oral treatment than intravenous. Um and you were only going to get IV or significantly more people got IV associated complications in the IV group. Not, not surprisingly. And, and you were also more sig significantly more likely to stop ivs and have to switch or switch, um, whichever path you'd been randomized to if you were on IV therapy rather than oral. So more people had to switch from ivs than orals. Um, but adverse events was quite a significant part. And you'll see here that 10% of patients had an antibiotic related, significant, um, so serious adverse event. So that's grade three or four on a trial protocol. So that means you've had to stop the drug or change drug or take some kind of intervention against the adverse event. Um, so that, and that's 10% of patients. Um, so it's, and 14% had to change strategy because of problems with the antibiotics. So, antibiotics is, you know, it's a complicated, um, part of the process. They also did um, a financial analysis, um, and, er, it was significantly lower cost to do oral antibiotics about 2740 lbs less. Um, so if you kind of scale that up in terms of the number of, um, orthopedic infections, um across the NHS, it was felt that it would be about a 17 million lb saving in a year, but sort of post aviva kind of trials are all one thing. But what happens in reality afterwards. Um, so, er, this is a paper from Stanmore. Um, so they changed completely, um, from having, er, an, a, so an intravenous antibiotic service to predominantly doing it as orals. So the default being orals and then only using IV if they couldn't use orals. And so they made that kind of change in May 2017, the study covered 328 patients. They were 100 and 45 before the change and, um, er, 100 and 83 after the change. Um, and, er, the definitive failure at, um, one year, so 13.6% failed in the pre changing group. So that's why you're defaulting to IV and 18.3 in the post um changing. So where you're defaulting to oral therapy, about a third of the patients had an adverse drug reaction. Um More common in the post group, particularly gi upset, which is understandable if you're predominantly giving oral antibiotics and if you look at the Ky, you just worry that there is a gap developing. So whether over time, if they'd continued longer than a year, follow up, whether that might have become significant. So just um yeah, the real world is always slightly different to trial. So good to see kind of as we get more data on that, how that pans out. What are we doing? Um in Cambridgeshire, we've just set up a copa service or a complex oral antibiotic service. So this means that um the, the same in the same antibiotic service runs whether you're on intravenous and under a or you're on orals and under copa um same team, same, follow up, same input. Um Just to see whether because previously, we weren't doing that much oral therapy or as much oral therapy as we could have because it was complicated, logistically, more complicated, logistically. Um So we wanted to iron out that difference. Um And then actively try and get more people on oral therapy. So our strategy is generally that if we've got culture growth, so we know what the infection we're treating is. And there are good oral options, thinking particularly about um bioavailability and bone penetration, then we would go for oral therapy as long as logistically, we can get that set up. Um And if they're culture negative, just because it's so much more difficult to predict the sensitivities with um oral antibiotics than it is intravenous. We tend to default more to intravenous if they're culture negative, how long um to treat. So, amazingly, the origin, the kind of six weeks as being standard therapy for Osteomyelitis actually comes from this um 19 seventies, er, New England paper, which just says in our experience clinically recurrent Osteomyelitis is rarely controlled without the combination of careful, complete surgical debridement and prolonged, plucked out of the air, 4 to 6 weeks, parenteral antibiotic therapy at a high dosage. So it's actually remark and that sort of just became the standard um without actually being particularly er challenged um since that time. Um but obviously, it depends on um the metalwork. So if you've got an external fixator or some kind of um frame, um so essentially counting as external metalwork, then six weeks should be enough. But if you've got internal metalwork, so an intimal nail or plating, then you're looking at double that um be because of the issue of biofilm and it being more difficult to treat an infection which has got metal to stick on to. So then we're thinking we basically always double it to 12 weeks and and surviving a lengthy antibiotic course, it can be really challenging for patients. You're either doing six weeks or 12 weeks of their long courses and many patients will get an adverse effect. So you can get aller allergy. So that can range from a rash to full on dress. So, um that's with systemic features or anaphylaxis, you've got the side effects of nausea and diarrhea, which can be pretty debilitating clostridium, difficile diarrhea um with IV therapy IV line infections and line associated um thrombo thrombosis. Um and it also promotes a change in your colonizing flora and that can lead to more difficult secondary infections. So there are lots of kind of bits to, to manage and it can be difficult for patients. Um Yeah, and we talked about the 10% in aviva. Um So sometimes you can't do oral therapy and you need to do intravenous. Um And so this is um so we set up um having basically this arm um that had been used by the medical students for kind of practicing um examinations on, but they managed to break the shoulder. So we were donated it very kindly by the clinical school we put a Picc line in. Um, and then this is the bag that when you inject the antibiotics into the Picc line they come out. Um, now in this er, nice bag so that patients and their relatives can practice self administering their own antibiotics to help, particularly those who live in an area where there isn't a district nurse service um that can do IV antibiotics or for the increased flexibility rather than having to wait in for a nurse. Um So we've also made videos, we've got patients demonstrating them doing it and giving testimonials. Um and these are all freely available. And so those are the films we've got thus far, the best accessed on Google Chrome and the website is vi um and you can also access them via the national op A website. So, um if you click on resources, then, er, fourth down on the list is our, our teaching videos um to help patients. Um And that, er, so using the videos and the plastic arm to help teach people, we had a 70% increase in self administration, universally positive feedback from patients. Um and it saved um 5 million lbs in the first year. Um So quite significant um er, savings to be made um from it. And then the other er, finally is local antibiotics. So given how challenging systemic antibiotics can be um you know what about using just local antibiotics? Um So they can either be used as adjunctive therapy or the principal therapy. So, in this paper from Sheffield would say that systemic antibiotics are not required for a successful two stage revision of a hip arthroplasty. So Sheffield have always been pioneers of local antibiotics. So their paper shows just under 302 stage revisions for total hip replacement. The medium was five days of POSTOP systemic antibiotics and there was no significant difference in their outcomes between less than 48 hours, less than five days or longer in terms of antibiotics. Um and they had success rates with gram positives, the highest 87 g negatives, 84 and then mixed um infections, 72% um and sort of along this vein. Um The celerio trial is still running. Um So this is where people um are given up to seven days of systemic antibiotics and then randomized to stop or continue with systemic therapy. Um And this is using local er so treating orthopedic infections with local antibiotic therapy. Um And but th for this, for the purposes of this trial to try and make sure it was consistent, you weren't allowed to be included if you were using something like stimulant and mixing the antibiotics yourself. So this trial only allowed you to use um products that were pre made so that they had a very set, standardized concentration of the antibiotics. Ok. And I'm keen to impress upon you how important teamwork is for fracture related infection. So it um it involves obviously yourselves as the orthopedic surgeons for the body resection and getting the cultures um the infectious diseases and microblog in terms of determining what the antibiotic therapy is, depending on how big a hole you make or how big a hole the patient made themselves as part of the trauma. You're gonna need a plastic surgeon for soft tissue coverage and all of us have different perspectives, different priorities. Um And teamwork is the essential to make sure that you're making the right decision for the patient in the right order and optimizing their care. And really without working closely with all between all those specialties, um the outcomes will not be nearly as good and it's so important wherever you work. Um that certainly between your infection, um doctors and the orthopedic surgeons, even if you don't have plastics that you really know them and um can work well together to understand um the issues from both sides. Yes. Um Just quickly prevention is obviously always better than cure. Um So this is er, the standards for the management of open fractures, which I'm sure you're aware of. Um and this talks about prophylactic um antibiotic therapy. So it talks about two phases. So the first, um initially, when you're thinking that this is the er community flora, so your initial injury cos you've got an open wound. Um er So ideally, the antibiotics are given within the first hour or until wound excision, there's some fudging that about continuing for 24 hours. But this is where you're thinking about um what kind of back are on your skin anyway, all the conditions of the injury. So what was the context of the injury? Did they fall into a ditch or were they in a sort of farmer context? And then phase two, which is the definitive skeletal stabilization, anticipating this is a day or two down the line and therefore, you're worrying more about nosocomial flora and therefore you need broader therapy um to cover for that. So, just thinking about the evolving situation um in terms of your prophylaxis, um and this is just screen er shots from. So this is the recommendations in um the standards er document. So, Comox Ala is up there cos that's gonna cover your kind of skin flora. Um and then recommendations if you're pen allergic or there's a reason to think you've got M RSA. Um And then this is from our Adam Brooks flow chart about um open fra management of open fractures, the prophylaxis. Um And similarly, we've got comm ICV and then think about Vancomycin, if you're M RSA colonized um or the situation of the injury, whether you might need anaerobic cover or gram negative cover. And then in terms of Gillo one and two open fractures, um that really you're hoping that the patient's gonna be go home, you're not necessarily going to have to admit them. So we've managed to ensure that all the antibiotics in this are oral. Um So that, that helps facilitate discharge if that's appropriate. And then phase two. So this is where you the definitive um stabilization, but you're more worried about kind of the nosocomial flora. So the recommendation is tightened um gent and that's exactly what we've got um in ours as well. It's important to just be aware that Oplan you can get um adverse reactions. They're actually more common than with penicillin. So the adverse drug reaction rate is 10 to the 10 to 14%. Whereas penicillin is 1 to 8% and you can get two types of reactions. You can either get the infusion related non IgE mediated mast cell degranulation with a histamine release. It occurs and it can occur on the first day. You don't need prior exposure. It usually occurs between 2045 minutes after the start of the administration. And the patients present um looking erythematous, they flush, they're pruritic and they get fever, they get hypotension and it can look exactly like a septic shower, they can look like they're eye goring. Um So it can be quite difficult to tell whether they're septic or reacting. Um And then obviously, you've got the I GE mediated anaphylaxis. So this is a paper from Stanmore. So they looked at, they changed their, um, surgical prophylaxis to predominantly involve Tylan back in September 2013. And then for the next 29 months, they looked at how many patients have been given Tylan in and then what their, um, adverse reaction rate was, they were dosing it at 10 mgs per pig. Um, and they had five definite anaphylaxis, four probable and two where it was very uncertain, giving them a kind of rate of, um, about 0.05% er, anaphylaxis and then just thinking about the antibiotics that are used for prophylaxis and what they cover. Um, so, er, in Aden Brooks, we still thought sort of, er, I guess, clean and metalwork, um, er, insertions, not in the trauma setting. Um, we would still use flu cl and gent. Um, so trying to give us both the gram positive cover and the gram negative cover. Um, lots of places use Oplan and gent. Um, and then Cefazolin is also sort of growing and we're aiming from later this month to have, um, Cefazolin on our formulary for those who are penicillin allergic, if it's not an anaphylaxis reaction to try and reduce the amount of Tila that we need to use, um, for in penicillin allergic patients, so that we can minimize the, um, anaphylaxis risk with that. Just think about which antibiotics do you use? Obviously, um, the cephalosporin. So, Cefuroxim and Cefazolin, there's a higher clostri difficile risk, the broader the cover less good for antimicrobial stewardship. H hence the advantage of flu cl and gent. Um and also think about adverse reactions particularly related to hyper planing. So a lot to weigh up in terms of what you decide for your prophylactic regimens. And then just thinking again from the standards document, um the section on infection talks about what the risk factors are and many of these risk factors you as the surgeon have no control over. So the circumstances of the trauma, you don't have any influence over your host, diabetes and smoking, you may possibly encourage them to give up smoking, um and better control their diabetes, but there's you can have limited impact here. So the bit that we can really influence is ensuring that they get speedy antibiotic, prophylaxis. So within an hour of the injury and then the the the soft tissue cover is not delayed. Um and that's obviously very challenging with theaters trying to get plastic surgeons, orthopedic surgeons in the same theater. But it, those are the things that we can control and need to make a valiant effort to optimize for our patients to minimize the risk of their infection. So the take home messages, um cultures are essential um and taking them carefully and labeling them carefully makes the massive difference because basically the better information that you put in, the better information you'll get out in terms of antibiotic therapy. And that um the other big important thing is that IV therapy, antibiotic therapy is not superior to oral, but you do need to think carefully about bioavailability and bone penetration. Um And then I think we've still got a little bit of time. Um, it was just to run through um some cases. Um and if you want to put your kind of thoughts um in the chat, so essentially the first case. Um, so this is a man who had a quad bike injury in France, he fractures his left clavicle, um and he has um an orif done locally er, in France and then presents to Aden Brooks three weeks later. Um this is his fever chart, so he's had no fevers, his white count and CRP are essentially very normal. That is um er the photograph of his um surgical wound. Um What are you going to, how are you, how are you thinking to management this? What are you gonna do? So, thoughts in the chat. Is it infected? What are you gonna do? No. Ok. Ok. Some good thoughts. Ok. So we're saying do some blood, do some more imaging CT imaging. Um So the person who suggested the CT, what are you hoping the CT might tell you? I mean, can you hear me? Yeah. Yes, I mean there is a concern that there's some, well, three weeks down the line, you might see some, some I want to see if there's any resorption of the fracture fragments, um which would point to sort of a more deeper infection also might help to see some to see whether there's any fluid or reenhancing lesions deeper down as well. Yeah, I mean, I think the difficulty with imaging, whether you were thinking an MRI is more likely to tell you about fluid, but an MRI only three weeks from an operation, you can predict the radiology report. They'll say you can't tell the difference between postoperative change and edema that might have occurred from infection. Um So I think it's, it's difficult. Um Do people generally think this is infected or not? Um I'm not that concerned looking at it three weeks down the line, uh looking at just the X ray, but I would want to take more of a history, find out a little bit about whether the injury was open initially, whether the patient had any antibiotic therapy and systemic features, et cetera. But three weeks, I wouldn't expect to see callus formation or anything like that. Yeah. So um it was a closed injury. Um and he's been feeling fine. Yeah. So I would probably just monitor this, give safety netting advice and bring them back to see how they were getting on at maybe the six week mark and see if there were any changes on the X ray at that point, but also give them obviously kind of things to look out for. So if there was any signs of any discharge from the wound, any sinus formation, any erythema spreading things like that, that would ask and ask them to present earlier if that happened. Yeah. Yeah. So it's always difficult and this kind of more indolent presentation, it, it's difficult to be certain. Um, uh, it, you can have, you can have an infection and have completely normal bloods and no fever. So, um, I think it's just the kind of redness, um, just seems not great for a closed injury. Um, Three weeks down the line. I, I'm naturally more um er suspicious. Um but a and I see less of the cases, you'll see where there is some erythema on the wound and then it all gets better. I tend not to see those. Um So I do appreciate that my um I have a biased perspective um but this er was actually managed so they took out the metalwork um and did um deep sampling. Um so six samples and he grew a mixture of cutibacterium acnes and Staph epidermidis. So this is your cutibacterium here, gra gram positive bacilli and staph epidermidis, gram positive Cocci. Um And er oh um so he did have an infection. These are both low virulence organisms really only effective because they've got metal to stick on to. So, from my infection perspective, delighted the metal workers out. Um er and the reason I wanted to highlight this case is um put bacteria acnes, there are very few breakpoints. So it's very difficult to know which antibiotic options you've got, so it was definitely resistant to penicillin and tazocin. It was definitely sensitive to Vancomycin, meropenem and Clindamycin. And then all the others were unknown. You were having, it was a sort of, you hadn't to make a judgment call on the zone size or, um, the, actually most of them were e tests. So, um, er, the minimum inhibitory concentrations but no defined cut offs. So you're having to extrapolate from other organisms. So tricky. Um if he had been staying in the UK, um that would have been great. I'd have definitely done intravenous therapy for him. Um on the basis that there's a lot of uncertainty about the oral options or more uncertainty about the oral options. Um but as it turns out, he really for a variety of social reasons, desperately needed to go back to the south of France. Um And so we were forced into having to do oral therapy. Um er, and so, um although the metal was taken out, we went for dual therapy, including Rifampicin, Coss Rifampicin looked like it had the best, the lowest. Um M IC. Um So, because it, it was so difficult to predict, we thought we'd hedge our bet and go for dual therapy because we were forced into oral therapy and didn't have anything that was certain. So we did Rifampicin and Clindamycin, Clindamycin, we did know was susceptible but we were just worried um er, er, as to whether that would be enough. So we, we did dual therapy for him. Um, but yes, these, these indolent presentations can be very difficult to know whether there is or isn't an infection. Um, and I think if you're in doubt going in and, and, and getting some really good samples, um, it, it, from my point of view, it's always very good, but I'm, I'm, I'm sure when you get the next talk, um, the, the kind of more surgical management will be thrashed out. Um Case number two. So this is a gentleman um in his seventies. Um So on the 23rd of June, he managed to um er trap his, the end of his middle finger in a car door. Um and he has AK wire, er, an E and K wire fixation of that er, distal um th er phalanx or the fragment of his distal phalanx. Um and then um in the intervening period between the 26th of June when that K wires put in and the 10th and him returning to clinic on the 10th of July, um A bit of the wire was poking out and so he decides to remove it himself at home. So he returns and um so the top X ray is from his original injury. The next two X rays are from when he returns to clinic on the 10th, having taken unfortunately, the K wire out himself. Um And so the decision was to do a internalization um er, and he has that, um, eight days later, my question to you, um, is, er, how long do you need to give antibiotics for? So, and, um, it do, er, we do get growth of, um, er, an organism, um, from this. So we're thinking we need to give antibiotics. But how long do you give, you can either chat them out or put them in the chat, whatever you prefer. Ok. So we've had a no antibiotics. We've had a six weeks. Good. We've got a good range. Two weeks. Excellent. Um, so, you know, potentially all three of those answers could be correct. Um, and it all depends on margin. So at the termination operation, they talk about a bit of the, um, the distal P two, still being soft, um, and then terminalizing um, midway through P two. so obviously if you've got an ankle infection or a foot infection and you do a bologna amputation, there's inches of normal tissue and normal bone between the two. But if you're in this situation where you've only got, um, er, a, a few millimeters, um, it's much more difficult to, to determine. So I had a long discussion with the surgeon. Um, and actually because it was possibly only one or two millimeters as a margin, we did decide to give the six weeks. So whoever wrote, who's responsible for the antibiotics. Yes, but he also potentially, um, meant the man kept the rest of his finger but it is always a judge. It is a judgment call. Um, if you've got a massive margin, then no antibiotics is legitimate. Two weeks if you're thinking about the soft tissues, um, uh, and you're not too worried about the bone. Um, er, so it O2 and six are all options. Um, it just depends and that's where it's really important to liaise between the surgeon and the person recommending the antibiotics to just understand exactly how confident you are about kind of margins. Um, and then the final case. Um, so this is a man um, who has a few beers, um, gets up in the middle of the night um, and slips over in his bathroom, um, and he has an iron nail um to fix his tibial fracture and a plate over his um fibular fracture. And then um three months later appears with this wound. This is actually the wound after it's been tidied up a little bit. It was looking a bit more um, parent and with some discharge um er, over the medial aspect of his, er, right lower leg. What would you do? Ok. Ok. Yeah, very good. Um Yeah. So you wanna see if there's burning union? Can you take the metal out? Unfortunately, it isn't United finish. Yeah. Blood. I mean, we do do blood but they're probably not gonna change what you do cos there's clearly a problem because you've got a hole over your metalwork. Ok. Ok. Yeah. Um, yes, you're gonna need to involve, um, your infection team. What, as you, as orthopedic surgeons, what could you do if you haven't got union? What could you do? Mhm. And that's the medial side. Yeah, it's the medial side case. We've had it. So, in case, so we've had the two options. So, either debride and metalwork retention or, um, if there's no union X fix and stabilize. So, as an infection doctor, I really want that metal out. It's just gonna, you're really gonna struggle to um heal that infection. If you've still got the infected, metalwork underneath, it's gonna be much harder. So, yes, getting the metal out and putting external metalwork. So we had a frame or an X fix M much more preferable. The distal, that distal part of your leg blood supply isn't great. There's almost no spare tissue. Whoever you are, it's always a tight area. You're gonna need your plastic surgeon to help heal that. And you know, if they do a flap, then that's gonna bring new blood supply and that's gonna help deliver more antibiotics. So, yeah, you're, you're really thinking about wanting to take the metal, the um metal out external fixation, plastic surgeon to put a flap on that because it's just such a difficult area to heal. As you take the metal, work out, you're gonna be able to get much better samples. Um And then you're gonna be able to return your antibiotics not having to worry about biofilm. Um And hopefully your plastic surgeon has given you a bit more blood supply. Um So this man actually um he did get a flap by plastics. Um He did get antibiotics. He did get the metal taken out in the end. He didn't get an X fix. He actually healed in a cast for variety of reasons. But yes, you want to get that internal metal out. Um You need to be thinking about getting a better blood supply and better soft tissue healing to cover over that area. Um But yeah, thank you for all your um ideas. A lot of you were on that um pathway. Um That was the final case I've got. Um So thank you very much for listening and any further questions for me. So, just a quick question about that last case would be from the plastic surgeon's point of view. Would there not be a concern that the flap may actually fail? Um So I think um if you've taken the, so taking the metal work out, they're gonna be much happier because you've removed er, more of the infective source. Um I'm pretty uh generally when we take the um the er surgeons, when they take the intramedullary nail out, they then ream the canal and then put stimulant with local antibiotics down as well. Um So yes, trying to minimize the chance that you're gonna have a deep infection underneath your nice new flap. Yes, because you don't want to lose it. Absolutely. And it's Doctor Nixon. Thanks a lot for the talk. You know, the first case um that we discussed with kind of the indolent infection. Um I just have a question about that with um with those kind of issues where there is metalwork in situ quite early post fracture fixation. Um I was always under the impression I understand completely that obviously metalwork um in situ uh doesn't help when you're trying to treat an infection. But I was always told that obviously stability is also essential to kind of aid with fracture healing. And absolutely, so I was pleasantly surprised they took it out. I was to take it out. Um Elizabeth may be able to explain why that was deemed the right idea. Yes, I appreciate often in the early stages. Yet you bride you have to leave the methyl in because as you say, stability is so important and so the work has to stay in. Um And we just treat for 12 weeks. Um And then generally, we stop antibiotics, the metal stays in for as long if the infection recurs um then we can always retreat at the point. Once you've got Bony Union, you can take the metal work out at that stage and then retreat at that stage if you need to. So if you don't succeed the first time, then you just aim to kind of ideally not give them antibiotics through, but sometimes you have to suppress them, um, until you've got Bony Union and then when you can take the metal out, then you retreat at that stage aiming for a cure at that point. Yeah. And then my other sorry small thing was in that wound that we were looking at. It may just be what I was looking at on my phone. But with that was there a bit of collection underlying the kind of because the erythema to me on the picture just looked quite isolated to the area not particularly spreading and quite, you know, sometimes you get these chronic changes over scars, but it could just be the picture I'm looking at and was there actually some evidence of a kind of collection or anything in this patient that it was very slightly frac not anything particularly dramatic? You could, you could, it might have been one where you did think, do you know what? I'm just not sure I'll wait another week. I think it, it wasn't so clear cut and I just want to make sure I'm not offending all these people. The slide where I had at the beginning for the indolent infection. One of those was one where I thought it was going to be infected and the surgeon said, no, just hang fire and then it turned out actually, it all resolved and it wasn't infected. Um And the other one was infected so it can be very difficult to tell it's always easier in hindsight. And I also really have a distorted perspective as I only really get involved in the infected cases. Um, so I see less frequently the, where it was a bit Red POSTOP and then it actually resolved and they were fine and they didn't have an infection. So, yeah, it, it can be really difficult, um, and keeping a close eye and, and just waiting until it becomes more obvious may be the right thing to do. Ok. All right. Thank you very much. If you, unless you think it's very much um a kind of superficial stitch infection or very superficial infection, generally, you don't want to give antibiotics. Um It's always a different judgment call about thinking about treating a very superficial infection versus antibiotics and then reducing the chance of you getting proper cultures later. And again, it's always easier in hindsight because you often see they come to you after seeing their GP two or three times, been given all antibiotics, like you already had two courses and then you're kind thinking, well, should I just stop everything and see how it declares? Or should I? Exactly. Luckily GPS will generally give flu clocks orally that it, because it makes no difference to the deep infection if there is one. So it, it'll suit the superficial bit and won't do many more than that. So, yeah, if it is just a very superficial infection, it will treat that and if there's an underlying one, it'll just come back. So, thank you very much. That's all right. Thank you, Doctor Nixon. That was a really interesting talk. So thanks for giving up the time for that. We'll let you get going and I think everyone will have a five minute break and then Mr Singh will take over the next talk. So we'll thank you Doctor Nixon. Meet back everyone in 3 35 35. Yeah, thanks.