Cadmore media player playing video Pragmatic Antiobiotics Prescribing in Polymicrobial Infection
Video Player
Accessibility
Using forms mode, you can utilize keyboard shortcuts to make usability more efficient.
Space bar will play and pause the video. Pressing escape will close all displays and pressing it again will jump to the end of the player.
You can press A to open the Keyboard Shortcut Dialog which also provides an audio description of the player and all of its features.
Language
1x
Play Speed
Adjust Volume
Transcript
Search
Result Count
of
Click to jump to result
Search
Re-center
Segments
Result Count
of
Click to jump to result
Search
Name:
Pragmatic Antiobiotics Prescribing in Polymicrobial Infection
Description:
Pragmatic Antiobiotics Prescribing in Polymicrobial Infection
Thumbnail URL:
https://cadmoremediastorage.blob.core.windows.net/1bdd9d4f-a4f6-45a7-ae4a-80b767a858a8/videoscrubberimages/Scrubber_1.jpg
Duration:
T00H23M48S
Embed URL:
https://stream.cadmore.media/player/1bdd9d4f-a4f6-45a7-ae4a-80b767a858a8
Content URL:
https://cadmoreoriginalmedia.blob.core.windows.net/1bdd9d4f-a4f6-45a7-ae4a-80b767a858a8/BAJIS_Webinar_Session_2-02.mp4?sv=2019-02-02&sr=c&sig=epmBiMLg4kgAfrpXFDeFhyG8uJUTMIf%2F47RwINh9yMo%3D&st=2024-11-21T10%3A31%3A48Z&se=2024-11-21T12%3A36%3A48Z&sp=r
Upload Date:
2024-08-23T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
BILAL JAMAL: Before we move on, I just wanted to remind everyone that the Bone and Joint Infection Society has been going now for about a year and a half. We're looking to take new members to try and advance the cause of musculoskeletal infection in the United Kingdom. We are a truly multidisciplinary society, of which we're very proud and our sister organization is the Bone and Joint Infection Registry, which has been set up by Mike Reid, however, has involvement from throughout the UK.
BILAL JAMAL: Both organizations are hugely supported by Biocomposites who manufacture Stimulan and they are also our corporate supporters of this evening's webinar so we're hugely supportive to them as well. I want to go on and introduce Neil Ritchie next, who's going to be giving the next talk. Neil's a good friend of mine. He works at the Queen Elizabeth University Hospital in Glasgow alongside myself. He's an infectious disease physician and has a strong interest in musculoskeletal infection and he has the dubious honor of being Clinical Director for all of medicine in what is a hugely busy unit.
BILAL JAMAL: And as part of that, of course, he manages musculoskeletal infection for about 2.5 million patients. And Neil's going to give us his thoughts on pragmatic antibiotic prescribing in polymicrobial infection. Thanks Neil.
NEIL RITCHIE: Thanks very much Bilal, and thanks Bilal for inviting me to speak. Hopefully you can see my slides. Bilal, is that, yes working? Fantastic so I always find the audience for these things slightly tricky because it's really, I think it's, I find it fair to assume that there'll be a reasonable number of orthopedic surgeons in the audience, but I have never any idea how many infection specialists there'll be
NEIL RITCHIE: so I've probably pitched this slightly in between so apologies to infection specialists if it feels a bit light. Hopefully, hopefully there'll still be some stuff there for you and just for my orthopedic colleagues to, to get a bit more insight into, into how we, how at least I use antibiotics in a, in, in this context. I thought that looking at polymicrobial infection would be a reasonable thing to do for, for this context because as we'll see polymicrobial infection is particularly common in fracture related infection.
NEIL RITCHIE: I'm not convinced that my strategy of antibiotic management of fracture related infection is fundamentally different from other bone and joint infections and so I didn't want to give a generic talk, so I thought I would focus on this area. Let's see if I can advance. So fracture related infection unquestionably has a different path of physiology to arthroplasty related infection as Deepa has
NEIL RITCHIE: already outlined. There's far less published research on fracture related infection and so much of the evidence, and particularly, I think around antibiotic evidence, around antibiotic management, a huge preponderance of the evidence is based on us inferring from other work and principally on arthroplasty related infection. But there are important differences in the patient population and the microbiology, not to mention the, not to mention the treatment goals.
NEIL RITCHIE: I've put some generic information on outcome on the right hand side of the slide but I guess, you know, the amputation rates with fracture related infection is not insignificant, certainly much higher than we see with, than we see with arthroplasty related infections and so these are high stakes infections for the patients that we're treating. And many of them are unaware of just how high the stakes are
NEIL RITCHIE: and that certainly feeds into feeds into the patient concordance and compliance as we come back to later, because some of the things that we do with antibiotics often make them feel pretty miserable for the duration of their therapy. Polymicrobial infections are overrepresented in fracture related infection. I've just selected a couple of papers here to put up
NEIL RITCHIE: but you know, there are any number that talk about the polymicrobial infections in fracture and that presumably happens for at least a couple of reasons. The site of the infection often on the extremities, so ankle and tib fib fractures and upper limb fractures probably lends itself to the development of polymicrobial infection because of the different microbiome of those skin surfaces,
NEIL RITCHIE: but also open fracture is strongly associated with polymicrobial infection and the extent of the polymicrobial infections in various case series which varies quite widely, may well be related to that. But there's a direct comparison in the plot at the bottom of the screen for fracture related infection is in blue compared to arthroplasty and other orthopedic implant infection with about twice the incidence of polymicrobial infection compared to those other orthopedic infection domains.
NEIL RITCHIE: And this is a UK paper on the right here with polymicrobial infection, particularly earlier after fracture fixation running to 50 to 60% if the presentation is within is within 10 weeks. So there's lots of polymicrobial infections in this population. What does that mean? Well, in general in infection, when we see polymicrobial infections, it tends to push us towards gram negative pathogens
NEIL RITCHIE: and that's certainly the case here. So this is one study that compares infections with just a single pathogen identified, which is on the left here with them, polymicrobial infection on the right. And you can see that the single infection, the mono microbial infections are dominated by gram positives in orange and particularly by staphylococcus aureus on this plot here so probably the majority of implant related infections that we see are caused by staph aureus
NEIL RITCHIE: and that's probably no great surprise to anyone. There's clearly a real mix of organisms and we do see the full variety of mono microbial infections, but driven by gram positives and by staph aureus in particular. Polymicrobial infection, on the other hand, tends to be driven by gram negative constituents in the tissue, lots of enterobacterales like E coli and Klebsiella, Intrivactors as well as much more diversity in the gram positives that we tend to see and we tend to see more beta hemolytic streptococci and more enterococci showing up in these polymicrobial infections than we do in mono microbial ones.
NEIL RITCHIE: So there are different pathogens and a greater proportion of these difficult to treat organisms. Organisms like the multidrug resistant Enterobacterales, E coli, Klebsiella, Pseudomonas aeruginosa, which is particularly difficult to treat with antibiotic therapy, Enterococcus faecalis, which is naturally resistant to a lot of the antibiotics that we use and fungi which are again overrepresented in, in polymicrobial infections.
NEIL RITCHIE: And so when you start to see these organisms coming through in your cultures, you know that you've got a real challenge in terms of selecting and encouraging the patient to tolerate antibiotic therapy. But difficult to treat organisms are, are also difficult in terms of how to weigh up their significance. I couldn't find any good data on this in fracture related infection
NEIL RITCHIE: but in many respects, the microbiology is quite similar to diabetic foot infection and so I've included one of the, one of the classic randomized controlled trials in diabetic foot infection that is useful in this context where we look at patients who were treated with either piperacillin tazobactam, which is an antibiotic, that's activity against Pseudomonas aeruginosa and intra cocci or ertapenem, which is a quite convenient once a day carbapenems or meropenem like drug which we quite often use in ambulatory care services because it's once rather than three times a day, in contrast to meropenem.
NEIL RITCHIE: But ertapenem doesn't have activity against Enterococcus faecalis and Pseudomonas and within the context of diabetic foot infection, isolating enterococci and Pseudomonas wasn't associated with a poorer outcome when patients were treated with an antibiotic that didn't treat it in the form of ertapenem. This study needs to be interpreted with a great deal of caution. Not all the patients,
NEIL RITCHIE: only about 50% of patients in the study had osteomyelitis and patients were carefully selected for entry into the study and so investigators may well have felt that their isolates weren't significant so that they could so that they could get into the study. But it does make an important point that some of these difficult to treat organisms that we encounter in polymicrobial infection often aren't the dominant species causing infection.
NEIL RITCHIE: And this really backs up the point that Deepa made earlier on about the, the importance of not taking superficial swabs, and it's not just that superficial swabs often don't give you the answer, it's that they're often downright misleading. So here's one of the studies looking back at microbiology and fracture related infection and the quality of their answers from superficial swabs.
NEIL RITCHIE: [MUSIC PLAYS] And you can see that in pretty much 50% of cases, there was no similarities in tissue culture, and particularly if you've got a patient who's been on antibiotics, that's likely to select out these difficult to treat organisms, enterococci and Pseudomonas and Candida. And then if you start growing them on superficial swabs, people get very anxious. But actually they may well not be the,
NEIL RITCHIE: the infection that's actually causing the causing the problem. Choosing to cover these if we do and it's why it's multi-disciplinary discussion is really important here in the context in which the samples were taken, what the field looked like, how convinced are that this infection there.
NEIL RITCHIE: But choosing to cover them often greatly broadens antibiotic spectrum, which increases complexity and the risk of harm and antifungal cover in particular greatly increases toxicity for our patients. I just want to demonstrate the difference that often comes with polymicrobial infection in practice. This is a typical mono microbial regime for a patient that I choose to treat with systemic antibiotic therapy for bone and joint infection.
NEIL RITCHIE: This is a patient getting 960 twice a day of Septrin and they get two tablets or if you get the bigger Septrin tablet, one tablet twice a day, which is obviously inconvenient, but isn't the end of the world. Here's a typical regime that we use for polymicrobial infection. This is clindamycin and ciprofloxacin so the type of regime that we might well choose for a mixed gram positive gram negative infection and sitting a patient down and encouraging them to take this many capsules is quite a big undertaking
NEIL RITCHIE: and it's no real surprise that most patients taking a regime like this, feel pretty nauseated and sick for the duration of their treatment. And we know that compliance with medication regimes drops off substantially as you increase tablet burden and medication frequency. So this is one of the pretty old study now about 40 years old but they looked at compliance with hypertension treatment based on how many times a day the treatment was given
NEIL RITCHIE: and you can see that whereas most patients who are taking their once daily treatment, most of the time the compliance is down in the 50% for a three times daily regime. And there's strong evidence, particularly in the field of cardiovascular therapeutics, that patients who are not taking their treatment, are unlikely to generate the benefit. And obviously, to some extent that's common sense. In infectious disease, physicians have a lot of experience with HIV
NEIL RITCHIE: and this is an area which has been a huge amount of work done on adherence rates. This is one of the classic pictures from the CDC on the early days of antiretroviral therapy for HIV, where patients were having to manage incredibly complex regimes and it's now the case that most patients are on just one tablet once a day to manage their HIV. But back then, patients were having to set various alarms to time when to get up and when to take their treatment.
NEIL RITCHIE: And it's very clear that there's a strong correlation between both between both the pill burden and the number of times a day that you have to take the tablets and how often the patient's going to take them and how successful that treatment that treatment is. So the more tablets, the more times a day, the less likely the patients would be to take their treatment and the less likely they would to be successful.
NEIL RITCHIE: Bit harder to come up with clear evidence and antibiotics, but it is there. Patients receiving combination antibiotic therapy are more likely to experience adverse reactions as well. So this is a randomized controlled trial in cellulitis where we added clindamycin into flucloxacillin and patients who got flucloxacillin and clindamycin are much more likely to have diarrhea, much more likely to have any side effect than the patients given just flucloxacillin on its own.
NEIL RITCHIE: Most antibiotic trials are exploring synergism, so it's a little bit hard to compare these because in these studies you've got the option of just giving one drug. Whereas, whereas in polymicrobial infection you might not have the option of just giving one or the one that you might give might be more toxic or much broader spectrum, so it doesn't directly, doesn't directly correlate in. Longer duration
NEIL RITCHIE: therapy is probably associated with higher adverse reaction rates and likely an escalating impact from combination therapy. So this is a study on Helicobacter pylori eradication therapy, where long courses of treatment were associated with pretty high rates of adverse reactions up in the 30% range for those getting long courses of combination therapy and so we have to take this quite seriously. How do we manage these kind of complex oral regimes in Glasgow?
NEIL RITCHIE: Well, this is, this is an editorial that we wrote a few years ago in the Journal of Antimicrobial Chemotherapy talking about this concept of COpAT - complex outpatient antibiotic treatment. It doesn't really matter whether it's given intravenously or orally. The point is that it places a heavy burden on patients and so we need to proactively follow them up and monitor them. And the other problem with these very complex regimes with multiple different antibiotics being used is the number of drug interactions that we see with antibiotics and particularly with oral antibiotic regimes on the right here.
NEIL RITCHIE: So these are patients from our MDT in Glasgow and the most common drugs that they were taking and you can see that most of the oral therapy that we prescribe has lots of drug interactions and once you start piling those up, two, three, four antibiotics, that soon becomes a real problem in terms of management. Combination antibiotics in our hands are much more likely to be toxic as well.
NEIL RITCHIE: These are some unpublished data from our unit in Glasgow. Some of the more common antibiotics we use in bone and joint infection and you can see that particularly for linezolid and the fluoroquinolones like ciprofloxacin or levofloxacin, when we combine those with other antibiotics in orange, the rate of toxicity requiring discontinuation goes up dramatically. So if I prescribe a linezolid antibiotic combination, the chances the patient will discontinue that due to lack of tolerability or toxicity is greater than 50% And we've now are beginning to reconsider whether we use these regimes at all or if we just use them in carefully selected patients who we feel are at higher, are at lower risk and more able to tolerate them.
NEIL RITCHIE: So many of these antibiotics are high risk. What does that mean? Well, it means that we have to recognize that prescribing combination antibiotic therapy has a higher risk of failure through toxicity and intolerance than monotherapy. And so we have to warn patients that might happen, that they're likely to experience significant side effects and offer support. And in our case, that means providing them with a contact number for an antibiotic clinical nurse specialist and giving them a patient information leaflet that helps remind them what they might experience and how to contact us.
NEIL RITCHIE: And it also means that we have a low threshold to convert these patients back onto an IV therapy regime and so patients who are going out with us on oral therapy, we'll counsel them that they might have to go back onto IV therapy if they don't tolerate their oral regime so that they know. I want to just present a couple of cases now before I conclude if I've got time.
NEIL RITCHIE: Hopefully, I can't get my clock up, so hopefully I do, but Bilal will cut me off if I'm running short. But this is a 42-year-old man. I think it might be one of yours Bilal actually, presenting with a lower limb fracture, managed with an early internal fixation who developed, with an internal fixation, who developed an early postoperative infection within a few weeks. He was treated with metalwork removal and application of an Ilizarov frame, had some calcium beads loaded with vancomycin and gentamicin added into the dead space and a polymicrobial infection was isolated on culture with an MSSA Klebsiella pneumoniae gram negative and a group G streptococcus isolated.
NEIL RITCHIE: And our initial management with piperacillin tazobactam on the ward was then I hosted to clindamycin
NEIL RITCHIE: and ciprofloxacin for discharge, and he was seen by a clinical nurse specialist and given the patient information leaflet before he went. After discharge, he developed marked nausea and vomiting and was struggling with the tablets and considered stopping. Fortunately, he contacted our nurse specialists, and they brought him up for review. His bloods were OK.
NEIL RITCHIE: We started him on some antiemetic, which helped with his nausea and discussed a conversion to intravenous ceftriaxone as an outpatient. But his symptoms settled over the next few days and he was keen to continue with oral therapy and did well and follow up with clinical resolution of his infection. And did really quite well out to about a year I think, when I last had contact with him.
NEIL RITCHIE: Just a shorter second case, a 74-year-old woman with a polymicrobial infection of a femoral gamma nail managed with a single stage exchange and she had a real horrible mixture of organisms; staph aureus, a beta hemolytic strep and two different types of coliform organisms, including intra faxers which are quite resistant and two different anaerobic organisms. And we contemplated a regime of doxycycline, ciprofloxacin and metronidazole to try and get her out on orals
NEIL RITCHIE: but actually, when we went to speak to the patient, she reported having significant nausea and diarrhea with most antibiotic courses and she really doesn't tolerate therapy for, for when she gets chest infections, which is quite frequent. So having heard that, we decided to go with an outpatient IV regime and this is actually one of the more common reasons that we give outpatient IV regimes in the Glasgow COpAC ServiceNow is because we don't think the patient will tolerate oral antibiotic therapy.
NEIL RITCHIE: The patient's daughter was trained to self-administer and she completed the course of treatment without incident and tolerated it well. So that's been a kind of whistle stop tour through my thoughts about polymicrobial infection and why it's a particular challenge. As we've seen, it's a common challenge in fracture related infection and so we have to really think about how to manage these patients carefully.
NEIL RITCHIE: Cases with polymicrobial infection often have multidrug resistant and difficult to treat organisms, and there's a greater necessity to construct very broad spectrum or complex regimes if we do have to give prolonged systemic therapy. Such cases emphasize the need for MDT discussion, an ongoing specialist input to ensure that patients are supported to complete the courses. And we have to have dynamic plans and a means of and a means of reviewing them based on toxicity and tolerability.
NEIL RITCHIE: So particularly where people have I know that many work in regional centers and so there needs to be a way to keep up with these patients after they go home and that we don't just prescribe antibiotics and then forget until the patient comes back a few months later to follow up. So, thanks very much.
BILAL JAMAL: That was great. Thank you so much.
BILAL JAMAL: I wanted to pick up a point, which relates to some of the patients who are referred into our service, which is some patients may have fracture related infection. They might have had an operation done in the index unit to try and address that fracture related infection and there can often be retained mental work or incomplete excision of bone and I suppose I wonder if that's on going long term circumstance whereby there is ongoing retained mental work or incomplete excision of bone.
BILAL JAMAL: How does that alter the clinical advice that you give about duration of antibiotics and indeed antibiotic choice?
NEIL RITCHIE: Yeah thanks, Bilal.
NEIL RITCHIE: I mean, I think that. So first of all, if there's retained metalwork and we can't remove it, that brings in the whole discussion around biofilm and how best to manage that, that we have frequently in prosthetic joint infection
NEIL RITCHIE: and you know, I do try to use rifampicin if it's appropriate in these circumstances. The evidence I don't think is there at all in fracture related infection and you know, it it's a bit stronger in prosthetic joint infection. But I think for me, I bring that across and I do use rifampicin in these cases if it's appropriate but I know not everyone does. In terms of duration,
NEIL RITCHIE: I think that's extremely difficult, you know, because there's no test of cure in these patients. As we've seen, many of them are in an extremely high stakes situation so they maybe already had so much bone cut out that a further surgical revision essentially would be amputation. And they're understandably very, very nervous about stopping their antibiotics if they've had significant infection.
NEIL RITCHIE: So, you know, I think these cases really emphasize the importance of the multidisciplinary team and also being in contact with the, being in contact with the patient, because, you know, there are some cases where we will carry on antibiotics for a very long time. And some of that might be treating ourselves and, you know, dealing with the worry that we have about these patients sometimes and what will happen if they go wrong, but particularly if there's been a big bit of infected bone left in, it's very difficult to know just how you sterilize that.
NEIL RITCHIE: And so, but it just emphasizes that every case is different, I think, and particularly in these cases, there's something that can be quite generic about a hip and knee there sometimes where you've got a staph aureus, we know what we do here. I think fracture related infection is much more heterogeneous so we're more likely to have individualized plans for those patients, I think.
BILAL JAMAL: Yeah, absolutely share that sentiment. Thank you very much. Thanks so much, Neil. That was really superb.
Segment:0 .
BILAL JAMAL: Before we move on, I just wanted to remind everyone that the Bone and Joint Infection Society has been going now for about a year and a half. We're looking to take new members to try and advance the cause of musculoskeletal infection in the United Kingdom. We are a truly multidisciplinary society, of which we're very proud and our sister organization is the Bone and Joint Infection Registry, which has been set up by Mike Reid, however, has involvement from throughout the UK.
BILAL JAMAL: Both organizations are hugely supported by Biocomposites who manufacture Stimulan and they are also our corporate supporters of this evening's webinar so we're hugely supportive to them as well. I want to go on and introduce Neil Ritchie next, who's going to be giving the next talk. Neil's a good friend of mine. He works at the Queen Elizabeth University Hospital in Glasgow alongside myself. He's an infectious disease physician and has a strong interest in musculoskeletal infection and he has the dubious honor of being Clinical Director for all of medicine in what is a hugely busy unit.
BILAL JAMAL: And as part of that, of course, he manages musculoskeletal infection for about 2.5 million patients. And Neil's going to give us his thoughts on pragmatic antibiotic prescribing in polymicrobial infection. Thanks Neil.
NEIL RITCHIE: Thanks very much Bilal, and thanks Bilal for inviting me to speak. Hopefully you can see my slides. Bilal, is that, yes working? Fantastic so I always find the audience for these things slightly tricky because it's really, I think it's, I find it fair to assume that there'll be a reasonable number of orthopedic surgeons in the audience, but I have never any idea how many infection specialists there'll be
NEIL RITCHIE: so I've probably pitched this slightly in between so apologies to infection specialists if it feels a bit light. Hopefully, hopefully there'll still be some stuff there for you and just for my orthopedic colleagues to, to get a bit more insight into, into how we, how at least I use antibiotics in a, in, in this context. I thought that looking at polymicrobial infection would be a reasonable thing to do for, for this context because as we'll see polymicrobial infection is particularly common in fracture related infection.
NEIL RITCHIE: I'm not convinced that my strategy of antibiotic management of fracture related infection is fundamentally different from other bone and joint infections and so I didn't want to give a generic talk, so I thought I would focus on this area. Let's see if I can advance. So fracture related infection unquestionably has a different path of physiology to arthroplasty related infection as Deepa has
NEIL RITCHIE: already outlined. There's far less published research on fracture related infection and so much of the evidence, and particularly, I think around antibiotic evidence, around antibiotic management, a huge preponderance of the evidence is based on us inferring from other work and principally on arthroplasty related infection. But there are important differences in the patient population and the microbiology, not to mention the, not to mention the treatment goals.
NEIL RITCHIE: I've put some generic information on outcome on the right hand side of the slide but I guess, you know, the amputation rates with fracture related infection is not insignificant, certainly much higher than we see with, than we see with arthroplasty related infections and so these are high stakes infections for the patients that we're treating. And many of them are unaware of just how high the stakes are
NEIL RITCHIE: and that certainly feeds into feeds into the patient concordance and compliance as we come back to later, because some of the things that we do with antibiotics often make them feel pretty miserable for the duration of their therapy. Polymicrobial infections are overrepresented in fracture related infection. I've just selected a couple of papers here to put up
NEIL RITCHIE: but you know, there are any number that talk about the polymicrobial infections in fracture and that presumably happens for at least a couple of reasons. The site of the infection often on the extremities, so ankle and tib fib fractures and upper limb fractures probably lends itself to the development of polymicrobial infection because of the different microbiome of those skin surfaces,
NEIL RITCHIE: but also open fracture is strongly associated with polymicrobial infection and the extent of the polymicrobial infections in various case series which varies quite widely, may well be related to that. But there's a direct comparison in the plot at the bottom of the screen for fracture related infection is in blue compared to arthroplasty and other orthopedic implant infection with about twice the incidence of polymicrobial infection compared to those other orthopedic infection domains.
NEIL RITCHIE: And this is a UK paper on the right here with polymicrobial infection, particularly earlier after fracture fixation running to 50 to 60% if the presentation is within is within 10 weeks. So there's lots of polymicrobial infections in this population. What does that mean? Well, in general in infection, when we see polymicrobial infections, it tends to push us towards gram negative pathogens
NEIL RITCHIE: and that's certainly the case here. So this is one study that compares infections with just a single pathogen identified, which is on the left here with them, polymicrobial infection on the right. And you can see that the single infection, the mono microbial infections are dominated by gram positives in orange and particularly by staphylococcus aureus on this plot here so probably the majority of implant related infections that we see are caused by staph aureus
NEIL RITCHIE: and that's probably no great surprise to anyone. There's clearly a real mix of organisms and we do see the full variety of mono microbial infections, but driven by gram positives and by staph aureus in particular. Polymicrobial infection, on the other hand, tends to be driven by gram negative constituents in the tissue, lots of enterobacterales like E coli and Klebsiella, Intrivactors as well as much more diversity in the gram positives that we tend to see and we tend to see more beta hemolytic streptococci and more enterococci showing up in these polymicrobial infections than we do in mono microbial ones.
NEIL RITCHIE: So there are different pathogens and a greater proportion of these difficult to treat organisms. Organisms like the multidrug resistant Enterobacterales, E coli, Klebsiella, Pseudomonas aeruginosa, which is particularly difficult to treat with antibiotic therapy, Enterococcus faecalis, which is naturally resistant to a lot of the antibiotics that we use and fungi which are again overrepresented in, in polymicrobial infections.
NEIL RITCHIE: And so when you start to see these organisms coming through in your cultures, you know that you've got a real challenge in terms of selecting and encouraging the patient to tolerate antibiotic therapy. But difficult to treat organisms are, are also difficult in terms of how to weigh up their significance. I couldn't find any good data on this in fracture related infection
NEIL RITCHIE: but in many respects, the microbiology is quite similar to diabetic foot infection and so I've included one of the, one of the classic randomized controlled trials in diabetic foot infection that is useful in this context where we look at patients who were treated with either piperacillin tazobactam, which is an antibiotic, that's activity against Pseudomonas aeruginosa and intra cocci or ertapenem, which is a quite convenient once a day carbapenems or meropenem like drug which we quite often use in ambulatory care services because it's once rather than three times a day, in contrast to meropenem.
NEIL RITCHIE: But ertapenem doesn't have activity against Enterococcus faecalis and Pseudomonas and within the context of diabetic foot infection, isolating enterococci and Pseudomonas wasn't associated with a poorer outcome when patients were treated with an antibiotic that didn't treat it in the form of ertapenem. This study needs to be interpreted with a great deal of caution. Not all the patients,
NEIL RITCHIE: only about 50% of patients in the study had osteomyelitis and patients were carefully selected for entry into the study and so investigators may well have felt that their isolates weren't significant so that they could so that they could get into the study. But it does make an important point that some of these difficult to treat organisms that we encounter in polymicrobial infection often aren't the dominant species causing infection.
NEIL RITCHIE: And this really backs up the point that Deepa made earlier on about the, the importance of not taking superficial swabs, and it's not just that superficial swabs often don't give you the answer, it's that they're often downright misleading. So here's one of the studies looking back at microbiology and fracture related infection and the quality of their answers from superficial swabs.
NEIL RITCHIE: [MUSIC PLAYS] And you can see that in pretty much 50% of cases, there was no similarities in tissue culture, and particularly if you've got a patient who's been on antibiotics, that's likely to select out these difficult to treat organisms, enterococci and Pseudomonas and Candida. And then if you start growing them on superficial swabs, people get very anxious. But actually they may well not be the,
NEIL RITCHIE: the infection that's actually causing the causing the problem. Choosing to cover these if we do and it's why it's multi-disciplinary discussion is really important here in the context in which the samples were taken, what the field looked like, how convinced are that this infection there.
NEIL RITCHIE: But choosing to cover them often greatly broadens antibiotic spectrum, which increases complexity and the risk of harm and antifungal cover in particular greatly increases toxicity for our patients. I just want to demonstrate the difference that often comes with polymicrobial infection in practice. This is a typical mono microbial regime for a patient that I choose to treat with systemic antibiotic therapy for bone and joint infection.
NEIL RITCHIE: This is a patient getting 960 twice a day of Septrin and they get two tablets or if you get the bigger Septrin tablet, one tablet twice a day, which is obviously inconvenient, but isn't the end of the world. Here's a typical regime that we use for polymicrobial infection. This is clindamycin and ciprofloxacin so the type of regime that we might well choose for a mixed gram positive gram negative infection and sitting a patient down and encouraging them to take this many capsules is quite a big undertaking
NEIL RITCHIE: and it's no real surprise that most patients taking a regime like this, feel pretty nauseated and sick for the duration of their treatment. And we know that compliance with medication regimes drops off substantially as you increase tablet burden and medication frequency. So this is one of the pretty old study now about 40 years old but they looked at compliance with hypertension treatment based on how many times a day the treatment was given
NEIL RITCHIE: and you can see that whereas most patients who are taking their once daily treatment, most of the time the compliance is down in the 50% for a three times daily regime. And there's strong evidence, particularly in the field of cardiovascular therapeutics, that patients who are not taking their treatment, are unlikely to generate the benefit. And obviously, to some extent that's common sense. In infectious disease, physicians have a lot of experience with HIV
NEIL RITCHIE: and this is an area which has been a huge amount of work done on adherence rates. This is one of the classic pictures from the CDC on the early days of antiretroviral therapy for HIV, where patients were having to manage incredibly complex regimes and it's now the case that most patients are on just one tablet once a day to manage their HIV. But back then, patients were having to set various alarms to time when to get up and when to take their treatment.
NEIL RITCHIE: And it's very clear that there's a strong correlation between both between both the pill burden and the number of times a day that you have to take the tablets and how often the patient's going to take them and how successful that treatment that treatment is. So the more tablets, the more times a day, the less likely the patients would be to take their treatment and the less likely they would to be successful.
NEIL RITCHIE: Bit harder to come up with clear evidence and antibiotics, but it is there. Patients receiving combination antibiotic therapy are more likely to experience adverse reactions as well. So this is a randomized controlled trial in cellulitis where we added clindamycin into flucloxacillin and patients who got flucloxacillin and clindamycin are much more likely to have diarrhea, much more likely to have any side effect than the patients given just flucloxacillin on its own.
NEIL RITCHIE: Most antibiotic trials are exploring synergism, so it's a little bit hard to compare these because in these studies you've got the option of just giving one drug. Whereas, whereas in polymicrobial infection you might not have the option of just giving one or the one that you might give might be more toxic or much broader spectrum, so it doesn't directly, doesn't directly correlate in. Longer duration
NEIL RITCHIE: therapy is probably associated with higher adverse reaction rates and likely an escalating impact from combination therapy. So this is a study on Helicobacter pylori eradication therapy, where long courses of treatment were associated with pretty high rates of adverse reactions up in the 30% range for those getting long courses of combination therapy and so we have to take this quite seriously. How do we manage these kind of complex oral regimes in Glasgow?
NEIL RITCHIE: Well, this is, this is an editorial that we wrote a few years ago in the Journal of Antimicrobial Chemotherapy talking about this concept of COpAT - complex outpatient antibiotic treatment. It doesn't really matter whether it's given intravenously or orally. The point is that it places a heavy burden on patients and so we need to proactively follow them up and monitor them. And the other problem with these very complex regimes with multiple different antibiotics being used is the number of drug interactions that we see with antibiotics and particularly with oral antibiotic regimes on the right here.
NEIL RITCHIE: So these are patients from our MDT in Glasgow and the most common drugs that they were taking and you can see that most of the oral therapy that we prescribe has lots of drug interactions and once you start piling those up, two, three, four antibiotics, that soon becomes a real problem in terms of management. Combination antibiotics in our hands are much more likely to be toxic as well.
NEIL RITCHIE: These are some unpublished data from our unit in Glasgow. Some of the more common antibiotics we use in bone and joint infection and you can see that particularly for linezolid and the fluoroquinolones like ciprofloxacin or levofloxacin, when we combine those with other antibiotics in orange, the rate of toxicity requiring discontinuation goes up dramatically. So if I prescribe a linezolid antibiotic combination, the chances the patient will discontinue that due to lack of tolerability or toxicity is greater than 50% And we've now are beginning to reconsider whether we use these regimes at all or if we just use them in carefully selected patients who we feel are at higher, are at lower risk and more able to tolerate them.
NEIL RITCHIE: So many of these antibiotics are high risk. What does that mean? Well, it means that we have to recognize that prescribing combination antibiotic therapy has a higher risk of failure through toxicity and intolerance than monotherapy. And so we have to warn patients that might happen, that they're likely to experience significant side effects and offer support. And in our case, that means providing them with a contact number for an antibiotic clinical nurse specialist and giving them a patient information leaflet that helps remind them what they might experience and how to contact us.
NEIL RITCHIE: And it also means that we have a low threshold to convert these patients back onto an IV therapy regime and so patients who are going out with us on oral therapy, we'll counsel them that they might have to go back onto IV therapy if they don't tolerate their oral regime so that they know. I want to just present a couple of cases now before I conclude if I've got time.
NEIL RITCHIE: Hopefully, I can't get my clock up, so hopefully I do, but Bilal will cut me off if I'm running short. But this is a 42-year-old man. I think it might be one of yours Bilal actually, presenting with a lower limb fracture, managed with an early internal fixation who developed, with an internal fixation, who developed an early postoperative infection within a few weeks. He was treated with metalwork removal and application of an Ilizarov frame, had some calcium beads loaded with vancomycin and gentamicin added into the dead space and a polymicrobial infection was isolated on culture with an MSSA Klebsiella pneumoniae gram negative and a group G streptococcus isolated.
NEIL RITCHIE: And our initial management with piperacillin tazobactam on the ward was then I hosted to clindamycin
NEIL RITCHIE: and ciprofloxacin for discharge, and he was seen by a clinical nurse specialist and given the patient information leaflet before he went. After discharge, he developed marked nausea and vomiting and was struggling with the tablets and considered stopping. Fortunately, he contacted our nurse specialists, and they brought him up for review. His bloods were OK.
NEIL RITCHIE: We started him on some antiemetic, which helped with his nausea and discussed a conversion to intravenous ceftriaxone as an outpatient. But his symptoms settled over the next few days and he was keen to continue with oral therapy and did well and follow up with clinical resolution of his infection. And did really quite well out to about a year I think, when I last had contact with him.
NEIL RITCHIE: Just a shorter second case, a 74-year-old woman with a polymicrobial infection of a femoral gamma nail managed with a single stage exchange and she had a real horrible mixture of organisms; staph aureus, a beta hemolytic strep and two different types of coliform organisms, including intra faxers which are quite resistant and two different anaerobic organisms. And we contemplated a regime of doxycycline, ciprofloxacin and metronidazole to try and get her out on orals
NEIL RITCHIE: but actually, when we went to speak to the patient, she reported having significant nausea and diarrhea with most antibiotic courses and she really doesn't tolerate therapy for, for when she gets chest infections, which is quite frequent. So having heard that, we decided to go with an outpatient IV regime and this is actually one of the more common reasons that we give outpatient IV regimes in the Glasgow COpAC ServiceNow is because we don't think the patient will tolerate oral antibiotic therapy.
NEIL RITCHIE: The patient's daughter was trained to self-administer and she completed the course of treatment without incident and tolerated it well. So that's been a kind of whistle stop tour through my thoughts about polymicrobial infection and why it's a particular challenge. As we've seen, it's a common challenge in fracture related infection and so we have to really think about how to manage these patients carefully.
NEIL RITCHIE: Cases with polymicrobial infection often have multidrug resistant and difficult to treat organisms, and there's a greater necessity to construct very broad spectrum or complex regimes if we do have to give prolonged systemic therapy. Such cases emphasize the need for MDT discussion, an ongoing specialist input to ensure that patients are supported to complete the courses. And we have to have dynamic plans and a means of and a means of reviewing them based on toxicity and tolerability.
NEIL RITCHIE: So particularly where people have I know that many work in regional centers and so there needs to be a way to keep up with these patients after they go home and that we don't just prescribe antibiotics and then forget until the patient comes back a few months later to follow up. So, thanks very much.
BILAL JAMAL: That was great. Thank you so much.
BILAL JAMAL: I wanted to pick up a point, which relates to some of the patients who are referred into our service, which is some patients may have fracture related infection. They might have had an operation done in the index unit to try and address that fracture related infection and there can often be retained mental work or incomplete excision of bone and I suppose I wonder if that's on going long term circumstance whereby there is ongoing retained mental work or incomplete excision of bone.
BILAL JAMAL: How does that alter the clinical advice that you give about duration of antibiotics and indeed antibiotic choice?
NEIL RITCHIE: Yeah thanks, Bilal.
NEIL RITCHIE: I mean, I think that. So first of all, if there's retained metalwork and we can't remove it, that brings in the whole discussion around biofilm and how best to manage that, that we have frequently in prosthetic joint infection
NEIL RITCHIE: and you know, I do try to use rifampicin if it's appropriate in these circumstances. The evidence I don't think is there at all in fracture related infection and you know, it it's a bit stronger in prosthetic joint infection. But I think for me, I bring that across and I do use rifampicin in these cases if it's appropriate but I know not everyone does. In terms of duration,
NEIL RITCHIE: I think that's extremely difficult, you know, because there's no test of cure in these patients. As we've seen, many of them are in an extremely high stakes situation so they maybe already had so much bone cut out that a further surgical revision essentially would be amputation. And they're understandably very, very nervous about stopping their antibiotics if they've had significant infection.
NEIL RITCHIE: So, you know, I think these cases really emphasize the importance of the multidisciplinary team and also being in contact with the, being in contact with the patient, because, you know, there are some cases where we will carry on antibiotics for a very long time. And some of that might be treating ourselves and, you know, dealing with the worry that we have about these patients sometimes and what will happen if they go wrong, but particularly if there's been a big bit of infected bone left in, it's very difficult to know just how you sterilize that.
NEIL RITCHIE: And so, but it just emphasizes that every case is different, I think, and particularly in these cases, there's something that can be quite generic about a hip and knee there sometimes where you've got a staph aureus, we know what we do here. I think fracture related infection is much more heterogeneous so we're more likely to have individualized plans for those patients, I think.
BILAL JAMAL: Yeah, absolutely share that sentiment. Thank you very much. Thanks so much, Neil. That was really superb.
Form Title Download
Transcript
Form Title Bookmark
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Form Title Share
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Form Title Accessibility and Keyboard Shortcuts
The cadmore media player is a professional video and audio player experience designed to deliver media as well as relevant transcript, segmentation, and metadata. On the screen is a traditional html video player with buttons such as play, pause, forward, captioning, language and play speed selection and more. Adjacent to the video player are generally tabs, one of which shows a scrolling transcript of the video and the other shows any segmentation of the media, sometimes referred to as chapters. At the top of the video is a menu bar containing an Explore button and Tools button. The Explore button allows you to dig deeper into the video by opening up an explore dialog which contains tabs for a visual navigation of the video using thumbnails, an about tab which contains rich metadata about the media, a segments tab which contains further information about the video, and a related tab which contains links to other media related to this media. The tools button opens a menu with options for sharing the media on social media, creating bookmarking links, creating embed codes for your website, generating citations, and more.
Keyboard Shortcuts
Keyboard shortcuts only work while you are in forms mode. By entering forms mode, you will be able to quickly access portions of the media player with single key commands.
Spacebar: Play/Pause Toggle
I: Info Menu,
O: Tools Menu
T: Transcript Tab,
S: Segments Tab
F: Forward 15,
R: Rewind 15
L: Languages,
P: Playspeed
M: Mute Toggle,
V: Volume Bar
N: Video Only Toggle,
B: Full Screen Toggle
C: Captions Toggle
Escape: Closes dialogs and menus / Exits Player
Z: Next Transcript Chapter
X: Previous Transcript Chapter
Q: Next Transcript Paragraph
W: Previous Transcript Paragraph
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Embed Size
-
You Size - Responsive
-
We Size - Responsive
-
Picture Overlay Popup
-
400 x 225
-
512 x 288
-
400 x 700
-
768 x 1024
-
1024 x 512
-
1280 x 608
Form Title Cite
No citation provided.
Info
Segments
Related
Thumbnails
Exit Clip Mode
You have requested to see a portion of the video outside of the clip.
Click OK to switch to the full video or click if you would like to stay inside the clip. You can always go back to the clip with Tools and Clip Mode