• LecturehallCan Osteomyelitis be Effectively Managed Non-Operatively?
  • Lecture Transcript
  • Male Speaker: It gives me a pleasure to talk about or to introduce discussion on one of the most controversial topics and the topic of greatest interest around the world diabetic foot community. And it often gives us much consternation. And of course, that is the topic of osteomyelitis. Do we or do we not treat this conservatively? Can we treat it conservatively alone? Or must we do a surgery as many of us had been taught for many years? And I have learned from my colleagues in Europe, and especially the next speaker, that you don't always need to treat osteomyelitis with a surgery. But that's predicated upon the notion, are you really treating osteomyelitis? Or do you just think you're treating osteomyelitis also? So it gives me great pleasure to introduce once again our 2013 Paul Brand lecturer, William Jeffcoate. Who I can say I've learned a lot from over the years. And I've asked him to speak on the topic, Can osteomyelitis be effectively managed non-operatively. So let's welcome Dr. Jeffcoate.

    William Jeffcoate: Thank you very much. So I'll repeat, can osteomyelitis be effectively managed non-operatively? I run over when I was talking yesterday, I thought I was finished at this point because that's the question you asked me. Should I carry on? Alright. If you insist. The history, of course, is very well-known to all of us. Really, the time when the antibiotics did not exist. And then earlier on, in the early antibiotic era, the agents that were introduced were effective but organisms rapidly became resistant to them. And then, obviously, surgery which had been the original on these method of treatment then became opposite as the prime treatment for bone infection. Until the 1980s when new classes of antibiotics emerged. And in particular, there were two new classes. One was the combination of lactam antibiotics or lactamases. And the other one was the quinolones. And at the same time, clindamycin was rehabilitated from -- you know, obviously been available since 1960s, but eventually been relegated to the backroom because of the first antibiotic associated with pseudomembranous colitis. But it was rehabilitated when it actually was realized that it was not specific that particular agent. But through the 1980s and, in fact, the modern day, although there are new effective antibiotics, there has been a tendency it may pass the world to regard surgery still as the first-line treatment to which the use of antibiotics is added. There are newer agents which have been increasingly deployed particularly that is active against MRSA when it was obviously essential. But also other agents active against Staph aureus which is a dominant pathogen. And also, in the modern era, you say that this debate continues. Well, it does. And one of the sad things -- well, sad but interesting -- is that people have entrenched attitudes. I haven't gotten entrenched attitude as I hope comes across. But there have the people who favor such and the people who favor antibiotics being daggers drawn with each other. Well, we're not really. We're quite sensible people. There is the biofilm stuff as well. One of the reasons why bacteria can become larger than bone is because they immerse themselves in polymeric slime to which it is difficult for antibiotic agents to get access. And this is one of the reasons why, in fact, so many antibiotic preparations have traditionally been resistant. But like Warren, I do share a certain amount of caution about the whole biofilm literature because I think there are some people who are promoting its importance because it suits their own ends. But I'll say no more because it obviously is a very important microbiological phenomenon nevertheless. I want to look at the facts.


    You asked me whether antibiotics alone may be effective. And I was working on this and persuaded Ben Lipsky [phonetic] to join in with me about ten years ago. And we reviewed the literature that was then available on the use of antibiotic preparations alone and eradicating or apparently eradicating infection because, of course, cure is a difficult concept to define when you have a disease which can relapse and remit. Nevertheless, this was the literature which was available to us. I said, I persuaded Ben Lipsky. He was, at that time, very familiar in the surgical camp. And I won't show you any quotes but nevertheless these were the data that we found. And there were a large number of papers with a moderate number of cases, 500 plus. And you could look at what we called remission rates. In other words, it seemed to have gotten better after a period of time. And if you just scan down those numbers with the exception of [indecipherable] [0:06:05], there was a sort of a feeling that perhaps 50 or 60 percent of people might get better with antibiotics alone. The regiments used obviously varies both in terms of the preparation chosen and the duration of therapy. The one problem with all these studies though is that nobody described the definition of osteomyelitis in detail. And that still is a problem whenever you're going to try and make a robust defense of one particular strategy or another. Do we all have to have histological evidence of osteomyelitis together with microbiological evidence and bone biopsy? Or can we use the criteria which we use in everyday clinical practice? And this is a fraught issue. And I'm not going to address it in any more detail. But the thing that is relevant to all these studies is they don't describe the others that they did not select for antibiotics alone. They didn't describe the people who came in, and it was obvious this person needed surgery before the day it was out. And in other words -- so these were all selected series including essentially one of our own from 1997. And so working with Fran Game [phonetic] in Nottingham, we decided to look at -- because we register every ordeal at that time because she now moves elsewhere -- every case that we manage over a five-year period. So we knew all the people who we had managed to have had osteomyelitis diagnosed. And there were 147 cases that we reviewed. And what we'd looked at -- and this is the value, if you like, over a retrospective case review as opposed to a formal study -- is that early surgery had been selected as the treatment of choice as sizeable minority of them. So this is not a selective series. Thirty-four had proceeded to early surgery and that was six majors and 28 minor amputations. There was a recurrence rate which I'll come back to in the minors and some of them being treated with antibiotics, some with further surgery. But then there was another group that didn't have surgery because that was our working strategy then as now that if we think that we can avoid surgery being pathologists, being endocrinologists, and not surgeons, then that is what we would do. And 113 of the 147 actually were treated without surgery as their initial treatment. And that, following a cross of antibiotics which was almost exclusively oral. But to some did have injuries when the infection was bad resulted in apparent eradication or apparent cure, apparent remission, however you want to call it in 66 of the 113. These follow-up dates are all the 12 months by the way. Of the 113, 35 recurred after an initial course of treatment with antibiotics. And they had further antibiotics. Twenty-seven of them had further antibiotics. And that resulted in apparent cure remission in 12 months. Some had minor amputation and two went on to have major amputation. But if you look at this, this means that 93, perhaps 66 and 35 -- is that right? Sorry, 66 and 27. Sixty-six and 27 actually had their bone infection eradicated without any surgical intervention. And that 63 percent of the total. But if you regard it as the percentage of those who had been selected for non-surgical treatment, we actually had an apparent effectiveness rate of 82.3 percent which is not too bad at all.


    So this is really the basis of the question you asked me, can it work? And the answer is yes, it can. Fran and I have actually done eight-year follow-ups of all these patients. The dates are unpublished. But there is no evidence of realistic recurrence in this group as opposed to any other. The third major amputation -- minor amputation is this 23 percent. It's the first of a 100 if you chose the surgical approach. Total major amputations in this group in 12 months was 9 percent which is again quite modest really. And so if we're talking about should you have a primary medical or primary surgical treatment, then, obviously, medical approach has no operations and doesn't cost so much. Surgery might have a benefit in terms of earlier resolution. Obviously, reduced exposure to antibiotics and all the problems that go with them. But I've just shown you it may be ineffective in 18 percent in our hands of people. But what about surgery? If we go to our people who are treated with surgery initially, of the ones who've had minor amputations, recurrence occurred in the 17 percent of that population which really isn't very good. And so we got 63 percent recurrence after a minor amputation. Now, you can say the Nottingham surgeons aren't very good. I accept that. No, I won't accept it. I'll accept it as a point to be made. Not as a truth. But very good. But surgical cure in their hands or our hands was 37 percent. And this was despite they have been given current antibiotics. And so you could say, well, actually, we did quite well the ones were those. But this group didn't do very well. But their counter-argument as well. These were ones that are obviously worse. And so they're not a comparative population. But if you look at the literature on the effectiveness of surgery and the literature is really quite sparse. There are two older papers. And this one looking at amputations that hallux therapy [phonetic] in San Antonio, I think, in 1981 to 1991, I'm sure that of the 90 cases who had hallux surgery, not all people with diabetes, 60 percent required repeat surgery within a min of ten months. And 17 of those was a major amputation. Now, that's not very good. Suggesting that initial surgery had a cure right in this particular series of hallux surgery of 40 percent. Another study also in the 1990s of 97 patients, amputations of a digit, any digit, all in diabetes with good circulation. And the apparent immediate cure rate after initial intervention was only 40 percent. And of those, there was recurrence in 15 making an apparent cure after initial surgery of 25 percent which isn't actually very good for a treatment of choice now. Obviously, you can question all sorts of things you can raise questions about details of the technique. But nevertheless, these are the people who've published the data. There are more -- there is more recent data from the last couple of years, really. And looking at, first of all, from the U.S. systematic review, again, the first three amputations of various types. And they selected eventually five studies using the systematic review criteria with 435 people follow-up for two years. And the reamputation rate in this group within the follow-up period was 20 percent. So it's a little bit better but it's still a little bit disappointing really depending on what the criteria [indecipherable] [0:14:01] osteomyelitis used for surgery. Then there was this other study also published recently of osteomyelitis and diabetes treated with a combination of strategy of surgery with antibiotics both parenteral and oral. But predominantly, parenteral, I think. And they had, of the series of 50 cases, 43 had initial minor amputation. They checked the microbiology of the wound margin. And if they were positive at surgery, they had a longer cause of parenteral antibiotics and IVs. I mean, parenteral, in other words, for six weeks if they're positive and a rather shorter period if the wound margin was microbiologically negative. Nevertheless, with this approach, 18 of the original 50 -- sorry, 18 of 43 but I have to express it as 18 of 53 needed further surgery within the two to 26 months of follow-up.


    In other words, again suggesting that the approach even when surgery is combined was pretty heavy effective. We presume antibiotic therapy is leading to need for further surgery within 30 percent. This study comes from Cambridge in England which also published recently of people with diabetes good circulation treated with primary closure after minor surgery. Follow through a median of 31 months in average of a year. And they had recurrent surgery there. There were incidents of recurrent surgery was need for was rather lower in 16 percent. So I'm saying that, okay, if you select people for conservative non-surgical therapy, you might have a failure of 18 percent which is what we found. But even in the better more recent data, you get just the same apparent failure rate with no surgical approach. The problems have caused a well-established that if you remove a hallux, even though the second toe is very difficult to surgery, you think you can decide what's infected by it and what isn't. The hallux looks good -- I'm sorry. The second digit looks good on x-ray as is the third. And yet, within six months, this is the result with both those rays being obviously affected when we presume osteomyelitis. And then you've got the risk of transfer losses as well, which to be fair can occur also with non-surgical treatment because the infected bone contracts down and the shape of the foot does change to some extent. So if we're talking about this sort of which should we choose, I say that I accepted that a non-surgical approach may be ineffective but a surgical approach can also be ineffective, sometimes much quite startlingly. So antibiotic choices, of course, are fairly standard. We know Staph aureus' dominant feature and dominant affecting organism. We're not quite sure if Staph aureus leads the gang of hoodies if there are more than one organism than if you actually select for treatment and stuff whether that actually results. And the other is wilting away as well. Nevertheless, that is the strategy that's used. But people would tend to use an empirical broad spectrum regimen. Either lactam antibiotics combination or clendo which is active gram-positive and anaerobes with something also covering both gram-positives and gram-negatives. And people use various strategies for sometimes frighteningly long periods of time assuming that the patients actually take them and with all the problems that go with that. More recently, people have tended to use rifampicin fusidic acid. Obviously, not solely but as combinations particularly starting with MRSA but also because they're both been having a very good bone penetrants. And although that's the empirical therapy which many people recommend, it is recommended by all the guidelines that we should be taking bone biopsies and identifying the organisms and determining their resistance. Their antibiotic sensitivity and then adjusting therapy if they are not responding. And just to mention, it does look as a pseudomonas aeruginosa is becoming an important pathogen as well especially perhaps in emerging nations in which I include UK as an emerging nation. And whereby we have particularly healed osteomyelitis where perhaps we're using casting as well as pseudomonas likes a damp environment. And it looks as though pseudomonas is becoming a realistic pathogen. And that's a problem because of the limited number of antibiotics effective against it. But going back to our overall strategy of our series that I described, total minors of 23 percent, total majors of 9 percent. And I'll just mention our antibiotic period, nearly all of this is oral. But the median antibiotic duration is just two months. And we weren't really laying it on a second what we do. And now, we'll just finish by showing you some recent quotes from the guidelines and reviewers. So we're saying, is there a role for non-surgical treatment? Here, we've got the international working group on diabetic representatives from all over the world including the U.S. And the conclusion of their last guidelines because they come out every four years, available studies do not provide information to inform which cases may require surgery. If you take your own Infectious Diseases Society of America published in 2012, clinicians can consider using either primary surgical or primary medical strategies.


    Ben Lipsky who's actually involved in both of these. I also know these are not impressed in diabetes care in which he says in a commentary that, this is a question of true equipoise. So when people like to say that the proponents of non-surgical and surgical therapy have daggers drawn and they're fighting each other, it's all a bit -- it’s not quite like that. We're trying to say there are two different approaches. In this case, the scales are not tilted either way. Some people will benefit for months, some people will benefit for another. And there are a whole host of different reasons why either should be selected. But in many cases, either approach is an option. And so that was the question that was asked. That's the answer. And now, I'm going to finish. Thank you.