Male Speaker: Now, I’d like to introduce once again Dr. Axel Navone [Phonetic] who’s going to give us her overview on current and diagnostic approaches to osteomyelitis, the other great conundrum that we all face each day. Let’s welcome back Dr. Navone to end up our busy day. Thank you.
Axel Navone: Okay. I’ll keep it 20 minutes, I promise. I’ll try to make up what Dr. Hartley’s [Phonetic] took a little bit. For the sake of time, I’m going to basically go just do a couple slides from the very beginning here. I have nothing to disclose and again, the learning objectives are available for you online. I won’t go over the different causes but mainly the cause of osteomyelitis are secondary to contiguous hematogenous and direct cause. Obviously, in our diabetic, it’s mainly from a contiguous cause. Diagnostic modalities are out there for us. Mainly there are labs, the probe-to-bone test, I think we’re all very familiar with, plain radiographs, radionuclide scans and/or bones scans. Some other radiological available that Dr. Hart has alluded to which is CT scans, MRI and then SPECT or PET-CT and then bone culture and bone biopsy. I want to focus mainly on the SPECT, PET-CT because it’s a relatively newer modality that I think we should be familiar with. We’ll talk about some of the evidence that have been used for SPECT and then introduce in the future. But in terms of labs, we know, unfortunately, there are no great lab test to determine whether a patient has osteomyelitis or not. At one point, we will discuss procalcitonin as a possible lab test. However, that’s mainly been studied on septic joints and not necessarily on diabetic foot patients. More recent study by Shen [Phonetic] in 2013 discussed the fact that procalcitonin was better use to rule out osteomyelitis versus ruling in osteomyelitis. In terms of probe-to-bone, I think we all everybody in this room basically does probe-to-bone. I know there are multiple studies that talk about accuracy of probe-to -bone. I think the best thing to keep in mind is that if you have a high clinical suspicion and the wound is infected and it probes-to-bone, that’s very highly suggestive of osteomyelitis. However, if for some reason, the wound isn’t infected and that doesn’t probe-to-bone, that’s most likely not osteomyelitis. Probe-to-bone is an excellent tool first to use especially when we combine it with our clinical examination. Plain radiograph, again, I won’t go into this because I believe we all are very familiar with plain radiographs. Importantly, we know there’s approximately two weeks delay compared to our clinical findings and clinical presentation. However, the advantages of plain radiographs are that it is readily available, it’s inexpensive, and if it’s positive, it’s fairly diagnostic. It’s only when it’s negative that it can’t help us rule out osteomyelitis. The disadvantage, again, you do not see changes until 10 to 14 days after the onset. The sensitivity and specificity is sometimes a little bit low. If you have Charcot which we discussed earlier, it’s indistinguishable from Charcot. Aragon Sanchez actually looked at probe-to-bone but he combined probe-to-bone and radiographs. Basically what he found out is if you look at the results there, probe-to-bone test was actually sensitive from his perspective because in his case, he looked at high risk inpatients. The bone sensitivity is 95%, specificity of 93% with a positive predictive value of 97 and a negative predictive value of 83. But when he combined probe-to-bone test and also radiographs, all the sensitivity, specificity, positive predictive value and negative predictive value actually increased. As I stated, probe-to-bone is great when we use it with clinical outcomes and also looking at radiographs. Other test, basically bone scans, they’re listed up here. Their tech scans are available, their other leukocytes scans available, gallium scan and indium scans. In terms of the tech scan, it basically only looks at abnormal bone. As you know, that’s very sensitive for osseous changes but not specific for osteomyelitis versus other bone abnormality. Gallium is actually good for chronic infections because it actually tags the membrane of the leukocytes while indium scan has leukocytes itself. But the advantages and disadvantages of these bone scans, the advantage is that you can see the changes within hours of an onset.
People utilize bone scan quite often when MRIs are contraindicate or not available. I’ve stated it’s actually very sensitive. However, the big disadvantages of utilizing bone scan, it is invasive and it’s obviously very timely. It takes up to a whole day for patient to be scanned. It’s only moderately expensive, however, bones scans itself provides you very poor anatomical detail. And then the sensitivity and specificity is actually pretty low. As I stated, there’s a lot of false positive in patients who have tumors, osteoarthritis, abscess, or any types of osteonecrosis. We all are very familiar with MRI, I won’t go into details with MRI. We know that MRI works for soft tissue and can actually look at osseous pathologies. Dr. Hart doesn’t like using MRIs. But it is available to you for looking at soft tissue and also osseous pathology. It’s especially helpful when you’re trying to plan your procedures. Again, advantages and disadvantages of an MRI. Advantages, it’s early detection. It’s very useful in terms of being able to give you structural and anatomical resolution. It is very sensitive in a positive predictive value and negative predictive value over 90%. Again, it helps you with your surgical planning. The disadvantages are that it’s very expensive, again, false positives are very common because it’s indistinguishable from pathology such as Charcot. And then it is operator and radiologist depending on how it’s actually read. This is what I want to focus on in terms of diagnostic is we’ve all seen this in the literature and we probably heard about all these different types of tests that are out there. There are single-photon emission computed tomography which is a SPECT. There is also SPECT combined with CT. There’s also the PET scan or the positron emission tomography that’s available. Again, depending on what the biological type is, it’s mainly using fluorodeoxyglucose or FDG along with PET. Again, that’s also PET-CT. What are all these? Briefly, what is SPECT and what is SPECT-CT. Actually, SPECT is very similar to a bone scan. The major difference is inside of a plainer view or a plainer image you get with a bone scan, a SPECT allows for you to have a 3D image, a very similar finding as a bone scan. It actually uses the same radioisotope which is the gallium and indium. And then the main difference is it actually uses gamma rays. In a SPECT, it actually uses a single gamma ray. That single gamma ray is actually measured by the system itself. It is less expensive than the PET. The reason I point out the single gamma ray is the PET actually uses two gamma rays. There has been some studies that looked at dual isotope which means using two different isotopes like a gallium or technetium and/or indium scan along with PET and CT. In the study that was done by Hiba [Phonetic] that actually showed that SPECT-CT can distinguish between soft tissue and bone infection. In their study, actually the followup study, they showed that using SPECT-CT can actually decrease major amputation hospital stay because they’d be able to obtain information on the anatomical location of the bone infection. What is PET and PET-CT? Well, PET, like I said, it’s very similar to SPECT. The only difference is that it emits a positron, which basically annihilates the electron that causes these two gamma rays to go into different directions. The reason why it’s more sensitive than the SPECT is because you get higher resolution with the two gamma rays. The only difference is it’s not measured directly, it’s actually measuring the motion of the two gamma rays versus looking at the gamma ray itself. As I said, the biological molecule that’s used is fludeoxyglucose. The way this works is the FDG actually is bound to the radionuclide aspect of it. As we know, glucose is a very high affinity to the neutrophils and leukocytes. Anytime there’s a high metabolic activity, there’s a higher glucose uptake and that’s how it works.
The difference between using PET-CT and/or other modalities is it can give us a semiquantitative information. Basically, it’s the SUVmax and the SUVmax is actually the standard uptake value. Unlike MRI where you get a reading of an uptake and the PET-CT actually gives you information on how much uptake occurred in that pathological area. It can’t be semiquantitative. To date, there was a study that looked at whether PET-CT, and PET, like I said it’s nuclide and then the CT aspect gives you the anatomical. But there was a study actually done by Hafner [Phonetic] that looked at whether PET-CT can distinguish between Charcot and osteo. In the studies, they actually did show that there was some capability of distinguishing it, however, both the studies actually showed that there was minimal osteo in their subjects. They only had patients with Charcot. Unfortunately, there has been several studies on using PET and looking at osteo. Some show excellent results up to 90, 100% sensitive and specific and that others show a very low sensitivity and specificity. Some studies even say if you compared it with an MRI, it gives you even a better sensitivity but that would be a very expensive examination. At this time, unfortunately, there is no recommendation for using PET to rule out osteomyelitis but I think it’s quite promising and I think you’ll hear a lot more about PET-CT or SPECT-CT. Keep an eye out for this great diagnostic tool that might be coming out in the future. I think something that we’re always very familiar with is bone biopsy and bone culture. As you know, bone biopsy and bone culture is very sensitive. I won’t go to that because I’m running out of time here. In terms of approach to our osteomyelitis patient, there are two main options for treatment and that is medical and surgical. Unfortunately, there has not been any head-to-head studies on medical or surgical but in both studies that looked at them separately, the success rate for both have been approximately 60% to 90%. When should we consider nonsurgical? We should consider nonsurgical when the sepsis actually decreases within the first two or three days. Also, when patients can’t tolerate these antibiotics and if the degree of bony destruction doesn’t compromise the foot mechanics at all. If patients don’t want surgery or the comorbidity is too high for patients to have surgery, and if there is no contraindications for patients to have long-term antibiotic. Also, if surgery requires a much more extensive than what the patients or the physician would like to see. What are some studies that looked at supporting treating osteomyelitis medically? Spellberg and Lipsky actually recently published a study that looked at osteomyelitis being treated with systemic antibiotics. They set up to answer a couple questions. What antibiotics should we use? And then are orals acceptable for some of these cases? And then how long should these antibiotics be given for? And then is surgery always necessary? Unfortunately, these studies were not just on diabetic, they were for a lot of different osteomyelitic patients. They found that these are the most common bugs, the gram-positives up to the gram-negatives and obligate anaerobes. What they found is that in their patients who had the best success were actually on the IV agents including the beta-lactamase antibiotics, the cephalosporins, the penicillins and also the vancomycin and daptomycin. In terms of oral antibiotics, they did find that oral antibiotics were effective, unfortunately they were effective mainly at a higher dose. The fluoroquinolones, instead of giving 750 mgs per day, it’s actually given 750 mgs twice a day, had a better outcome. Same thing with Bactrim. Bactrim, they increase the dosage to 7 to 10 mgs per kg per day for 8 to 16 weeks so they actually extended the use of these antibiotics. Listed here are antibiotics that can be utilized for the gram-positive, gram-negatives and anaerobes.
Additionally, what they also found out is adjunctive, maybe used rifampin. You have a better outcome for cure rate. I’m going to go straight to basically their final results. In terms of antibiotics recommendation, the Infectious Diseases Society of America, after looking at all the literature, they basically said there was no evidence in determining whether p.o. works better but more importantly would antibiotics works better versus surgical. There is no data supports whether a specific antibiotic actually works better. There was no support as to whether IV or oral worked any better. And then they stated that if you [indecipherable] [15:52] resect bone, you should only continue antibiotics for two to five days. However, if resected bone still is positive for necrotic tissue then you need to increase it to four to six weeks. When to consider? I think we all know this. But when there’s persistent sepsis, it’s important, when patients cannot tolerate antibiotics, if there is progressive destruction despite being on the oral antibiotics, if the destruction actually is compromising the foot biomechanics, if patients don’t want long-term antibiotic therapy, and if the tissue, even despite the fact that they have osteoarticular, the tissue is still not cured and if antibiotics is contraindicated. In terms of surgery, if you’re going to consider surgery, what are the some things that you need to consider with surgery? Basically, this study that was done by Ten [Phonetic] stated that if you’re going to do surgery, consider doing surgery earlier. What they found out is patients who had surgical interventions within the first three days had a significantly much lower above the knee amputation, 13 versus 28% compared to those who had a delayed surgery. They also found out that surgery admission day was significantly less with early surgery versus late surgery. Another study by Atway actually looked at an interesting lead, looked at positive margins after resection. What they found out is patients who had positive margins postoperatively had much worst outcome. You can see here the overall outcome of this but those with positive margins had a poor outcome of about 82% while those who had negative outcome had a poor outcome of only 25%. It’s really important to know that positive margins actually have much poorer outcome. Another study that was done by Kowalski [Phonetic] had the same finding and they actually looked at patients who had positive margins postoperatively. Again, what they found out is those that were treated that had positive outcome had a 44% failure in terms of their treatments and those who had negative outcome only had 15% failure rate. Again, positive margins result in poorer outcome. Another study that was done by Flaj [Phonetic] they actually looked at if you’re doing surgery what type of surgery can you do? They looked at internal pedal amputation which is just resecting the bone like an arthroplasty versus doing a partial ray or digit amputation. What they found out is the dehiscent rate, the reulceration rate, and also the contralateral ulcer rate was very equal and whether you did an internal pedal amputation versus a partial ray, so something to consider. Another study done by Cecilia [Phonetic] here is looking at locations of osteomyelitis and their healing. Importantly, look at the results here. Basically, what they found out is osteomyelitis in the toe had the best healing outcome in 12 weeks versus the other areas. The one that had the worst healing rate was the first metatarsophalangeal joint. Consider where the osteomyelitis is. When you’re doing surgery, these are some things to consider. One, early approach has a best outcome. Two, surgery does have a much lower recurrence rate.
If you’re doing bone resection, it’s important to culture the margin, make sure the margins are negative, consider the biomechanics transfer lesion, and then osteomyelitis in certain location is still better than others. Toes heal much better than the first metatarsophalangeal joint. In summary, in 20 seconds, what are our findings? Clinical is how you should be diagnosing osteomyelitis like what Dr. Hartley said. However, use the other diagnostic modalities that you have to just augment your clinical diagnosis. Bone culture and bone biopsy are your definitive possibilities. Also, when you’re doing bone biopsies, consider where you’re culturing from. In terms of treatment, unfortunately, there’s still no consensus as to whether we should treat our patients conservatively versus surgically. But if you are going to do surgery on your patients earlier, it’s actually better and make sure your margins are negative. In terms of medical therapy, again, there is no consensus on what type of antibiotics to use, the duration of antibiotics, your route of antibiotics either but knowing that p.o. could work for osteomyelitis. And then adding rifampin has improved outcome, also increasing the strength of your antibiotics has increased all positive outcome. And then more recently, people just classified that combining both antibiotics and surgery has the best outcome. In a study by the Infectious Disease Society of America, they basically said no adjunctive therapy have actually improved outcome with HBO, growth factors, maggot or negative wound therapy. Thank you. I went over one minute.