March 27th, 2010 by Warren S. Joseph DPM FIDSA
Edward James Olmos, my wife Judy and me at DFCON
Up to this point I have resisted using this blog as a “social networking” tool to just post pictures of myself lecturing someplace or another. It has been my contention that readers of this site are interested in new science about lower extremity infections and the last thing you care to see is my visage staring out at you. So, you will please indulge me this post. Besides, I will still discuss some more substantive issues further down.
I was extremely honored to receive the 7th Annual Edward James Olmos Award for Advocacy in Amputation Prevention given annually at the DFCON (International Diabetic Foot Conference) Meeting held each March in Los Angeles, California. The Olmos award is named for the actor Edward James Olmos who has been active in raising awareness of the ravages of diabetes and the importance of limb preservation in the Latino community. Each year during the presentation of the award Ed relates how every male member of his family including his father and all of his uncles had either died or lost limbs as a result of diabetes. He himself has not been diagnosed with the disease but is a realist about the potential that he will eventually. For this reason he carefully watches what he eats and exercises regularly. He tells a particularly touching tale about how one of his uncles, upon learning that he would have to lose one of his legs, decided to commit suicide rather than having to face the prospect of an amputation. He has made it his mission to educate the community which has one of the highest rates of diabetes and limb amputation in the country. Each year he personally attends DFCON so that he can present the award himself. On a personal note, I should say that I found him to be the antithesis of what one expects from a Hollywood celebrity. My wife and I found him to be warm, gracious, human and a very grounded individual.
Past winners of the Olmos award have included true “Superstars” in the international world of diabetic foot disease. They have included Karel Bakker, Andrew Boulton, Gary Gibbons, Chris Attinger, Ben Lipsky and Peter Cavanaugh. To even have been considered amongst people I have looked up to for much of my professional career is an incredibly humbling feeling. I am also the first podiatrist to win the award despite others, including Lee Sanders, Larry Harkless and Bob Frykberg being incredibly deserving.
Enough about me and the award and on to DFCON! As far as I am concerned, this meeting is the scientific highlight of the year. It has become the largest annual international diabetic foot meeting attracting close to 1000 delegates from all 50 states and over 40 countries. It is one of the most egalitarian meetings I attend. It does not matter what degree you hold or in which part of the world you practice. All are listened to and respected, there united by a conviction to save limbs in this at risk population. Probably my favorite day of the meeting is on the first day, Thursday. During this session speakers from all over the world present information on what is being achieved in diabetic limb salvage in their countries. This year in particular there were two incredible presentations about work being done in Kosovo and Pakistan. Despite incredible hardships, healthcare providers in these two countries have managed to begin to save limbs by simply setting up diabetic foot screening centers. Streams of these lectures will soon be posted on the meeting’s website www.dfcon.com and I highly recommend them to my readers (not to mention all of the other talks from the conference). What I always find slightly disturbing is that the US frankly lags behind many 2nd and 3rd world countries in codifying the concept of amputation prevention and setting up dedicated centers. If Pakistan can manage, primarily through the efforts of a single individual, Dr. Basit, to set up screening centers throughout that country, why can’t we? Currently, in the US, there are maybe 6 true, multidisciplinary, dedicated “limb salvage” centers, the latest being the incredible facility just dedicated on the Wednesday before DFCON at Valley Presbyterian Medical Center in Van Nuys, CA. Kudos to Dr. George Andros who has invested blood, sweat and tears to achieve this life goal. All in the Los Angeles area owe it to themselves to stop by for a look at this state of the art center.
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March 12th, 2010 by Warren S. Joseph DPM FIDSA
(My thanks to David Armstrong, DPM, PhD for bringing this press release to my attention)
TaiGen Announces Nemonoxacin (TG-873870) Once-A-Day Oral Dosing in Diabetic Foot Infection Met Primary Endpoints
According to its manufacturer TaiGen, nemonoxacin, a novel, non-fluorinated quinolone has shown promising results in a single armed, multinational, proof of concept Phase II clinical trial against diabetic foot infections (DFI). What is unique about this drug is that, unlike other currently available quinolones, nemonoxacin has activity against MRSA and vancomycin resistant gram positive organisms. Those who have heard me lecture know that I have not been a huge fan of quinolones in the treatment of gram positive infections since, especially earlier generation drugs such as ciprofloxacin could, and often did, cause rapid development of resistance in these organisms. In fact, a number of quinolones have been implicated in potentiating MRSA development. Seeing a new agent in this class with this broadened gram positive coverage is really interesting and has potential to be an important therapeutic advance.
The use of quinolones in the treatment of DFI has an interesting history. The first antibiotic ever officially labeled by the FDA for the treatment of “complicated skin and skin structure infections including diabetic foot infections” was a quinolone…trovafloxacin (Trovan®, Pfizer). Unfortunately, the drug, having been granted the most indications of any new antibiotic at the time of release, 14, was heavily marketed and possibly over utilized. A number of deaths resulted, although there has been question about the agent’s role in those deaths, and the drug was essentially pulled from the market (although it was technically still available it had extreme restrictions placed on its use by the FDA). Trovan was unique in that it was extremely broad spectrum including activity against many common gram-positives, gram-negatives, and even anaerobes. So, its spectrum of activity was extremely promising for use in DFI. Few other quinolones that have been developed share the broad spectrum that Trovan possessed. A number of other broad spectrum, anti-anaerobic quinolones looked to show promise in the treatment of DFI but were never pursued. Gemifloxacin received indications only for respiratory infections. Gatifloxacin was marketed for skin and skin structure infections but was pulled from the market when it was found to cause problems with glucose homeostasis. Moxifloxacin has a spectrum of activity very similar to Trovan and should be useful in DFI. It does have an indication for complicated skin and skin structure infections, is given orally and once daily. However, it has not received a DFI indication. A number of years ago a DFI trial was started but, from what I understand, was stopped mid stream. I am not privy to the reasons the trial was halted and development for this indication stalled. The drug has recently been acquired my Merck in its merger with Schering Plough. Merck has a long history of DFI drug development so it will be interesting to see if anything comes of this.
Quinolone have been perhaps the most abused class of antibiotic. They have been massively overused because of their perceived broad spectrum and safety. However, a significant number of these drugs have been pulled from the market for toxicities. I mentioned 2 above, trovafloxacin and gatifloxacin. There have been others. Be aware of problems ranging from liver and renal toxicity to neurotoxicity and photosensitivity. Last but not least, in the past few years they have received the dreaded FDA “Black Box” warning for the role they can play in tendon ruptures, particularly of the Achilles tendon. Please use these antibiotics prudently when indicated.
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March 3rd, 2010 by Warren S. Joseph DPM FIDSA
For a number of years I have been presenting a lecture entitled “Differentiating infected from non-infected wounds”. As part of that talk I discuss the role of topical antimicrobials in wound healing. Despite there being a countless number of silver impregnated dressings along with multiple other antimicrobial dressings and solutions filled with all different types of product there is little evidence to support that their antimicrobial activity does, in fact, contribute to wound healing. We know that wounds become contaminated with multiple bacteria and we know that at least some of these organisms are capable of forming biofilm over the wound bed. It is felt that the presence of these organisms sets up a low-grade chronic inflammatory process that produces byproducts such as MMPs which inhibit wound healing. The thought behind using a topical antimicrobial is to kill these organisms thus allowing for improved healing. This certainly makes empirical sense since we have always been taught that these bacteria on a wound have to be bad. In my mind, however, there are three questions that should be adequately answered before we haphazardly continue using these dressings.
1. Does the use of a topical antimicrobial decrease the wound of bioburden?
2. By decreasing the wound of bioburden do we hasten wound healing?
3. By decreasing the wound of bioburden do we prevent colonized wounds from becoming clinically infected?
Surprisingly, really none of these questions have been answered to my satisfaction. For this particular discussion I will concentrate on question #2. An interesting study entitled “Bacterial burden and wound outcomes as influenced by negative pressure wound therapy” with just published in the February 2010 issue of Wounds by Boone, Braitman, Gentics, et.al out of St. Luke’s – Roosevelt Hospital in New York City. In this small pilot study using a porcine wound model infected wounds were created using a combination of bacteria including Pseudomonas, Staphylococcus and Bacteroides, and then treated with V.A.C. therapy using either regular or silver impregnated foam along with a moist wound dressing control. Both quantitative and semi-quantitative bacterial cultures were performed. To quote the Abstract “The wounds continue to show gross and microscopic improvement when treated with standard NPWT and NPWT with silver compared to moist wound care controls. However, the bacterial burden in all wounds continued to increase and broaden to include local skin flora, which had been absent immediately after wounding.” The authors concluded that the improvement in healing of the wounds could not be explained by a change in their bacterial burden.
The results of this study are actually similar to some of the earlier work performed using the V.A.C. Wounds healed more rapidly when the device was applied yet, almost paradoxically, the bioburden of the healing wounds seemed to increase rather than decrease as the wounds continued to heal. This certainly seems counterintuitive to the entire concept that the bacteria are somehow inhibiting wound healing. Maybe this all points to the ancient concept of “laudable pus”! Of course many factors must be considered. Probably more important than the number of bacteria is which types of bacteria are actually present. Certainly there is a difference in pathogenicity of some bacteria over others. Also of interest in this study is that the silver impregnated foam did not decrease the bioburden any more than the standard foam (question #1 anybody?)
Please do not take that to mean that I am somehow “dissing” all antimicrobial wound products. I certainly use them and will continue to in the foreseeable future. The bottom line to this entire discussion is that, although we are programmed to feel that somehow all bacteria in wounds are detrimental, perhaps the presence is not always necessary to eliminate. Before we jump on any bandwagon promoting the “latest and greatest” in antimicrobial wound therapies perhaps we should step back and ask the three critical questions I posed above. By prodding industry to produce high levels of evidence-based medicine it can only improve our overall treatment of these difficult patient problems.
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