There is a small group of us that, when we find an interesting article dealing with infections, we pass them on so we can all be stay up to date.  Some of the journals are fairly obscure and are not in my usual monthly reading so I find this a great way to read articles I wouldn’t normally come across.  Below are three such recent papers, all either still ePub ahead of print or recently published about which I find interesting enough to say a few words.

McCarthy NL, et al.  Health care-associated and community associated MRSA infections: A comparison of Definitions.  American Journal of Infection Control, 2010:  This retrospective chart review attempts to determine risk factors for CA-MRSA and HA-MRSA based on two commonly used definitions; the epidemiology of the infection and the phenotypic antibiotic sensitivity without looking at the genotype (i.e. looking for the SCCmecIV gene to determine a USA300 strain).  Not surprisingly, to quote their Conclusion from the Abstract “We found few differences between CA- and HA-MRSA infections regardless of how health care association was found. We believe that the migration of CA-MRSA into health care settings and the recent increasing antibiotic resistance of CA-MRSA strains contribute to the lack of factors associated with HA (vs CA) MRSA.”  One finding I did think was particularly relevant was that CA-MRSA accounted for the overwhelming majority of skin and soft tissue infections (p <.0001).

For the past year or two I have been lecturing and writing that the use of classic “risk factors” to determine HA vs CA was a technique of the past. This was recently driven home to me when I saw 3 patients in the hospital with MSSA, 2 of whom were 80+ years old and lived in long term care facilities while I had a perfectly healthy 30 something with no pertinent medical history whatsoever present with a CA-MRSA.  I still continue to use the phenotypic method of looking at antibiotic susceptibilities, particularly toward Bactrim and tetracyclines since we have not seen much CA-MRSA resistance to these drugs at our facility.  It is becoming clearer that perhaps we will need to do the genetic typing, such as the TEM-PCR I discussed in a recent post to really know what we have.  Of course, it may be a moot point in skin and skin structure infections since, as validated by this report, I don’t remember seeing an HA-MRSA in over 2 years.

Nagoba BS et al. A Simple and effective approach for the treatment of diabetic foot ulcers with different Wagner grades.  International Wound Journal, April 23, 2010:  This is a retrospective case series from India that collected data from 1998 into 2009.  They looked at the application of a 3% citric acid gel preparation onto 115 diabetic foot ulcerations of various Wagner classification severities up to, and not including grades IV and V.  Of interest to me was that they took cultures of all of the wounds and performed broth dilution sensitivities of all the organisms against the citric acid.  They found that in grade I-II ulcerations they had 94%+ healing in 5-34 applications.  They also found that in deeper wounds there was marked decrease in slough and drainage with increases in healthy granulation.  They concluded that citric acid was safe and maybe even promoted granulation tissue while killing the bacteria found on the wounds.   

I find various problems with the design of this study and am not reporting it because I consider it an earth shattering breakthrough.  Rather, I bring it to your attention because, currently, one of the “Holy Grails” of wound healing is to find an safe, effective, affordable topical antimicrobial to, perhaps, assist in wound healing.  Heck, I am still not even convinced that bioburden reduction is all that many claim it is, as I have blogged before, however, we are all programmed to kill bacteria on a wound and maybe this is an option.  It should probably at least be looked at in more detail.

Traunmuller F, et al. Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections.  International Journal of Antimicrobial Agents, 2010:  This study assayed fluid from interstitial spaced, inflamed subcutaneous adipose tissue and metatarsal bone from patients with inflamed diabetic foot infections who were at steady state condition after 600 mg twice daily dosing of linezolid.  What they found was not particularly surprising; in all tissues linezolid penetrated to a level that was similar, if not slightly higher than what was found in plasma.  To quote their Abstract “We conclude that linezolid administered at 600 mg twice daily may be considered an effective treatment in diabetic patients suffering from bacterial foot infections complicated by osteomyelitis”. 

We all know that linezolid is not FDA indicated for the treatment of osteomyelitis.  In fact, NO antibiotic marketed in the past 10-12 years has been indicated for osteo, not because they don’t work but because the FDA has not developed “Guidance for Industry” on how to perform an osteomyelitis study.  I have also never been a believer in the concept of “bone penetration” as being an important indicator of osteo efficacy.  They techniques have never been standardized and really, to my mind, penetration numbers mean nothing. That all being said, at least this paper gives those of you who remain stuck on the concept of bone penetration evidence that linezolid does get into, not only bone but also frankly infected diabetic foot tissues.  This is not unlike data published by Gary Stein, PharmD and recently reviewed in the Jan/Feb 2010 issue of the Journal of the American Podiatric Medical Association (Nicolau DP, Stein GE. Therapeutic options for diabetic foot infections: A review with an emphasis on tissue penetration characteristics)

I will be in Columbus, OH for the Region IV (Ohio) meeting to lecture on June 3, 2010.  I have been given the “Learning Lunch” spot from 12:00 to 1:30 and plan on covering a broad range of lower extremity infectious diseases topics including MRSA, antibiotic therapy for osteomyelitis and diabetic foot infections.

Prior to my session, I will be in the Exhibit Hall from 9:30 – 11:30 at the Data Trace Booth to sign copies of the Handbook, talk about this blog and just answer questions anyone might have about treating infections.

I hope to see folks there!

The following is from the text I sent to Podiatry Today Magazine for an upcoming feature they are planning on Innovations in Podiatry.  I really feel that molecular diagnosis of infection has the potential to change the way we diagnose and ultimately treat lower extremity infections.  The company I discuss in the article below, Diatherix, has a unique technology that allows the identification of up to 25 organisms from a single specimen and a single run of the test yielding results in just a few hours.  Just for full disclosure, although I have met with the CEO of the company to discuss the technology I have no financial interest or other conflicts at this time:

The current standard for making a bacteriologic diagnosis of a lower extremity infection is the use of a culture and sensitivity.   The problem with this test is that it may take several days to obtain a result while the patient has been placed on empiric antibiotic therapy that may be either too broad or too narrow spectrum.  Although Polymerase Chain Reaction (PCR), to look at the DNA of the organisms found on a specimen, has been used for a number of years to rapidly identify the bacteria, it has been limited mostly to reference laboratories and is hindered by usually only being able to identify one organism at a time.  This is changing with the use of Target Enriched Multiplex-PCR (Tem-PCR) which has the ability to identify up to 25 or more organisms with a single sample and to do it within just a few hours. A company based out of Huntsville, AL, Diatherix, is now commercializing this technology so that any physician in an office or wound center can order this test.  The clinician receives swabs and transfer materials, including overnight mailers from the company.  They take a specimen, as they would a standard C&S; place it in the mailer to Diatherix which receives it the next morning.  By that afternoon a result is communicated to the clinician including the identity of the organism, its relative frequency compared to other bacteria found in the specimen and any genetic markers for resistance, such as the presence of the mecA gene indicating MRSA.

By accurately identifying disease-producing pathogens early, Tem-PCR results can assist physicians in forming a more accurate diagnosis. This provides them the opportunity to accurately diagnosis the condition which leads to the appropriate treatment rather than treating empirically. By enabling physicians to link diagnostics to therapeutics, Tem-PCR results can assist by eliminating the inappropriate use of antibiotics eliminating unnecessary treatments, reducing the development of genetic drug resistance, potentially reducing cost of therapy and providing a better patient outcome.

The Tem-PCR technology provides multiplex amplification of genomic material from multiple pathogens with greatly increased sensitivity compared to standard multiplex PCR.  Standard multiplex PCR in general cannot amplify multiple pathogens in a single analysis due to each set of primers requiring differing optimum conditions for best amplification.  Tem-PCR works around this by essentially turning the multiplex into a singleplex reaction needing one primer set and one set of optimum conditions so that the best amplification can be obtained.  This allows more results from a single sample as a benefit of Tem-PCR over both singleplex PCR and qPCR (real time PCR).

Three significant benefits of producing multiple results from a single sample are being able to accurately identify pathogens causing infection in a rapid fashion, the identification of co-infections and the identification of genetic drug resistance. If a patient presents with a wound that is not healing a physician will perform a culture in order to identify the pathogen or pathogens present. At this point the physician will often treat the symptoms empirically due to the multitude of pathogens that could be causing the infection.  If the patient is on antibiotics at the time the sample is taken for culture there is a very good chance the culture will be negative which leaves the physician to continue empiric treatment. If on the other hand the physician had obtained a sample to be performed by Tem-PCR up to 25 pathogens would be tested including genetic drug resistance providing the physician with definitive information leading to proper treatment.

Diatherix claims that the test is covered by most insurance companies.

I just returned from a lecture trip to Turkey where I had the privilege of giving 5 talks, one in the Mediterranean resort city of Antalya at a nationwide Hospital Infection Congress and 4 to the faculties at various medical universities throughout the country. Before getting into details about specifics dealing with lower extremity infections I first wanted to say that, if you have never visited, and this was my first time, Turkey is an unbelievable country with warm, welcoming people, incredible history, scenery and great food.   Istanbul, a bustling metropolis of over 12 million people, has to be one of the great cities of Europe. 

A Diabetic Foot Infection in Malatya, Turkey

In preparation for my talks I was asked to concentrate on the importance of a team approach to amputation prevention. Having just returned from DFCON I was up to date with the latest published data and reports from around the world about the successes that true amputation prevention teams have achieved in reducing the rates of “major” amputation. I have always found it amazing, if not a bit troubling, that smaller, less developed nations can codify a network of diabetic foot centers throughout their countries more than we have accomplished here in the United States. Even Pakistan and Kosovo, as discussed at this year’s DFCON, are able to reduce amputation rates by starting these centers. Turkey has made some progress towards the goal of developing amputation prevention teams.  Just last year Yesil, et al from Dokuz Eylul University Medical Center in Izmir (a facility, unfortunately, I did not have a chance to visit) reported a reduction of major amputations after starting such a team. (Yesil S. et.al. Exp Clin Endocrinol Diabetes, 2009).  In Istanbul I was honored to meet Dr. N. Saltoglu at Cerrahpasa Medical School, Istanbul University, when I gave one of my lectures to their Infectious Diseases faculty.  Dr. Saltoglu has just recently started a multidisciplinary diabetic foot team at this large institution of >1800 beds.  They are already beginning to see positive outcomes. 

During my trip I also lectured to the infectious disease faculties at Universities in the cities of Malatya and Kayseri both in the Eastern Provinces of the country.  They were very interested in the concept of starting comprehensive diabetic foot teams but were stymied by much the same turf battles and, dare I say, ego issues that we find here in the US.  Patients are treated by their local primary physicians for protracted periods before being sent to the hospital specialists.  Once admitted they are shuttled between various services including endocrinology, vascular surgery, orthopedic surgery and internal medicine with each passing the patient off to another service once their particular part of the job is completed with little coordination of effort.  The ID physicians, in particular, play a very primary role in the treatment of DFI and expressed frustration that, by the time they see the patient, it is often very late in the progression of the disease and they are dealing with infections that have received multiple, often inadequate antibiotics and now present with multi drug resistant pathogens.  The universal regret, oft expressed at DFCON, about the patient being seen too late in the progression of the disease was repeated time and time again.  It just goes to show that you can travel 5000 miles from home to a totally different culture, yet some issues are universal! 

A few other thoughts and interesting findings about lower extremity infections in Turkey:

1.  MRSA is not the problem we have here.  In fact, in most hospitals the rates have been decreasing the past 5 years.  Furthermore, they do not differentiate MRSA into HA- vs. CA- strains. The common thinking is that CA-MRSA is not a widespread problem and they just do not worry about it.  This is a huge difference from here where I need to treat everybody as if they have CA-MRSA until proven otherwise. 

2.  There are different antibiotics.  Whereas we use so much vancomycin for our MRSA in-patient soft tissue infections, their drug of first choice is teicoplanin.  This is another glycopeptides that, although widely used in other parts of the world, never received its US approval.  Like vancomycin, teicoplanin presents its own set of problems with dosing including having to give adequate loading dose, measuring troughs and the potential for liver toxicity. There may also be “MIC Creep” issues with MRSA and teicoplanin.  Another unique antibiotics is cefoperazone/sulbactam a β-lactamase inhibitor combination I remember reading about 20 years ago when it was thought that it might be brought into the US.  Other drugs are the same including piperacillin/tazobactam, ertapenem and imipenem. 

3.  ESBLs are a major problem.  Whereas we are just now beginning to see extended spectrum β-lactamase (ESBL) producing gram negative rods here in our US diabetic foot infections, Turkey has had them for years.  In fact, there are enzymes found in Turkey that you would be hard pressed to find anywhere else in the world.   Surveillance surveys have found gram negative resistance rates to cephalosporins and even quinolones in the 50-60% range.  It is felt that some of this may be caused by the long term, inadequate antibiotic therapy that is often started by primary physicians or even pharmacists before the patient is seen by the ID specialists.  And, of course, the universal overuse of the flouroquinolones is thought to contribute.   

4.  Acinetobacter, especially multi-drug resistant strains, is a problem.  I found this particularly interesting given the well documented outbreak of Acinetobacter infections that has been reported in our troops returning from the current Middle Eastern conflict.  When in some of these Eastern sections of Turkey one is not far from Iraq and Syria.  Perhaps there is something in the environment or the locale that propagates this organism.

With Dr. Bayindir, Director of Infectious Diseases, University Hospital, Malatya, Turkey

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 7^th 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 2^nd and 3^rd 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. 

(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.

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.

One of our readers recently sent the blog the following comment:

“Anything new to add to comments in book about laser treatment of fungal nails?  In my area there are ads for DPMs offering this $1000 per treatment!  My question is; does it work?”

Up to this point I have been tacitly avoiding this topic waiting for all of the chips to fall into place.  I guess it is time to, at least give my initial thoughts.  I will start by disclosing that I was a member of the original Patholase/PinPointe Advisory Board although I am currently not working with that company and I am a current Advisory Board member for Nomir. Being under a non-disclosure agreement with both I must therefore be very careful to only give background information that is in the public domain and give only MY OPINION based on the information in the public domain so as not to let slip any confidential information that I may have picked up along the way.  This is another reason I have not written about this topic.     

Although there may be more than two commercial products to mention, I will limit my discussion to the two best known, the PinPointe Laser from Patholase and the Noveon Laser from Nomir.  These are totally different devices that use different forms of laser energy. As I write this NEITHER is FDA approved specifically for the treatment of onychomycosis although both have a device clearance for general podiatric and dermatologic use.  Interestingly, if you actually look for the specifics of that general definition, onychomycosis is not included.

To this point each company has taken very different marketing approaches.  PinPointe, despite not having the FDA approval, has been aggressively marketing the device to podiatrists based on their general usage clearance.  Up to this point, their publically available data supporting the use of the device for onychomycosis has been limited to a small number of patients originally treated pre-marketing and by early adapters of the device.  This data is not from a prospective, IRB approved, randomized controlled trial. To their credit, a quick search on www.clinicaltrials.gov under the term “onychomycosis” does reveal that they are currently engaged in such a clinical trial.  They also continue to collect retrospective data from current users.  To the best of my knowledge they have published no studies based on their clinical data or their technology. 

Nomir has taken the path of performing an initial three IRB approved, prospective clinical trials and has submitted their pivotal trial to the FDA in an attempt to receive an onychomycosis indication.  Their technology, using a dual wavelength (870 & 930 nm) near infrared (IR) laser light to cause photoinactivation of  both fungus and bacteria, including T. rubrum and MRSA, at physiologic temperatures, has been shown to be successful in vitro and in vivo, and was recently published by its developer Dr. Eric Bornstein http://www.nomirmedical.com/products/publications.htm in the Nov/Dec 2009 issue of Photochemistry and Photobiology.  They have also submitted the preliminary results of their pivotal clinical data for the treatment of onychomycosis which has been accepted for publication in a peer reviewed, indexed journal.  Although they have signed up podiatrists to be trained on the device, it has not yet been made commercially available. 

Enough background…to answer the question that initiated this discourse, I guess I would have to say that, yes, given the data I have seen, these two laser therapies do, in fact, show positive results in the treatment of onychomycosis.  Will they work in every patient with nail fungus?  Of course not!  Even oral terbinafine only had a 38% total cure rate in its clinical trials.  Which brings up another question…do they work even as well as the oral agents?  Frankly, no one can say at this point without seeing the results of the same type of well designed, controlled trials that those drugs went through.  I will say this much for certain, there is no risk of systemic toxicity with the lasers as there is with the oral drugs, no matter how rare.  Is the treatment worth $1000?  That is something that only an individual patient can answer.  I hear through the proverbial grapevine that there has been no shortage of folks willing to pay that or similar amounts for the treatment.  Heck, there are scores of physicians specializing in cosmetic treatments, some without rigidly controlled and studied FDA approved data, that have done quite well promoting their services.

Until more information is available on which definitive statements can be made, I would have to advise each of my readers to use their own moral and ethical compass in determining what is appropriate for their patients and their practice.   I would really appreciate any comments you may have if you are currently using a laser on either your own patient experience or if you have seen patients treated by other docs and their satisfaction level.

To any of my readers planning on attending the NY Clinical Conference this coming weekend, I will be in the exhibit hall at the DataTrace booth on Saturday January 30th.  I will be there to discuss this blog, sign copies of the 3rd Edition (not that it will increase the value of it…heck, it may diminish it!) and just generally hang out and meet anyone interested in discussing lower extremity infectious diseases.  Please come by and say “Hi”.

Two studies published in the January 7, 2010 issue of the New England Journal of Medicine have received a tremendous amount of play in the popular press.  One paper out of Baylor in Houston looked at comparing chlorhexidine + alcohol vs. povidone iodine as a preoperative surgical prep.  In a total of 849 subjects in the ITT analysis they found that the surgical site infection rate was significantly lower with the chlorhexidine + alcohol than it was with the old “standby” povidone iodine (9.5% v. 16.1% P=0.004) Here is a link to that abstract http://content.nejm.org/cgi/content/short/362/1/18.

The second study, out of the Netherlands, explored the issue of decolonization in nasal carriers of S. aureus.  http://content.nejm.org/cgi/content/short/362/1/9.  A total of 6771 patients were screened on admission using PCR for rapid identification of the Staph.  1270 swabs were positive, 808 underwent a surgical procedure.  The patients were all treated with mupirocin nasal ointment and chlorhexidine soap vs. a placebo.  The rate of S. aureus infection was 3.4% in the treated group vs. 7.7% in the placebo group.    Interestingly, ALL were methicillin susceptible (MSSA) so the study may, or may not be able to be extrapolated to MRSA carriage.

Hospital acquired infections, particularly surgical site infections cause a tremendous amount of morbidity and mortality not to mention costing billions of dollars to treat.  The monetary situation is complicated by CMS guidelines that may not pay a hospital for treatment of any nosocomial infection.  Therefore, new and improved techniques for minimizing these infections are being studied.  Some of what is done today for infection prevention in the surgical suite has not changed much in decades i.e. the use of the povidone iodine prep.  I remember doing those back when I was a surgical resident in the early 1980s!  Chlorhexidine is by no means a new product.  In fact, it may be older than povidone iodine.  A quick PubMed search finds papers going back to the 1960s.  More recently, the combination of chlorhexidine with alcohol has shown to be a better antiseptic with longer activity than chlorhexidine alone.  This is true not only for prepping the patient but also as a hand prep for the physician.  This recent study just shows us that as new high level evidence becomes available, we may have to change some very ingrained thoughts and practices.

As for the nasal carriage paper, I find that interesting and not unexpected.  What needs to be looked at is carriage of MRSA and surgical site infections.  There are some papers out there and I do discuss them in the book.  This is a more involved topic for another post.