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)

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!

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. 

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.

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.

Without going into too much detail (which may infringe on copyright?), I would like to point out a few important take home messages that I got out of this paper and from my review of other literature on the subject. First some of the positives:

1.  The usual dose is 10mg/kg q24h.  Thus, we have the ease of a once daily dosing

2.  The drug is consistently bactericidal against most S. aureus.   Various reviews have shown that this probably has little impact in the treatment of cSSSI and may be more important in blood stream infections for which this drug is not approved.

3.  It is effective against MSSA, MRSA, VISA and hVISA.  It is also effective against daptomycin and linezolid resistant strains.  It does not have activity against the most common strains of VRE.

4.  Unlike vancomycin, there is no call to monitor serum trough levels

5.  In two pivotal cSSSI clinical trials it was found to be “non inferior” (FDA speak) to vancomycin. 63% of the S. aureus strains were MRSA making it the largest number of MRSA patients in a cSSSI study to date.

Now some downsides:

 1.  It is primarily excreted through the kidneys so significant dosage modification must be made in cases of renal insufficiency. The recommendations are the full 10 mg/kg q24h if the creatinine clearance is >50 mL/min, 7.5 mg/kg if 30-50 and 10 mg/kg q48h if the clearance is <30.

2.  Chronic, infected diabetic foot ulcerations were specifically excluded from the two pivotal trials!  I don’t see this drug receiving the coveted “…including diabetic foot infections” approval anytime soon.

3.  Although the overall safety looked comparable to vancomycin there were higher rates of some significant adverse events including altered taste, nausea and vomiting along with an increase in renal events.  On the other hand, vancomycin had higher rates of infusion reactions

4.  The drug has received a black box warning for fetal risk.

So what is the bottom line?  I agree with the authors of this review that we need new novel antibiotics to combat MRSA especially given all of the increasing reports of vancomycin MIC creep and treatment failures.  Many of the drugs that looked promising earlier in their development have either been slowed considerably (ceftobiprole) or stopped totally (oritavancin, iclaprim) so the once fertile pipeline is looking a bit thin.  Telavancin gives us one more drug to add to that relatively short list of alternatives to vanco especially with organisms that have developed resistance (although extremely rare) to those other antibiotics.  At this early point in its history, I am somewhat concerned about its lack of diabetic foot infection data and its increase in adverse events compared to vanco.  The black box may also impact some potential patients.  Given that we have other vanco alternatives with years of clinical experience, including diabetic foot data, and well known safety profiles I may feel more comfortable seeing more clinical data and published AE experiences before jumping in with both feet.

http://money.cnn.com/news/newsfeeds/articles/marketwire/0572888.htm

Many of us had pretty high hopes for this antibiotic as it was to be the first cephalosporin active against MRSA.  Although it is IV only, the idea of having a new MRSA agent that was in a class of drugs well liked and trusted by most, was appealing.  It is also broad spectrum against a wide range of other Gram positive and Gram negative organisms. J&J even performed a clinical trial specifically looking at diabetic foot infections with promising results thus hoping to become only the 4^th antibiotic (after linezolid, ertapenem and piperacillin/tazobactam) with that specific FDA indication.  The drug was initially submitted for approval way back in 2007.  The FDA sent an Approvable Letter questioning conduct at some of the study sites.  The action taken yesterday by the Agency now seems to totally question the viability of the two pivotal trials.  This may mean that entirely new studies would have to be completed thus delaying this drug for years more.  It will be interesting to continue to watch this.

In the meantime, all is not lost for anti-MRSA cephalosporins.  The drug most thought would be the late-comer to this party, ceftaroline, seems to be moving ahead.  I will keep you all informed as I hear anything new.

I wish all of my readers a healthy, happy and prosperous, New Year

In the 3^rd Edition of the Handbook I review the evidence that shows that perhaps we should rethink this “Standard”.  The entire concept of 4-6 weeks of IV antibiotics as being some magical bullet that will treat osteomyelitis is based on 30-40 year old animal studies.  There is really no human evidence to support that this is the optimum therapy.  In fact, much of the recent data that has been presented, particularly out of Europe, suggests that ORAL antibiotics alone with either NO surgery or just “conservative” debridement of infected bone may be just as effective therapy.  The literature supporting this approach is actually quite a bit more hefty that that supporting the old traditional “standard”.  I explore this question in detail in a lecture I frequently present entitled (thanks to David Armstrong for the catchy title) Antibiotics for Osteomyelitis: Boneheaded or brilliant? One of these presentations can be viewed for free at the website for the always stimulating Diabetic Foot Global Conference (to be held this coming year in Hollywood, CA March 18-20, 2010): http://www.dfcon.com/presentations2009/sat_joseph.html

In no way do I mean to say that surgery is unnecessary.  In fact, if ablative surgery can be performed, it is curative without the use of any antibiotic therapy.  But, sometimes, patients either do not want, or can’t undergo a surgical procedure.  In those cases I am relieved to see that we do have data to support the non surgical treatment of these cases with oral antibiotics alone.  Of course, this approach is not perfect and there are still unanswered questions.  Probably the greatest is the question of duration of therapy.  Do we only need the orals for 4-6 weeks or longer?  One study, referenced in the lecture, by John Embil incorporated 41 weeks +/- 31 weeks of therapy!  This needs to be addressed.  The other literature I would direct you to review is the consensus statement put out by the International Working Group on the Diabetic Foot (IWGDF) http://iwgdf.org  whose recent systematic reviews of the diagnosis and treatment of diabetic foot osteomyelitis should be reviewed by everyone treating this condition. 

To me, this is one of the most fascinating and important areas that we need to explore in the future.

Osteomyelitis of the 1st MTP Joint

Dr. Joseph,

I listened to the lecture you have on PRESENT podiatry for the “Diabetic Foot Infections” involving the IDSA classification system.  This was excellent.  I will also be checking into a slide show share lecture you have placed available online for the “Current Emerging Antibiotics for MRSA”.

I agree that expressing the “tough love” passion with the patient is important.  Some of these patients just don’t get it that they are really suffering increased susceptibility to losing a leg or even a life.

I would like to know any journal readings you would highly recommend regarding this topic.  I have a few thoughts to share.  For example, do we as podiatrist need to worry about Proteus, Serratia, Klebsiella, E. coli, or Citrobacter in the diabetic foot infections?  You mentioned a study which gave the impression we don’t have to worry too much about treating Pseudomonas aeruginosa because there is a fairly high cure rate with the Pseudomonas when treated with a 1st gen cephalosporin (an interesting thought).  However, I think the point should be emphasized to avoid applying this concept across the board on Gram neg infections, with the thinking that they will heal secondarily alongside of therapy focused on Gram pos infections.  My thinking is based a great deal on the fact that once we have taken a culture and the presence of a certain bug is documented in the chart, if we don’t treat because of this concept, then an infection turn bad (and sometimes fast).  I am worried this type of complication could lead us into a higher risk case and expose the practitioner to increased legal liabilities.  Shouldn’t I have to follow the tendency of the infectionist in my area, since working on a multidisciplinary basis is important.   I did pick up on your point that using aztreonam or the like (depending on the culture report) could provide good combination therapy to get coverage for the Gram neg infections.

Thank you for your contributions.  Much appreciated.

Todd Divan, DPM

MY RESPONSE

Todd,

Thank you for the kind words and the thoughtful questions.  I have attached a copy of the Infectious Diseases Society of American Diabetic Foot Guidelines where we go into the concept of gram positive organisms in more detail.  This paper was published in 2004 and we have a new manuscript in the works, hopefully for publication summer of 2010.  The primary importance of gram positive infections does not change with the new document.

When you read the guidelines you will see that we stress the primacy of aerobic gram positive cocci as the major causative organism.  This is particularly true in mild and many moderate infections.  We do say that as the infection becomes more severe, if there is the presence of necrotic tissue, or of the patient has been exposed to previous courses of antibiotics, then gram negative aerobes and anaerobic organisms become more prevalent.  Even if you culture these organisms, the evidence is not clear that you have to treat them.  Tony Berendt, Ben Lipsky and I refer to this as the “head of the snake” philosophy.  In other words, Staph and Strep make up the “head of the snake” and the other bugs you list below make up the body.  If you “cut off the head” i.e. use antibiotic therapy directed at the Staph and Strep, then the “body” dies.  Again, this is primarily true of the mild and moderate levels.  We are NOT advocating only using gram positive coverage for the more severe infections.

Even with this concept, and it is just that, a concept, even though it is based in excellent data, I tend to start empirically with broad spectrum coverage (perhaps partly for the legal exposure reason you mention below).  In the case with our hospital I even need to use MRSA coverage.  Almost all patients are begun on Zosyn + Vanco.  Certainly Invanz can be substituted for the Zosyn and Zyvox for the Vanco depending on your local formulary.  Please note I do NOT use the Zosyn for Pseudomonal coverage.  I am still of the FIRM believe that no evidence supports needing to cover Pseudo empirically in just about any diabetic foot infection.  In fact, I don’t remember the last time I even grew that bug from a DFI.

Regards

Warren

IDSA Moderate DFI