Dr. Todd Divan, a podiatric physician from Potomac, IL, sent me an excellent question via personal email.  On the belief that if one person asks a question, many others may be thinking the same thing, I reprint the question and answer here with Dr. Divan’s kind permission.

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

I am pleased to announce that we have just posted a few pages from the Ulceration and Infection section of the newly revised Diabetic Foot Infection chapter of the 3rd Edition of the Handbook. Just go to “Preview the Book” in the header above and you will find the pdf link.

I chose this section to include in the book and as a preview since I feel it is important information for anyone treating lower extremity infections to understand. It contains the entire “Executive Summary” of the Infectious Diseases Society of America (IDSA) diabetic foot infection guidelines published in 2004. The Guidelines in their entirety can be found at www.idsociety.org by clicking on the link for “Clinical Practice Guidelines”. These are evidenced based recommendations based on the best available data at the time they were written. The DFI guidelines have been revised and a draft is being presented at the IDSA meeting in Philadelphia later this month  with the hopes of publishing sometime in 2010. This summary includes important points such as #4 – almost all DFIs are caused by gram positive cocci. #5 – Wound infections should be based on clinical, not laboratory grounds. #9 – evidence does not support the antibiotic treatment of clinically uninfected ulcerations, along with 16 other recommendations.

Also in this preview section is the IDSA DFI severity classification system. Unlike other classifications that look at diabetic foot ULCERATIONS, this one is specific for severity of INFECTION. It is easy to understand with only 4 categories and has been independently validated by Larry Lavery and colleagues in a paper published in Clinical Infectious Diseases in 2007 showing that, as the severity increases so do the number of hospitalizations and amputations. This system has now been accepted by most investigators in DFI and is widely used in clinical trials of the condition. It can also be used by everyday clinicians in their clinical practice. For example, under your patient assessment, consider using this system. i.e. “Patient presents today with an IDSA Moderate DFI of the 2nd metatarsal region”.

I hope that you find this new Preview interesting and useful.

It has been about 2 weeks since my first post about ICAAC which has given me some time to ruminate a bit over the happenings there. I have always enjoyed this meeting because its emphasis on new antibiotic development, an area of great interest to me. It is sometimes a bit short on clinical information relevant to lower extremity infections and this year was no different. In fact, other than my poster on the use of daptomycin in diabetic foot infections there were only two other posters, out of thousands, in which the term “diabetic foot infection” even appeared. Both of those studies supported the efficacy of linezolid in the treatment of DFI caused by MRSA. To review some other information I found interesting:

1. During a major symposium on the treatment of gram positive infections, Robert Moellering, MD, one of the gram positive deities in the ID world from Harvard, discussed vancomycin dosing with a lecture entitled “New Approaches to Vancomycin Dosing: Does a higher trough help”. He discussed the new guidelines suggesting troughs between 15-20, a topic I have addressed in this blog. Once again, at least to me, it became clear that the data to support this is very limited, is based on a pharmacokinetic theory, and mostly deals with pneumonia. Dr. Moellering suggested using the vancomycin MIC as a surrogate marker for the appropriate trough for which to aim. The most surprising statement he made was that for an MRSA with a vanco MIC of >1 there is no way to achieve a high enough trough that would still be safe and alternative treatments should be considered (my emphasis). Considering many of us don’t remember the last time we saw an MIC of <1, maybe it is time to finally put vanco to bed??

2. During that same symposium another speaker, David Snydman, MD out of Tufts, discussed linezolid and daptomycin resistance reports. What I found most interesting out of this lecture is that, even after 9+ years of clinical use, the current resistance rates of MRSA for linezolid are sitting at 0.03%. This is a pretty amazingly low number that belays the conventional wisdom, stated throughout the Handbook, that the bugs are always going to be smarter than us. In fairness, resistance rates of coagulase negative staphylococci to linezolid are higher, in some series approaching 5%.

3. I don’t know if the timing of the announcement coinciding with ICAAC was planned or not, but it was announced that another antibiotic, Telavancin, has been approved by the FDA for the treatment of complicated skin and skin structure infections caused by MRSA. This makes the 5th drug for this indication behind vancomycin, linezolid, daptomycin and tigecylcine. Telavancin (Vibativ), developed by Theravance and Astellas, is an IV only lipoglycopeptide. I saw some of their early data a few years ago but am not up on the latest so I really don’t know how to place this drug yet. I am also concerned about some adverse event rates and black box warnings. More to come in the future on this one.

4. An upstart out of the UK, NovaBiotics, presented 2 posters on a “novel fungicidal peptide” for the treatment of onychomycosis. This was really preliminary, mostly in vitro stuff but I do think that the entire peptide class of antibiotics show promise for lots of different applications (can anyone remember Pexiganin?).

5. David Nicolau, PharmD out of Hartford, has done some great work in skin and skin structure infections. Amongst the many posters he presented was one that looked at the development of carbapenem resistance to Pseudomonas aeruginosa when 25 hospitals started using ertapenem. His results echo that of previous authors who have shown time and time again that Pseudomonal cross resistance to other carbapenems does not occur just because a hospital uses ertapenem. This has been a concern voiced by many ID specialists and pharmacists effectively blocking the use of this once daily drug in many hospitals specifically in diabetic foot infections. It is one of only three drugs (along with linezolid and piperacillin/tazobactam) currently approved for this indication.

Well, that is it for my review of ICAAC. Sorry for the long post but I wanted to get as much information as I could out to you in a timely manner.

This past week I attended the American Society for Microbiology’s 49^th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held in San Francisco.  ICAAC is the largest conference in the world dealing with infectious diseases and antimicrobial agents.  It routinely gathers over 10,000 microbiologists, infectious diseases specialists, pharmacists, etc. from all over the globe for lectures, posters, symposia dealing with all aspects of antimicrobial therapy and infectious diseases. Although I have attended the meeting many times over the past 25 years this was the first ICAAC in which I actually participated.  I was lead author of a poster on the use of daptomycin in the treatment of diabetic foot infections which was included in the Monday poster session.  I have always liked poster sessions at these meetings since you actually get to meet the author and ask questions one-on-one.  Our poster was no exception with folks coming up throughout the session to discuss diabetic foot infections.

On Tuesday afternoon I was honored to be asked to participate in a “Meet the Expert” session on the treatment of diabetic foot infections along with Dr. Tony Berendt from Oxford, UK.  Although the timing was late in the meeting and late in the day, beginning at 5:30PM, we easily had a few hundred attendees who stayed throughout the entire 75 minute session.  Tony and I decided to try an approach successfully employed for sessions like this by Dr. Ben Lipsky called the “What Do You Want to Learn Today” method.  We started by asking the audience to step to the mic and announce topics they would like to hear covered.  After a few seconds of initial reluctance the floodgates opened and attendees lined up to call out subjects.  We could have spent the entire 75 minutes just listing all of the topics!  Most revolved around the diagnosis and treatment of osteomyelitis, antibiotic selection, length of therapy and the use of “adjunctive” therapies such as hyperbaric oxygen.

Interestingly to both of us, a topic mentioned by a number of attendees seemed so basic that we were surprised that it was a concern…what to do if your surgeon refuses to do surgery? Apparently, there is some reluctance out there for surgeons to do the necessary I&D work not to mention minor amputations of the toe/foot to try to save the leg.  One very prescient question asked if by failing to perform the necessary aggressive surgery we are causing more antibiotic resistance.  I found this a particularly timely and important question since during the session I presented a current case of mine concerning a patient with osteomyelitis of the 2^nd toe and 2^nd metatarsal who adamantly refused to have her toe removed.  Instead of my podiatric surgical colleague being able to essentially “cure” the infection with a scalpel and bone saw I was left sending the patient to an SNF unit with an IV line for 4 weeks of vancomycin.  And we wonder why we have issues with MIC creep!

I will include some interesting tidbits I picked up at ICAAC in a subsequent post.