Right off the top, I apologize for the obviousness of the Mr. Spock reference.  I couldn’t resist! A few months ago I was invited by Robert Kirsner, MD, PhD and Stephanie Wu, DPM to write a chapter on “Antimicrobial Therapy” in their upcoming Wound Healing Society Yearbook. The design of the chapter is a review of a recently published primary study and 2 or more secondary studies.  Although I was extremely familiar with the primary topic, the randomized controlled trial on pexiganin vs. ofloxacin by Ben Lipsky, MD, one of the secondary papers really struck a chord with me.  The study in the British Journal of Surgery by Micahels, et al out of the UK reported on the VULCAN trial, a large randomized trial looking at the use of silver dressing in venous leg ulcerations (VLU) http://www.ncbi.nlm.nih.gov/pubmed/19787753

This study of 213 recruited patients not only looked at wound healing differences between silver containing dressings and non-silver low adherence dressings in the treatment of VLU but also the cost effectiveness of the two.  The primary measure was complete ulcer healing at 12 weeks with secondary measures being; time to healing, quality of life and the aforementioned cost-effectiveness.  Although I do have some issues with the study design including the leeway given in dressing selection, compression definition and number of visits, I do find the results interesting. 

As one might reasonably expect given the paucity of good evidence on the effectiveness of silver dressings as a class, the VULCAN study found that there were no significant differences between dressings in the number of ulcers healed at 12 weeks (59.6% silver, 56.7% non-sliver) nor to median time to healing. As could also be expected, silver dressings cost significantly more to use ($46.60 vs. $8.70 as converted from the reported £).  The authors concluded that “There was no evidence to support the routine use of silver-donating dressings beneath compression for venous ulcerations”. 

This finding won’t surprise anyone who has heard me lecture on “Differentiating infected from non-infected wounds” as I did at the APMA meeting, who has read the chapter on Diabetic Foot Infections in the 3^rd Edition (specifically page 120), or has read my blog post from March 3, 2010 entitled “Bioburden and Wound Healing”.  Silver dressings are everywhere.  Just about every wound healing product line includes a number of silver donating products in every imaginable format.  Yet, there is little to no evidence to support that they are of any benefit in wound healing or preventing wound infection.  This revelation first came to me upon reading the Cochrane Collaborative systematic review of the literature on silver dressings which, like the VULCAN trial, found little evidence to support their routine use.  This does not mean I don’t use them.  Like most clinicians, if I see a heavily colonized wound I am seemingly genetically programmed to reduce the bioburden and kill the bugs. 

What I am saying is that we should be practicing evidenced based medicine and not costing our patients or the health care system dollars that none of us can afford to spend on a therapy without solid science behind it.  So, next time a sales rep comes to speak to you about their latest and greatest silver product, ask for scientific proof, not some pretty “before and after” pictures, that it contributes to wound healing.  Unfortunately, I doubt you will get much.  These products are all approved by the FDA as 510k medical devices.  Therefore, there is little clinical science necessary to get them approved.   

REFERENCES

Lipsky BA, Holroyd KJ, Zasloff M. Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream. Clin Infect Dis.  2008;47:1537-45.

Michaels JA, Campbell B, King B, Palfreyman SJ, Shackley P, Stevenson M. Randomized controlled trial and cost-effectiveness analysis of silver-donating antimicrobial dressings for venous leg ulcers (VULCAN trial). Br J Surg. 2009;96:1147-56.

 Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005486

I am just back from the APMA National in Seattle. During the meeting not only did we have a successful Book Signing for the 3^rd Edition but I also discussed this blog during both of my lectures to large audiences on Saturday.  I am also pleased to announce that digests from this blog are being published on the Podiatry Today website (www.podiatrytoday.com) and we have already garnered a number of new viewers through that portal. Given the interest generated as evidenced by folks asking for information about this site I felt that I should restate my thoughts on what I want to accomplish with this blog for those newcomers checking in for the first time.  As I have previously written in an earlier introductory entry:

“The purpose of this site is twofold; to allow me to interact with anyone interested in the treatment of lower extremity infections and to give me an opportunity to update the readership on new developments in infectious diseases as they become available.  I regularly review the ID literature for manuscripts that have a direct bearing on the way we treat the lower extremity and attend ID meetings.  This blog allows me to disseminate that information rapidly which would be impossible if I had to wait for my next book revision.

I envision this site as being interactive.  If you have a question about an interesting case (you can even post pictures), have recently heard a lecture, been detailed by an antibiotic representative or just randomly thought of a question on which you would like my thoughts, ASK AWAY!  I will do my best to answer in a timely manner with the best available evidence to support what I say, not to mention a dose of my opinion/experience.    In the future I hope to start running the occasional poll to capture what others may do in a given situation.  If you have any other ideas for this site, please let me know.  I am open to suggestions on how to make it of value to you”

When you register, it is completely free with no obligation; you will get an email notification whenever I post something.  I don’t have a strict timeframe for posting.  I only put up something when I feel it will be of interest.  I may go a few weeks without any or do a few in a row. The best, most convenient way to know is to register. 

Although loaded with information, any textbook is static.  Once it is published, the information does not change.  Given the rapid pace of development in ID, diabetic foot and wound care, I feel it is important to have a means of keeping folks up to date with the latest information.   Thank you for your interest and please feel free to contact me with your thoughts and suggestions.

Those of you who have read my chapter on MRSA in the 3^rd Edition of the Handbook of Lower Extremity Infections (haven’t you all by now?!) or listened to me lecture about MRSA know that I am less than happy with what I perceive to be the overuse of trimethoprim/sulfamethoxazole (TMP/SMX, Bactrim® or Septra®) used empirically against this bug.  It seems to be first line therapy by just about every Emergency Department, Urgent Care, Primary Physician or anyone else treating skin and skin structure infections. My primary objections, spelled out in detail on pages 332-333 of the book, are based on published reports of adverse events when using this drug.  It is not benign when used in the dosages and durations that may be needed to treat CA-MRSA.  In particular, I have concerns with allergies, renal problems, neurological AEs and drug-drug interactions.  Well, a brand new paper just published in the June 28, 2010 issue of Archives of Internal Medicine by Antoniou, Gomes, Juurlink, et. al. entitled Trimethoprim-Sulfamethoxazole Induced Hyperkalemia in Patients Receiving Inhibitors of the Renin-Angiotensin System gives one more reason for concern.

(Link to PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/20585070) 

This was a population based, nested control study of a population >66 year olds who were receiving Angiotensin Converting Enzyme Inhibitors and various antibiotics.  The numbers were impressive.  This was a 14 year study with 4148 identified admissions involving hyperkalemia.  To quote the Conclusions, it was found that “Compared with amoxicillin, the use of TMP/SMX was associated with a nearly 7 fold increased risk of hyperkalemia-associated hospitalization.  No such risk was found with the use of comparator antibiotics”.

I still believe that if you have a mild CA-MRSA infection or are considering a “step down” from either vancomycin or linezolid, then doxycycline or minocycline is frequently preferable over TMP/SMX for therapy. Sure, I have used TMP/SMX in some cases.  One of the more recent that comes to mind was a patient with CA-MRSA plus Stenotrophomonas maltophilia.  Using TMP/SMX gave me a single agent I could use to cover both bugs.  I don’t want to “trash” TMP/SMX but given all of the data out there on potential problems with it, I would encourage you to chose it with a full understanding of the issues surrounding it and not just because you see others prescribing it so freely and randomly.