I received this question from a reader: In suspected osteomyelitis do you stop antibiotics prior to obtaining a bone culture? For how long?

This comment came in under my entry on the VULCAN trial but I actually covered the question in a post almost exactly a year ago.  I am reprinting my response here for more recent readers who may not have reviewed all of the earlier posts I will also summarize my current thinking at the bottom:

The question of whether or not the patient needed to be off of all antibiotic therapy prior to the culture was always less clearly delineated.  It was almost an empirical belief that if a patient was on antibiotics at the time of the culture then the results would be unreliable.  After all, if a culture is reported as showing “no growth” was this because the specimen was poor, the patient never had osteomyelitis in the first place, or the antibiotics had prevented the organism from growing?

A recent study by Louis Bernard and colleagues out of University Hospital of Geneva Switzerland, and published in the September 6, 2009 issue of the International Journal of Infectious Diseases challenges much of what we currently hold as sacrosanct.  In this non-randomized, prospective trial 141 patient with 154 episodes of osteomyelitis each underwent 4 microbiological samplings.  Sample “A” consisted of 2 consecutive sinus tract cultures with bone contact (“A1” & “A2”) after only local cleansing of the sinus tract with 0.9% saline.  Sample “B” consisted of a surgical bone biopsy through the sinus.  Sample “C” was a surgical biopsy obtained through an uninfected sited, referred to as the “gold standard”.  Their results showed that when both sinus tract cultures “A1 & A2” revealed the same organism the concordance between “A” and gold standard “C” was 96%.  They calculated the sensitivity as 91%, specificity as 86% and accuracy as 90%.  On top of that, they found that the result was not affected depending on whether the patient was on antibiotics prior to the cultures or not.

In their Discussion the authors go out of their way to state that “in no way should these consecutive deep sinus tract specimens replace bone culture in situations where a biopsy can be readily obtained because bone culture remains the gold standard for the microbiological diagnosis of osteomyelitis”.  There are sometimes, however, when a surgical culture is just not practical and that patient has already been started on antibiotic therapy, as the authors call it “clinical reality”.

Since this original post, my thought process has not changed much.  I still believe that, if they have not yet been started, it is best to HOLD antibiotics if at all possible, until after the patient is taken to the OR for deep bone (or, for that matter, soft tissue) cultures. The “real world” gets involved, however, when you admit a patient through the Emergency Dept for the stated diagnosis of “infection” and do not plan on taking the pt to the OR until the next day. Unfortunately, in a case like this, you cannot realistically hold antibiotics or the hospital runs the risk of losing the admission.  If the patient is going to the OR later the same day then I believe in holding the drug unless the pt is sick i.e. metabolically unstable, systemically unwell or septic.

What if the patient has already been started on antibiotics?  Conventional wisdom still calls for the pt to be off antibiotics for at least 48 hours.  I don’t believe there is any evidence to support that thinking.  The Bernard study cited above does give us some hope that it doesn’t matter if the patient is still on antibiotics or not but I would still recommend, again if at all possible, taking the patient off the drugs for as long as it is feasible. Heck, I would go for a week if you can.  There is no magic to 48 hours.  The problem is that if the culture is negative, you don’t know whether it is negative because it is not osteo or if it is negative just because of the antibiotics.  Also, the International Working Group on the Diabetic Foot (www.iwgdf.org) has shown in their diabetic foot osteomyelitis guidelines that the only independent factor leading to a positive response to antibiotic therapy for osteo is bone culture directed antibiotic therapy.  We could really use those deep reliable cultures!

Well, as I expected and predicted in my previous post, the FDA did not waste much time approving ceftaroline (trade name – Teflaro) for complicated skin and skin structure infections (cSSSI).  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm231594.htm (thanks to Lee Rogers, DPM for forwarding me this link).  What does this mean for those of us treating lower extremity infections? It is hard to say.  As I discussed in my September 27 post, the clinical trials actually excluded diabetic foot infections (DFI) and decubitus ulcerations but still managed to include lower extremity infections as almost ½ of their cases.  Because of this, I am guessing that Forest, the company marketing the drug, may be reluctant to call on us for fear that by doing so it may be perceived that they are de facto promoting DFI.   I have seen this with other drugs.  When Schering-Plough was selling Avelox (moxifloxacin, now with Merck) although it would be an excellent drug for DFI given the broad spectrum of activity including anaerobes, the company would not market to podiatric medicine for since they only had the cSSSI indication and not the DFI addition.  I do not know any of the folks at Forest and do not know how aggressive they may be in their marketing campaign so this all remains up in the air.  I am hoping that given the number of lower extremity infections that were included in their trial, they see the value in calling on those of us treating these infections.

Ceftaroline now becomes the 6^th antibiotic FDA approved for the treatment of cSSSI caused by MRSA.  It is the first cephalosporin with this indication which is both good and bad.  It is good because it seems to have a typical cephalosporin safety profile, which is to say, very safe with only a few adverse events noted in the trials and nothing untoward was found.  Most clinicians are really comfortable with this class of antibiotic.  It is also broad spectrum including gram negatives but without Pseudomonas.  Most of the other anti-MRSA drugs, with the exception of tigecycline, are pretty limited to gram positive cocci.  The downside is that cephalosporins are not the “golden child” they once were.  I know that my personal use has declined significantly.  The greatest problem is that these drugs can lead to an increasing incidence of some of the new multi drug resistant gram negative rods including E. coli, P. mirablis and Klebsiella that produce “extended spectrum beta-lactamase” (ESBL) or Klebsiella pneumonae carbapenemase (KPC).  Although usually found in sick patients in the ICU, I have started to see these cropping up in lower extremity infections.  Heck, even Katie Couric did a piece on these new “Superbugs” on her evening news show.

The bottom line is that ceftaroline (Teflaro) should be a welcome new addition to treat mixed infections including those containing MRSA.  Where it will pan out to treat lower extremity infections, and in particular DFI, and the attention Forest pays to those of us treating these infections, remains up in the air.

For a number of years it was widely felt that the first of the new so-called “5^th Generation”, or anti-MRSA cephalosporins would be ceftobiprole.  This drug, a joint venture by the Swiss company Basilea and Johnson & Johnson had come under some fire from the FDA (see my blog entry from Dec 31, 2009) and now looks like it has pretty much been abandoned, at least here in the US.  Even in Canada, where it had been approved for complicated skin and skin structure infections (cSSSI), as of April 2010 sales have been discontinued.

While all of the hoopla surrounded ceftobiprole, another drug was pretty quietly making its way through the clinical trial process; ceftaroline.  Ceftaroline is being developed by Cerexa Inc., a wholly owned subsidiary of New York’s Forest Pharmaceuticals under license from Takeda in Japan.  This month has proven to be an important one for this antibiotic.  In the September 15 issue of Clinical Infectious Diseases the results of their cSSSI trial, named the CANVAS study have been published (PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20695801) and on September 8, the Anti-infective Drug Advisory Panel of the FDA gave the drug a very positive endorsement for 2 indications including cSSSI.

The CANVAS trials were two identical, phase 3, international, multicenter, randomized, double blind studies which compared IV ceftaroline (600mg q12h) to the combination of vancomycin + aztreonam for cSSSI.  Inclusion criteria pretty much followed the FDA’s Guidance for cSSSI.  Unfortunately, diabetic foot ulcers were excluded! That being said, almost a full 50% of all infections in both groups occurred in the lower extremity.  (NOTE to Cerexa…how about a diabetic foot infection trial? We desperately need more drugs with that indication!)  1378 patients received study drug with 693 in the ceftaroline group and 685 in the comparator with demographics being similar in both. As expected, S. aureus was the most common pathogen with MRSA found in 40% of the ceftaroline group and 34% of the comparator group.

I would direct the reader to the full paper for all of the different efficacy measures.  Suffice it to say that results were similar in all measured endpoints including the clinically evaluable group (91.6% ceftaroline vs. 92.7% comparator) as were the rates of adverse reactions and discontinuations, all really pretty low, in the single digits.   One other point of interest is that although ceftaroline is not effective, in vitro, against Pseudomonas aeruginosa, the clinical cure rates when this organism was found in combination with others was still very high.  Again, this brings up the issue I have addressed many times, as to the relative lack of importance of this bug as a primary pathogen.

As for the news about the FDA, a press release put out by the company and found from many sources, including Medscape reported that the Advisory Panel enthusiastically and unanimously voted (18-0 for the cSSSI indication) to support the drugs application for approval.  It has frequently been repeated that the FDA itself does not have to follow the Panel’s recommendation but it almost always does.  Especially when it was as positive as this.  The bottom line is that I think we will see a new option for the IV treatment of cSSSI caused by mixed infections including MRSA in the next few months.  It will be interesting to see the impact this has on the marketplace since many people have a very high comfort level with cephalosporins.  Furthermore, this drug can be used for mixed gram positive and gram negative infections.  One major downside is the obvious lack of coverage of ESBL and KPC producing gram negatives.  These are becoming an issue in cSSSI.

Reference:

Corey GR, Wilcox M, Talbot GH, Friedland HD, Baculik T, Witherell GW, Critchley I, Das AF, Thye D. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin Infect Dis. 2010 Sep 15;51(6):641-50.

Instead of a formal literature review, I just wanted to post a quick clinical comment on something that came up with a patient I saw on consultation in the hospital about 2 weeks ago.  This 91 y/o female nursing home resident was admitted with a diagnosis of “cellulitis”  of the right foot (of course much of this “cellulitis” resolved with elevation of the leg making it more PAD, than infection, but that is a topic for another time).  As is common practice by some services in our hospital she was started on piperacillin/tazobactam 3.375g q6h and vancomycin 1g q12h. 

When I saw the patient the next morning I noticed that her serum creatinine was 0.9.  I was with a resident and I mentioned to him “Now, this is a problem”.  His response was “How come?  It is totally within normal limits?” You see where I am going with this…you CANNOT depend on the serum creatinine to determine renal function especially in an elderly patient.   Although, I know there are newer, more sophisticated techniques that have been developed, the determination of creatinine clearance using the Cockcroft and Gault equation is an easy and handy way to determine the patient’s renal function for the purpose of antibiotic dosing.  I know it is not easy to remember the equation.  Most practitioners I ask can give me the “(140 – age)” part but that is about it.  Just to refresh memories:

(140-age) x Wt(kg) / 72 x serum Creat all (x 0.85) for a female

I know it is not the easiest thing to remember.  The good news is that…don’t worry, there’s an app for that!  It doesn’t matter if you are on iPhone or Droid you can download a free application, usually bundled with multiple other medical calculators, which makes it easy to just plug in the appropriate numbers.  If you don’t happen to have a smartphone handy, just go to a computer at the nursing station and Google “Cockcroft gault equation” and you will end up with about 31,000 results. Don’t bother fishing through, I like the very first one. 

Back to this patient.  She only weighed 110 lbs.  Upon plugging in the numbers we found her Creatinine clearance to be about 30.  This means she was receiving too much antibiotic.  I changed her pip/tazo to the renal dose of 2.25g g6h, held the vancomycin and ordered it to be restarted after 24 hrs at 750mg q24h.  (In a case like this, linezolid which does not have to be adjusted for renal insufficiency would have been an excellent alternative).

The bottom line of this brief anecdote is to just remind you that, when dosing antibiotics cleared through the kidney, you should be determining creat clearance and not just depending on the serum creatinine.  You may be surprised at the result.

It is a rare study I read that makes me want to literally stop everything else I am doing and write a blog post about it.  It is a dreary, gray Sunday morning and I was just catching up on some backlogged journal reading when I picked up the August 2010 issue of Antimicrobial Agents and Chemotherapy.  I came across a paper out of the University of Antioquia in Medellin, Columbia by Omar Vesga and colleagues entitled “Generic Vancomycin Products Fail in vivo despite Being Pharmaceutical Equivalents of the Innovator” (PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20547818) .  Regular readers of this blog and the Handbook, and those who have attended my lectures, know that I have not been particularly kind to vancomycin given significant failure rates reported in numerous studies. This study might explain why there are so many failures.

Vancomycin was first developed by Eli Lilly after it was discovered as a fermentation product of Amycolatopsis orientalis found in a sample of dirt sent to Lilly from Borneo in 1955.  Early formulations had significant impurities which, along with lending the product a brown color, hence leading to its’ early moniker “Mississippi Mud”, also was felt to lead to significant adverse events.  Lilly eventually found ways to highly purify the product to the relatively safe drug we know today.  Apparently, those extra steps were kept secret until they were finally sold as recently as 2005.  I clearly remember a Lilly sales rep calling on me 20 some years ago when the drug first went generic.  He pulled out a vial of the newly generic vancomycin and it was sandy brown in color.  He then pulled out a vial of the brand named Vancocin and it was, indeed, Lilly white…pun intended.  His point was simply, “Doc, which would you rather have going into your patients’ vein?”  Of course, hospital formularies being the way they were/are we really did not have a choice as to which we wanted to use. 

Back to the Vesga study: The investigators studied 3 generic versions of vancomycin vs. the “innovator” product to determine concentrations and clinical efficacy via numerous techniques both in vitro and in an in vivo mouse model.  In my opinion this was an elegantly designed, complex study which used multiple techniques including time-kill curves (TKC), broth microdilution and a neutropenic mouse thigh infection model, along with others, while using different strains of S. aureus.  Their findings were fascinating!  To directly quote the Abstract:

 “Vancomycin generics were virtually undistinguishable from the innovator based on concentrations and potency, protein binding, in vitro antibacterial effect determined by minimal inhibitory or bactericidal concentration and TKC, and serum pharmacokinetics.  Despite such similarities, all generic products failed in vivo to kill S. aureus while the innovator displayed the expected bactericidal efficacy…” (Emphasis added) 

The authors conclude that the current standard of “pharmaceutical equivalence predicting therapeutic equivalence” is not true, at least for vancomycin.  They make it clear that they are not claiming that the tested generics were in any way poor quality.  They certainly met all of the current regulations governing the necessary equivalence to make it to the market.  But this study raises a number of questions:  Is this finding of pharmacologic equivalence not equaling clinical efficacy unique to vancomycin or could it be a factor in other generic antibiotics?  Could the universal use of generic vancomycin in hospital pharmacies account for the increasing clinical failures being seen not only in clinical trials but everyday practice?

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.

I know that this title seems like I am tying in a number of fairly diverse topics but hear me out on this one.  I was browsing through USA Today while sitting in an airplane last week and came across a story whose title read “Safety Breaches at Surgery Centers”.  That, in and of itself was interesting enough to me but upon reading the story I learned that “A federal study finds many same day surgery centers – where patients get such things as foot operations (my emphasis added) and pain injections – have serious problems with infection control.”

This short piece in the paper was reporting on the results reported in a study published in the June 9, 2010 issue of the Journal of the American Medical Association by Schaefer MK, et al entitled “Infection Control Assessment of Ambulatory Surgical Centers.” Ambulatory surgical centers in 3 states were assessed specifically looking at hand hygiene, injection safety and medication handling, equipment reprocessing, environmental cleaning and handling of blood glucose monitoring equipment.  Despite the centers knowing that they were being observed 67.6% had at least one lapse.  Also of interest was the breakdown on numbers and types of procedures.  Almost a full 1/3 of all of the procedures performed at these surgi-centers were classified as “Podiatry”.  I did not find where the study differentiated lapses in infection control by types of procedure and, unlike the USA Today piece, the JAMA article did not specifically single out “foot operations”.

The reason for me reporting on this study, besides the public relations nightmare from the USA Today piece, is that I know many podiatric physicians have financial interest in an ambulatory surgical center.  All I can do is plead with you to maintain the absolute highest level of vigilance in your infection control practices.  This WILL come back and “bite” you if you do not.  After a report like this in a journal like JAMA you know that more regulations are not far behind!

Along the same vein, I sit on my hospital’s Infection Prevention and Control Committee.  At our most recent meeting the RN Infection Control Coordinator passed out an article which was a position paper from the Association for Professionals in Infection Control and Epidemiology (APIC) on safe injection practices:  Dolan SA, et al. APIC position paper: Safe injection, infusion and medication vial practices in health care. Am J Infect Control 2010, 38:167-72.  Why I found this particularly pertinent to what we do in lower extremity practice is that it discusses the use of multi-dose medication vials.  I have personally reviewed a few mal-practice cases of docs being sued for allegedly causing infection by using these vials.  Apparently, there is some controversy about how long one of these vials can be used. The United States Pharmacopeia (USP) requires that a multi dose vial must be disposed of 28 days after the initial stopper penetration unless the Product Insert states otherwise.  The Centers for Disease Control and Prevention (CDC), however, takes the stance that the bottle can be used until the manufacturers’ expiration date or if there are concerns about its sterility.

Taking these different opinions into account the APIC Guidelines suggests “…adhering to strict aseptic technique when accessing the vial, using a new sterile needle and a new sterile syringe for every access, removing all access devices from the vial, storing the vial in a clean protected location according to the manufacturer’s directions and ensuring that any vial whose sterility may be compromised is immediately discarded.”  I rather like one of their other comments and suggest to  you that, although not economically viable, and not currently “standard of care”, may be the best advice to protect your patient and yourself…”Use multi-dose medication vials for a single patient whenever possible…Infection transmission risk is reduced when multi-dose vials are dedicated to a single patient”.

In the July 2010 issue of Consumer Reports there is a short (less than one page) “5-Minute Consult” article from the magazine’s chief medical advisor Marvin Lipman, MD entitled “Treating Toenail Fungus”. Overall, I think it is a well written and accurate piece that gives consumers some valuable information.  I do, however, find a few points on which Dr. Lipman and I would not totally agree.

1.  The article starts out by talking about all of the attention and “millions of dollars” spent each year for drug company marketing of onychomycosis in a “futile” attempt to treat the condition.  Apparently, Dr. Lipman has not been watching for direct-to-consumer (DTC) ads on TV, looking for journal advertisement about onycho products or seeing Pharma reps in his office.  If he did, he would know that there is not, nor has there been for about 2-3 years, ANY money spent on onychomycosis product advertisements at all!  All 3 FDA approved products are currently generic and no money is spent on marketing them.  I would also take exception to his classification of the treatment as “futile”.  Both clinical trials, and clinical experience showed terbinafine and itraconazole to be rather effective agents.  Even if they do not work all of the time, their use is far from futile. 

2.  Dr. Lipman states that the treatment is “only occasionally medically necessary” except to prevent secondary bacterial infection particularly in diabetic patients and the immunocompromised. Despite many studies showing quality of life issues and other medical complications of onycho, the entire “cosmetic vs. medically necessary” argument has been going on for years, mainly perpetuated by the insurance companies who used it as an excuse to not pay for the drug.   It is interesting that, now that the drugs are generic and inexpensive, suddenly there seems to be little trouble getting them covered.  I guess the generic forms are medically necessary while the name brands were not. 

3.  His comments on the “do it yourself” Internet market for onychomycosis products is right on target.  Although some are capable of killing fungus few if any have been subject to randomized controlled trials.  This also goes for most of those products being sold by our colleagues out of their offices. (Anecdotal testimony perpetuated by representative, i.e. “According to Drs. Smith and Jones, it works 90% of the time” does NOT equal medical evidence!)

4. Dr. Lipman’s discussion on prescription options is also mostly correct.  I would challenge his comment that a “3-month course of treatment can run up to several hundreds of dollars not including doctor’s visits and cost of tests”.  Now that these drugs are generic we are all familiar with the $4 Rx of terbinafine that many of our patients are now able to receive from discount pharmacies.  In fact, oral therapy of onychomycosis is actually quite inexpensive. The downside to his is that it has stymied any new oral therapy development since few Pharma companies want to develop a new, expensive drug to challenge such inexpensive therapy.

5. My final comment is in regard to his comment that a single laser treatment, “usually by a podiatrist, may be effective nearly 90% of the time but at around $1200 a pop”.  I find it quite interesting that Dr. Lipman is critical of prescription orals and topical and all of the anecdotal remedies holding them up to scrutiny for their lack of clinical evidence yet he mentions a 90% success rate with lasers. I need to point out that NONE of the lasers have been proven to work anywhere near the 90% mark with a single treatment and only one, the Noveon system, has any published data whatsoever.  (For full disclosure, I have been a consultant to both Nomir and Patholase).  The Noveon data just published last week by Adam Landsman, DPM, PhD and colleagues in the May/June issue of the Journal of the American Podiatric Medical Association used 4 treatments and evaluated at 180 days.  They found that 85% of the nails were improved as judged by an independent, blinded expert panel. Patholase has just completed their prospective study on the PinPointe system but it has not yet been published.

Do yourselves a favor and find the piece since you know that your patients are going to be questioning you about it!   

Ulceration under a mycotic nail in a patient with diabetes