I recently came across some fascinating data which breaks down the number of outpatient prescriptions written by podiatrists for all different classes of drug in 2010.  Unlike various surveys that have been done over the years by different magazines, this is hard data based on the actual number of scripts.  I would like to comment on some findings I find interesting in the use of antibiotics. 

Antibiotics were the third most commonly prescribed class of drug following narcotic analgesics and NSAIDs with over 1.6 million scripts written.  This is followed closely by antifungals at about 1.4 mil prescriptions. (Perhaps a topic for a future post?).  I don’t think it would come as any surprise that cephalexin is the most prescribed (530,000) and is actually the second most common drug written by DPMs.  The number two most common antibiotic would also probably not come as a big surprise, amoxicillin/clavulanic acid (Augmentin) down the line a bit at number 15 (177K).  Although amox/clav is a good antibiotic with a favorable spectrum for more complicated lower extremity infections, it is probably a bit unnecessarily broad spectrum for everyday use. I have started to limit my use of this drug after I personally had to take it for an endodontic problem.  First, the 875mg is an amazingly large pill which is not easy to swallow.  Also, I always knew that the drug could be a bit hard on the GI tract and I knew to take it with food and a full glass of water.  Despite those precautions, about 20 minutes after I took each dose, I found my stomach wanting to jump out of my abdomen!  It is true what they say about how a physician can change his way of treating folks after he becomes a patient. 

The third most commonly used antibiotic is trimethoprim/sulfamethoxazole (Bactrim/Septra) with 117K Rx’s.  Not surprisingly, this drug’s use has increased dramatically over the past few years with as few as 34K scripts only 2 years before, a stunning increase in such a short period of time.  Probably all of this usage is for the presumptive treatment of MRSA even before cultures have been returned.  I have said it before; I will repeat is again here, I do NOT like to routinely use this drug.  There are reasons this drug was rarely used before the MRSA epidemic we find ourselves facing.  Although broad spectrum, generic and inexpensive it is not benign. Toxicities range from life threatening skin reactions, such as Stevens-Johnson syndrome to renal, neurologic, psychiatric and hematologic problems, not to mention sulfa allergy, drug-drug interactions with other sulfa based drugs and the inability to use in patients with a G6PD deficiency (and, YES, you will see this as I recently did in a patient with a multi-drug resistant Enterobacter cloacae where the ONLY drug to which the organism was reported as susceptible was TMP/SMX).  Because of the lack of studies showing clinical efficacy against MRSA there is also some question as to how it should be dosed for MRSA infections.  It has been suggested that the usual 1DS b.i.d. is insufficient and that should be routinely increased to 2DS b.i.d. thus potentially increasing the rate of adverse events even further.  That is not to say I don’t use TMP/SMX, I just don’t routinely give it to every patient empirically to cover MRSA or even with a positive MRSA culture unless there are other reasons to use it, such as a mixed infection where the use of one drug obviates the need for combination therapy. 

I often get asked the question; “if not TMP/SMX, then what oral antibiotic you using for your MRSA cases”.  That depends on severity.  For my more mild infections where most of you are probably using TMP/SMX, I much prefer doxycycline 100mg q12h.  Minocycline can also be used.  I find that there is more data to support their use and they are well tolerated even for longer courses of therapy such as in osteomyelitis.  Interestingly, NEITHER of these antibiotics is found in the top 60 drugs written by podiatrists.  I would like to see that change.

The next most commonly prescribed antibiotics drive me crazy!  They are ciprofloxacin at 101K followed by levofloxacin at 75K.  Those who have heard me lecture know that I have been preaching avoidance of quinolones, particularly ciprofloxacin since it was first released and people were sold a “bill of goods” about how broad spectrum it was and how wonderfully it penetrated bone.  As time has gone on, my feelings have only intensified. If I am going to use a quinolone, it is levofloxacin rather than ciprofloxacin because of its better gram positive activity and the once daily dosing.  The only time I see a use for ciprofloxacin is for a documented Pseudomonas infection, something that is extremely rare in lower extremity infections (see post on “Pseudomonaphobia”).   Even then, there is no data to suggest that levofloxacin would not be equally efficacious.  Another quinolone, moxifloxacin, has the advantage of better anaerobic coverage in the case of a diabetic foot infection.  My quinolone usage is on a significant decline.  As a class, these drugs can potentiate the development of MRSA infections, have significant toxicities and, probably most importantly, have been implicated in the development of multi-drug resistant (MDRO) gram negative infections.  In fact, at Roxborough a recent antibiogram shows only about 50% of our E. coli still susceptible to ciprofloxaxin.  Furthermore, I have been noticing lately that every patient who gets sent out on a quinolone invariably returns to the hospital but now with an organism resistant to the entire class.  PLEASE, use these drugs sparingly and only when appropriate!!

The final drug on the list I would like to discuss is amoxicillin, currently being prescribed 28,000 times per year.  This, I just don’t understand at all.  Frankly, I don’t think I have ever written for straight amoxicillin nor do I see any reason to ever do so.  Perhaps, if the patient presents with an infection solely caused by Enterococcus or a straight Streptococcal infection, then it may be a reasonable choice but these are extremely rare and I seriously doubt they are occurring 28K times.  This leads me to believe that there is some inappropriate use of amoxicillin in the profession.  Please remember that this drug is not beta-lactamase stable and is therefore ineffective against essentially all clinically relevant S. aureus. 

These data reveals some interesting information about how lower extremity infections are being treated.  Overall, I find the usage pretty reasonable however, when it comes to what I perceive as an overuse of TMP/SMX, quinolones and amoxicillin, we can always do better.

A few weeks ago my old Podiatric College roommate sent me a link to a fascinating YouTube video.  I then sent it to a few friends who, in turn, posted it on a few other blogs so it has become a minor viral (or should I say “bacterial”) success.  This lecture, by Professor Eshal Ben-Jacob of Tel Aviv University, covers aspects of bacterial communication and their “social interactions” as regulated by various stimuli.  It is an utterly fascinating subject presented in a clear, understandable manner with incredible videos and photographs.  This work has major implications in the way bacteria become pathogenic, are currently treated and some future directions that could be considered.  Just as a “heads-up” it will take a commitment of time from you, the viewer, as the lecture is an hour long but please don’t let that keep you from viewing it in its entirety.  It is absolutely worth it.  http://www.youtube.com/watch?v=yJpi8SnFXHs

I wish all of my readers a healthy, happy and prosperous 2012.  With this post I am trying something a bit different.  In the past I usually waited to put up a post until I come up with an “ah ha” moment on something I have seen, heard or read about which I then pontificate on this site.  These could occur only days apart, but usually it was a much longer time period leading to relatively infrequent additions to the blog.  My “resolution” for 2012 is to try to put up more frequent, quick hits where I don’t have as much to write and you don’t have as much to read.  That’s not to say that I won’t still post the occasional tome on a particular topic.  Sometimes, I just have to vent!  I have one coming up shortly on antibiotic usage in podiatric medicine…just a heads up.

A recent paper has been published in Clinical Infectious Diseases by Brad Spellberg at UCLA and Ben Lipsky at the Puget Sound VA titled Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults (http://www.ncbi.nlm.nih.gov/pubmed?term=Spellberg%20B%20AND%20Lipsky%20BA).  I consider it a MUST READ for followers of this site.  This excellent review covers topics including the pharmacology of osteo therapy (i.e. parenteral vs. oral, bone penetration), animal models of osteo, human non-randomized clinical trials and randomized clinical trials.  It is THOROUGH yet quite readable at only 11 pages (there are, however, 172 references!) with 5 tables outlining all of the studies discussed. 

The authors arrive at 4 conclusions which I quote directly from the paper:

1.  “Oral antibiotic therapy with highly bioavailable agents is an acceptable alternative to parenteral therapy.”

2.   “Adding rifampin to a variety of antibiotic regimens has been shown to improve cure rates”

3.   “Clinicians must individualize the duration of antibiotic therapy based on the patient’s clinical and radiographic response…”

4.   “Surgical resection of necrotic and infected bone, in conjunction with antibiotic therapy, appears to increase the cure rate of chronic osteomyelitis. However, not all cases of chronic osteomyelitis require surgical debridement for cure, and we need studies to clarify which may and which may not.”

None of these conclusions should come as a surprise to regular readers of this blog or those who have heard me lecture on the topic, as I have discussed these very points in the past.  Dr. Lipsky and I collaborate frequently and I find it almost frightening how often we agree.  In this one paper he and Dr. Spellberg have eloquently laid out all of the evidence supporting these positions.  If I have said it once, I have said it a thousand times…We MUST rethink the universally pervasive dogma of 4-6 weeks of IV antibiotic therapy for osteomyelitis based on the best available evidence!