Emerging Trends In Antibiotic Prescriptions By Podiatrists

I recently came across some fascinating data that breaks down the number of outpatient prescriptions written by podiatrists for all different classes of drugs 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 nonsteroidal anti-inflammatory drugs (NSAIDs) with over 1.6 million scripts written. This is followed closely by antifungals at about 1.4 million prescriptions.

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, with amoxicillin/clavulanic acid (Augmentin, GlaxoSmithKline) down the line a bit at number 15 (177,000).

Although amoxicillin/clavulanic acid 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 875 mg is an amazingly large pill that is not easy to swallow. Also, I always knew that the drug could be a bit hard on the gastrointestinal 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 117,000. Not surprisingly, this drug’s use has increased dramatically over the past few years with as few as 34,000 scripts only two years before, a stunning increase in such a short period of time. Probably all of this usage is for the presumptive treatment of methicillin resistant Staphylococcus aureus (MRSA) even before cultures have been returned.

I have said it before and I will repeat is again here: I do not like to routinely use trimethoprim/sulfamethoxazole. 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 trimethoprim/sulfamethoxazole).

Due to the lack of studies showing clinical efficacy against MRSA there is also some question as to dosing for MRSA infections. It has been suggested that the usual 1 DS b.i.d. is insufficient and that should be routinely increased to 2 DS b.i.d. thus potentially increasing the rate of adverse events even further. That is not to say I don’t use trimethoprim/sulfamethoxazole. 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 trimethoprim/sulfamethoxazole, 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 trimethoprim/sulfamethoxazole, I much prefer doxycycline 100 mg q12h. One can also use minocycline (Minocin). 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 in the top 60 drugs written by podiatrists. I would like to see that change.

Are Podiatrists Overdoing It With Quinolones And Amoxicillin?

The next most commonly prescribed antibiotics drive me crazy. They are ciprofloxacin (Cipro, Bayer) at 101,000 followed by levofloxacin (Levaquin, Janssen Pharmaceuticals) at 75,000. 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 http://bit.ly/iLJb6k ). Even then, there is no data to suggest that levofloxacin would not be equally efficacious. Another quinolone, moxifloxacin (Avelox, Bayer), 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 gram negative infections. In fact, at Roxborough Memorial Hospital, a recent antibiogram shows only about 50 percent 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. I just don’t understand this 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 28,000 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.

In Conclusion

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 trimethoprim/sulfamethoxazole, quinolones and amoxicillin, we can always do better.

Editor’s note: This blog was originally published at http://www.leinfections.com/antibiotics/antibiotic-prescribing-in-podiat... and has been adapted with permission from Warren Joseph, DPM, FIDSA, and Data Trace Publishing Company. For more information about the Handbook of Lower Extremity Infections, visit www.leinfections.com/ .



Al Musellasays: January 31, 2012 at 12:53 pm

Excellent article.

Why is cephalexin preferred over cefuroxime?

Reply to this comment »
Warren Josephsays: January 31, 2012 at 4:06 pm

Thanks for the compliment. It is an excellent question. I really just believe it is force of habit. Most people have been taught about cephalexin/Keflex since their earliest days of training. I would venture a guess that few know about cefuroxime (or more exactly, cefuroxime axetil/Ceftin). Cefuroxime has always been a terrific anti-staph drug, arguably better than cephalexin, and it is a true bid dosing. It was never actively marketed to podiatry so there just hasn't been much exposure to it in the field.

Good drug, good question!

Thanks for reading the blog.

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Kevin Lapoff, DPMsays: January 31, 2012 at 9:02 pm

Warren, what are your thoughts on adding rifampin with either Minocin or Bactrim, or clindamycin to enhance MRSA effectiveness?

Reply to this comment »
Warren Josephsays: February 1, 2012 at 4:19 pm

Hi Kevin.

The evidence has really gotten quite good about the addition of rifampin. Honestly, I never really did it since I had good success with the drugs by themselves. But, more and more people are seeing that by adding rifampin, success rates increase. It may be a true synergistic effect or it has been postulated that it could also be because rifampin acts intra-cellularly where some of the MRSA may be "hiding."

I would direct you to the paper I discussed in the previous post on osteomyelitis. One of the conclusions reached in this review paper by Spellberg and Lipsky is that the addition of rifampin can aid in the treatment of staph osteo.

So, bottom line is, I am starting to use it, especially for oral outpatient therapy of MRSA osteo when we can't be sure all of the bone is debrided.

Thanks for the great question!

Warren

Reply to this comment »
Briansays: February 2, 2012 at 6:50 pm

I would venture to guess that a lot of the prescriptions for Bactrim are in cases of documented PCN allergy. Would your go-to empiric drug then be doxy over Levaquin ?

Reply to this comment »
Warren Josephsays: February 5, 2012 at 9:51 am

I think that the Bactrim use is more fear of MRSA than PCN allergy. There are other choices to use if you don't suspect MRSA in a PCN pt. Clinda comes to mind. Also, make sure that the "PCN allergy" is REALLY a PCN allergy! It is amazing what responses you get when someone says that they are allergic and you ask them to describe the reaction!

As for doxy, I guess that depends on your local MRSA problem. If there is a better than average chance (difficult to define) that the infection may have MRSA then, yes, I would choose doxy over Levo. It's not that I don't use Levo, I just don't use it on every patient that walks in the door, even in PCN allergic.

Reply to this comment »
Jeff Mennutisays: February 3, 2012 at 12:02 pm

Thanks for the great article/rant!

I see a lot of consults in which the first caregiver initiates a fluorquinolone. I usually perform the same rant in my head, but never speak out about it.

I didn't see linezolid listed in your article. I quiver at the thought of having to prescribe it due to cost and the fact that infectious disease gets angry when I do. However, there is still very good reason to prescribe it. I currently have a patient with VRE and have been successful with it for prior MRSA.

That being said, I very much hope that Zyvox does not get overused. There are recent articles in Infectious Disease and the JAMA regarding linezolid resistant MRSA. Also, there are at least 2 new IV antibiotics indicated for MRSA: telavancin (basically a 2nd generation vanco) and ceftaroline (a cephalosporin).

Still, there is no antibiotic that is clinically indicated for osteomyelitis.

Reply to this comment »
Warren Josephsays: February 5, 2012 at 10:14 am

Thanks for the thoughtful comments Jeff. I agree that it is tough to have that rant in front of the patient! Great job containing it to your "head."

That being said, I think there is a general misconception in our profession that the average primary doc knows his or her antibiotics and how to use them in foot infections. Many do but most do not. They have too many other problems and drugs to know. It is not their specialty. I have no problem changing their prescription if I don't think it is correct.

As for linezolid, regular readers of my actual blog (these posts are adapted from that site: www.leinfections.com ) know I have posted many times about the overuse of vancomycin and the proper alternatives that are out there. This, of course, includes linezolid, a drug which I think is a tremendous alternative to vanco for moderate to severe MRSA infections. I have also posted about the other drugs you mentioned, telavancin and ceftaroline. The reason for not including linezolid in this post is because it was not listed in the data I reviewed of most commonly used drugs. Most of the drugs on this list are used for more mild infections as evidenced by the appearance of cephalexin at the top of the list.

I don't think that linezolid should be used when you have a mild infection that can be treated by some of the "older generic orals" such as doxy, mino or Bactrim. It is a drug that should be used in place of IV vanco for inpatient or outpatient therapy of more moderate to severe infections, in patients reluctant to be hospitalized, in cases of decreased vanco susceptibility ("MIC Creep"), and, as you pointed out, it is an excellent drug for PO or IV therapy of VRE.

As to resistance and overuse, yes, it certainly can occur. The best known report was an outbreak in a critical care unit in Spain a few years back. However, even 12 years after its release, worldwide resistance rates to MRSA are still well below 1%.

Finally, to your question of osteomyelitis, I would direct you to the original blog (see www.leinfections.com ). On the left-hand side, there are "Categories" listed. If you click on the osteomyelitis tab, you will see I have addressed this issue many times.

I also will disclose that I am a consultant and speaker for Pfizer.

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