Another Reason To Avoid Overuse Of Trimethoprim/ Sulfamethoxazole (TMP/SMX)

Warren S. Joseph DPM FIDSA

Those of you who have read my chapter on MRSA in the 3rd Edition of the Handbook of Lower Extremity Infections 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 care physician or anyone else treating skin and skin structure infections.

My primary objections, spelled out in detail on pages 332-333 of the book (see ), 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 recently published paper by Antoniou and colleagues in the Archives of Internal Medicine gives one more reason for concern.1 See

This was a population-based, nested control study of patients 66 years of age or older who were receiving angiotensin converting enzyme (ACE) inhibitors and various antibiotics. The numbers were impressive. This was a 14-year study with 4,148 identified admissions involving hyperkalemia. To quote the study 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 ones that come to mind involved a patient with CA-MRSA and Stenotrophomonas maltophilia. Using TMP/SMX gave me a single agent I could use to cover both bugs.

I do not 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.


1. Antoniou T, Gomes T, Juurlink DN, et al. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Arch Intern Med. 2010; 170(12):1045-9.

Editor’s note: This blog originally appeared at 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

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