Sulfa Antibiotic Allergy: Common and Frequently Misunderstood

Sulfa drugs were the first antibiotics

Sulfa drugs were the first chemicals available to treat bacterial infections in humans.  The proper designation for this class of drugs is sulfonamide but they became knows as “sulfa” antibiotics with their widespread use as powders and pills during WW ll.  Although sulfa antibiotics saved lives, their use decreased significantly after the introduction of penicillin because of frequent adverse reactions and emerging bacterial resistance.

Seven Percent of Patients Taking Sulfa Antibiotics Have Adverse Reactions

Approximately 6-8% of patients who take these drugs have adverse skin reactions ranging from a measles-like rash,  hives and swelling, to severe life-threatening skin blistering conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.  In HIV- infected patients, the adverse reaction rate to sulfonamide antibiotics is as high as 25 to 50 percent!

For a number of years, the drugs Bactrim DS and Septra DS (which contain two antibiotics: trimethoprim and sulfamethoxazole) were used to treat ear infections in children.  Sulfamethoxazole is a sulfonamide antibiotic.  If patients developed a rash while taking these drugs, they were told that they were allergic to sulfa and should avoid all sulfa drugs in the future.  These antibiotics were widely prescribed and so the number of adults now reporting a history of sulfa allergy is significant.

Sulfa vs Sulfur vs Sulfite vs Sulfate vs…..

As mentioned, “sulfa” is a colloquial designation for sulfonamide antibiotic, but the prefix “sulf” is found in an enormous number of other medications that may contain sulfur, sulfites or bisulfate including penicillin antibiotics, reflux medications, pain medications, blood pressure medications, and a variety of supplements. For example ferrous sulfate is a common medication used to treat iron deficiency.  The chemical structure for the popular diuretic Lasix (furosemide) contains sulfur.   Neither of these medications cross react with sulfonamide antibiotics.

The use of trimethoprim/sulfamethoxazole to ear infections in children has decreased significantly because of an increase in bacterial resistance to these antibiotics.  However, this and other sulfonamide antibiotics are still frequently used to to treat urinary track infections and skin infections with MRSA.

Medications to avoid if you are allergic to sulfa antibiotics

Patients who have had adverse reactions to sulfonamide antibiotics should avoid all sulfonamide antimicrobials including:

  • Sulfamethoxazole, cotrimoxazole
  • Sulfasalazine
  • Sodium sufacetamide
  • Silver sulfadiazine

Other drugs that should be avoided include:

  • Dapsone
  • Darunavir
  • Fosamprenavir
  • Trimethoprim

Drugs that you do not need to avoid if you are allergic to sulfa

Drug class
Drug or compound
Sulfonamide non-antimicrobials
Cross-reactivity is unlikely between sulfonamide antimicrobials and sulfonamide non-antimicrobials
Ibutilide, sotalol
Carbonic anhydrase inhibitors
Acetazolamide, methazolamide, dorzolamide, brinzolamide
COX-2 inhibitors
Diuretics, loop
Furosemide, bumetanide
Glimepiride, glyburide, gliclazide
Diuretics, thiazide
Hydrochlorothiazide, chlorthalidone, indapamide, metolazone, diazoxide
Sumatriptan, naratriptan
No sulfonamide moiety and therefore no cross-reactivity
Sulfate (eg, ferrous sulfate, magnesium sulfate)
Sulfites (eg, sodium metabisulfite)