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By Hans P. Schlecht, MD, MSc, Assistant Professor of Medicine, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Drexel University College of Medicine
Christopher Bruno, MD, Assistant Professor of Medicine, Division of infectious Diseases & HIV Medicine, Drexel University College of Medicine

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Sulfonamides (see Table: Sulfonamides) are synthetic bacteriostatic antibiotics that competitively inhibit conversion of p-aminobenzoic acid to dihydropteroate, which bacteria need for folate synthesis and ultimately purine and DNA synthesis. Humans do not synthesize folate but acquire it in their diet, so their DNA synthesis is less affected.










Two sulfonamides, sulfisoxazole and sulfamethizole, are available as single drugs for oral use. Sulfamethoxazole is coformulated with trimethoprim (as TMP/SMX—see Trimethoprim and Sulfamethoxazole).

Sulfonamides available for topical use include silver sulfadiazine, vaginal cream and suppositories containing sulfanilamide, and ophthalmic sulfacetamide.


Most sulfonamides are readily absorbed orally and, when applied to burns, topically. Sulfonamides are distributed throughout the body. They are metabolized mainly by the liver and excreted by the kidneys. Sulfonamides compete for bilirubin-binding sites on albumin.


Sulfonamides are active against

  • A broad spectrum of gram-positive and many gram-negative bacteria

  • Plasmodium and Toxoplasma spp

However, resistance is widespread, and resistance to one sulfonamide indicates resistance to all.

Sulfasalazine can be used orally for inflammatory bowel disease.

Sulfonamides are most commonly used with other drugs (eg, for nocardiosis, UTI, and chloroquine-resistant falciparum malaria).

Topical sulfonamides can be used to treat the following:

  • Burns: Silver sulfadiazine and mafenide acetate

  • Vaginitis: Vaginal cream and suppositories with sulfanilamide

  • Superficial ocular infections: Ophthalmic sulfacetamide


Sulfonamides are contraindicated in patients who have had an allergic reaction to them or who have porphyria.

Sulfonamides do not eradicate group A streptococci in patients with pharyngitis and should not be used to treat group A streptococcal pharyngitis.

Use During Pregnancy and Breastfeeding

Most sulfonamides are in pregnancy category B (animal studies show no risk and human evidence is incomplete, or animal studies show risk but human studies do not). However, use near term and in breastfeeding mothers is contraindicated, as is use in patients < 2 mo (except as adjunctive therapy with pyrimethamine to treat congenital toxoplasmosis). If used during pregnancy or in neonates, these drugs increase blood levels of unconjugated bilirubin and increase risk of kernicterus in the fetus or neonate.

Sulfonamides enter breast milk.

Adverse Effects

Adverse effects can result from oral and sometimes topical sulfonamides; effects include

  • Hypersensitivity reactions, such as rashes, Stevens-Johnson syndrome (see Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)), vasculitis, serum sickness, drug fever, anaphylaxis, and angioedema

  • Crystalluria, oliguria, and anuria

  • Hematologic reactions, such as agranulocytosis, thrombocytopenia, and, in patients with G6PD deficiency, hemolytic anemia

  • Kernicterus in neonates

  • Photosensitivity

  • Neurologic effects, such as insomnia, and headache

Hypothyroidism, hepatitis, and activation of quiescent SLE may occur in patients taking sulfonamides. These drugs can exacerbate porphyrias.

Incidence of adverse effects is different for the various sulfonamides, but cross-sensitivity is common.

Sulfasalazine can reduce intestinal absorption of folate (folic acid). Thus, use of this drug may trigger folate deficiency in patients with inflammatory bowel disease, which also reduces absorption, especially if dietary intake is also inadequate.

Mafenide may cause metabolic acidosis by inhibiting carbonic anhydrase.

Dosing Considerations

To avoid crystalluria, clinicians should hydrate patients well (eg, to produce a urinary output of 1200 to 1500 mL/day). Sulfonamides can be used in patients with renal insufficiency, but peak plasma levels should be measured and sulfamethoxazole levels should not exceed 120 μg/mL.

Sulfonamides can potentiate sulfonylureas (with consequent hypoglycemia), phenytoin (with increased adverse effects), and coumarin anticoagulants.

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