Sulfonamides are a class of antibiotics used to treat a variety of bacterial infections. The most common sulfonamide drug is sulfamethoxazole, abbreviated SMX, although other sulfonamides used include sulfadiazine and sulfisoxazole. Sulfonamides work by inhibiting bacterial folate synthesis. Clinically, sulfonamides like sulfamethoxazole are frequently used in combination with trimethoprim to treat a variety of bacterial infections. Sulfonamides commonly cause hypersensitivity reactions and should not be given to patients who have a sulfa allergy. Other side effects include hemolysis in patients with G6PD deficiency, and development of photosensitive rashes, infantile kernicterus, and nephrotoxicity. Sulfonamides also inhibit CYP enzymes and can cause several drug interactions.

Key Points

  • Sulfonamides
    • Drug Names
      • Sulfamethoxazole (SMX)
      • Sulfisoxazole
      • Sulfadiazine
    • Mechanism
      • Impairs folate synthesis in bacteria
        • Chemical analogs of para-aminobenzoic acid (PABA), a folic acid precursor for bacteria
        • Bind to and inhibit dihydropteroate synthase, preventing bacterial conversion of PABA to folic acid
        • Note: people rely on dietary folate (cannot synthesis folate), so the drug does not affect humans
      • Bacteriostatic
        • Bactericidal when combined with trimethoprim
    • Clinical Use
      • Broad-coverage, especially when used in combination with Trimethoprim (TMP-SMX, trade name: Bactrim)
        • Synergistic block of bacterial folate synthesis
        • Gram-positive organisms (e.g. Nocardia)
        • Gram-negative organisms
    • Adverse Effects
      • Hypersensitivity reactions (sulfa allergy)
        • Sulfa allergies are caused by hypersensitivity to sulfonamide groups
      • Hemolysis with G6PD deficiency
        • Sulfonamides are oxidizing agents
      • Nephrotoxicity
        • e.g. tubulointerstitial nephritis
        • Sulfonamides may precipitate in the tubules of the kidney and cause tubular obstruction and necrosis
      • Photosensitive rash
        • Can develop into Stevens-Johnson syndrome (SJS)
      • Infantile kernicterus
        • Can displace bilirubin from albumin
      • Inhibits CYP Enzymes
        • Synergistic inhibition with trimethoprim (TMP)
        • Causes drug interactions (e.g. raises warfarin levels)
    • Resistance
      • Mutations in enzyme (bacterial dihydropteroate synthase)
      • Decreased uptake
      • Increased PABA synthesis