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Sulfonamides / TMP-SMX (Bactrim, Septra)

Sulfonamide antibiotic — folate synthesis inhibitor

Mechanism of action

Sulfamethoxazole inhibits dihydropteroate synthase and trimethoprim inhibits dihydrofolate reductase — together, they sequentially block bacterial folate synthesis. Bactericidal in combination. Used for uncomplicated UTI, MRSA skin infections, Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment, traveler's diarrhea, and toxoplasmosis prophylaxis.

Adverse effects

Life-threatening / NCLEX-tested

  • Stevens-Johnson syndrome / toxic epidermal necrolysis (high relative risk vs other antibiotics)
  • Severe hyperkalemia (trimethoprim blocks distal sodium channels — additive with ACE/ARB/spironolactone)
  • Hemolytic anemia in G6PD deficiency
  • Bone marrow suppression — agranulocytosis, thrombocytopenia, megaloblastic anemia (folate-related)
  • Acute kidney injury — crystalluria; ensure adequate hydration
  • Hepatotoxicity
  • DRESS syndrome
  • Kernicterus risk in late-pregnancy/neonates (avoid)

Side effects

Common — what to teach

  • Photosensitivity
  • GI upset, nausea, anorexia
  • Maculopapular rash (more common than other antibiotics; distinguish from SJS prodrome)
  • Headache
  • Vaginitis, thrush

Food & drug interactions

Warfarin INR rises markedly — recheck within days of starting. Methotrexate levels rise — fatal toxicity reported. Phenytoin levels rise. ACE inhibitors, ARBs, spironolactone, and potassium supplements compound hyperkalemia risk (significant). Sulfonylureas (glipizide, glyburide) cause severe hypoglycemia. Folate antagonist effects — caution in pregnancy and folate-deficient patients.

Nursing implications

Assessment, monitoring, patient teaching

  • Clarify sulfa allergy thoroughly — true sulfa antibiotic allergy can be life-threatening; cross-reactivity with non-antibiotic sulfa drugs (some diuretics, sulfonylureas) is debated and usually not absolute
  • Encourage 8 oz of water with each dose and good total intake to prevent crystalluria
  • Counsel sun protection — sunscreen, long sleeves
  • Teach to STOP and call at first sign of new rash, mouth sores, fever, or peeling skin (SJS prodrome)
  • Monitor K+ in patients on ACE/ARB/spironolactone, in older adults, and in renal impairment
  • For PJP treatment: high-dose IV regimens require close monitoring of CBC, K+, creatinine, LFTs
  • Reconcile warfarin and methotrexate before starting; recheck INR if on warfarin

When to hold / contraindications

  • Documented sulfa antibiotic allergy
  • Severe rash, mouth sores, fever (suspected SJS/TEN/DRESS)
  • Severe hyperkalemia
  • G6PD deficiency (avoid in routine use)
  • Late pregnancy (third trimester, near-term) and breastfeeding neonates
  • Severe acute kidney injury
  • Severe bone marrow suppression

Memory anchor

TMP-SMX = "sulfa antibiotic, watch K+, watch INR, watch for rashes." Push fluids; sunscreen; STOP at any new rash with fever or mouth sores.

Reminder: Drug cards are study aids, not clinical guidance. Always cross-check doses, holds, and contraindications with your facility's formulary and your clinical instructors before patient care.

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