Sulfadiazine

Sulfadiazine is a synthetic antibiotic in the sulfonamide class. It acts as a competitive inhibitor of dihydropteroate synthase, blocking bacterial synthesis of dihydrofolic acid and thereby disrupting folate metabolism. Like other sulfonamides, it is generally more effective against certain Gram-positive cocci and some Gram-negative organisms, but resistance is common in many pathogens.

Clinical use varies by country, but sulfadiazine is employed systemically for susceptible bacterial infections and, in combination with pyrimethamine and leucovorin, as part of therapy for toxoplasmosis and congenital toxoplasmosis. In addition, topical formulations of sulfadiazine, typically as silver sulfadiazine, are used for burn wound care and related skin injuries.

Pharmacokinetics and administration: when administered orally, sulfadiazine is absorbed and distributed widely in body tissues. It is partially protein-bound and undergoes hepatic metabolism with renal excretion as a major elimination route. The drug is often given with pyrimethamine to achieve a synergistic antimicrobial effect, but this combination increases the risk of hematologic toxicity, hence the use of leucovorin rescue in toxoplasmosis regimens.

Adverse effects and safety: potential adverse effects include hypersensitivity reactions (rashes, Stevens–Johnson syndrome in rare cases), gastrointestinal upset, photosensitivity, and crystalluria. Hematologic toxicity can occur, particularly when used with other antifolate agents. In pregnancy, sulfonamides are generally avoided in the third trimester due to risk of kernicterus in the fetus; caution is advised during breastfeeding and in neonates. Drug interactions include enhanced anticoagulant effects with warfarin and possible interactions with other folate pathway inhibitors.

Resistance: widespread resistance limits routine use for many infections; mechanisms include mutations in dihydropteroate synthase and reduced drug uptake.