any member of a group of synthetic antibiotics (antibiotic) containing the sulfanilamide molecular structure. Sulfa drugs were the first chemical substances systematically used to treat and prevent bacterial infections in humans.

The antibacterial effects of sulfonamides were first observed in 1932, when German bacteriologist and pathologist Gerhard Domagk (Domagk, Gerhard) noted the effects of the red dye Prontosil on Streptococcus infections in mice. It was later proved by French researchers that the active agent of Prontosil was sulfanilamide, or para-aminobenzenesulfonamide, a product of the body's metabolism of Prontosil. By the 1940s sulfanilamide was a widely used drug. During World War II white sulfanilamide powders became standard in first aid kits for the treatment of open wounds, and sulfanilamide tablets were taken to fight intestinal infections. Though the medicine was relatively safe, allergic reactions such as skin rashes, fever, nausea, vomiting, and even mental confusion were common. With the introduction of less toxic derivatives and especially with the mass production of penicillin, its use declined.

Many other sulfa drugs were derived from sulfanilamide in the 1940s, including sulfathiazole (systemic bacterial infections), sulfadiazine (urinary tract and intestinal tract infections), and sulfamethazine (urinary tract infections). However, all sulfa drugs induced some of the side effects listed above, and bacteria developed resistant strains after exposure to the drugs. Within a few decades the sulfa drugs had lost favour to more effective and less toxic antibiotics.

Trisulfapyrimidine (triple sulfa), a combination of sulfadiazine, sulfamerazine, and sulfamethazine, is used in the treatment of vaginal infections, and several sulfa drugs are used in combination with antibiotics to treat a wide range of conditions, from skin burns to malaria to pneumonia in AIDS patients.

Sulfa drugs are bacteriostatic; i.e., they inhibit the growth and multiplication of bacteria but do not kill them. They act by interfering with the synthesis of folic acid (folate), a member of the vitamin B complex present in all living cells. Most bacteria make their own folic acid from simpler starting materials; humans and other higher animals, however, must obtain folic acid in the diet. Thus, sulfa drugs can inhibit the growth of invading microorganisms without harming the host.