Antibacterial Agents, Sulfonamides

AbstractSulfonamides derived from sulfanilamide (p‐aminobenzenesulfonamide) are commonly referred to as sulfa drugs. The sulfa drugs are still important as antimicrobials, although they have been replaced in many systemic infections by the natural and semisynthetic antibiotics. They are of great value in Third‐World countries where problems of storage and lack of medical personnel make appropriate use of antibiotics difficult. They are especially useful in urinary tract infections, particularly the combination of sulfamethoxazole with trimethoprim, and the combination of sulfamethoxazole with trimethoprim is of value in treatment of a number of specific microbial infections. The introduction of this combination (cotrimoxazole) in the late 1960s (1973 in the United States) resulted in increased use of sulfonamides. The sulfas also remain clinically useful in the treatment of chancroid, lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and the fungus‐related nocardiosis. The sulfone, dapsone, remains an accepted treatment for all forms of leprosy. Currently used sulfas vary widely in their absorption, distribution, and excretion patterns. Some of those in clinical practice, past or present, are sulfanilamide, sulfacetamide, sulfadiazine, sulfadimethoxine, sulfaguanidine, sulfisomidine, sulfisoxazole, sulfamethazine, sulfamethizole, sulfamethoxazole, sulfamethoxypyridazine, sulfamoxole, sulfaphenazole, sulfapyridine, sulfapyrazine, and sulfathiazole. The action of the sulfa drugs and related sulfones is bacteriostatic rather than bactericidal. Numerous studies have been made to find a correlation between the physicochemical properties of the sulfonamides and their bacteriostatic activity. Degree of ionization, lipid–water solubility, electron distribution values, and protein binding have all been observed. One of the principal disadvantages of sulfonamide therapy is the emergence of drug‐resistant strains of bacteria. The most common method for the preparation of sulfonamides is by the action ofN‐acetylsulfanilyl chloride with the appropriate amine. A small percentage of patients treated with sulfa drugs have shown toxic effects, such as drug fever, rashes, mild peripheral neuritis, and mental disturbance. In 1966 the FDA required that two long‐acting sulfas, sulfamethoxypyridazine and sulfadimethoxine carry a label warning of the possibility of death due to Stevens‐Johnson syndrome, an extremely severe dermatologic reaction. Blood dyscrasias are quite uncommon, but if they occur may be serious enough to cause discontinuance of the therapy. Administration of sulfas can cause hypersensitivity reactions, but in general, use of sulfonamide therapy is considered relatively safe.