Sulfonamides are infrequently used as single agents. Many strains of formerly susceptible species, including meningococci, pneumococci, streptococci, staphylococci, and gonococci, are now resistant. The fixed-drug combination of trimethoprimsulfamethoxazole is the drug of choice for infections such as Pneumocystis jiroveci (formerly P carinii) pneumonia, toxoplasmosis, and nocardiosis.
A. Oral Absorbable Agents
Sulfamethoxazole is a commonly used absorbable agent; however, in the USA, it is available only as the fixed-dosed combination trimethoprim-sulfamethoxazole. Typical dosing and indications are discussed below.
Administration of sulfadiazine with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. Using sulfadiazine plus pyrimethamine, a potent inhibitor of dihydrofolate reductase, is synergistic because these drugs block sequential steps in the folate synthesis pathway (Figure 46–2). However, since 2015, there have been challenges with manufacturing, supply, and pricing of pyrimethamine in the USA. In some cases, clinicians have obtained a compounded product through specialty pharmacies or prescribed alternate agents, such as trimethoprimsulfamethoxazole. Sulfadoxine is a long-acting sulfonamide that is coformulated with pyrimethamine (Fansidar). This combination is no longer commercially available in the USA but may be found in other parts of the world where it is used as a second-line treatment for malaria (see Chapter 52).
B. Oral Nonabsorbable Agents
Sulfasalazine (salicylazosulfapyridine) is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease (see Chapter 62).
C. Topical Agents
Sodium sulfacetamide ophthalmic solution or ointment is effective in the treatment of bacterial conjunctivitis and as adjunctive therapy for trachoma. Another sulfonamide, mafenide acetate, is used topically but can be absorbed from burn sites. The drug and its primary metabolite inhibit carbonic anhydrase and can cause metabolic acidosis, a side effect that limits its usefulness. Silver sulfadiazine is a less toxic topical sulfonamide and is preferred to mafenide for prevention of infection of burn wounds.
Historically, drugs containing a sulfonamide moiety, including antimicrobial sulfas, diuretics, diazoxide, and the sulfonylurea hypoglycemic agents, were considered to be cross-allergenic. However, more recent evidence suggests cross-reactivity is uncommon and many patients who are allergic to nonantibiotic sulfonamides tolerate sulfonamide antibiotics. The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea, and difficulties referable to the urinary tract (see below). Stevens-Johnson syndrome, although relatively uncommon (<1% of treatment courses), is a particularly serious and potentially fatal type of skin and mucous membrane eruption associated with sulfonamide use. Other unwanted effects include stomatitis, conjunctivitis, arthritis, hematopoietic disturbances (see below), hepatitis, and, rarely, polyarteritis nodosa and psychosis.
A. Urinary Tract Disturbances