Allergic adverse reactions to sulfonamides

Abstract

Antimicrobial sulfonamides were the first antimicrobial agents used effectively to treat infectious diseases. However, because they may cause severe adverse drug reactions (ADRs) and because more effective agents have since been developed, sulfonamides now are used for only a few indications in specific groups, such as AIDS patients. Skin reactions, from benign rash to potentially lethal toxidermias, are the most frequent ADRs to sulfonamides. Other major ADRs include acute liver injury, pulmonary reactions, and blood dyscrasias. Although the mechanisms involved have not been fully elucidated, reactive metabolites appear to play a pivotal role. The hydroxylamine and nitroso metabolites of sulfamethoxazole, the most frequently used sulfonamide today, can bind covalently to proteins because of their chemical reactivity, resulting in the induction of specific adverse immune responses. Therefore, changes in the activity of metabolic and detoxification pathways are associated with a greater risk for developing allergic reactions to sulfonamides. Allergies to sulfonamides, particularly sulfamethoxazole (often used in combination with trimethoprim as co-trimoxazole), are more frequent in AIDS patients, but the reason for this increased risk is not fully understood. No valid tools are available to predict which patients have a greater risk for developing allergies to sulfonamides. Diagnosis is essential to avoid a possible evolution toward severe reactions and readministration of the offending drug. In patients who absolutely require further treatment, successful desensitization may be achieved.

Antibiotics in dust originating from a pig-fattening farm: a new source of health hazard for farmers?

“…In particular, tylosin and sulfamethazine, which occurred in 80% and 65% of the samples, respectively, are drugs with known allergic potential (Barbera and de la Cuadra 1989;Caraffini et al 1994;Choquet-Kastylevsky et al 2002;Danese et al 1994;Hjorth and RoedPetersen 1980). In addition, farmers have been exposed to chloramphenicol, an antibiotic with severe side effects (Holt et al 1993).…”

Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

“…Current clinically used inhibitors of HCA II include acetazolamide and brinzolamide, which incorporate a sulfonamide functional head group, have detrimental side effects including augmented diaeresis, fatigue, paresthesias and anorexia owing to the nonspecific inhibition of CA isoforms in other tissues than those targeted (Aggarwal et al, 2013). Additionally, an estimated 3% of the total population has an adverse drug reaction to sulfonamide-containing compounds, with higher rates of sulfa allergies seen in individuals with low metabolic process rates and in immunocompromised patients (Choquet-Kastylevsky et al, 2002). Thus, BA inhibition of HCA II is an attractive therapeutic agent as they are nonsulfur-containing compounds that are easily transported across the cellular membrane and are extremely soluble in water compared with conventional drugs such as acetazolamide and methazolamide.…”

Antimicrobial Susceptibilities of a Worldwide Collection of Stenotrophomonas maltophilia Isolates Tested against Tigecycline and Agents Commonly Used for S. maltophilia Infections

“…Resistance to TMP/ SMX has been described and varies geographically, being shown by as many as 10% of isolates in Europe (7). In addition, allergic reactions to the combination TMP/SMX are common and can be severe, which further compromises its application (1). Clearly, therapeutic alternatives are needed to treat infections caused by S. maltophilia.…”