title: Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose.
abstract: Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. As a result of the increasing number of AIDS patients requiring therapy for Pneumocystis carinii pneumonia, high dose trimethoprim-sulfamethoxazole use had dramatically increased. A previously unreported and potentially lethal adverse reaction associated with high dose trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Subsequent to this work, a handful of cases noted the development of hyperkalemia with standard dose trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A prospective surveillance study of patients treated with standard dose trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium concentration associated with trimethoprim-sulfamethoxazole therapy. Patients with mild renal insufficiency were the only group at significant risk for more severe hyperkalemia. Hence, trimethoprim-sulfamethoxazole therapy can be complicated by hyperkalemia regardless of the dose employed.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8029, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Perazella
authors.forename: R L
authors.initials: RL
authors.lastname: Mahnensmith
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000367:Age Factors; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy; D011188:Potassium / Q000097:blood; D051437:Renal Insufficiency / Q000150:complications; D012307:Risk Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011188:Potassium