• M A Perazella and R L Mahnensmith.
• Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8029, USA.
• Clin Nephrol. 1996 Sep 1;46(3):187-92.

AbstractTrimethoprim-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.

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