Antibiotic treatment with oral trimethoprim-sulfamethoxazole rather than amoxicillin is associated with a more than 3-fold higher risk of a hospital encounter with hyperkalemia, especially among patients with nondialysis-dependent chronic kidney disease.

The finding is from a population-based cohort study of adults aged 66 years and older in Ontario, Canada. Investigators compared 58,999 matched pairs of outpatients initiating oral trimethoprim-sulfamethoxazole vs oral amoxicillin from 2008 to 2020. Median prescription duration for both antibiotics was 7 days.

The primary outcome, an emergency department visit or hospital admission with hyperkalemia (defined as serum potassium level of 5.5 mmol/L or greater) within 14 days, occurred in a higher proportion of patients treated with trimethoprim-sulfamethoxazole vs amoxicillin: 0.46% vs 0.14%, Y. Joseph Hwang, MD, MSc, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues reported in Nephrology Dialysis Transplantation. Trimethoprim-sulfamethoxazole recipients had a significant 3.4-fold increased relative risk of a hospital encounter with hyperkalemia.

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In trimethoprim-sulfamethoxazole vs amoxicillin recipients, the absolute difference in hyperkalemia risk increased significantly with decreasing estimated glomerular filtration rate (eGFR; in mL/min/1.73 m2), from 0.12% among those with an eGFR of 60 or higher to 0.42%, 0.85%, and 1.45% among those with an eGFR of 45-59, 30-44, and less than 30, respectively. The absolute risk of hyperkalemia was higher in men than women.

Among trimethoprim-sulfamethoxazole recipients with an eGFR less than 30, 62.5% received a daily dose that was higher than appropriate. According to the investigators, an appropriate daily dose of trimethoprim-sulfamethoxazole is 160 mg or less for patients with an eGFR of 15-29 and 80 mg or less for patients with an eGFR less than 15 not on dialysis.

The investigators also found that the risk of a hospital encounter with acute kidney injury (AKI) was 3.2-fold higher among the trimethoprim-sulfamethoxazole than amoxicillin group. The risk of all-cause hospitalization was 1.4-fold higher for the trimethoprim-sulfamethoxazole group.

Dr Hwang’s team recommended that clinicians consider alternate, non-renally cleared antibiotics guided when treating patients with chronic kidney disease or prescribe an appropriate dose of trimethoprim-sulfamethoxazole with monitoring.

Trimethoprim-sulfamethoxazole is mostly excreted through the kidneys, and it can cause hyperkalemia by reducing potassium excretion. Amoxicillin is not associated with hyperkalemia.


Hwang YJ, Muanda FT, McArthur E, et al. Trimethoprim-sulfamethoxazole and the risk of a hospital encounter with hyperkalemia: a matched population-based cohort study. Nephrol Dial Transplant. Published online October 7, 2022. doi:10.1093/ndt/gfac282