Influence of concomitant prednisolone on trimethoprim-associated hyperkalaemia

Trimethoprim-sulfamethoxazole may cause hyperkalaemia by the amiloride-like effect of trimethoprim on sodium channels in the distal nephron. Hyperkalaemia usually occurs after 7-10 days and has been reported in 20%-50% of patients receiving trimethoprim-sulfamethoxazole. Patients with Pneumocystis jiroveci pneumonia and severe hypoxaemia benefit from the use of prednisolone as an adjuvant to trimethoprim-sulfamethoxazole. The addition of prednisolone may lower the incidence of trimethoprim-related hyperkalaemia due, in part, to its mineralocorticoid activity. We studied the effect of concomitant prednisolone on trimethoprim-related hyperkalaemia.

Thirty patients qualified for inclusion and were reviewed. Patients were divided into two groups: one group received trimethoprim-sulfamethoxazole plus prednisolone (18 patients); and the other group received trimethoprim-sulfamethoxazole alone (12 patients).

The two groups were comparable at baseline, except for the severity of the P. jiroveci pneumonia. Hyperkalaemia developed in seven patients: all in the prednisolone and trimethoprim-sulfamethoxazole group. The greater incidence of hyperkalaemia in this group is surprising and was counter to our expectation.

Although it is possible that there is an unexplained interaction between trimethoprim and prednisolone, we postulate that our observation is a result of the catabolic effect of prednisolone. The patients treated with trimethoprim-sulfamethoxazole plus prednisolone appear to be more likely to develop hyperkalaemia than patients treated with trimethoprim-sulfamethoxazole alone.