Can trimethoprim and sulphamethoxazole (Bactrim forte) give rise to increased creatinine and urea l

Fråga: Can trimethoprim and sulphamethoxazole (Bactrim forte) give rise to increased creatinine and urea levels in serum? A man with prostate hypertrophy has had surgery twice, the last operation being done 11 October. He was treated with Bactrim forte (160 mg trimetoprim, 800 mg sulphamethoxazole) October 16-22 with the dose of 2 tablets a day because of a urinary tract infection. His laboratory values of creatinine in serum were until October 11, 122-147 umol/l but increased after that as follows: October 18, 200 umol/l; October 31, 235 umol/l; November 2, 243 umol/l; November 6, 212 umol/l. Urea in serum was similarly increased from 6.0 mmol/l (October 11), to 15.7 mmol/l (November 3) (normal value 3.0-7.5 mmol/l).

Sammanfattning: Increased levels of serum creatinine have been reported during treatment with trimethoprim-sulphamethoxazole combination, as trimethoprim interferes with the tubular secretion of creatinine. Occasionally the combination may also have a nephrotoxic effect.

Svar: At dosages used in the treatment and prophylaxis of urinary tract infections trimethoprim has generally been well tolerated (1).

Increased serum levels of creatinine while using the trimethoprim-sulphamethoxazole combination have been reported to the Swedish Adverse Drug Reactions Advisory Committee in 27 cases with probable connection to the drug treatment (2).

Trimethoprim interferes with the tubular secretion of creatinine, causing an increased serum creatinine level and a lowered creatinine clearance without affecting renal function or true glomerular filtration rate (3-5).

The trimethoprim-sulphamethoxazole combination may also occasionally exert a direct nephrotoxic effect, mainly in patients receiving a relative overdosage due to pre-existing renal impairment. A small increase in serum creatinine concentration is not necessarily indicative of a decreased glomerular filtration rate in patients without renal insufficiency at the beginning of this treatment (4).

In the present case, the simultaneous increase in creatinine and urea speaks in favour of a decreased renal function. Whether this is causally related to the trimethoprim-sulphamethoxasole treatment or to other reasons such as the operation, is difficult to judge.