Comment: The level of evidence is upgraded by large magnitude of effect.
A cohort study 1 assessed whether trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the elderly. UK electronic primary care records, Clinical Practice Research Datalink and the Hospital Episode Statistics database were used (years 1997 - 2015). Among a cohort of 1 191 905 patients aged 65 and over (80% women), 178 238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422 514 episodes of UTIs. Used antibiotics were trimethoprim (59%), amoxicillin (5%), cefalexin (15%), ciprofloxacin (5%), or nitrofurantoin (15%). The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio [aOR] 1.72, 95% CI 1.31 to 2.24) and ciprofloxacin (1.48, 95% CI 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (aOR 2.27, 95% CI 1.49 to 3.45) compared with amoxicillin. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury.
A population based nested case-control study 2 for 14 years in Canada assessed the risk of hyperkalemia-associated hospitalization in elderly patients (66 years or older) who were being treated with trimethoprim-sulfamethoxazole along with either an angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Case patients were those with a hyperkalemia-associated hospitalization within 14 days of receiving a prescription for trimethoprim-sulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. For each case, up to 4 controls ere identified from the same cohort matched for age, sex, chronic renal disease, and diabetes. 4148 admissions involving hyperkalemia were identified , 371 of which occurred within 14 days of antibiotic exposure. Compared with amoxicillin, the use of trimethoprim-sulfamethoxazole was associated with a nearly 7-fold increased risk of hyperkalemia-associated hospitalization (aOR 6.7; 95% CI 4.5 to 10.0). No such risk was found with the use of comparator antibiotics.
Another nested case-control study 3 for 18 years in Canada assessed the risk of hyperkalemia-associated hospitalization in elderly patients (66 years or older) who were being treated with trimethoprim-sulfamethoxazole along with spironolactone. 6903 hospital admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with an increase in the risk of admission to hospital for hyperkalaemia (aOR 12.4, 95% CI 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (aOR 2.4, 95% CI 1.3 to 4.6), but no such risk was found with norfloxacin (aOR 1.6, 95% CI 0.8 to 3.4).
Date of latest search: 2019-06-24
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