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, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the aOR was 0.90 (95% CI 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (95% CI 0.80 to 1.57).
A population based nested case-control study 2 in Canada (years 1994 - 2012) assessed whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death in the elderly (aged 66 years or older). Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes. Of 39879 sudden deaths, 1027 occurred within 7 days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, an increased risk of sudden death was associated with co-trimoxazole (aOR 1.38, 95% CI 1.09 to 1.76) and with ciprofloxacin (aOR 1.29, 95% CI 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin. The risk with co-trimoxazole was marginally higher at 14 days (aOR 1.54, 95% CI 1.29 to 1.84). This corresponds to approximately 3 sudden deaths within 14 days per 1000 co-trimoxazole prescriptions.
Another population based nested case-control study 3 in the elderly (aged 66 years or older), in Canada, assessed whether the prescription of trimethoprim-sulfamethoxazole with spironolactone is associated with sudden death, a consequence of severe hyperkalemia. Of the 11 968 patients who died of sudden death while receiving spironolactone, 328 were identified with death occurring within 14 days after antibiotic exposure. Compared with amoxicillin, an increased risk of sudden death was documented with trimethoprim-sulfamethoxazole (aOR 2.46, 95% CI 1.55 to 3.90), with ciprofloxacin (aOR 1.55, 95% CI 1.02 to 2.38), and with nitrofurantoin (aOR 1.70, 95% CI 1.03 to 2.79), although the risk with nitrofurantoin was not apparent in a sensitivity analysis.
Date of latest search: 2019-06-24
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