TRIMETHOPRIM INCREASE ADVERSE EVENTS IN ELDERLY

Trimethoprim use is associated with increased adverse outcomes in older patients with urinary tract infection (UTI), compared with other antibiotics used to treat UTIs, according to a retrospective study.

"The results weren't a complete surprise, as we were building on previous research,” said Dr. Laurie A. Tomlinson from London School of Hygiene and Tropical Medicine in the UK.

“However, we were interested to see that the risk of acute kidney injury (AKI) and high potassium levels was increased across the whole population of older patients, not just those taking renin-angiotensin system (RAS) blockers and spironolactone,” she told Reuters Health by email.

The use of co-trimoxazole, which contains trimethoprim and sulfamethoxazole, has been associated with an increased risk of sudden death in patients taking RAS blockers, and both individual antibiotics have been associated with hyperkalemia, which can cause fatal cardiac arrhythmias.

Dr. Tomlinson's team used data from the UK Clinical Practice Research Datalink and Hospital Episode Statistics database to investigate the association between trimethoprim and AKI, hyperkalemia and sudden death in patients age 65 or over being treated for UTI, compared with the same outcomes in similar patients taking amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin.

In the 14 days after antibiotic initiation for a UTI, 0.4% of trimethoprim patients developed AKI, 0.2% developed hyperkalemia, and 0.5% died, the researchers report in The BMJ, online February 9.

Patients treated with trimethoprim had 72% higher adjusted odds of AKI and 2.27-fold higher odds of hyperkalemia, compared with the other antibiotics (both risk increases were significant).

Ciprofloxacin was also associated with a 48% increased odds of AKI, but no increased risk of hyperkalemia.

The odds of death within 14 days of antibiotic initiation for UTI did not differ significantly among these antibiotics.

Odds ratios for these outcomes differed only minimally after sensitivity analyses or after adjustment for lifestyle factors, ethnicity and socioeconomic status.

“Of course we want people to remember the risk of AKI and high potassium levels after trimethoprim use and to think about the recommendations for monitoring already suggested in the drug information,” Dr. Tomlinson said. “However, what we would really like to get across is that the actual risk of patients developing these outcomes is very low for the general population, so trimethoprim may still be a valuable antibiotic.”

“It is only in patients already at high risk of AKI and high potassium levels that the actual number of affected people increases substantially after trimethoprim - patients such as those with chronic kidney disease, those taking RAS blockers or spironolactone (especially both groups in combination), or people with high baseline potassium,” she said.