Which drugs raise risk of urinary tract infections?

Some medications may directly cause the occurrence of urinary tract infections (UTIs), and a recent study presented at the 37th Annual European Association of Urology Congress (EAU 2022) has identified six drugs that appear to contribute to “significant reporting levels” for infections.

Of these medications, tacrolimus and natalizumab have been found to account for the greatest number of reports and have produced the strongest signal of disproportionate reporting.

“Prescribers should inform those treated about the risk of infections,” according to the researchers, led by Dr C De Nunzio from the Sant'Andrea Hospital, Sapienza University of Rome in Italy.

In the study, De Nunzio and colleagues identified which drugs were associated with most UTI reports and compared their potential to cause UTIs through a disproportionality analysis within the high-risk list of medications. Only drugs with a minimum of 200 UTI reports were included in the analysis.

The researchers explored the FDA Adverse Event Reporting System databases to name those drugs that had the most UTI reports until June 2021. They also recorded the number of reports for these medications. Finally, the Proportional Reported Ratios (PRRs) were used for all the drugs.

Of the 6,152 UTI reports identified, 1,798 (30 percent) were associated with six medications that had a minimum of 200 reports each, namely tacrolimus, natalizumab, interferon beta-1a, prednisone, adalimumab, and mycophenolate mofetil. [EAU 2022, abstract A0108]

Overall, 3,178 were E. coli infections (3,038 or 96 percent were deemed serious), 842 were enterococcal (824 or 98 percent were serious), 441 were pseudomonal (427 or 97 percent were serious), and 332 were staphylococcal (311 or 94 percent were serious).

Of these drugs, tacrolimus mainly contributed to enterococcal (70 events, 8 percent) and E. coli infections (224 events, 7 percent). Another medication, natalizumab, significantly correlated with pseudomonal infections (46 events, 10 percent). Treatment with interferon beta-1a, on the other hand, sometimes resulted in staphylococcal infections (30 events, 10 percent).

Within this group of high-risk drugs, tacrolimus delivered the greatest risk of UTI as compared with prednisone (PRR, 1.48, 95 percent confidence interval [CI], 1.29‒1.71; p<0.01) and adalimumab (PRR, 1.71, 95 percent CI, 1.48‒1.99; p<0.01).

Database analysis revealed that natalizumab had the greatest number of UTI reports, with a total of 1,433 events. Escherichia UTIs were mostly reported with tacrolimus and mycophenolate mofetil, with 78 events each. Most reports for enterococcal UTIs were for natalizumab (18 events), as well as those for pseudomonal and staphylococcal UTIs, with 22 and 11 events, respectively.

In a separate study that was not part of EAU 2022, opioids were the most used medication in the 6 months prior to UTI incidence among patients with diabetes and/or heart failure. In contrast, SGLT2 inhibitors were not commonly initiated in the same time period prior to UTI occurrence. [Curr Drug Saf 2022;doi:10.2174/1574886317666220414132328]