As UTI Drug Resistance Increases, Treatment Choices Critical

BY DAVID WILD

With recent data indicating that roughly 60% of antibiotics prescribed for urinary tract infections (UTIs) in the outpatient setting do not conform with clinical guidelines, and some UTI drug resistance rates markedly rising over the past several years, one expert urged pharmacists to carefully review the appropriateness of UTI prescriptions.

“With a lot of UTI infections comes a lot of prescribing of antibiotics, and sometimes our providers don’t do the greatest job,” said Ryan Moenster, PharmD, a clinical pharmacy specialist in infectious diseases, VA St. Louis Health Care System, during a virtual session at the 2021 American College of Clinical Pharmacy Virtual Annual Meeting.

The most recent data on the epidemiological burden of outpatient UTI treatment, as cited by Dr. Moenster, indicated there were 10.5 million office visits in 2007 for UTIs and 2 to 3 million emergency department visits in that year (Nat Rev Microbiol 2015;13[5]:269-284). Moreover, an analysis published in 2021 included 44.9 million female outpatient visits for uncomplicated UTIs from 2015 to 2019 and found that only 58.4% of prescriptions for these infections were concordant with treatment guidelines (Am J Obstet Gynecol 2021;225[3]:272.e1-272.e11).

“That’s not fantastic data,” said Dr. Moenster, also a professor of pharmacy practice at University of Health Sciences and Pharmacy in St. Louis.

Rise in E. coli Resistance

Coinciding with those prescribing patterns has been a rise in the prevalence of extended-spectrum cephalosporin-resistant urinary Escherichia coli, which increased from 14% to 19% of UTI isolates between 2013 and 2017, Dr. Moenster said (Clin Infect Dis 2020 Jul 23).

Room for improvement in UTI medical treatment prompted Dr. Moenster to urge attendees to review their “go-to stable” of outpatient antibiotics for this indication. “We all know about the unacceptably high rates of fluoroquinolone resistance and the limitations of using that as empiric antibiotic therapy, but less is discussed about trimethoprim-sulfamethoxazole [TMPSMX], nitrofurantoin and fosfomycin.”

Regarding TMP-SMX, a hospital study conducted in South Carolina revealed that roughly 20% of 351 patients with community-onset UTIs had Enterobacterales isolates with resistance to the agent (J Glob Antimicrob Resist 2020;21:218-222). Use of TMP-SMX in the prior 12 months was associated with a 2.58fold increased risk for Enterobacterales resistance to the drug, the researchers found (adjusted odds ratio, 2.58; 95% CI, 1.135.89; P=0.02).

Dr. Moenster said a randomized controlled trial shed light on the relative efficacy of nitrofurantoin and fosfomycin for the treatment of lower UTIs (JAMA 2018;319[17]:1781-1789). Specifically, those findings showed that 70% of patients who received a five-day course of nitrofurantoin and 58% of recipients of a single dose of fosfomycin experienced a clinical response at 28 days (P=0.004), while 74% and 63%, respectively, experienced a microbiological response at the same time (P=0.04).

“We can’t talk about these agents without talking about some of their notable limitations,” Dr. Moenster stressed. For example, some patients have an allergy to TMP-SMX, while there is a risk for renal dysfunction with the drug, he said. As for nitrofurantoin, one limitation is its “relatively high” creatinine clearance cutoff (<60 mL per minute), as indicated in the package insert, while nitrofurantoin and fosfomycin are not recommended for the management of pyelonephritis, Dr. Moenster noted. Furthermore, only the single-dose regimen of fosfomycin is FDA approved, “although clinicians do use alternative dosing recommendations for certain patients,” he said.

In addition to general considerations of antibiotic resistance and safety and efficacy, he urged attendees to consider their own local resistance rates when choosing an outpatient UTI treatment. For example, in 2020, the VA St. Louis Health Care System identified high levels of E. coli susceptibility to nitrofurantoin (92%) but lower levels of susceptibility to TM-SMX (72%).

“This is one of the best examples I can think about in terms of basing your decisions on your local antibiogram,” Dr. Moenster said. ■

Dr. Moenster reported financial relationships with Allergan-AbbVie and Shionogi.