Clinical
Pharmacy Practice News • February 2022
3
Infectious Disease
As UTI Drug Resistance Increases, Treatment Choices Critical By David Wild
W
ith 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, one expert urged pharmacists to carefully review the appropriateness of UTI prescriptions. “With a lot of UTI infections comes a lot of antibiotic prescribing, and sometimes our providers don’t do the greatest job [with stewardship],” said Ryan Moenster, PharmD, a clinical pharmacy specialist in infectious diseases, VA St. Louis Health Care System, during the 2021 annual meeting of the American College of Clinical Pharmacy (ACCP), held virtually. One recent analysis 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 fanstastic data,” Dr. Moenster said. Coinciding with those prescribing patterns has been a rise in the prevalence of extended-spectrum cephalosporinresistant urinary Escherichia coli, which increased from 14% to 19% of UTI isolates between 2013 and 2017, he noted (Clin Infect Dis 2021;73[11]:e4552-e4559).
Dr. Moenster urged 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 trimethoprimsulfamethoxazole [TMP-SMX], nitrofurantoin and fosfomycin,” he said. 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 TMPSMX in the prior 12 months was associated with a 2.58-fold increased risk for Enterobacterales resistance to the drug, the researchers found (P=0.02). A randomized controlled trial shed light on the efficacy of nitrofurantoin and fosfomycin for the treatment of lower UTIs (JAMA 2018;319[17]:1781-1789). Specifically, 70% of patients who received a five-day course of nitrofurantoin and 58% given a single dose of fosfomycin experienced a clinical response at 28 days (P=0.004), while 74% and 63%, respectively, experienced a microbiological response (P=0.04). However, “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
14% ➡ 19% The increase in prevalence of extended-spectrum cephalosporin-resistant urinary Escherichia coli between 2013 and 2017 Source: Clin Infect Dis 2021;73(11):e4552-e4559.
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. Additionally, nitrofurantoin and fosfomycin are not recommended for 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. Dr. Moenster also 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 TMP-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.
EDITORIAL BOARD ADMINISTRATION Robert Adamson, PharmD, Livingston, NJ
Lisa Dumkow, PharmD, the antimicrobial stewardship program director at Mercy Health Saint Mary’s, in Grand Rapids, Mich., echoed the importance of selecting outpatient UTI treatments based on local antibiograms. “We try to avoid treating asymptomatic bacteriuria and stress the importance of using nitrofurantoin as first-line therapy whenever possible, limiting the use of cephalosporin agents to patients who do not qualify for nitrofurantoin,” she said. “It’s a delicate balance with our firstgeneration cephalosporins, because while their empiric chance of targeting our urinary pathogens is high—based on our local antibiogram—there is also a big risk of increasing ESBL [extended-spectrum beta-lactamase] rates with overuse.” Dr. Dumkow reported no relevant financial disclosures. Dr. Moenster reported financial relationships with Allergan-AbbVie and Shionogi.
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