Disclosures: Butler reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
July 28, 2021
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Among first-line UTI agents, TMP/SMX associated with higher risk for adverse drug events

Disclosures: Butler reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Between two first-line agents for uncomplicated UTIs, trimethoprim-sulfamethoxazole was associated with a higher risk for several adverse drug events compared with nitrofurantoin, researchers reported in Clinical Infectious Diseases.

Non-first-line agents also were associated with a higher risk for adverse drug events compared with nitrofurantoin, in addition to potential microbiome-related adverse events, including diarrhea, according to Anne M. Butler, PhD, assistant professor of medicine in the division of infectious diseases at Washington University, and colleagues.

Anne M. Butler

“Urinary tract infection is among the most common indications for antibiotics, but we have limited understanding of the relative benefits and harms of different antibiotic regimens prescribed to treat UTI,” Butler told Healio. “Existing evidence is predominantly from randomized clinical trials, which are limited by small sample size, short follow-up, heterogeneous study populations, and wide variation in duration of antibiotic prescriptions. Additionally, randomized clinical trials only compare antibiotic agents in limited combinations, for example, ciprofloxacin vs. amoxicillin-clavulanate.”

According to Butler, for this reason, there is a wide variation in prescribing practices for UTIs, which led to the current study comparing the risk for adverse events associated with commonly used oral antibiotic regimens for the outpatient treatment of uncomplicated UTIs among young women in the United States.

Butler and colleagues used a commercial insurance database to identify more than 1.1 million otherwise healthy, nonpregnant women aged 18 to 44 years with uncomplicated UTI who initiated an oral antibiotic with activity against common uropathogens between July 1, 2006, and Sept. 30, 2015.

Compared with nitrofurantoin, trimethoprim-sulfamethoxazole (TMP/SMX) was associated with a higher risk for hypersensitivity reaction (HR = 2.62; 95% CI, 2.30-2.98), acute renal failure (HR = 2.56; 95% CI, 1.55-4.25), skin rash (HR = 2.42; 95% CI, 2.13-2.75), urticaria (HR = 1.37; 95% CI, 1.19-1.57), abdominal pain (HR = 1.14; 95% CI, 1.09-1.19) and nausea and/or vomiting (HR = 1.18; 95% CI, 1.10-1.28), Butler and colleagues reported.

Additionally, they found that fluoroquinolones and beta-lactams — non-first-line agents — were associated with a higher risk for several adverse drug events and potential microbiome-related adverse events, including non-Clostridioides difficile diarrhea, C. difficile infection, vaginitis and/or vulvovaginal candidiasis and pneumonia.

Butler and colleagues also noted that — consistent with previous evidence — the duration of treatment modified the risk for potential microbiome-related adverse events, “likely due to antibiotic-induced disruption of the microbiota.”

Specifically, treating patients with durations of TMP/SMX and fluoroquinolones that were longer than is recommended by guidelines resulted in a higher 30-day risk for non-C. difficile diarrhea, and inappropriately long durations of TMP/SMX, fluroquinolones and broad-spectrum beta-lactams were all associated with a higher 90-day risk for pneumonia.

“Addressing the threat of antimicrobial resistance requires a better understanding of the consequences of antibiotic prescribing, including adverse effects, which are commonly managed by drug discontinuation and subsequent prescriptions with alternative agents,” Butler said.