UF study: FDA label change requirement helped reduced antibiotic misuse

The U.S. Food and Drug Administration in 2016 took action to reduce the overuse of fluoroquinolones, a type of antibiotic associated with serious side effects. That step helped cut the use of these antibiotics for uncomplicated urinary tract infections, or UTIs, by more than half, according to a University of Florida study published in JAMA’s Internal Medicine.

Almut Winterstein Headshot_web
Almut Winterstein, Ph.D., a professor and the Dr. Robert and Barbara Crisafi Chair of Pharmaceutical Outcomes and Policy

Fluoroquinolones, the most common class of quinolones, became one of the world’s most widely used antibiotics in the 1990s, but concerns about serious side effects emerged in the 2000s. The FDA warned about the risk of tendon ruptures and severe nerve damage, but the drug’s use for uncomplicated infections, for which there are safer alternatives, continued.

Almut Winterstein, Ph.D., a professor and the Dr. Robert and Barbara Crisafi Chair of Pharmaceutical Outcomes and Policy in the UF College of Pharmacy and director of the UF Center for Drug Evaluation and Safety, participated in a 2015 FDA advisory committee meeting that re-evaluated the risk-benefit of quinolones. Instead of banning the drug, which proves useful in cases of severe infection and antibiotic resistance, the committee supported the removal of labeling indications for uncomplicated UTIs, acute sinusitis and acute exacerbations of chronic obstructive pulmonary disease, or COPD.

In the recent study, Winterstein and her research team evaluated the effect of this decision. “The effect of regulatory action on prescribing behavior can vary tremendously,” she said. “For example, previously issued box warnings to alert prescribers about the serious side effects of quinolones had limited effect. Our study aimed to find out whether the FDA’s action resulted in a shift in prescribing practice, and it did.”

In 2015, quinolones were used to treat 41.6% of antibiotic-treated UTIs. When the relabeling policy went into effect in 2016, the number immediately dropped by 7.2% and ultimately decreased to 19.2% by the end of 2018. Prevalence of quinolone treatment for sinusitis dropped from 8.3% to 2.9% and 31.9% to 14.6% for COPD.

Treatment mostly shifted to recommended antibiotics: nitrofurantoin for UTIs, amoxicillin for sinusitis and macrolides for COPD. However, use of non-recommended antibiotics like tetracycline for COPD also increased.

“Removal of indications for sinusitis and acute exacerbations of COPD showed smaller but recognizable decreases, demonstrating that the FDA action succeeded across all examined medical specialties,” Winterstein said. While she is pleased with the results, Winterstein noted room for improvement in further reducing the number of UTIs treated with quinolones.

In addition to Winterstein, researchers from the UF College of Pharmacy included assistant professor Juan Hincapie-Castillo, Pharm.D., Ph.D., and graduate student Phuong T. Tran, M.P.H.

Patrick J. Antonelli, M.D., the George T. Singleton Professor and chair of the UF College of Medicine’s department of otolaryngology, co-led the study with Winterstein.