Consider Risk Vs. Benefit of Fluoroquinolones

In the United States, fluoroquinolones are the third most commonly prescribed outpatient class of antibiotic with an estimated 115 prescriptions per 1000 persons annually.¹ In 2014, 31.5 million fluoroquinolones prescriptions were dispensed for visits related to skin, respiratory, genitourinary, and gastrointestinal conditions.¹ I

t is estimated that 25% of fluoroquinolones prescriptions were for medical conditions where antibiotics are not recommended or specifically fluoroquinolones are not recommended first-line therapy.¹ These conditions include acute bronchitis, acute sinusitis, and uncomplicated urinary tract infections. Inappropriate antibiotic use, specifically fluoroquinolone use, can put patients at increased risk of adverse reactions and unnecessary antibiotic resistance.

The FDA first added a boxed warning to fluoroquinolones in July 2008 regarding increase risk of tendon rupture and tendinitis.² Fast forward few years and in February 2011, another boxed warning regarding risk of worsening symptoms for those with myasthenia gravis was added. In August 2013, updates to the label required description of potential for irreversible peripheral neuropathy.²

Given the potential for irreversible impairment with use of fluoroquinolones, an FDA advisory committee concluded in November 2015 to restrict use of fluoroquinolones for treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, or uncomplicated urinary tract infection for patients who have no alternative treatment option.^1,2

A labeling change in July 2018 regarding class of fluoroquinolones, requires mental health adverse effects to be listed separately from other central nervous system side effects. In addition, blood glucose disturbances subsection for all systemic fluoroquinolones will be required to reflect risk of hypoglycemic coma.³

A safety announcement by the FDA regarding fluoroquinolones was released in December 2018 to warn about increased risk of ruptures or tears in the aortic artery. It noted that fluoroquinolones use should be limited in patients who have an aortic aneurysm or at risk for developing an aortic aneurysm related to vessel blockages, hypertension, genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients.⁴

Fluoroquinolones are concentration dependent and offer bactericidal activity by inhibiting DNA gyrase and topoisomerases, key enzymes for bacterial DNA replication.⁵ This class of antibiotic provides broad spectrum of activity with great efficacy covering many common pathogens including but not limited to haemophilus influenzae, streptococci species, legionella species, etc.

Older considered fluoroquinolones include ciprofloxacin, norfloxacin and ofloxacin with delafloxacin, Gemifloxacin, levofloxacin, and moxifloxacin considered newer.⁵ Many antibiotic classes are experiencing resistance with increased use, including fluoroquinolones.

It is important to realize the risk vs benefit of using all antibiotics for conditions. Antibiotic resistance is reality and changes in prescribing practices may need to occur to help limit building resistance.

Resistance to ciprofloxacin has been increasing with Escherichia coli in adult female population.¹ For conditions such as, but not limited to, acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, or uncomplicated urinary tract infection, risk versus benefit of using a fluoroquinolone should be considered. In doing so, the patient may benefit from reduced amounts of antibiotic resistance due to unnecessary antibiotic exposure.

As fluoroquinolone antibiotic class has an extensive safety profile, other antibiotic classes present their own safety restrictions. Appropriate antibiotic use will help limit antibiotic resistance and provide patients with optimal evidence based medicine care.

Resources

• Sarah Kabbani, Adam L Hersh, Daniel J Shapiro, Katherine E Fleming-Dutra, Andrew T Pavia, Lauri A Hicks, Opportunities to Improve Fluoroquinolone Prescribing in the United States for Adult Ambulatory Care Visits, Clinical Infectious Diseases, Volume 67, Issue 1, 1 July 2018, Pages 134—136, https://doi.org/10.1093/cid/ciy035
• FDA News Release. FDA updates warnings for fluoroquinolone antibiotics. U.S. Food and Drug Administration. 26 July 2016. Available at https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics
• FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions [news release]. Silver Spring, MD; July 10, 2018: FDA website. https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics-risks-mental-health-and-low-blood-sugar-adverse. Accessed July 2019.
• FDA In Brief: FDA warns that fluoroquinolone antibiotics can cause aortic aneurysm in certain patients [news release]. Silver Spring, MD; December 20, 2018: FDA website. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-warns-fluoroquinolone-antibiotics-can-cause-aortic-aneurysm-certain-patients. Accessed July 2019.
• Werth BJ. Fluoroquinolones. Merck Manual. https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/fluoroquinolones Reviewed July 2018. Accessed July 2019.