Fluoroquinolones Not First Line: FDA Advisory Reinforces Standard Practice in Ambulatory Care

Paul G. Auwaerter, MD

June 02, 2016

This is Paul Auwaerter, with Medscape Infectious Diseases and the Johns Hopkins University School of Medicine. The US Food and Drug Administration (FDA) recently announced[1] that it will upgrade its package warnings on fluoroquinolones to include instructions that they should not be used for routine respiratory tract infections or uncomplicated urinary tract infections unless there is no suitable alternative agent.
Why these warnings are being reinforced at this point rests on several foundational issues. When I was a medical student the late 1980s, fluoroquinolones were embraced as "wonder drugs." We had ciprofloxacin, which offered oral treatment forPseudomonas aeruginosa and was thought to be effective forStaphylococcus aureus, even in deep bone infections. Over time, these drugs have been widely embraced with new additions, such as levofloxacin and moxifloxacin. But a number of other drugs (eg, trovafloxacin, lomefloxacin, and others) have fallen to the wayside, deservedly, because of serious toxicities.
It seems to be true, however, that the fluoroquinolones remain broadly prescribed both by primary care practitioners and in hospital settings and skilled nursing facilities. Studies looking at the use of fluoroquinolones in ambulatory settings for uncomplicated urinary tract and respiratory infections show that over the past few years there has been little diminishment in the use of fluoroquinolones.[2] Because of their wide use and adoption, we are experiencing problems such as pathogen resistance. The fluoroquinolones are no longer recommended for gonorrhea because of widespread resistance. They are no longer recommended for routine first-line treatment of uncomplicated cystitis because of increased resistance of Escherichia coli to this class of drugs.[3]
Another issue is that, over the years, the remaining fluoroquinolones have been associated with adverse effects, including increased risk for Clostridium difficile infection (compared with many other antibiotics), tendinopathy, arthropathy, QT prolongation, retinal issues, and central and peripheral nervous system toxicities.[4] These adverse effects have been reported, although perhaps not thoroughly vetted through careful analysis. However, the FDA now feels that owing to potential irreversible or permanent side effects, these drugs should not be used for first-line treatment.
Many infectious diseases practitioners, out of concern about antibiotic resistance, have been broadly beating the drum for many years that these drugs should not be used in office settings and practices for mundane and pedestrian upper respiratory tract infections such as bronchitis or sinusitis, or for urinary tract infections.
So why are these drugs still so widely used? There is a perception (and perhaps a reality) that the fluoroquinolones are still quite safe. I have never seen a case of peripheral neuropathy although I have certainly seen C difficile infection, tendinopathy, and arthropathy. Obviously as drugs are getting more attention and being looked at in terms of adverse effects, it does not make sense to prescribe these drugs, which have quite broad-spectrum activity, to treat conditions that could be treated with a narrower-spectrum and more targeted drug.
The FDA is upgrading its warnings about these drugs in spite of what practitioners are seeing. The diminished use of these broad-spectrum antibiotics for certain conditions is a worthy goal and probably will benefit patient care, either by avoiding the use of antibiotics altogether if appropriate, or targeting antibiotics, as recommended in guidance on sinusitis, bronchitis, exacerbations of bronchitis, and urinary tract infections..
References
1) US Food and Drug Administration. Fluoroquinolone antibacterial drugs. Drug Safety Communication - FDA advises restricting use for certain uncomplicated infections. Posted May 12, 2016.http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm500665.htmAccessed May 15, 2016.
2) Lee GC, Reveles KR, Attridge RT, et al. Outpatient antibiotic prescribing in the United States: 2000 to 2010. BMC Med. 2014;12:96
3) .Kim M, Lloyd A, Condren M, Miller MJ. Beyond antibiotic selection: concordance with the IDSA guidelines for uncomplicated urinary tract infections. Infection. 2015;43:89-94. Abstract
4) Douros A, Grabowski K, Stahlmann R. Safety issues and drug-drug interactions with commonly used quinolones. Expert Opin Drug Metab Toxicol. 2015;11:25-39. Abstract