Beware Overuse of Fluoroquinolones

Fluoroquinolone antibiotics (Ciprofloxacin, Levofloxacin, Moxifloxacin, among others) are an important class of antibiotics that are used in a variety of settings. Ciprofloxacin remains one of the primary treatment options for cystitis. It is used routinely for inpatient treatment of pneumonia and many still consider it part of the first-line treatment for diverticulitis. But in the last few years, questions about its safety profile have led to growing concerns. The quinolones are associated with tendonitis and potential Achilles tendon rupture. Unfortunately, its potential for significant adverse effects don't stop there.

In 2008, the FDA added its first black box warning to fluoroquinolones, indicating the risk for tendon injuries. Despite this, in 2010, Levofloxacin was the best-selling antibiotic in the United States, with sales of over $1.5 billion. But by 2012, it was the subject of more than 3,000 lawsuits from patients who had suffered severe reactions after taking the medication.

The first successful lawsuit was a case involving an 82 year-old male who was prescribed Levofloxacin and a corticosteroid for an upper respiratory infection. He suffered bilateral Achilles tendon ruptures and was ultimately awarded $1.8 million. In a large population-based case control analysis, patients treated with fluoroquinolones had a 4.1 fold increase in risk of Achilles tendon rupture and a 46 times higher risk if there was concomitant use of corticosteroids. Risk factors include elderly males (over the age of 60), patients with chronic renal disease, and those taking corticosteroids. Symptoms of tendinopathy typically begin about six days after the onset of treatment, but the risk of tendon rupture persists for up to 90 days. Over 50% of patients experience symptoms that began after their treatment was completed.

A 2012 case-control study published in JAMA concluded that oral fluoroquinolones were associated with an increased risk of developing retinal detachment. Current users of oral fluoroquinolones were nearly 5 times more likely to be diagnosed with retinal detachment than non-users, although the risk did not translate to patients who had already completed treatment. Another case-control study attempted to quantify the risk of acute kidney injury. Researchers found a two-fold increase in the risk of acute kidney injury in patients currently taking fluoroquinolones.

A recent study published in JAMA Surg found that patients who received fluoroquinolones had a higher risk for aneurysms, ruptures, or dissections than those who did not receive the antibiotics. The study showed that normal, unstressed mice who took the antibiotic did not show significant negative effects on the aorta. Mice with moderately stressed aortas developed aortic aneurysm and dissection 79% of the time, compared to 45% of those moderately stressed mice who did not receive the antibiotic. This led the FDA to issue the following statement in December 2018: "A U.S. Food and Drug Administration (FDA) review found that fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the main aftery of the body, called the aorta....Fluoroquinolones should not be used in patients at increased risk unless there are no other treatment options available. People at increased risk include those with...high blood pressure, certain genetic disorders that involve blood vessel changes, and the elderly..."

How can one balance providing optimal care for the patient with the significant potential risks of this class of antibiotics? Instead of being reserved for serious, life-threatening bacterial infections, these antibiotics are often used for bronchitis, sinusitis, earaches, and other conditions that simply don't need them. A 2018 study in Clinical Infectious Diseases found that approximately 5% of adult ambulatory fluoroquinolone prescriptions were for conditions that did not require antibiotics, and nearly 20% were for conditions where fluoroquinolones are not recommended first-line therapy. There are very few conditions for which fluoroquinolones are still considered first-line treatment: anthrax and plague. In the absence of these conditions, strongly consider an alternate class of antibiotic. For instance, for years, the go-to outpatient treatment for patients diagnosed with diverticulitis has been ten days of Ciprofloxacin and Metronidazole. Many providers don't realize that Amoxicillin-clavulanate 875mg every eight hours (or one gram every 12 hours) is an acceptable alternative. Trimethoprim-sulfamethoxazole (1 double-strength tablet every twelve hours) can also replace Ciprofloxacin and be used in concert with Metronidazole. A 2017 study questioned the use of antibiotics altogether in a first episode of CT-proven uncomplicated acute diverticulitis. Approximately 260 patients were randomized to observation and 260 to antibiotics: there were no significant differences between the groups for complications, ongoing diverticulitis, recurrence, sigmoid resecetion, readmission, or mortality. Antibiotics remain the standard of care and should be prescribed, but this study does provide some food for thought.

Think twice before prescribing fluoroquinolones and if there is an alternate choice, strongly consider it. If there is no other option, have a candid conversation with your patient and discuss the risks and benefits of each choice.

Dr. Sajid Khan,MD, is a board-certified Emergency Medicine physician with over 10 years of experience working in a variety of settings from inner-city level 1 trauma centers serving 100,000 patients per year to 3-bed rural Eds. A published author, Dr. Khan has written a number of books including, The Ultimate Emergency Medicine Guide, a comprehensive review book that is the highest-rated and most up-to-date text for Emergency Medicine physicians preparing to certify.

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