Since the early 1980s, the Food and Drug Administration (FDA) has been flooded with consumer complaints from patients treated with a popular class of antibiotics. According to reports, fluoroquinolones—a broad spectrum antibiotic that includes Cipro, Levaquin, Avelox, and others—have been associated with a host of devastating side effects, including joint and muscle pain, tendon rupture, aortic aneurysm, nerve damage, delirium, and even death.

Finally, in 2008, the FDA started requiring manufacturers to add a “black box label”—the organization's most stringent warning—to the packaging of fluoroquinolone antibiotics. At the time, the consumer rights organization Public Citizen counted over 400 reported cases of tendon rupture and over 300 cases of tendinitis in patients who used the drug.

But over a decade later, despite additional warnings from the FDA, fluoroquinolone antibiotics are still the third most commonly prescribed outpatient drug in the United States.

The reasons for the drugs’ popularity are complex, says Dr. Valerie Vaughn, assistant professor of medicine at the University of Michigan, who studies antibiotic overuse in hospital patients.

“In part, I think the information [about fluoroquinolone risks] hasn't really reached doctors everywhere,” Vaughn says. “I prescribe over 200 different kinds of medication, so keeping up with all the warnings is difficult to do.”

Another factor is cost, Vaughn says. Fluoroquinolone antibiotics are notoriously cheap—only a few cents for most doses, as opposed to newer antibiotic treatments that can cost upwards of $100 per dose. But most importantly, fluoroquinolone antibiotics are good at killing bacteria, and are equally effective through pill form or used intravenously, making them a popular choice in hospitals and outpatient settings. “Doctors have been using fluoroquinolones for decades and have seen them work,” Vaughn says. “What they worry about isn't a side effect but what would happen if they treat a patient with a narrow-spectrum antibiotic and the patient comes back with a resistant infection.”

Fluoroquinolones, which have been commercially available since 1978, are broad-spectrum antibiotics, useful for killing a wide variety of bacteria in a short amount of time. “Doctors like to prescribe broad-spectrum antibiotics because we don't always know what we're treating,” says Vaughn. “We don't want to miss anything.” But now, thanks to their popularity, doctors are now struggling with antibiotic resistance as well as the devastating patient side effects.

To fix the fluoroquinolone problem, hospitals and long-term care facilities are starting to steer doctors away from prescribing unnecessary antibiotics, as well as choosing more appropriate treatments when antibiotics are indicated. Many of these initiatives, called antibiotic stewardship programs, have made reducing fluoroquinolone antibiotics specifically a top priority.

“Fluoroquinolones are a really good example of where the benefits and rationale for antibiotic stewardship is well exemplified, both from the standpoint of wanting to reduce resistance, and also because these drugs have a lot of adverse side effects,” says Dr. David Hyun, senior officer of the antibiotic resistance project at the Pew Charitable Trusts.

Stewardship programs have been in hospitals for nearly two decades, says Hyun, but only recently have initiatives really started to take off: In 2016, the Joint Commission, a nonprofit agency that accredits hospitals, made antibiotic stewardship programs a part of their accreditation criteria. As a result, stewardship programs boomed, giving officials hope that the rate of patient complications and the pattern of drug resistance will be greatly diminished.

“We've seen good data that shows stewardship programs can reduce inappropriate or broad spectrum antibiotic use,” Hyun says. “These studies show that when antibiotic stewardship programs target specific antibiotics, it reduces adverse effects within the hospital system and it changes the resistance patterns within that facility toward the positive.”

But while stewardship programs can reduce antibiotic prescriptions, doctors are still lacking alternatives to fluoroquinolones when antibiotics are critically needed—and few pharmaceutical companies are stepping up to invest in antibiotic development. In 2018 alone, four major pharmaceutical companies announced an exit from antibiotic research, leaving only a select few invested in finding alternative treatments.

The reason, says Vaughn, is a lack of financial incentive. “If a drug company creates an antibiotic, the first thing that resistance programs do is not allow it to be prescribed. They want to save it for when it's necessary, and only for the sickest patients,” she says. “It's a great way to not breed resistance, but unfortunately it's a bad way for the drug companies to make money.”

The good news, Hyun says, is that most hospitals in 2019 have antibiotic stewardship programs, and data has shown that they work. But the challenge to decreasing fluoroquinolone use remains thorny: Pharmaceutical companies need to be incentivized to develop alternatives on one end, even as doctors need to be dissuaded from prescribing them on the other, particularly in outpatient centers where stewardship programs are rare.

“This is where patients can start to advocate for themselves,” Vaughn says. “I know just from speaking to doctors myself, a lot of them were shocked when I brought up [fluoroquinolone risks]—it takes a long time for them to be aware. It might be easier for patients to check the warnings on the label, and tell the doctor that they're concerned.”