Fluoroquinolone stewardship may end at hospital door

A study today by researchers in Michigan found that while programs to limit fluoroquinolone prescribing are reducing use of the antibiotics among hospital inpatients, many patients are still being discharged with fluoroquinolone prescriptions.

The study, published in Clinical Infectious Diseases, evaluated fluoroquinolone prescribing in patients with pneumonia and urinary tract infection (UTI) at 48 Michigan hospitals participating in a collaborative quality initiative to improve antibiotic prescribing.

Nearly a third of these hospitals had stewardship programs that specifically targeted fluoroquinolone use among inpatients. The results showed that fluoroquinolone stewardship was associated with fewer inpatients receiving the drugs and fewer fluoroquinolone treatment days.

Those same hospitals, however, were more than twice as likely to send patients home with a new fluoroquinolone prescription, even if they had been treated with another agent in the hospital.

"When hospitals tried to reduce fluoroquinolone prescribing, they were actually successful," lead study author Valerie Vaughn, MD, a hospitalist at the University of Michigan's academic medical center, told CIDRAP News. "But what we found really interesting is that in these hospitals, what appeared to happen is that some of this fluoroquinolone prescribing shifted to after patients left the hospital."

Although the study focused on fluoroquinolones, Vaughn said the findings highlight a potential blind spot for all hospital stewardship programs, which target the antibiotics that are used in the hospital but don't track the antibiotics patients consume once they leave.

Benefits, drawbacks of fluoroquinolones

Fluoroquinolones, Vaughn explained, are "really good drugs" that cover a broad spectrum of pathogens and have been shown to be very effective at improving infectious disease outcomes. They're also cheap and easy for patients to take. For many years, fluoroquinolones like ciprofloxacin, levofloxacin, and moxifloxacin have been a mainstay of the antibiotic toolbox and used for a variety of bacterial infections.

But growing concerns about the promotion of antibiotic resistance and increased risk of Clostridioides difficile infection, along with a string of recent US Food and Drug Administration (FDA) warnings about adverse effects—including tendon ruptures, aortic dissection, and mental health issues—have resulted in efforts to reduce fluoroquinolone use in lieu of other agents.

The 14 hospitals in the study that targeted fluoroquinolone prescribing among inpatients used one of two strongly recommended stewardship interventions—pre-prescription approval and/or prospective audit and feedback, in which prescribers received feedback from peers after prescribing—to get providers to choose other options for patients who have pneumonia or UTIs, two of the conditions most frequently treated with antibiotics. "We wanted to see if these stewardship initiatives to reduce fluoroquinolone prescribing were actually successful," Vaughn said.

To determine that, Vaughn and her colleagues looked at detailed prescribing data on 11,748 hospital patients (6,820 with pneumonia, 4,928 with positive urine culture) and the results of a hospital survey on stewardship interventions, then compared fluoroquinolone exposure at the hospitals with fluoroquinolone stewardship programs to those without. The primary outcomes of interest were the proportion of patients prescribed a fluoroquinolone (as an inpatient or after discharge) and the aggregate number of days of fluoroquinolone therapy per 1,000 patients (during hospitalization or after discharge).

After controlling for hospital clustering and patient factors, the researchers found that fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%, P = .01) and fewer fluoroquinolone treatment days per 1,000 patients (2,282 vs 3,096 days/1,000 patients, P = .01). These results were driven by reductions in inpatient prescribing.

But 66.6% of total fluoroquinolone treatment days at all the hospitals occurred after discharge, and the proportion of fluoroquinolone treatment days that occurred after discharge was higher in hospitals that targeted fluoroquinolone use than in the hospitals that didn't (78.3% vs 68.1%, P = .02).

"If you look at pneumonia and urinary tract infection, only about a third of all fluoroquinolone use occurs while patients are still in the hospital," Vaughn said. "The rest of that occurs in the post-discharge time period."

In addition, the hospitals with fluoroquinolone stewardship programs had twice as many new fluoroquinolone starts (patients who were treated with a different agent during hospitalization, then were switched to fluoroquinolones) after discharge as hospitals without (15.6% vs 8.4%, P = .003).

"Stewardship might have been trying to reduce inpatient fluoroquinolone use, but that was being missed at these transitions of care, and providers were going back to old habits of prescribing fluoroquinolones at discharge," she said.

While the study did not assess whether any of the fluoroquinolone prescriptions were inappropriate, Vaughn and her colleagues also noticed that nearly a third of patients in the study with asymptomatic bacteria, which doesn't require antibiotic treatment, were getting fluoroquinolones, as were some patients with uncomplicated UTIs. This is noteworthy because the FDA recommends against using the drugs for uncomplicated UTIs unless no other options are available.

Post-discharge antibiotic use

Vaughn spotlighted several possible explanations for the findings. One is that many patients are being switched from intravenous therapy as they leave the hospital, and an exact oral correlate may not be available for the drug they were receiving. But she also suggested that, because the fluoroquinolone restrictions don't apply to post-discharge prescriptions, prescribers may easily fall back into the habit of prescribing them for patients.

"If there aren't strong recommendations about what to do as patients leave the hospital, perhaps doctors go back to doing what they've done before," she said.

The surprising results, Vaughn said, have taught her that hospitalists and other clinicians need to be as mindful about the antibiotics they prescribe at discharge as they are about the drugs they use in the hospital. And this doesn't apply to just fluoroquinolone prescribing. "The antibiotics we prescribe at discharge need to be more of an active thought than an afterthought," she said.

Vaughn and her colleagues also note in the study that previous research has shown that prescribing at discharge could account for nearly half of all antibiotic use related to hospitalization and may also account for excess durations. Yet because most hospital stewardship programs don't have a way of tracking antibiotic use after patients leave the hospital, their impact on overall antibiotic use, and patient safety, could be limited.

"On a national level, we really should start to think about monitoring antibiotic prescribing that happens at discharge, not just during hospitalization," Vaughn said.

See also:

Feb 13 Clin Infect Dis study

Dec 21, 2018, CIDRAP News story "FDA: Fluoroquinolones may cause aortic rupture for some"

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