Overall outpatient antibiotic use among older US adults has remained steady in recent years, with a slight drop in inappropriate prescribing, according to a study today in the British Medical Journal (BMJ). But the use of certain antibiotics has seen significant shifts.
In an examination of outpatient pharmacy claims from 4.5 million Medicare beneficiaries, researchers with Harvard Medical School and Harvard T.H. Chan School of Public Health found that the number of outpatient antibiotic claims fell by 0.2% from 2011 through 2015, with trends varying by age-group, race, and region. Use of antibiotics fell from 1,364.7 to 1,309.3 claims per 1,000 beneficiaries during 2011-2014, then rebounded to 1,364.3 in 2015.
From 2011 to 2014, potentially inappropriate prescribing—which the researchers defined as prescriptions linked to diagnoses for which antibiotics are not indicated—fell from 552.7 to 522.1 claims per 1,000 beneficiaries, an adjusted decrease of 3.9%. But the proportion of claims that were potentially inappropriate remained steady, changing from 40.5% in 2011 to 39.9% in 2014.
Looking at the top 10 most frequently prescribed antibiotics, the researchers found that the use of azithromycin, ciprofloxacin, and trimethoprim/sulfamethoxazole fell, while the use of levofloxacin, amoxicillin, amoxicillin/clavulanate, clindamycin, doxycycline, celefexin, and nitrofurantoin rose. The biggest changes were seen in azithromycin (a decline of 18.5%) and levofloxacin (an increase of 27.7%). For levofloxacin, amoxicillin-clavulanate, and azithromycin, trends in use were similar across both appropriate and inappropriate respiratory conditions.
'Shifting palette' of antibiotic use
Because overall prescribing was relatively unchanged, and inappropriate prescribing declined only modestly, the authors of the study argue that the trends in the use of individual antibiotics are the real story, and these trends suggest shifting preferences for antibiotics across indications, rather than clinically oriented changes in use or concerns about rising antibiotic resistance.
This is highlighted by the increased use of levofloxacin over azithromycin for all respiratory conditions, regardless of whether the drug was appropriate for the patient's diagnosis.
In 2007, the researchers note, the Infectious Diseases Society of America and the American Thoracic Society recommended the use of fluoroquinolones instead of macrolides for community-acquired pneumonia (CAP) in certain patients. That could help explain why the use of azithromycin for CAP decreased by 17% and the use of levofloxacin for CAP increased by 27%.
Likewise, concerns about macrolide resistance in pneumonia could explain declining use of azithromycin for the illness. But the use of azithromycin for all respiratory conditions fell, while use of levofloxacin for those conditions rose, suggesting that providers were simply swapping one drug for another.
"In our study, changes in antibiotic prescribing practice reflected shifting use between antibiotics rather than decreasing inappropriate prescribing across antibiotics, which implied that attempts to reduce outpatient antibiotic prescribing could generally result in a shifting palette, rather than a reduced amount, of antibiotic use," the authors write.
More likely explanations for this shifting palette, they suggest, are safety concerns and market factors, such as pricing, availability, and advertising. In particular, they cite the US Food and Drug Administration's (FDA's) 2013 warning that azithromycin might increase the risk of cardiovascular death in certain patients as a potential contributor to the declining popularity of the drug. More recent FDA warnings about using levofloxacin for uncomplicated respiratory conditions could reverse that trend.
The authors conclude that since efforts to reduce outpatient antibiotic prescribing have produced only incremental gains, stewardship programs should instead focus on a more feasible goal of shifting prescribing from newer, broad-spectrum drugs to older, narrow-spectrum drugs.
Jul 27 BMJ study