Boston—If pharmacists have wondered if the primary cause of antibiotic resistance is frequent use by certain patients who always seem to be filling prescriptions for the medications, they might want to rethink that.

A report online in eLife suggests, instead, that growing resistant to antibiotics appears to be more associated with the drug’s occasional use across the entire population.

The Harvard T.H. Chan School of Public Health–led study also details how antibiotic use varies across the nation, with more antibiotic resistance in areas where specific agents are used more frequently.

“We know that efforts to reduce inappropriate use of antibiotics are critical to addressing the problem of antibiotic resistance. We wondered whether every antibiotic prescription contributes equally to resistance, and whether, as some previous research has suggested, the most effective way to minimize antibiotic resistance would be to focus on the small fraction of people who use most of the antibiotics,” explained senior author Yonatan Grad, MD, PhD. “Our results show that most antibiotic use is occasional—by people taking just one antibiotic course in a year—and that this occasional use is more closely linked with antibiotic resistance than intense, repeated use.”

The study is touted as the first to take a population-wide look at the link between distribution of antibiotic use and resistance to those antibiotics.

For the research, the study team used two nationwide pharmacy prescription-claims databases, Truven Health MarketScan Research Database and Medicare, to determine antibiotic use among 60 million Americans—about 20% of the United States population—from 2011 to 2014. That data was then compared with information from 2012 to 2015 from ResistanceOpen, which tracks antibiotic resistance across the U. S.

To calculate if rates of antibiotic use for a specific drug are linked to rates of antibiotic resistance for that drug, the researchers focused on 72 pairs of antibiotics and bacteria across the country.

Results indicated that in 2011, 34% of people received antibiotics, with 10% of the population using 57% of the antibiotics—a distribution that held up across the study period.

The researchers were able to correlate greater resistance to more use of an antibiotic. An example was that in U.S. states that use more quinolones, more Escherichia coli-caused infections tend to be resistant to quinolones.

Yet the study team also determined that occasional, low-intensity use by many people versus intense use by a few people was directly associated with resistance rates.

“Our findings suggest that combatting inappropriate antibiotic use among people who don’t take many antibiotics may be just as important, or more important, to fighting resistance than focusing on high-intensity users,” said lead author Scott Olesen, PhD, a postdoctoral fellow in the Department of Immunology and Infectious Diseases. “More antibiotic use generally means more antibiotic resistance, but it seems like the number of people taking antibiotics might matter more than the amount they’re taking.”

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