Stewardship / Resistance Scan for Dec 19, 2018

Sparse antibiotic use and resistance
Metronidazole for mild C diff

Study finds link between occasional antibiotic use and resistance

Antibiotic resistance in the United States appears to be more closely linked to occasional antibiotic use by many people rather than heavy use by few people, and resistance to certain antibiotics is higher in areas where they are used more often, according to a comprehensive study yesterday in eLife.

US and Canadian experts analyzed 99.8 million outpatient pharmacy antibiotic prescription fills among 108 million unique people (about 20% of the US population) from 2011 through 2014 using the MarketScan database. They noted that, in 2011, 34% of the people took an antibiotic, but 10% of them received 57% of all prescriptions, which is similar to previously published UK data. The distribution varied by population but was similar across all 4 years.

The researchers also examined data from 2012 to 2015 from ResistanceOpen, which tracks antibiotic resistance across the country. To correlate antibiotic use for a particular drug with rates of antibiotic resistance against that drug, the researchers looked at 72 pairs of antibiotics and bacteria.

The investigators found that the more a particular antibiotic was used, the greater the resistance. For instance, in states that use more quinolones, more infections caused by Escherichia coli tend to be resistant to quinolones.

When comparing occasional, low-intensity antibiotic use by many people to intense use by a few people, however, they found that occasional, low-intensity use was more closely associated with rates of resistance.

"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 at the Harvard TH Chan School of Public Health, in a Harvard news release. "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."
Dec 18 eLife abstract
Dec 18 Harvard news release


VA study: Metronidazole still appropriate for mild C diff in select patients

A study yesterday in Clinical Infectious Diseases suggests metronidazole may be considered for treating initially mild Clostridioides difficile infection (CDI) in patients 65 years old or younger.

Until recently, metronidazole was recommended as the first-line treatment option for mild-to-moderate CDI, but updated guidelines now recommend vancomycin for initial non-severe CDI. Despite these guidelines, some reports still recommend that metronidazole be considered in certain patients who have mild CDI and a low risk for disease complications. But limited data exist to identify these patients.

To answer the question of which patients can still be treated with metronidazole, researchers with the Providence Veterans Affairs (VA) Medical Center conducted a two-stage analysis in a cohort of veterans from 125 VA centers with a first episode of mild CDI. The first stage was a predictive analysis regarding which patients treated with metronidazole have successful outcomes, and the second stage compared clinical outcomes in patients treated with metronidazole versus those treated with vancomycin.

Among 3,656 patients treated with metronidazole, the researchers identified 3,282 patients with success and 374 patients without success. Younger age was the only independent predictor of success, with patients 65 and younger associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29 to 2.06) than those over 65. Among 115 propensity-score matched pairs of patients under 65, no significant differences were observed between metronidazole and vancomycin for all-cause mortality (hazard ratio [HR], 0.29; 95% CI, 0.06 to 1.38), CDI recurrence (HR, 0.62; 95% CI, 0.26 to 1.49), or treatment failure (HR, 0.50; 95% CI, 0.23 to 1.07).

The authors of the study say continued work is needed to investigate which severity criteria are most useful in defining mild disease that can be successfully treated with metronidazole.
Dec 18 Clin Infect Dis abstract

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