The distribution of antibiotic use and its association with antibiotic resistance.

Scott W Olesen,Yonatan H Grad,Marc Lipsitch,John S Brownstein,Derek R Macfadden,Sonia Hernández-Díaz,Michael L Barnett

doi:10.7554/elife.39435

Abstract

Antibiotic use is a primary driver of antibiotic resistance. However, antibiotic use can be distributed in different ways in a population, and the association between the distribution of use and antibiotic resistance has not been explored. Here, we tested the hypothesis that repeated use of antibiotics has a stronger association with population-wide antibiotic resistance than broadly-distributed, low-intensity use. First, we characterized the distribution of outpatient antibiotic use across US states, finding that antibiotic use is uneven and that repeated use of antibiotics makes up a minority of antibiotic use. Second, we compared antibiotic use with resistance for 72 pathogen-antibiotic combinations across states. Finally, having partitioned total use into extensive and intensive margins, we found that intense use had a weaker association with resistance than extensive use. If the use-resistance relationship is causal, these results suggest that reducing total use and selection intensity will require reducing broadly distributed, low-intensity use.

Highlights

Antibiotic use is a primary driver of antibiotic resistance, and reducing antibiotic use is a central strategy for combatting resistance (Gould, 1999; Harbarth and Samore, 2005)
We examined the distribution of antibiotic use for each drug group and US state
To quantify the distribution of antibiotic use, we labeled each antibiotic pharmacy claim as ‘first’ if it was the first pharmacy fill for that drug group made by that individual in that calendar year, and ‘repeat’ if it was a second, third, etc. fill for an antibiotic in the same drug group made by the same individual in the same calendar year

Summary

Introduction

Antibiotic use is a primary driver of antibiotic resistance, and reducing antibiotic use is a central strategy for combatting resistance (Gould, 1999; Harbarth and Samore, 2005). Multiple studies have identified cross-sectional relationships between antibiotic use and resistance, especially across European countries and US states (Goossens et al, 2005; Garcıa-Rey et al, 2002; Bronzwaer et al, 2002; Bell et al, 2014; European Centre for Disease Prevention and Control et al, 2017; van de Sande-Bruinsma et al, 2008; MacFadden et al, 2018a). These studies compare total outpatient antibiotic use with population-level resistance.

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Conclusion