# The Association Between Antibiotic Use and the Incidence of Third-Generation Cephalosporin-Resistance in Escherichia coli Bloodstream Infections: An Ecological Study

## TL;DR

The study found that reduced antibiotic use during the COVID-19 period led to a temporary decrease in resistance to a specific antibiotic in E. coli bloodstream infections.

## Contribution

This study uses the natural experiment of the COVID-19 period to show a direct link between reduced outpatient antibiotic use and decreased resistance in E. coli bloodstream infections.

## Key findings

- Reduced outpatient antibiotic use during the pandemic led to a significant drop in third-generation cephalosporin-resistant E. coli bloodstream infections.
- There is a significant positive linear relationship between antibiotic use and the proportion of E. coli BSI that are resistant to third-generation cephalosporins.
- Post-pandemic, resistance levels began to rise again as antibiotic use increased.

## Abstract

Background/Objectives: The COVID-19 period was marked by changes in antibiotic use and in the incidence of bacterial infections. We examined the association between antibiotic use and the proportion of Escherichia coli bloodstream infections (BSI) that were third-generation cephalosporin-resistant (3GC-R), using the COVID-19 period as a natural experiment. Methods: Data for this ecological study came from Israeli national surveillance systems for BSI and antibiotic consumption in 2015–2023. We performed interrupted time series analyses with a 1-year lag to examine the impact of COVID-19 on the proportion of E. coli BSI that were 3GC-R. We used linear regression to test the association between antibiotic use and 3GC resistance. Results: The majority of national antibiotic use was in outpatient settings; it was stable between 2015–2019, dropped by 19.4% in 2020, then increased gradually, but in 2023 remained 10.8% lower than before the pandemic. Incidence of E. coli BSI per 100,000 population increased from 62.6 in 2015 to a peak of 66.0 in 2019, with a small, non-significant change in the proportion of E. coli BSI that were 3GC-R (0.339 in 2015 vs. 0.335 in 2020). In 2020, the incidence of both 3GC-susceptible and 3GC-R E. coli BSI decreased. In 2021, only 3GC-R BSI declined, resulting in the proportion resistant dropping significantly by 0.05 (95% CI: 0.03–0.07). Post-pandemic, BSI incidence rose but remained below the 2019 rate. The proportion resistant after 2021 rose by 0.02 per year relative to the pre-COVID slope (95% CI: 0.02–0.03), such that it was higher in 2023 (0.341) than in 2019 and 2015. There was a significant positive linear relationship between antibiotic use and resistance: the proportion of E. coli BSI that were 3GC-R increased by 0.02 for each increase of one defined daily dose of antibiotic per person (95% CI: 0.001–0.03). Conclusions: Reduced outpatient antibiotic use during COVID-19 was followed by a reduction in the proportion of E. coli BSI that were 3GC-R.