Abstract
The evolution and dissemination of antibiotic resistance genes throughout the world are clearly affected by the selection and migration of resistant bacteria. However, the relative contributions of selection and migration at a local scale have not been fully explored. We sought to identify which of these factors has the strongest effect through comparisons of antibiotic resistance gene abundance between a distinct location and its surroundings over an extended period of six years. In this work, we used two repositories of extended spectrum β-lactamase (ESBL)-producing isolates collected since 2013 from patients at Dignity Health Mercy Medical Center (DHMMC) in Merced, California, USA, and a nationwide database compiled from clinical isolate genomes reported by the National Center for Biotechnology Information (NCBI) since 2013. We analyzed the stability of average resistance gene frequencies over the years since collection of these clinical isolates began for each repository. We then compared the frequencies of resistance genes in the DHMMC collection with the averages of the nationwide frequencies. We found DHMMC gene frequencies are stable over time and differ significantly from nationwide frequencies throughout the period of time we examined. Our results suggest that local selective pressures are a more important influence on the population structure of resistance genes in bacterial populations than migration. This, in turn, indicates the potential for antibiotic resistance to be controlled at a regional level, making it easier to limit the spread through local stewardship.
Highlights
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The continuous selection and evolution of β-lactamase genes by β-lactam antibiotic use has led to the diversification of successful β-lactamase genes: blaTEM, blaSHV, blaCTX-M, and blaOXA [4]. β-lactamase genes produce extended spectrum β-lactamase (ESBL) enzymes that work by hydrolyzing βlactam antibiotics, rendering them ineffective. blaTEM and blaSHV were the first β-lactamase enzymes identified in 1963 and 1972, respectively, and were implicit in outbreaks in the 1990s [5,6,7]
We chose to compare the frequencies of ESBLs in a local repository of ESBL positive isolates collected from a single hospital, with average frequencies nationwide across the U.S obtained from ESBL-positive clinical isolates whose genomic sequences have been deposited in the National Center for Biotechnology Information (NCBI) Isolates Browser Database
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. BlaCTX-M enzymes are the most identified ESBLs, and have displaced blaTEM and blaSHV in many individual hospitals [6,9,12,13,14] This trend is not uniform across publications originating from different surveillance locations [11,15,16]. One recent survey of 26 hospitals identified blaTEM as the most abundant ESBL enzyme in clinical isolates (47%), followed by blaCTX-M (36%), blaSHV (35%), and blaOXA (20%) [18]. Unstable (alternating) frequencies over time and uniformity between populations indicate strong alternating selective pressures in large areas (or populations) This signal indicates rapid migration because variation between populations averages out as immigration leads to a decrease in genetic differentiation between populations [21]. We compared ESBL gene frequencies from Dignity Health Mercy Medical Center (DHMMC) and the rest of the U.S over a period of six years as follows
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