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275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli

BACKGROUND: Most Escherichia coli reside as commensal intestinal microflora without harming human health. But some E. coli strains are pathogenic and can cause deadly infections. Antimicrobial resistant E. coli is associated with more than 1.5 million deaths globally. Here, we studied the prevalence...

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Autores principales: Hwang, Munok, Choi, Hosoon, Navarathna, Thanuri, Boykin, Katherine, Corona, Brandon, Dhar, Sorabh, Donskey, Curtis, Cadnum, Jennifer, Chatterjee, Piyali, Kaye, Keith S, Jinadatha, Chetan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676880/
http://dx.doi.org/10.1093/ofid/ofad500.347
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author Hwang, Munok
Choi, Hosoon
Navarathna, Thanuri
Boykin, Katherine
Corona, Brandon
Dhar, Sorabh
Donskey, Curtis
Cadnum, Jennifer
Chatterjee, Piyali
Kaye, Keith S
Jinadatha, Chetan
author_facet Hwang, Munok
Choi, Hosoon
Navarathna, Thanuri
Boykin, Katherine
Corona, Brandon
Dhar, Sorabh
Donskey, Curtis
Cadnum, Jennifer
Chatterjee, Piyali
Kaye, Keith S
Jinadatha, Chetan
author_sort Hwang, Munok
collection PubMed
description BACKGROUND: Most Escherichia coli reside as commensal intestinal microflora without harming human health. But some E. coli strains are pathogenic and can cause deadly infections. Antimicrobial resistant E. coli is associated with more than 1.5 million deaths globally. Here, we studied the prevalence of antimicrobial resistance in E. coli isolates from two cities based on the antimicrobial(AMR) genes and MIC values. By correlating genotypic and phenotypic antimicrobial resistance, we also examined the performance of whole genome sequencing (WGS) based prediction of phenotypic resistance. METHODS: A total 109 E. coli isolates from Detroit, MI and Cleveland, OH hospitals underwent WGS. Antibiotic susceptibility testing (AST) was performed using the gram-negative AST cards on the VITEK 2 system. WGS was performed with Nextseq 550 using Nextera flex kits. After de novo assembly, AMR genes were identified using AMR gene database, ResFinder. RESULTS: The resistance to beta-lactam antibiotics including 1(st) and 3(rd) generation cephalosporins were very high among the E. coli isolates. They were susceptible to penicillin combinations and 2(nd) generation cephalosporins. While resistance to quinolone antibiotics was high, resistance to aminoglycoside, tetracycline, and sulfonamide/trimethoprim were relatively low (Figure 1). As shown in Table 1, WGS-based method accurately predicted the majority of antimicrobial resistance phenotypes with accuracy of 0.89 ∼ 1.0. However, for cephalothin (0.36), piperacillin/tazobactam (0.69), and amikacin (0.63), the prediction accuracy was low which could potentially lead to false predictions of antimicrobial resistance. Extended Spectrum Beta-Lactamase (ESBL) genes such as blaCTX-M, blaOXA, and blaTEM were abundant, though subtle difference in the prevalence of AMR genes between two cities was observed (Figure 2). [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: Most of the E. coli isolates contained various ESBL genes and their gyrA genes were mutated to quinolone resistant forms. Therefore, most of the isolates were resistant to many beta-lactam and quinolone drugs. WGS based prediction of phenotypic resistance showed good predictive values but needs more studies to increase sensitivity and specificity. DISCLOSURES: Keith S. Kaye, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Entasis: Advisor/Consultant|Entasis: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|VenatoRx: Advisor/Consultant|VenatoRx: Honoraria
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spelling pubmed-106768802023-11-27 275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli Hwang, Munok Choi, Hosoon Navarathna, Thanuri Boykin, Katherine Corona, Brandon Dhar, Sorabh Donskey, Curtis Cadnum, Jennifer Chatterjee, Piyali Kaye, Keith S Jinadatha, Chetan Open Forum Infect Dis Abstract BACKGROUND: Most Escherichia coli reside as commensal intestinal microflora without harming human health. But some E. coli strains are pathogenic and can cause deadly infections. Antimicrobial resistant E. coli is associated with more than 1.5 million deaths globally. Here, we studied the prevalence of antimicrobial resistance in E. coli isolates from two cities based on the antimicrobial(AMR) genes and MIC values. By correlating genotypic and phenotypic antimicrobial resistance, we also examined the performance of whole genome sequencing (WGS) based prediction of phenotypic resistance. METHODS: A total 109 E. coli isolates from Detroit, MI and Cleveland, OH hospitals underwent WGS. Antibiotic susceptibility testing (AST) was performed using the gram-negative AST cards on the VITEK 2 system. WGS was performed with Nextseq 550 using Nextera flex kits. After de novo assembly, AMR genes were identified using AMR gene database, ResFinder. RESULTS: The resistance to beta-lactam antibiotics including 1(st) and 3(rd) generation cephalosporins were very high among the E. coli isolates. They were susceptible to penicillin combinations and 2(nd) generation cephalosporins. While resistance to quinolone antibiotics was high, resistance to aminoglycoside, tetracycline, and sulfonamide/trimethoprim were relatively low (Figure 1). As shown in Table 1, WGS-based method accurately predicted the majority of antimicrobial resistance phenotypes with accuracy of 0.89 ∼ 1.0. However, for cephalothin (0.36), piperacillin/tazobactam (0.69), and amikacin (0.63), the prediction accuracy was low which could potentially lead to false predictions of antimicrobial resistance. Extended Spectrum Beta-Lactamase (ESBL) genes such as blaCTX-M, blaOXA, and blaTEM were abundant, though subtle difference in the prevalence of AMR genes between two cities was observed (Figure 2). [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: Most of the E. coli isolates contained various ESBL genes and their gyrA genes were mutated to quinolone resistant forms. Therefore, most of the isolates were resistant to many beta-lactam and quinolone drugs. WGS based prediction of phenotypic resistance showed good predictive values but needs more studies to increase sensitivity and specificity. DISCLOSURES: Keith S. Kaye, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Entasis: Advisor/Consultant|Entasis: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|VenatoRx: Advisor/Consultant|VenatoRx: Honoraria Oxford University Press 2023-11-27 /pmc/articles/PMC10676880/ http://dx.doi.org/10.1093/ofid/ofad500.347 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstract
Hwang, Munok
Choi, Hosoon
Navarathna, Thanuri
Boykin, Katherine
Corona, Brandon
Dhar, Sorabh
Donskey, Curtis
Cadnum, Jennifer
Chatterjee, Piyali
Kaye, Keith S
Jinadatha, Chetan
275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli
title 275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli
title_full 275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli
title_fullStr 275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli
title_full_unstemmed 275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli
title_short 275. Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli
title_sort 275. genotype-to-phenotype agreement of antimicrobial resistance in escherichia coli
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676880/
http://dx.doi.org/10.1093/ofid/ofad500.347
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