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469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales

Part of: JCTS_2024_ABSTRACT_COLLECTION

Published online by Cambridge University Press:  03 April 2024

Cody Black ,
Cody A. Black ,
Raymond Benavides ,
Sarah M. Bandy ,
Steven S. Dallas ,
Gerard Gawrys ,
Wonhee So ,
Alvaro G. Moreira ,
Samantha Aguilar  and
Kevin Quidilla
...Show all authors
Cody Black
Affiliation:
The University of Texas Health Science Center at San Antonio
Cody A. Black
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA
Raymond Benavides
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA
Sarah M. Bandy
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA
Steven S. Dallas
Affiliation:
Department of Pathology and Laboratory Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA University Health System, San Antonio, USA
Gerard Gawrys
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA University Health System, San Antonio, USA
Wonhee So
Affiliation:
College of Pharmacy, Western University of Health Sciences, Pomona, USA
Alvaro G. Moreira
Affiliation:
Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, USA
Samantha Aguilar
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA University Health System, San Antonio, USA
Kevin Quidilla
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA
Dan F. Smelter
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA
Kelly R. Reveles
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA
Christopher R. Frei
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA University Health System, San Antonio, USA
Jim M. Koeller
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA
Grace C. Lee
Affiliation:
College of Pharmacy, The University of Texas at Austin, Austin, USA Joe R. and Teresa Lozano Long School of Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, USA
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Abstract

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OBJECTIVES/GOALS: In this study, we aim to report the role of porins and blaCTX-M β-lactamases among Escherichia coli and Klebsiella pneumoniae, focusing on emerging carbapenem resistant Enterobacterales (CRE) subtypes, including non-carbapenemase producing Enterobacterales (NCPE) and ertapenem-resistant but meropenem-susceptible (ErMs) strains. METHODS/STUDY POPULATION: Whole genome sequencing was conducted on 76 carbapenem-resistant isolates across 5 hospitals in San Antonio, U.S. Among these, NCP isolates accounted for the majority of CRE (41/76). Identification and antimicrobial susceptibility testing (AST) results were collected from the clinical charts. Repeat speciation was determined through whole genome sequencing (WGS) analysis and repeat AST, performed with microdilution or ETEST®. Minimum inhibitory concentrations (MIC) were consistent with Clinical and Laboratory Standards Institute (CLSI M100, ED33). WGS and qPCR were used to characterize the resistome of all clinical CRE subtypes, while western blotting and liquid chromatography with tandem mass spectrometry (LC-MS-MS) were used to determine porin expression and carbapenem hydrolysis, respectively. RESULTS/ANTICIPATED RESULTS: blaCTX-Mwas found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)®” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p < 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p < 0.001). ErMs strains carrying blaCTX-M, had 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem-susceptible isolates (3.7 v. 0.9, p < 0.001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage ofompC. DISCUSSION/SIGNIFICANCE: Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. Clinically, CRE subtypes are not readily appreciated, potentially leading to mismanagement of CRE infected patients. A greater focus on optimal treatments for CRE subtypes is needed.

Type
Precision Medicine/Health
Information
Journal of Clinical and Translational Science , Volume 8 , Issue s1 , April 2024 , pp. 138
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2024. The Association for Clinical and Translational Science