469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales
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-resi...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2024-04-01
|
| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124003972/type/journal_article |
| _version_ | 1797226861513670656 |
|---|---|
| author | Cody Black Cody A. Black Raymond Benavides Sarah M. Bandy Steven S. Dallas Gerard Gawrys Wonhee So Alvaro G. Moreira Samantha Aguilar Kevin Quidilla Dan F. Smelter Kelly R. Reveles Christopher R. Frei Jim M. Koeller Grace C. Lee |
| author_facet | Cody Black Cody A. Black Raymond Benavides Sarah M. Bandy Steven S. Dallas Gerard Gawrys Wonhee So Alvaro G. Moreira Samantha Aguilar Kevin Quidilla Dan F. Smelter Kelly R. Reveles Christopher R. Frei Jim M. Koeller Grace C. Lee |
| author_sort | Cody Black |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T14:31:38Z |
| format | Article |
| id | doaj.art-e706816644514ef5b1898589f34a6f55 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-24T14:31:38Z |
| publishDate | 2024-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-e706816644514ef5b1898589f34a6f552024-04-03T02:00:34ZengCambridge University PressJournal of Clinical and Translational Science2059-86612024-04-01813813810.1017/cts.2024.397469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant EnterobacteralesCody Black0Cody A. Black1Raymond Benavides2Sarah M. Bandy3Steven S. Dallas4Gerard Gawrys5Wonhee So6Alvaro G. Moreira7Samantha Aguilar8Kevin Quidilla9Dan F. Smelter10Kelly R. Reveles11Christopher R. Frei12Jim M. Koeller13Grace C. Lee14The University of Texas Health Science Center at San AntonioCollege 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, USACollege 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, USACollege 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, USADepartment of Pathology and Laboratory Medicine, The University of Texas Health at San Antonio, San Anto-nio, USA University Health System, San Antonio, USACollege 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, USACollege of Pharmacy, Western University of Health Sciences, Pomona, USAJoe 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, USACollege 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, USACollege 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, USACollege 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, USACollege 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, USACollege 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, USACollege 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, USACollege 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, USAOBJECTIVES/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.https://www.cambridge.org/core/product/identifier/S2059866124003972/type/journal_article |
| spellingShingle | Cody Black Cody A. Black Raymond Benavides Sarah M. Bandy Steven S. Dallas Gerard Gawrys Wonhee So Alvaro G. Moreira Samantha Aguilar Kevin Quidilla Dan F. Smelter Kelly R. Reveles Christopher R. Frei Jim M. Koeller Grace C. Lee 469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales Journal of Clinical and Translational Science |
| title | 469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales |
| title_full | 469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales |
| title_fullStr | 469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales |
| title_full_unstemmed | 469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales |
| title_short | 469 Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance Among Carbapenem Resistant Enterobacterales |
| title_sort | 469 diverse role of blactx m and porins in mediating ertapenem resistance among carbapenem resistant enterobacterales |
| url | https://www.cambridge.org/core/product/identifier/S2059866124003972/type/journal_article |
| work_keys_str_mv | AT codyblack 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT codyablack 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT raymondbenavides 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT sarahmbandy 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT stevensdallas 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT gerardgawrys 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT wonheeso 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT alvarogmoreira 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT samanthaaguilar 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT kevinquidilla 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT danfsmelter 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT kellyrreveles 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT christopherrfrei 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT jimmkoeller 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales AT graceclee 469diverseroleofblactxmandporinsinmediatingertapenemresistanceamongcarbapenemresistantenterobacterales |