A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

Antibacterial Resistance Leadership Group

doi:10.1128/aac.00208-24

A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

Antibacterial Resistance Leadership Group

Hackensack Meridian School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased bla_KPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	68
Issue number	10
DOIs	https://doi.org/10.1128/aac.00208-24
State	Published - Oct 2024

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

Keywords

Klebsiella pneumoniae carbapenemase
OmpK35
OmpK36
Vabomere resistance
antimicrobial resistance
meropenem
meropenem vaborbactam resistance
vaborbactam

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/aac.00208-24

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title = "A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae",

abstract = "We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased blaKPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.",

keywords = "Klebsiella pneumoniae carbapenemase, OmpK35, OmpK36, Vabomere resistance, antimicrobial resistance, meropenem, meropenem vaborbactam resistance, vaborbactam",

author = "{Antibacterial Resistance Leadership Group} and Mohamad Yasmin and Marshall, {Steven H.} and Liang Chen and Rhoads, {Daniel D.} and Jacobs, {Michael R.} and Rojas, {Laura J.} and Federico Perez and Hujer, {Andrea M.} and Hujer, {Kristine M.} and {van Duin}, David and Vance Fowler and Chambers, {Henry F.} and Kreiswirth, {Barry N.} and Bonomo, {Robert A.}",

year = "2024",

month = oct,

doi = "10.1128/aac.00208-24",

language = "English",

volume = "68",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "10",

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TY - JOUR

T1 - A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

AU - Antibacterial Resistance Leadership Group

AU - Yasmin, Mohamad

AU - Marshall, Steven H.

AU - Chen, Liang

AU - Rhoads, Daniel D.

AU - Jacobs, Michael R.

AU - Rojas, Laura J.

AU - Perez, Federico

AU - Hujer, Andrea M.

AU - Hujer, Kristine M.

AU - van Duin, David

AU - Fowler, Vance

AU - Chambers, Henry F.

AU - Kreiswirth, Barry N.

AU - Bonomo, Robert A.

PY - 2024/10

Y1 - 2024/10

N2 - We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased blaKPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.

AB - We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased blaKPC copy numbers. KPC-KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.

KW - Klebsiella pneumoniae carbapenemase

KW - OmpK35

KW - OmpK36

KW - Vabomere resistance

KW - antimicrobial resistance

KW - meropenem

KW - meropenem vaborbactam resistance

KW - vaborbactam

UR - http://www.scopus.com/inward/record.url?scp=85206018474&partnerID=8YFLogxK

U2 - 10.1128/aac.00208-24

DO - 10.1128/aac.00208-24

M3 - Article

C2 - 39162528

SN - 0066-4804

VL - 68

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 10

ER -

A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

Abstract

ASJC Scopus subject areas

Keywords

UN SDGs

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