In vitro activity of meropenem-vaborbactam plus aztreonam against metallo-β-lactamase-producing Klebsiella pneumoniae

Astrid V. Cienfuegos-Gallet; Elena Shashkina; Tingyu Chu; Zhichen Zhu; Bingjie Wang; Barry N. Kreiswirth; Liang Chen

doi:10.1128/aac.01346-23

In vitro activity of meropenem-vaborbactam plus aztreonam against metallo-β-lactamase-producing Klebsiella pneumoniae

Astrid V. Cienfuegos-Gallet
, Elena Shashkina
, Tingyu Chu
, Zhichen Zhu
, Bingjie Wang
, Barry N. Kreiswirth
, Liang Chen

Pharmacy

Hackensack Meridian Health
Universidad de Antioquia
The Second Affiliated Hospital of Soochow University
Tongji University

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

4 Scopus citations

Abstract

We evaluated the in vitro activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae isolates. Among them, 25 isolates (17.9%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.0%) had MIC ≤ 2 µg/mL. Genomic analysis and subsequent gene cloning experiments revealed OmpK36 134-135GD-insertion and increased carbapenemase gene (bla_NDM-1 and bla_OXA-48-like) copy numbers are the main factors responsible for MEV-ATM non-susceptibility. Notably, MEV-ATM is actively against aztreonam-avibactam-resistant mutants due to CMY-16 mutations.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	68
Issue number	4
DOIs	https://doi.org/10.1128/aac.01346-23
State	Published - Apr 2024

Keywords

aztreonam
carbapenemase
meropenem-vaborbactam
metallo-β-lactamase

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10.1128/aac.01346-23

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title = "In vitro activity of meropenem-vaborbactam plus aztreonam against metallo-β-lactamase-producing Klebsiella pneumoniae",

abstract = "We evaluated the in vitro activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae isolates. Among them, 25 isolates (17.9\%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.0\%) had MIC ≤ 2 µg/mL. Genomic analysis and subsequent gene cloning experiments revealed OmpK36 134-135GD-insertion and increased carbapenemase gene (blaNDM-1 and blaOXA-48-like) copy numbers are the main factors responsible for MEV-ATM non-susceptibility. Notably, MEV-ATM is actively against aztreonam-avibactam-resistant mutants due to CMY-16 mutations.",

keywords = "aztreonam, carbapenemase, meropenem-vaborbactam, metallo-β-lactamase",

author = "Cienfuegos-Gallet, \{Astrid V.\} and Elena Shashkina and Tingyu Chu and Zhichen Zhu and Bingjie Wang and Kreiswirth, \{Barry N.\} and Liang Chen",

year = "2024",

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doi = "10.1128/aac.01346-23",

language = "English",

volume = "68",

journal = "Antimicrobial Agents and Chemotherapy",

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publisher = "American Society for Microbiology",

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T1 - In vitro activity of meropenem-vaborbactam plus aztreonam against metallo-β-lactamase-producing Klebsiella pneumoniae

AU - Cienfuegos-Gallet, Astrid V.

AU - Shashkina, Elena

AU - Chu, Tingyu

AU - Zhu, Zhichen

AU - Wang, Bingjie

AU - Kreiswirth, Barry N.

AU - Chen, Liang

PY - 2024/4

Y1 - 2024/4

N2 - We evaluated the in vitro activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae isolates. Among them, 25 isolates (17.9%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.0%) had MIC ≤ 2 µg/mL. Genomic analysis and subsequent gene cloning experiments revealed OmpK36 134-135GD-insertion and increased carbapenemase gene (blaNDM-1 and blaOXA-48-like) copy numbers are the main factors responsible for MEV-ATM non-susceptibility. Notably, MEV-ATM is actively against aztreonam-avibactam-resistant mutants due to CMY-16 mutations.

AB - We evaluated the in vitro activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae isolates. Among them, 25 isolates (17.9%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.0%) had MIC ≤ 2 µg/mL. Genomic analysis and subsequent gene cloning experiments revealed OmpK36 134-135GD-insertion and increased carbapenemase gene (blaNDM-1 and blaOXA-48-like) copy numbers are the main factors responsible for MEV-ATM non-susceptibility. Notably, MEV-ATM is actively against aztreonam-avibactam-resistant mutants due to CMY-16 mutations.

KW - aztreonam

KW - carbapenemase

KW - meropenem-vaborbactam

KW - metallo-β-lactamase

UR - https://www.scopus.com/pages/publications/85189864213

U2 - 10.1128/aac.01346-23

DO - 10.1128/aac.01346-23

M3 - Article

C2 - 38426743

AN - SCOPUS:85189864213

SN - 0066-4804

VL - 68

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 4

ER -

In vitro activity of meropenem-vaborbactam plus aztreonam against metallo-β-lactamase-producing Klebsiella pneumoniae

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Keywords

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