In vitro activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against Mycobacterium abscessus

Liang Chen; Elena Shashkina; Natalia Kurepina; Vinicius Calado Nogueira de Moura; Charles L. Daley; Barry N. Kreiswirth

doi:10.1128/aac.00174-24

In vitro activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against Mycobacterium abscessus

Liang Chen
, Elena Shashkina
, Natalia Kurepina
, Vinicius Calado Nogueira de Moura
, Charles L. Daley
, Barry N. Kreiswirth

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

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

Abstract

Mycobacterium abscessus (MAB) infections pose a growing public health threat. Here, we assessed the in vitro activity of the boronic acid-based β-lactamase inhibitor, vaborbactam, with different β-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC₅₀/₉₀ reduction). CRISPRi-mediated bla_MAB gene knockdown showed a fourfold MIC reduction to ceftaroline but not the other β-lactams. Our findings demonstrate vaborbactam’s potential in combination therapy against MAB infections.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	68
Issue number	5
DOIs	https://doi.org/10.1128/aac.00174-24
State	Published - May 2024

UN SDGs

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

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

Keywords

CRISPR interference
Mycobacterium abscessus
peptidoglycan synthesis
vaborbactam
β-lactamase inhibitors

Access to Document

10.1128/aac.00174-24

Cite this

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title = "In vitro activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against Mycobacterium abscessus",

abstract = "Mycobacterium abscessus (MAB) infections pose a growing public health threat. Here, we assessed the in vitro activity of the boronic acid-based β-lactamase inhibitor, vaborbactam, with different β-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC50/90 reduction). CRISPRi-mediated blaMAB gene knockdown showed a fourfold MIC reduction to ceftaroline but not the other β-lactams. Our findings demonstrate vaborbactam{\textquoteright}s potential in combination therapy against MAB infections.",

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author = "Liang Chen and Elena Shashkina and Natalia Kurepina and \{de Moura\}, \{Vinicius Calado Nogueira\} and Daley, \{Charles L.\} and Kreiswirth, \{Barry N.\}",

year = "2024",

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doi = "10.1128/aac.00174-24",

language = "English",

volume = "68",

journal = "Antimicrobial Agents and Chemotherapy",

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AU - Chen, Liang

AU - Shashkina, Elena

AU - Kurepina, Natalia

AU - de Moura, Vinicius Calado Nogueira

AU - Daley, Charles L.

AU - Kreiswirth, Barry N.

PY - 2024/5

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N2 - Mycobacterium abscessus (MAB) infections pose a growing public health threat. Here, we assessed the in vitro activity of the boronic acid-based β-lactamase inhibitor, vaborbactam, with different β-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC50/90 reduction). CRISPRi-mediated blaMAB gene knockdown showed a fourfold MIC reduction to ceftaroline but not the other β-lactams. Our findings demonstrate vaborbactam’s potential in combination therapy against MAB infections.

AB - Mycobacterium abscessus (MAB) infections pose a growing public health threat. Here, we assessed the in vitro activity of the boronic acid-based β-lactamase inhibitor, vaborbactam, with different β-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC50/90 reduction). CRISPRi-mediated blaMAB gene knockdown showed a fourfold MIC reduction to ceftaroline but not the other β-lactams. Our findings demonstrate vaborbactam’s potential in combination therapy against MAB infections.

KW - CRISPR interference

KW - Mycobacterium abscessus

KW - peptidoglycan synthesis

KW - vaborbactam

KW - β-lactamase inhibitors

UR - https://www.scopus.com/pages/publications/85192112844

U2 - 10.1128/aac.00174-24

DO - 10.1128/aac.00174-24

M3 - Article

C2 - 38557171

SN - 0066-4804

VL - 68

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

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ER -

In vitro activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against Mycobacterium abscessus

Abstract

UN SDGs

ASJC Scopus subject areas

Keywords

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