ZN148 Is a Modular Synthetic Metallo-β-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo-Reference-Cited by-同舟云学术

ZN148 Is a Modular Synthetic Metallo-β-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo

Published:2020-05-21 Issue:6 Volume:64 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Samuelsen Ørjan¹²^ORCID,Åstrand Ove Alexander Høgmoen³^ORCID,Fröhlich Christopher¹⁴^ORCID,Heikal Adam⁵^ORCID,Skagseth Susann⁴,Carlsen Trine Josefine Olsen⁴,Leiros Hanna-Kirsti S.⁴^ORCID,Bayer Annette⁶^ORCID,Schnaars Christian³,Kildahl-Andersen Geir³,Lauksund Silje¹²,Finke Sarah⁵,Huber Sandra⁷,Gjøen Tor⁵,Andresen Adriana Magalhaes Santos⁵,Økstad Ole Andreas⁵^ORCID,Rongved Pål³^ORCID

Affiliation:

1. Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway

2. Department of Pharmacy, UiT The Arctic University of Norway, Tromsø, Norway

3. Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, Oslo, Norway

4. The Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, UiT The Arctic University of Norway, Tromsø, Norway

5. Centre for Integrative Microbial Evolution and Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway

6. Department of Chemistry, UiT The Arctic University of Norway, Tromsø, Norway

7. Department of Laboratory Medicine, Division of Diagnostic Services, University Hospital of North Norway, Tromsø, Norway

Abstract

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited.

Funder

Norges Forskningsråd

Helse Nord RHF

Novo Nordisk Fonden

Statoil

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.02415-19

Reference58 articles.