Targeting Multidrug-Resistant Acinetobacter spp.: Sulbactam and the Diazabicyclooctenone β-Lactamase Inhibitor ETX2514 as a Novel Therapeutic Agent-Reference-Cited by-同舟云学术

Targeting Multidrug-Resistant Acinetobacter spp.: Sulbactam and the Diazabicyclooctenone β-Lactamase Inhibitor ETX2514 as a Novel Therapeutic Agent

Published:2019-04-30 Issue:2 Volume:10 Page:
ISSN:2161-2129
Container-title:mBio
language:en
Short-container-title:mBio

Author:

Barnes Melissa D.¹²,Kumar Vijay³^ORCID,Bethel Christopher R.¹,Moussa Samir H.⁴,O’Donnell John⁴,Rutter Joseph D.¹,Good Caryn E.⁵,Hujer Kristine M.¹²,Hujer Andrea M.¹²,Marshall Steve H.¹,Kreiswirth Barry N.⁶,Richter Sandra S.⁷,Rather Philip N.⁸⁹,Jacobs Michael R.²⁵,Papp-Wallace Krisztina M.¹²³^ORCID,van den Akker Focco³,Bonomo Robert A.¹²³¹⁰¹¹

Affiliation:

1. Louis Stokes Cleveland Veterans Affairs Medical Center Research Service, Cleveland, Ohio, USA

2. Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

3. Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA

4. Entasis Therapeutics, Waltham, Massachusetts, USA

5. Department of Pathology, University Hospitals, Cleveland Medical Center, Cleveland, Ohio, USA

6. Public Health Research Institute Tuberculosis Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA

7. Cleveland Clinic Foundation, Cleveland, Ohio, USA

8. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA

9. Research Service, Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA

10. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA

11. Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA

Abstract

The number and diversity of β-lactamases are steadily increasing. The emergence of β-lactamases that hydrolyze carbapenems poses a significant threat to our antibiotic armamentarium. The explosion of OXA enzymes that are carbapenem hydrolyzers is a major challenge (carbapenem-hydrolyzing class D [CHD]). An urgent need exists to discover β-lactamase inhibitors with class D activity. The sulbactam-ETX2514 combination demonstrates the potential to become a treatment regimen of choice for Acinetobacter spp. producing class D β-lactamases.

Funder

Veterans Affairs Merit Review Program Award

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/mBio.00159-19

Reference38 articles.

1. Reversibility of Covalent, Broad-Spectrum Serine β-Lactamase Inhibition by the Diazabicyclooctenone ETX2514

2. ETX2514 is a broad-spectrum β-lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria including Acinetobacter baumannii