Avibactam Restores the Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia to Aztreonam

Author:

Mojica Maria F.12,Papp-Wallace Krisztina M.123,Taracila Magdalena A.23,Barnes Melissa D.23,Rutter Joseph D.2,Jacobs Michael R.45,LiPuma John J.6,Walsh Thomas J.7,Vila Alejandro J.89,Bonomo Robert A.13101112

Affiliation:

1. Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

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

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

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

5. Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

6. Department of Pediatrics and Communicable Disease, University of Michigan Medical School, Ann Arbor, Michigan, USA

7. Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medical Center, New York, New York, USA

8. Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), Rosario, Argentina

9. Área Biofísica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina

10. Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

11. Medical Service and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA

12. CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA

Abstract

ABSTRACT Stenotrophomonas maltophilia is an emerging opportunistic pathogen, classified by the World Health Organization as one of the leading multidrug-resistant organisms in hospital settings. The need to discover novel compounds and/or combination therapies for S. maltophilia is urgent. We demonstrate the in vitro efficacy of aztreonam-avibactam (ATM-AVI) against S. maltophilia and kinetically characterize the inhibition of the L2 β-lactamase by avibactam. ATM-AVI overcomes aztreonam resistance in selected clinical strains of S. maltophilia , addressing an unmet medical need.

Funder

Veterans Affairs Merit Review Program

HHS | NIH | National Institute of Allergy and Infectious Diseases

Cystic Fibrosis Foundation

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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