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

Maria F Mojica; Krisztina M Papp-Wallace; Magdalena A Taracila; Melissa D Barnes; Joseph D Rutter; Michael R Jacobs; John J LiPuma; Thomas J Walsh; Alejandro J Vila; Robert A Bonomo

doi:10.1128/AAC.00777-17

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

Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00777-17. doi: 10.1128/AAC.00777-17. Print 2017 Oct.

Authors

Maria F Mojica^{1

2}, Krisztina M Papp-Wallace^{1

2

3}, Magdalena A Taracila^{2

3}, Melissa D Barnes^{2

3}, Joseph D Rutter², Michael R Jacobs^{4

5}, John J LiPuma⁶, Thomas J Walsh⁷, Alejandro J Vila^{8

9}, Robert A Bonomo^{10

3

11

12

13}

Affiliations

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 Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA Robert.Bonomo@va.gov.
¹¹ Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹² Medical Service and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
¹³ CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA.

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.

Keywords: S. maltophilia; avibactam; aztreonam.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Azabicyclo Compounds / pharmacology*
Aztreonam / pharmacology*
Drug Combinations
Drug Resistance, Multiple, Bacterial / drug effects
Gram-Negative Bacterial Infections / drug therapy
Gram-Negative Bacterial Infections / microbiology
Humans
Microbial Sensitivity Tests
Stenotrophomonas maltophilia / drug effects*
Stenotrophomonas maltophilia / isolation & purification
beta-Lactamase Inhibitors / pharmacology*
beta-Lactamases / drug effects*

Substances

Anti-Bacterial Agents
Azabicyclo Compounds
Drug Combinations
beta-Lactamase Inhibitors
avibactam
beta-lactamase L2
beta-Lactamases
Aztreonam

Abstract

Publication types

MeSH terms

Substances

Grants and funding