In vitro activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant Acinetobacter baumannii collected in U.S. hospitals

Alina Iovleva; Christi L McElheny; Erin L Fowler; Eric Cober; Erica S Herc; Cesar A Arias; Carol Hill; Keri Baum; Vance G Fowler Jr; Henry F Chambers; Kerryl E Greenwood-Quaintance; Robin Patel; David van Duin; Robert A Bonomo; Yohei Doi

doi:10.1128/aac.01258-23

In vitro activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant Acinetobacter baumannii collected in U.S. hospitals

Antimicrob Agents Chemother. 2024 Mar 6;68(3):e0125823. doi: 10.1128/aac.01258-23. Epub 2024 Jan 30.

Authors

Alina Iovleva¹, Christi L McElheny¹, Erin L Fowler¹, Eric Cober², Erica S Herc³, Cesar A Arias^{4

5

6}, Carol Hill⁷, Keri Baum⁷, Vance G Fowler Jr^{7

8}, Henry F Chambers⁹, Kerryl E Greenwood-Quaintance¹⁰, Robin Patel^{10

11}, David van Duin¹², Robert A Bonomo^{13

14

15

16

17

18

19

20}, Yohei Doi^{1

21

22}

Affiliations

¹ Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
² Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio, USA.
³ Division of Infectious Diseases, Henry Ford Hospital, Detroit, Michigan, USA.
⁴ Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.
⁵ Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA.
⁶ Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
⁷ Duke Clinical Research Institute, Durham, North Carolina, USA.
⁸ Division of Infectious Diseases, Duke University School of Medicine, Durham, North Carolina, USA.
⁹ Division of Infectious Diseases, University of California San Francisco School of Medicine, San Francisco, California, USA.
¹⁰ Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
¹¹ Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
¹² Division of Infectious Diseases University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
¹³ Department of Medicine, Division of Infectious Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹⁴ Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹⁵ Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
¹⁶ CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA.
¹⁷ Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹⁸ Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Cleveland, Ohio, USA.
¹⁹ Department of Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
²⁰ Clinician Scientist Investigator, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
²¹ Departments of Microbiology and Infectious Diseases, Fujita Health University, Toyoake, Japan.
²² Center for Innovative Antimicrobial Therapy, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Abstract

The activity of a novel β-lactamase inhibitor combination, sulbactam-durlobactam (SUL-DUR), was tested against 87 colistin-resistant and/or cefiderocol-non-susceptible carbapenem-resistant Acinetobacter baumannii clinical isolates collected from U.S. hospitals between 2017 and 2019. Among them, 89% and 97% were susceptible to SUL-DUR and imipenem plus SUL-DUR, with MIC₅₀/MIC₉₀ values of 2 µg/mL/8 µg/mL and 1 µg/mL/4 µg/mL, respectively. The presence of amino acid substitutions in penicillin-binding protein 3, including previously reported A515V or T526S, was associated with SUL-DUR non-susceptibility.

Keywords: antimicrobial resistance; diazabicyclooctane; surveillance.

MeSH terms

Acinetobacter Infections* / drug therapy
Acinetobacter baumannii*
Anti-Bacterial Agents / pharmacology
Azabicyclo Compounds*
Cefiderocol
Colistin / pharmacology
Drug Combinations
Hospitals
Humans
Imipenem / pharmacology
Microbial Sensitivity Tests
Sulbactam / pharmacology

Substances

sulbactam-durlobactam
Colistin
Anti-Bacterial Agents
Cefiderocol
Sulbactam
Imipenem
Drug Combinations
Azabicyclo Compounds

Abstract

MeSH terms

Substances

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