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Diagn Microbiol Infect Dis. 2015 May;82(1):65-9. doi: 10.1016/j.diagmicrobio.2015.02.003. Epub 2015 Feb 14.

Activities of ceftazidime, ceftaroline, and aztreonam alone and combined with avibactam against isogenic Escherichia coli strains expressing selected single β-lactamases.

Author information

1
Department of Medicine, Case Western Reserve University, Cleveland, OH; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH.
2
Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH.
3
Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH.
4
Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH.
5
AstraZeneca Pharmaceuticals, Infection Innovative Medicines, Waltham, MA.
6
Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH; Department of Pharmacology, Case Western Reserve University, Cleveland, OH; Department of Biochemistry, Case Western Reserve University, Cleveland, OH; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH. Electronic address: robert.bonomo@med.va.gov.
7
Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH. Electronic address: mrj6@cwru.edu.

Abstract

Avibactam is a novel β-lactamase inhibitor that restores the activity of otherwise hydrolyzed β-lactams against Gram-negative bacteria expressing different classes of serine β-lactamases. In the last decade, β-lactam-avibactam combinations were tested against a variety of clinical isolates expressing multiple commonly encountered β-lactamases. Here, we analyzed isogenic Escherichia coli strains expressing selected single β-lactamase genes that were not previously tested or were not characterized in an isogenic background. The activities of ceftazidime, ceftaroline, and aztreonam alone and in combination with 4 mg/L of avibactam, as well as comparator agents, were assessed against a unique collection of isogenic strains of E. coli carrying selected extended-spectrum, inhibitor-resistant, and/or carbapenem-hydrolyzing bla genes. When combined with avibactam, ceftazidime, ceftaroline, or aztreonam MICs were reduced for 91.4%, 80.0%, and 80.0% of isolates, respectively. The data presented add to our understanding of the microbiologic spectrum of these β-lactams with avibactam and serve as a reference for further studies.

KEYWORDS:

Avibactam; Carbapenemase; ESBL; Inhibitor-resistance; β-Lactamase

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