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

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...

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Published in:Diagnostic microbiology and infectious disease 2015-05, Vol.82 (1), p.65-69
Main Authors: Papp-Wallace, Krisztina M, Bajaksouzian, Saralee, Abdelhamed, Ayman M, Foster, Altreisha N, Winkler, Marisa L, Gatta, Julian A, Nichols, Wright W, Testa, Raymond, Bonomo, Robert A, Jacobs, Michael R
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Avibactam
Azabicyclo Compounds - pharmacology
Aztreonam - pharmacology
beta-Lactamase Inhibitors - pharmacology
beta-Lactamases - genetics
beta-Lactamases - metabolism
beta-Lactams - pharmacology
Carbapenemase
Ceftaroline
Ceftazidime - pharmacology
Cephalosporins - pharmacology
ESBL
Escherichia coli
Escherichia coli - drug effects
Escherichia coli - enzymology
Escherichia coli - genetics
Humans
Infectious Disease
Inhibitor-resistance
Internal Medicine
Microbial Sensitivity Tests
β-Lactamase
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Summary: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.
ISSN:0732-8893
1879-0070
DOI:10.1016/j.diagmicrobio.2015.02.003