4.3 Article

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

Journal

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
Volume 82, Issue 1, Pages 65-69

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.diagmicrobio.2015.02.003

Keywords

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

Funding

  1. AstraZeneca Pharmaceuticals
  2. Actavis
  3. Medical Scientist Training Program Training Grant, Case Western Reserve University [T32 GM07250]
  4. Cleveland Department of Veterans Affairs
  5. Veterans Affairs Career Development Award
  6. Department of Veterans Affairs Merit Review Program [1I01BX001974]
  7. Veterans Integrated Service Network 10 Geriatric Research, Education, and Clinical Center (VISN 10 GRECC)
  8. National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01 AI100560, R01 AI063517]

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Avibactam is a novel beta-lactamase inhibitor that restores the activity of otherwise hydrolyzed beta-lactams against Gram-negative bacteria expressing different classes of serine beta-lactamases. In the last decade, beta-lactam-avibactam combinations were tested against a variety of clinical isolates expressing multiple commonly encountered beta-lactamases. Here, we analyzed isogenic Escherichia coli strains expressing selected single beta-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 Escherichia 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 beta-lactams with avibactam and serve as a reference for further studies. Published by Elsevier Inc.

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