Activities of ceftazidime, ceftaroline, and aztreonam alone and combined with avibactam against isogenic Escherichia coli strains expressing selected single β-lactamases.
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.
Department of Medicine, Case Western Reserve University, Cleveland, OH; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH.
Krisztina M
KM
Papp-Wallace
Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH.
Saralee
S
Bajaksouzian
Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH.
Ayman M
AM
Abdelhamed
Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH.
Altreisha N
AN
Foster
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.
Marisa L
ML
Winkler
Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH.
Julian A
JA
Gatta
AstraZeneca Pharmaceuticals, Infection Innovative Medicines, Waltham, MA.
Wright W
WW
Nichols
AstraZeneca Pharmaceuticals, Infection Innovative Medicines, Waltham, MA.
Raymond
R
Testa
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.
Robert A
RA
Bonomo
Department of Medicine, Case Western Reserve University, Cleveland, OH; Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH. Electronic address: mrj6@cwru.edu.
Michael R
MR
Jacobs
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology*; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001398:Aztreonam; D002442:Ceftazidime; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D047090:beta-Lactams; D000097583:Ceftaroline; C543519:avibactam
Avibactam; Carbapenemase; ESBL; Inhibitor-resistance; β-Lactamase