Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam

Yunliang Zhang; Ankita Kashikar; C Adam Brown; Gerald Denys; Karen Bush

doi:10.1128/AAC.00389-17

Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam

Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00389-17. doi: 10.1128/AAC.00389-17. Print 2017 Aug.

Authors

Yunliang Zhang¹, Ankita Kashikar¹, C Adam Brown¹, Gerald Denys², Karen Bush³

Affiliations

¹ Indiana University, Bloomington, Indiana, USA.
² Indiana University School of Medicine, Indianapolis, Indiana, USA.
³ Indiana University, Bloomington, Indiana, USA [email protected].

Abstract

Carbapenemase-producing Enterobacteriaceae isolates (n = 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC₅₀/MIC₉₀ values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftaroline-avibactam), and 0.25/0.5 μg/ml (aztreonam-avibactam.) A β-lactam MIC of 8 μg/ml was reported for the three combinations against one Escherichia coli isolate with an unusual TIPY insertion following Tyr344 in penicillin-binding protein 3 (PBP 3) as the result of gene duplication.

Keywords: CRE; PBP 3; avibactam; aztreonam; carbapenem-resistant; carbapenemase; ceftaroline; ceftazidime; resistance.

MeSH terms

Amino Acid Sequence
Anti-Bacterial Agents / pharmacology*
Azabicyclo Compounds / pharmacology*
Aztreonam / pharmacology*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Carbapenem-Resistant Enterobacteriaceae / drug effects
Carbapenem-Resistant Enterobacteriaceae / genetics*
Ceftaroline
Ceftazidime / pharmacology*
Cephalosporins / pharmacology*
DNA Transposable Elements / genetics
Drug Combinations
Escherichia coli / drug effects*
Escherichia coli / genetics*
Escherichia coli Proteins / genetics*
Gene Duplication / genetics
Humans
Penicillin-Binding Proteins / genetics*
Peptidoglycan Glycosyltransferase / genetics*
beta-Lactamases / genetics
beta-Lactamases / metabolism

Substances

Anti-Bacterial Agents
Azabicyclo Compounds
Bacterial Proteins
Cephalosporins
DNA Transposable Elements
Drug Combinations
Escherichia coli Proteins
FtsI protein, E coli
Penicillin-Binding Proteins
avibactam, ceftazidime drug combination
Ceftazidime
Peptidoglycan Glycosyltransferase
beta-lactamase KPC-2
beta-Lactamases
beta-lactamase TEM-1
carbapenemase
Aztreonam