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Antimicrob Agents Chemother. 2015 Oct 19;60(1):215-21. doi: 10.1128/AAC.01559-15. Print 2016 Jan.

Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations.

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Département d'Anesthésie-Réanimation, CHU Amiens-Picardie, Amiens, France, and INSERM U1088, Université de Picardie Jules Verne, Amiens, France.
Service de Bactériologie, Pôle de Biologie Pathologie Génétique du CHU de Lille, Lille, France.
Laboratoire de Biologie Médicale, Hôpital d'Abbeville, Abbeville, France.
Département de Biologie Médicale, Centre Hospitalier de Beauvais, Beauvais, France.
Laboratoire de Biologie Médicale, Hôpital de Compiègne, Compiègne, France.
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France.
CHU de Caen, Service de Microbiologie, Caen, France, and Université de Caen Basse Normandie, EA 4655 (Équipe Antibio-Résistance), Caen, France.
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France INSERM, IAME, UMR 1137, Paris, France


An interregional surveillance program was conducted in the northwestern part of France to determine the prevalence of carbapenem-nonsusceptible Enterobacteriaceae (CNSE) isolates and their susceptibility to ceftazidime-avibactam and aztreonam-avibactam combinations. Nonduplicate CNSE clinical isolates were prospectively collected from six hospitals between June 2012 and November 2013. MICs of ceftazidime and aztreonam, alone or combined with a fixed concentration of avibactam (4 μg/ml), and those of carbapenems (comparator agents) were determined. MICs of ertapenem in combination with phenylalanine arginine-naphthylamide dihydrochloride (PAβN) were also determined to assess active efflux. Genes encoding carbapenemases, plasmid-mediated AmpC enzymes, extended-spectrum β-lactamases (ESBLs), and major outer membrane proteins (OMPs) were amplified and sequenced. OMPs were also extracted for SDS-PAGE analysis. Among the 139 CNSE isolates, mainly Enterobacter spp. and Klebsiella pneumoniae, 123 (88.4%) were ertapenem nonsusceptible, 12 (8.6%) exhibited reduced susceptibility to all carbapenems, and 4 Proteeae isolates (2.9%) were resistant to imipenem. Carbapenemase production was detected in only two isolates (producing OXA-48 and IMI-3). In contrast, OMP deficiency, in association with AmpCs and/or ESBLs (mainly CTX-M-9, SHV-12, and CTX-M-15), was largely identified among CNSE isolates. The ceftazidime-avibactam and aztreonam-avibactam combinations exhibited potent activity against CNSE isolates (MIC50/MIC90, 1/1 μg/ml and 0.5/0.5 μg/ml, respectively) compared to that of ceftazidime and aztreonam alone (MIC50/MIC90, 512/512 μg/ml and 128/512 μg/ml, respectively). This study reveals the in vitro activity of ceftazidime-avibactam and aztreonam-avibactam combinations against a large collection of porin-deficient enterobacterial isolates that are representative of the CNSE recovered in the northern part of France.

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