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.
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.
Département d'Anesthésie-Réanimation, CHU Amiens-Picardie, Amiens, France, and INSERM U1088, Université de Picardie Jules Verne, Amiens, France.
Hervé
H
Dupont
Service de Bactériologie, Pôle de Biologie Pathologie Génétique du CHU de Lille, Lille, France.
Olivier
O
Gaillot
Laboratoire de Biologie Médicale, Hôpital d'Abbeville, Abbeville, France.
Anne-Sophie
AS
Goetgheluck
Département de Biologie Médicale, Centre Hospitalier de Beauvais, Beauvais, France.
Claire
C
Plassart
Laboratoire de Biologie Médicale, Hôpital de Compiègne, Compiègne, France.
Jean-Philippe
JP
Emond
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France.
Marion
M
Lecuru
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France.
Nicolas
N
Gaillard
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France.
Sarah
S
Derdouri
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France.
Baptiste
B
Lemaire
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France.
Marion
M
Girard de Courtilles
CHU de Caen, Service de Microbiologie, Caen, France, and Université de Caen Basse Normandie, EA 4655 (Équipe Antibio-Résistance), Caen, France.
Vincent
V
Cattoir
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France INSERM, IAME, UMR 1137, Paris, France hedi.mammeri@wanadoo.fr.
Hedi
H
Mammeri
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D002442:Ceftazidime / Q000494:pharmacology*; D004151:Dipeptides / Q000378:metabolism; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D062665:Epidemiological Monitoring; D000077727:Ertapenem; D005602:France / Q000453:epidemiology; D015870:Gene Expression; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D015995:Prevalence; D011446:Prospective Studies; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001425:Bacterial Outer Membrane Proteins; D004151:Dipeptides; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D047090:beta-Lactams; C419365:phenylalanine arginine beta-naphthylamide; C543519:avibactam; D002442:Ceftazidime; D001618:beta-Lactamases; D001398:Aztreonam; D000077727:Ertapenem