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Mechanisms of Resistance

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

Hervé Dupont, Olivier Gaillot, Anne-Sophie Goetgheluck, Claire Plassart, Jean-Philippe Emond, Marion Lecuru, Nicolas Gaillard, Sarah Derdouri, Baptiste Lemaire, Marion Girard de Courtilles, Vincent Cattoir, Hedi Mammeri
Hervé Dupont
Département d'Anesthésie-Réanimation, CHU Amiens-Picardie, Amiens, France, and INSERM U1088, Université de Picardie Jules Verne, Amiens, France
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Olivier Gaillot
Service de Bactériologie, Pôle de Biologie Pathologie Génétique du CHU de Lille, Lille, France
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Anne-Sophie Goetgheluck
Laboratoire de Biologie Médicale, Hôpital d'Abbeville, Abbeville, France
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Claire Plassart
Département de Biologie Médicale, Centre Hospitalier de Beauvais, Beauvais, France
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Jean-Philippe Emond
Laboratoire de Biologie Médicale, Hôpital de Compiègne, Compiègne, France
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Marion Lecuru
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France
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Nicolas Gaillard
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France
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Sarah Derdouri
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France
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Baptiste Lemaire
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France
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Marion Girard de Courtilles
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, France
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Vincent Cattoir
CHU de Caen, Service de Microbiologie, Caen, France, and Université de Caen Basse Normandie, EA 4655 (Équipe Antibio-Résistance), Caen, France
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Hedi Mammeri
Service de Bactériologie, Centre Hospitalo-Universitaire d'Amiens, Hôpital Sud, Amiens, FranceINSERM, IAME, UMR 1137, Paris, France
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DOI: 10.1128/AAC.01559-15
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    FIG 1

    OMP profiles of representative CNSE isolates compared to wild-type reference strains. OMPs were profiled by SDS-PAGE. Lanes: 1, E. coli porin-deficient strain BH01043; 2, E. coli porin-deficient strain DP02127; 3, E. coli wild-type strain TOP10; 4, E. cloacae porin-deficient strain BH01124; 5, E. cloacae porin-deficient strain AJP01076; 6, E. cloacae wild-type strain ATCC 13047; 7, K. pneumoniae porin-deficient strain AG02123; 8, K. pneumoniae wild-type strain NTUH-K2044. The arrows indicate the positions of the OMPs OmpC and OmpF.

Tables

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  • TABLE 1

    β-Lactamase production and OMP profiles for the 139 CNSE isolates

    OMP profileOrganism with β-lactamase production, β-lactamase(s) (no. of strains)
    CarbapenemaseESBLAmpCESBL + AmpCNo β-lactamase
    Wild-type outer membrane profileE. cloacae, IMI-3 (1)M. morganii (3)P. mirabilis (1)
    K. pneumoniae, OXA-48 (1)
    Loss of one major outer membrane porinK. pneumoniae, CTX-M-15 (10)E. aerogenes (4)E. cloacae, CTX-M-9/SHV-12 (36)
    E. coli, CTX-M-15 (2)E. cloacae (39)E. cloacae, CTX-M-9 (20)
    C. freundii (4)E. cloacae, SHV-12 (4)
    S. marcescens (1)C. freundii, CTX-M-9 (1)
    E. coli, ACC-1 (1)
    Loss of OmpC-like and OmpF-like porinsK. pneumoniae, CTX-M-15 (1)K. pneumoniae, CMY-2 (4)E. cloacae, CTX-M-9/SHV-12 (4)
    S. marcescens (1)E. aerogenes, TEM-24 (1)
  • TABLE 2

    MIC distributions for the 139 carbapenem-nonsusceptible Enterobacteriaceae clinical isolates, with cumulative percentages

    Organism (no. of strains)Agent(s)aMIC (μg/ml) (cumulative %)MIC50MIC90
    ≤0.060.1250.250.5124816≥32
    E. cloacae (104)CAZ2 (2)3 (5)99 (100)≥32≥32
    CAZ-AVI9 (9)21 (29)58 (85)12 (96)4 (100)0.51
    ATM2 (2)3 (5)14 (18)85 (100)≥32≥32
    ATM-AVI14 (13)23 (36)63 (96)4 (100)0.50.5
    ERTA82 (79)12 (90)5 (93)5 (100)12
    IMP5 (5)8 (13)76 (86)10 (95)4 (99)b1 (100)c0.51
    MERO11 (11)79 (87)9 (95)4 (99)b1 (100)c0.51
    DORI18 (17)71 (86)9 (94)1 (95)4 (99)b1 (100)c0.251
    K. pneumoniae (16)CAZ1 (6)15 (100)≥32≥32
    CAZ-AVI3 (19)8 (69)1 (75)4 (100)0.254
    ATM1 (6)15 (100)≥32≥32
    ATM-AVI1 (6)9 (63)2 (75)4 (100)0.1254
    ERTA7 (44)3 (63)2 (75)5 (100)b2≥32
    IMP2 (13)8 (63)1 (69)1 (75)b4 (100)b0.5≥32
    MERO2 (13)9 (69)1 (75)b4 (100)b1≥32
    DORI2 (13)7 (56)2 (69)1 (75)b4 (100)b0.516
    E. aerogenes (5)CAZ1 (20)4 (100)≥32≥32
    CAZ-AVI2 (40)2 (80)1 (100)0.52
    ATM1 (20)1 (40)3 (100)≥32≥32
    ATM-AVI3 (60)1 (80)1 (100)0.251
    ERTA4 (80)1 (100)b2≥32
    IMP4 (80)1 (100)b18
    MERO4 (80%)1 (100)b18
    DORI1 (20%)3 (80%)1 (100%)b0.54
    E. coli (3)CAZ2 (67)1 (100)2≥32
    CAZ-AVI1 (33)2 (100)0.250.25
    ATM2 (66)1 (100)8≥32
    ATM-AVI1 (33)1 (67)1 (100)0.1250.25
    ERTA2 (67)1 (100)12
    IMP3 (100)0.250.25
    MERO3 (100)0.250.25
    DORI1 (33)2 (100)0.250.25
    C. freundii (5)CAZ5 (100)≥32≥32
    CAZ-AVI2 (40)3 (100)0.50.5
    ATM4 (80)1 (100)16≥32
    ATM-AVI4 (80)1 (100)0.250.5
    ERTA1 (20)3 (80)1 (100)24
    IMP1 (20)2 (60)2 (100)0.51
    MERO3 (60)2 (100)0.51
    DORI3 (60)1 (80)1 (100)0.251
    S. marcescens (2)CAZ2 (100)≥32≥32
    CAZ-AVI1 (50)1 (100)0.51
    ATM2 (100)≥32≥32
    ATM-AVI1 (50)1 (100)0.251
    ERTA1 (50)1 (100)b1≥32
    IMP1 (50)1 (100)b0.5≥32
    MERO1 (50)1 (100)b0.25≥32
    DORI1 (50)1 (100)b0.254
    P. mirabilis (1)CAZ1 (100)≤0.06≤0.06
    CAZ-AVI1 (100)≤0.06≤0.06
    ATM1 (100)≤0.06≤0.06
    ATM-AVI1 (100)≤0.06≤0.06
    ERTA1 (100)≤0.06≤0.06
    IMP1 (100)88
    MERO1 (100)≤0.06≤0.06
    DORI1 (100)≤0.06≤0.06
    M. morganii (3)CAZ1 (33)1 (67)1 (100)8≥32
    CAZ-AVI1 (33)1 (67)1 (100)0.1250.25
    ATM1 (33)1 (67)1 (100)0.1251
    ATM-AVI3 (100)≤0.06≤0.06
    ERTA3 (100)≤0.06≤0.06
    IMP2 (67)1 (100)816
    MERO3 (100)≤0.06≤0.06
    DORI3 (100)≤0.06≤0.06
    • ↵a CAZ, ceftazidime; CAZ-AVI, ceftazidime-avibactam; ATM, aztreonam; ATM-AVI, aztreonam-avibactam; ERTA, ertapenem; IMP, imipenem; MERO, meropenem; DORI, doripenem.

    • ↵b CNSE isolates with a complete loss of OmpC and OmpF porins.

    • ↵c True carbapenemase producers.

Additional Files

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  • Supplemental material

    • Supplemental file 1 -

      Supplemental Table S1: list of primers used to amplify the ompC-like and ompF-like genes.

      PDF, 84K

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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
Hervé Dupont, Olivier Gaillot, Anne-Sophie Goetgheluck, Claire Plassart, Jean-Philippe Emond, Marion Lecuru, Nicolas Gaillard, Sarah Derdouri, Baptiste Lemaire, Marion Girard de Courtilles, Vincent Cattoir, Hedi Mammeri
Antimicrobial Agents and Chemotherapy Dec 2015, 60 (1) 215-221; DOI: 10.1128/AAC.01559-15

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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
Hervé Dupont, Olivier Gaillot, Anne-Sophie Goetgheluck, Claire Plassart, Jean-Philippe Emond, Marion Lecuru, Nicolas Gaillard, Sarah Derdouri, Baptiste Lemaire, Marion Girard de Courtilles, Vincent Cattoir, Hedi Mammeri
Antimicrobial Agents and Chemotherapy Dec 2015, 60 (1) 215-221; DOI: 10.1128/AAC.01559-15
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