Poirel, Laurent Kieffer, Nicolas Nordmann, Patrice 2015-08-23 Objectives: This study aimed to analyse the in vitro activity of dual combinations of carbapenems against Klebsiella pneumoniae producing the main carbapenemase types.Methods: MIC values of the carbapenems, imipenem, meropenem, ertapenem and doripenem were determined alone and in dual combinations for 20 clinical K. pneumoniae isolates producing representative carbapenemases, i.e. OXA-48 (n = 6), NDM-1 (n = 4), NDM-1 + OXA-48 (n = 2) and KPC-2 (n = 8). MICs were also determined for Escherichia coli recombinant strains with or without permeability defects producing NDM-1, OXA-48 or KPC-2. In vitro synergy combination testing was performed using the microdilution and chequerboard techniques. Fractional inhibitory concentration indexes were calculated to determine whether the combinations were synergistic, indifferent or antagonistic.Results: All carbapenemase producers were resistant to the tested carbapenems, with most isolates showing MICs of carbapenems >32 mg/L. None of the combinations was antagonistic. For KPC producers, synergistic combinations were observed with imipenem/ertapenem (5/8 isolates), imipenem/doripenem (4/8), imipenem/doripenem (4/8), meropenem/doripenem (3/8) and ertapenem/doripenem (3/8), while no synergy was observed with meropenem/ertapenem. For OXA-48 producers, synergies were observed with imipenem/ertapenem and with imipenem/meropenem for both isolates tested. Notably, combining imipenem with a non-carbapenem β-lactam (cefalotin) did not give any synergistic result. No synergy was observed for all NDM-1 and NDM-1+OXA-48 producers. Time–kill assays confirmed most of the data obtained by chequerboard testing.Conclusions: The data strongly support the hypothesis that dual carbapenem combinations might be effective against serine-β-lactamase producers (KPC, OXA-48). The imipenem-containing combinations appeared to be the most efficient. application/pdf https://folia.unifr.ch/global/documents/304726 https://folia.unifr.ch/documents/304726/files/nor_ved.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1093/jac/dkv294 info:eu-repo/semantics/openAccess License undefined Journal of Antimicrobial Chemotherapy. - 2016, vol. 71, no. 1, p. 156–161 info:eu-repo/classification/udc/57 In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae http://purl.org/coar/resource_type/c_6501