Format

Send to

Choose Destination
J Antimicrob Chemother. 2016 Jan;71(1):156-61. doi: 10.1093/jac/dkv294. Epub 2015 Sep 27.

In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae.

Author information

1
Medical and Molecular Microbiology 'Emerging Antibiotic Resistance' Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland laurent.poirel@unifr.ch.
2
Medical and Molecular Microbiology 'Emerging Antibiotic Resistance' Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
3
Medical and Molecular Microbiology 'Emerging Antibiotic Resistance' Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland Hôpital Fribourgeois-Hôpital Cantonal, Fribourg, Switzerland.

Abstract

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.

PMID:
26416781
DOI:
10.1093/jac/dkv294
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center