In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae.
- Poirel L Medical and Molecular Microbiology 'Emerging Antibiotic Resistance' Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland laurent.poirel@unifr.ch.
- Kieffer N Medical and Molecular Microbiology 'Emerging Antibiotic Resistance' Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
- Nordmann P 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.
- 2015-09-30
Published in:
- The Journal of antimicrobial chemotherapy. - 2016
Anti-Bacterial Agents
Bacterial Proteins
Carbapenems
Drug Interactions
Escherichia coli
Humans
Klebsiella Infections
Klebsiella pneumoniae
Microbial Sensitivity Tests
beta-Lactamases
English
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.
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1093/jac/dkv294
- PMID 26416781
- Persistent URL
- https://sonar.ch/global/documents/138887
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