Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates
- Dénervaud Tendon, Valérie Emerging Antibiotic Resistance, Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Switzerland - INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Fribourg, Switzerland
- Poirel, Laurent Emerging Antibiotic Resistance, Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Switzerland - INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Fribourg, Switzerland
- Connolly, Lynn E. Achaogen, Inc., South San Francisco, CA, USA
- Krause, Kevin M. Achaogen, Inc., South San Francisco, CA, USA
- Nordmann, Patrice Emerging Antibiotic Resistance, Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Switzerland - INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Fribourg, Switzerland - Institute for Microbiology, University of Lausanne and University Hospital Centre, Lausanne, Switzerland
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10.08.2017
Published in:
- Journal of Antimicrobial Chemotherapy. - 2017, vol. 72, no. 10, p. 2787-2791
English
Objectives: Plazomicin, a novel aminoglycoside with in vitro activity against MDR Gram-negative organisms, is under development to treat patients with serious enterobacterial infections. We evaluated the activity of plazomicin and comparators against colistin-resistant enterobacterial isolates.Methods: Susceptibility to plazomicin and comparators was tested by broth microdilution for a collection of 95 colistin-resistant enterobacterial isolates collected from 29 hospitals in eight countries. Forty-two isolates (Klebsiella pneumoniae and Klebsiella oxytoca) possessed chromosomally encoded resistance mechanisms to colistin, 21 isolates (Escherichia coli and Salmonella enterica) expressed the mcr-1 gene, 8 isolates (Serratia, Proteus, Morganella and Hafnia) were intrinsically resistant to colistin and 24 isolates (K. pneumoniae, E. coli and Enterobacter spp.) had undefined, non-mcr-1 mechanisms. Susceptibility profiles were defined according to CLSI for aminoglycosides and to EUCAST for colistin and tigecycline.Results: Plazomicin inhibited 89.5% and 93.7% of the colistin-resistant enterobacterial isolates at ≤ 2 and ≤4 mg/L, respectively. MICs of plazomicin were ≤2 mg/L for all of the mcr-1 positive isolates and ≤4 mg/L for all the intrinsic colistin-resistant Enterobacteriaceae. Non-susceptibility to currently marketed aminoglycosides was common: amikacin, 16.8%; gentamicin, 47.4%; and tobramycin, 63.2%. Plazomicin was the most potent aminoglycoside tested with an MIC90 of 4 mg/L, compared with 32, >64 and 64 mg/L for amikacin, gentamicin and tobramycin, respectively.Conclusions: Plazomicin displayed potent activity against colistin-resistant clinical enterobacterial isolates, including those expressing the mcr-1 gene. Plazomicin was more active than other aminoglycosides against this collection of isolates. The further development of plazomicin for the treatment of infections due to MDR Enterobacteriaceae is warranted.
- Faculty
- Faculté des sciences et de médecine
- Department
- Médecine 3ème année
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 305110
- DOI 10.1093/jac/dkx239
- Persistent URL
- https://folia.unifr.ch/unifr/documents/306050
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