Journal article

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
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/306050
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