Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates.

Details

Serval ID
serval:BIB_517BD7A5C0DC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates.
Journal
The Journal of antimicrobial chemotherapy
Author(s)
Denervaud-Tendon V., Poirel L., Connolly L.E., Krause K.M., Nordmann P.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Publication state
Published
Issued date
01/10/2017
Peer-reviewed
Oui
Volume
72
Number
10
Pages
2787-2791
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
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.
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.
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.
Keywords
Africa/epidemiology, Anti-Bacterial Agents/pharmacology, Bacterial Proteins/biosynthesis, Bacterial Proteins/genetics, Colistin/pharmacology, Colombia/epidemiology, Drug Resistance, Multiple, Bacterial, Enterobacteriaceae/drug effects, Enterobacteriaceae/enzymology, Enterobacteriaceae/genetics, Enterobacteriaceae/isolation & purification, Enterobacteriaceae Infections/drug therapy, Enterobacteriaceae Infections/epidemiology, Enterobacteriaceae Infections/microbiology, Escherichia coli/drug effects, Escherichia coli/genetics, Escherichia coli/metabolism, Escherichia coli Proteins/biosynthesis, Escherichia coli Proteins/genetics, Europe/epidemiology, Humans, Klebsiella oxytoca/drug effects, Klebsiella oxytoca/genetics, Klebsiella oxytoca/metabolism, Klebsiella pneumoniae/drug effects, Klebsiella pneumoniae/genetics, Klebsiella pneumoniae/metabolism, Microbial Sensitivity Tests, Sisomicin/analogs & derivatives, Sisomicin/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
02/11/2017 20:28
Last modification date
20/08/2019 14:07
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