uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii
Univ Zurich, Inst Med Microbiol, Gloriastr 30, CH-8006 Zurich, Switzerland.
Cardiff Univ, Sch Med, Div Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
Natl Univ Singapore Hosp, Dept Lab Med, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
Vise andre og tillknytning
2019 (engelsk)Inngår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, nr 4, s. 944-952Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objectives: Widespread antimicrobial resistance often limits the availability of therapeutic options to only a few last-resort drugs that are themselves challenged by emerging resistance and adverse side effects. Apramycin, an aminoglycoside antibiotic, has a unique chemical structure that evades almost all resistance mechanisms including the RNA methyltransferases frequently encountered in carbapenemase-producing clinical isolates. This study evaluates the in vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii, and provides a rationale for its superior antibacterial activity in the presence of aminoglycoside resistance determinants.

Methods: A thorough antibacterial assessment of apramycin with 1232 clinical isolates from Europe, Asia, Africa and South America was performed by standard CLSI broth microdilution testing. WGS and susceptibility testing with an engineered panel of aminoglycoside resistance-conferring determinants were used to provide a mechanistic rationale for the breadth of apramycin activity.

Results: MIC distributions and MIC90 values demonstrated broad antibacterial activity of apramycin against Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Morganella morganii, Citrobacter freundii, Providencia spp., Proteus mirabilis, Serratia marcescens and A. baumannii. Genotypic analysis revealed the variety of aminoglycoside-modifying enzymes and rRNA methyltransferases that rendered a remarkable proportion of clinical isolates resistant to standard-of-care aminoglycosides, but not to apramycin. Screening a panel of engineered strains each with a single well-defined resistance mechanism further demonstrated a lack of cross-resistance to gentamicin, amikacin, tobramycin and plazomicin.

Conclusions: Its superior breadth of activity renders apramycin a promising drug candidate for the treatment of systemic Gram-negative infections that are resistant to treatment with other aminoglycoside antibiotics.

sted, utgiver, år, opplag, sider
OXFORD UNIV PRESS , 2019. Vol. 74, nr 4, s. 944-952
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-382394DOI: 10.1093/jac/dky546ISI: 000463812100014PubMedID: 30629184OAI: oai:DiVA.org:uu-382394DiVA, id: diva2:1307007
Forskningsfinansiär
EU, FP7, Seventh Framework Programme, 115583Tilgjengelig fra: 2019-04-25 Laget: 2019-04-25 Sist oppdatert: 2019-04-25bibliografisk kontrollert

Open Access i DiVA

fulltext(648 kB)48 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 648 kBChecksum SHA-512
67af9aa333edd154959f8ed2b2ada090f7058b651877fc32e611a7aa919643a28c664404bdfb5918b27fa99f2fb22a4874d4c1a5bc563ffe441f2b7fd3c0ced7
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Huseby, Douglas LCao, ShaHughes, Diarmaid

Søk i DiVA

Av forfatter/redaktør
Huseby, Douglas LCao, ShaHughes, Diarmaid
Av organisasjonen
I samme tidsskrift
Journal of Antimicrobial Chemotherapy

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 48 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 69 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf