Evidence map›Paper›PMID 30629184›Full record

ArticleThe Journal of antimicrobial chemotherapy2019

In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii.

Mario Juhas, Emma Widlake, Jeanette Teo, Douglas L Huseby, Jonathan M Tyrrell, Yury S Polikanov, Onur Ercan, Anna Petersson, Sha Cao, Ali F Aboklaish and 6 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.

  1. Apramycin resistance in bacteria isolated from animals: A systematic review and meta-analysis.The Canadian veterinary journal = La revue veterinaire canadienne · 2026
    Pooled it
  2. Membrane-Focused Strategies AgainstAntibiotics (Basel, Switzerland) · 2026
    Review
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  15. Phenotypic Differentiation Within theAntibiotics (Basel, Switzerland) · 2024
    Article
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  17. Unveiling the Secrets ofInternational journal of molecular sciences · 2024
    Review
  18. Article
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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 5 countries.

Mario JuhasInstitute of Medical Microbiology, University of Zürich, Gloriastrasse 30, Zürich, Switzerland.
Emma WidlakeDivision of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Jeanette TeoDepartment of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore, Singapore.
Douglas L HusebyDepartment of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, Uppsala, Sweden.
Jonathan M TyrrellDivision of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Yury S PolikanovDepartment of Biological Sciences, College of Liberal Arts and Sciences, University of Illinois at Chicago, 900 South Ashland Avenue, MBRB 4170, Chicago, IL, USA.
Onur ErcanDepartment of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, Uppsala, Sweden.
Anna PeterssonDepartment of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, Uppsala, Sweden.
Sha CaoDepartment of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, Uppsala, Sweden.
Ali F AboklaishDivision of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Anna RominskiInstitute of Medical Microbiology, University of Zürich, Gloriastrasse 30, Zürich, Switzerland.
David CrichDepartment of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI, USA.
Erik C BöttgerInstitute of Medical Microbiology, University of Zürich, Gloriastrasse 30, Zürich, Switzerland.
Timothy R WalshDivision of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Diarmaid HughesDepartment of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, Uppsala, Sweden.
Sven N HobbieInstitute of Medical Microbiology, University of Zürich, Gloriastrasse 30, Zürich, Switzerland.
Uppsala University · SECardiff University · GBUniversity of Zurich · CHNational University Hospital · SGUniversity of Illinois Chicago · USWayne State University · US

Funding

NovaSeq Shared Instrumentation Grant for Wayne State UniversityS10OD025170 · OD · WAYNE STATE UNIVERSITY · PI RUDEN, DOUGLAS M · 2018 to 2018
$600k
Medical Research Council MR/N028317/1Medical Research Council MR/P007295/1Medical Research Council MR/S013768/1NIH HHS S10 OD025170
6 · The paper itself

Abstract

objectivesWidespread 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.

methodsA 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.

resultsMIC 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.

conclusionsIts 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.

Indexed as

Drug Resistance, BacterialAcinetobacter baumanniiAcinetobacter InfectionsAfricaAminoglycosidesAnti-Bacterial AgentsAsiaCarbapenemsEnterobacteriaceaeEnterobacteriaceae InfectionsEuropeGenotypeHumansMicrobial Sensitivity TestsNebramycinSouth AmericaAminoglycosidesAnti-Bacterial AgentsapramycinCarbapenemsNebramycin

Identifiers

PMID30629184
PMCPMC6419615
OpenAlexW2909123417

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.