Evidence map›Paper›PMID 30358879›Full record

ArticleThe Journal of infectious diseases2019

Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis.

Beatrice L Colon, Christopher A Rice, R Kiplin Guy, Dennis E Kyle

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  4. Drug susceptibility of a clinical isolate ofAntimicrobial agents and chemotherapy · 2026
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  8. Miconazole-like Scaffold is a Promising Lead forJournal of medicinal chemistry · 2023
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  9. Cyanomethyl Vinyl Ethers AgainstACS chemical neuroscience · 2023
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  11. Frontiers in public health · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Differential Growth Rates andMicrobiology spectrum · 2022
    Article
  16. Novel 1, 2, 4-Triazoles as Antifungal Agents.BioMed research international · 2022
    Review
  17. Review
  18. Article
  19. Article
  20. Article
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

4 authors at 2 institutions in 1 country.

Beatrice L ColonDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa.
Christopher A RiceDepartment of Global Health, College of Public Health, University of South Florida, Tampa.
R Kiplin GuyDepartment of Chemical Biology and Therapeutics, St Jude Children's Research Hospital, Memphis, Tennessee.
Dennis E KyleDepartment of Global Health, College of Public Health, University of South Florida, Tampa.
University of Georgia · USSt. Jude Children's Research Hospital · US

Funding

New Therapies for Pathogenic Free-Living AmoebaeR21AI103664 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI KYLE, DENNIS E · 2013 to 2014
$464k
Lead Optimization of Bis-benzimidazole Analogs for Pathogenic Free-living AmoebaeR21AI119787 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI KYLE, DENNIS E · 2015 to 2016
$425k
NIAID NIH HHS R21 AI103664NIAID NIH HHS R21 AI119787
6 · The paper itself

Abstract

Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis (PAM), which is fatal in >97% of cases. In this study, we aimed to identify new, rapidly acting drugs to increase survival rates. We conducted phenotypic screens of libraries of Food and Drug Administration-approved compounds and the Medicines for Malaria Venture Pathogen Box and validated 14 hits (defined as a 50% inhibitory concentration of <1 μM). The hits were then prioritized by assessing the rate of action and efficacy in combination with current drugs used to treat PAM. Posaconazole was found to inhibit amoeba growth within the first 12 hours of exposure, which was faster than any currently used drug. In addition, posaconazole cured 33% of N. fowleri-infected mice at a dose of 20 mg/kg and, in combination with azithromycin, increased survival by an additional 20%. Fluconazole, which is currently used for PAM therapy, was ineffective in vitro and vivo. Our results suggest posaconazole could replace fluconazole in the treatment of PAM.

Indexed as

Amphotericin BAnimalsAntiprotozoal AgentsAzithromycinCentral Nervous System Protozoal InfectionsDisease Models, AnimalDrug CombinationsDrug DiscoveryDrug SynergismFemaleFluconazoleHumansInhibitory Concentration 50MiceNaegleria fowleriPhenotypeAmphotericin BAntiprotozoal AgentsAzithromycinDrug CombinationsFluconazoleposaconazoleTriazolesazithromycindrug discoverymiltefosineNaegleria fowleriphenotypic screenposaconazoleprimary amoebic meningoencephalitis

Identifiers

PMID30358879
PMCPMC6420171
OpenAlexW2898432410

What OpenQuestion holds

Textmetadata
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.