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

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 c...

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Bibliographic Details
Published in:The Journal of infectious diseases 2019-03, Vol.219 (7), p.1095-1103
Main Authors: Colon, Beatrice L, Rice, Christopher A, Guy, R Kiplin, Kyle, Dennis E
Format: Article
Language:English
Subjects:
Amoeba
Amphotericin B - pharmacology
Amphotericin B - therapeutic use
Animals
Antibiotics
Antifungal agents
Antiprotozoal Agents - pharmacology
Antiprotozoal Agents - therapeutic use
Azithromycin
Azithromycin - pharmacology
Azithromycin - therapeutic use
Central Nervous System Protozoal Infections - drug therapy
Disease Models, Animal
Drug Combinations
Drug Discovery - methods
Drug Synergism
Encephalitis
Female
Fluconazole
Fluconazole - pharmacology
Fluconazole - therapeutic use
Genotype & phenotype
Humans
Inhibitory Concentration 50
Major and Brief Reports
Malaria
Meningitis
Mice
Naegleria fowleri
Naegleria fowleri - drug effects
Neurological disorders
Parasitic diseases
Phenotype
Posaconazole
Primary amebic meningoencephalitis
Survival
Time Factors
Triazoles - pharmacology
Triazoles - therapeutic use
United States
United States Food and Drug Administration
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Summary: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
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiy622