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

J Infect Dis. 2019 Mar 15;219(7):1095-1103. doi: 10.1093/infdis/jiy622.


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.

Keywords: Naegleria fowleri; azithromycin; drug discovery; miltefosine; phenotypic screen; posaconazole; primary amoebic meningoencephalitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology
  • Amphotericin B / therapeutic use
  • Animals
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / therapeutic use
  • Azithromycin / pharmacology
  • Azithromycin / therapeutic use
  • Central Nervous System Protozoal Infections / drug therapy*
  • Disease Models, Animal
  • Drug Combinations
  • Drug Discovery / methods*
  • Drug Synergism
  • Female
  • Fluconazole / pharmacology
  • Fluconazole / therapeutic use
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Naegleria fowleri / drug effects*
  • Phenotype
  • Time Factors
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use
  • United States
  • United States Food and Drug Administration


  • Antiprotozoal Agents
  • Drug Combinations
  • Triazoles
  • posaconazole
  • Amphotericin B
  • Azithromycin
  • Fluconazole