Phenotypic screens reveal posaconazole as rapidly cidal combination partner for treatment of Primary Amoebic Meningoencephalitis.

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Phenotypic screens reveal posaconazole as rapidly cidal combination partner for treatment of Primary Amoebic Meningoencephalitis.

J Infect Dis. 2018 Oct 24;:

Authors: Colon BL, Rice CA, Guy RK, Kyle DE

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 FDA-approved compounds and the MMV Pathogen Box and validated 14 hits (IC50s < 1μM). 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 20mg/kg and in combination with azithromycin increased survival further by 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.

PMID: 30358879 [PubMed - as supplied by publisher]