Voriconazole as a first-line treatment against potentially pathogenic Acanthamoeba strains from Peru

Abstract

Pathogenic strains of Acanthamoeba genus are the causative agents of fatal granulomatous amoebic encephalitis and a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. In a previous study, Acanthamoeba strains were isolated from nasal swabs collected from healthy individuals in Peru. In the present study, the pathogenic potential of the isolated strains was established based on temperature and osmotolerance assays as well as the secretion rate of extracellular proteases. Based on these experiments, four strains that showed the highest pathogenic potential were selected for sensitivity assays against two molecules (voriconazole and chlorhexidine) which are currently used for the treatment of Acanthamoeba infections. After performing sensitivity and activity assays, it was found that both drugs were active against the tested strains. However, voriconazole showed higher activity against the studied strains compared to chlorhexidine. Therefore, voriconazole should be established as a first-line treatment against Acanthamoeba infections at least in the studied region of Peru.

Cysticidal Activity of Antifungals against Different Genotypes of Acanthamoeba

“…These drugs inhibit the synthesis of ergosterol, which is a major component of the Acanthamoeba cell membrane. Our results are in line with what previously reported by other authors in previous studies (6,8,9). In the studies by Cabello-Vilchez and Martín-Navarro, the voriconazole 90% inhibitory concentration (IC) for cysts was shown to be around 5 to 15 g/ml for the tested isolates.…”

Characterisation of sterol biosynthesis and validation of 14α-demethylase as a drug target in Acanthamoeba

“…Importantly, this study also noted that voriconazole and itraconazole had lower dissociation constants for Acanthamoeba 14α - demethylase than fluconazole 18 . The results from previous studies that found voriconazole to have an IC 50 of 1.24 µM and 7.16 µM against a variety of Acanthamoeba species are also broadly consistent with the ranges found in this study 6 , 19 . The fact that voriconazole has also been reported to show efficacy against cysts over a period of 7 days is encouraging 20 .…”

Statins and Voriconazole Induce Programmed Cell Death in Acanthamoeba castellanii

“…The enzyme converts HMG-CoA to mevalonate, a precursor of cholesterol in humans and ergosterol in plants, fungi, and protozoa (23,24). In Acanthamoeba, ergosterol and 7-dehyrostigmasterol have been reported to be the main sterols of the membrane in both the trophozoite and the cyst stages (25)(26)(27)(28) (29)(30)(31).…”