Preliminary studies on the in vitro efficacy of the antibiotic nitroxoline in Naegleria lovaniensis

Abstract text

Species of the genus Naegleria belong to the free-living amoebae that are ubiquitously distributed in the environment. Naegleria fowleri is a pathogenic species of this genus, which can cause fatal amoebic meningoencephalitis in humans. Therefore, progress in developing effective therapies against such pathogenic free-living amoebae is of great importance, however only few novel drugs are being developed. We report the efficacy of the old antimicrobial nitroxoline on the non-pathogenic species Naegleria lovaniensis, which is closely related to N. fowleri.

To investigate the activity of the old and currently repurposed antimicrobial nitroxoline against N. lovaniensis.

Nitroxoline (Rosen Pharma, St. Ingbert, Germany) diluted in DMSO (MP Biomedicals, Eschwege, Germany) was incubated at different concentrations (range: 0,1 to 32 mg/l) with axenic cultures of N. lovaniensis in 24-well-diagnostic plates (Greiner Bio-one, Frickenhausen, Germany). Physical characteristics of cells and cellcounts were constantly assessed with light microscopy including encystation, and hemocytometric determination of living and dead cells within each well. Growth controls were taken from each well to asses the ability of the nitroxoline-exposed amoebaes to regenerate in xenic and axenic cultures. To rule out confounding amebicidal effects of DMSO, each dilution was also investigated with DMSO only, without nitroxoline. E. coli ATCC 25922 was used for quality controle of nitroxoline.

Inhibition and even killing of viable trophozoites and cysts of N. lovaniensis was demonstrated at nitroxoline concentrations of 1.0 mg/L - 8.0 mg/L (see Fig. 1)

Based on the current EUCAST breakpoint for treatment of uncomplicated urinary tract infection (susceptible ≤ 16mg/L for E. coli) activity of nitroxoline against N. lovaniensis can be considered excellent. Nitroxoline should be further investigated as a promising candidate for treatment of Naegleria-infections.