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Invest Ophthalmol Vis Sci 2004;45: E-Abstract 4967.
© 2004 ARVO


4967—B291

Efficacy of anti–neoplastic drugs against Acanthamoeba

T.K. Beattie1, A. Tomlinson1 and D.V. Seal2

1 Vision Sciences, Glasgow Caledonian Univ, Glasgow, United Kingdom
2 Applied Vision Research Centre, City University, London, United Kingdom

Commercial Relationships: T.K. Beattie, None; A. Tomlinson, None; D.V. Seal, None.

Grant Identification: none

Abstract

Purpose:Late presenting cases of Acanthamoeba keratitis are particularly difficult to treat. The organism can persist, despite treatment with chlorhexidine or PHMB, maintaining an active infection. New drug therapies with enhanced activity are therefore needed to treat this painful, potentially blinding infection. This study was undertaken to determine the efficacy of three anti–cancer drugs against Acanthamoeba.

Methods:Doubling dilutions of MGBG [10–0.15mg/ml (38.5–0.6mM)], CHS 828 [660–10µg/ml (1782–27µM)] and hexadecyl–phosphocholine [HePC, Miltefosine; 660–10µg/ml (1782–27µM)] were tested alone or in combination with chlorhexidine, PHMB and propamidine, for efficacy against Acanthamoeba castellanii trophozoites or cysts. Sensitivity assays were performed over 48h in 96–well microtitre plates.

Results: MGBG killed trophozoites at 300µg/ml (1.2mM) and cysts at 1250µg/ml (4.6mM). The combination drugs had no effect on the cysticidal concentration of MGBG, but PHMB and propamidine may have an additive effect against trophozoites. CHS 828 caused rounding up of trophozoites, but had no effect on amoebal viability. HePC killed both trophozoites and cysts at 330µg/ml (0.8µM). Against trophozoites, propamidine had an additive effect on HePC reducing the inhibitory concentration to 82µg/ml (0.2mM) and 165µg/ml (0.4mM) when added at high (4µg/ml) and low (1µg/ml) concentrations, respectively. Synergy between HePC and the combination drugs was found against cysts, being most active for chlorhexidine when added at a concentration of 2µg/ml, reducing the minimum cysticidal concentration of HePC to <10µg/ml.

Conclusions:At the concentrations tested CHS 828 did not demonstrate any amoebicidal activity and as such is unlikely to be a potential therapeutic agent. The concentration of MGBG required to eradicate cysts may prevent its use in therapy. HePC shows potential as a therapeutic agent as synergy was demonstrated between HePC and the biguanides against cysts, but there may be some antagonism against trophozoites. Further work is necessary to determine the full potential of HePC as a therapeutic agent in the treatment of Acanthamoeba infection, in particular keratitis.

Keywords: Acanthamoeba • keratitis • contact lens

 © 2004, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.





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