Enhanced killing of Acanthamoeba cysts in vitro using dimethylsulfoxide.
OBJECTIVE
Acanthamoeba keratitis is difficult to treat and requires prolonged therapy despite the well-documented in vitro effectiveness of a variety of drugs. The authors propose that this may be due to the cysts formed by the organism in response to hostile conditions. Consequently, the study concentrates on increasing penetration of drugs effective against the parasite into the cysts using dimethylsulfoxide (DMSO).


METHODS
The organism is forced to encyst in vitro on solid media by nutrient deprivation. In the first set of experiments, serial dilutions of a standard treatment regimen are applied to the organisms, and these treated cysts are then subcultured onto nutrient-rich material and observed for growth. The experiments are then repeated with DMSO added to the serially diluted standards. In a second set of experiments, the effects of retreatment on a larger concentration of organisms is examined.


RESULTS
When applied to a cyst-only population of Acanthamoeba, none of three standard drugs, propamidine isethionate 0.1%, neomycin 1%, or miconazole 1%, was cysticidal. When combined with DMSO 30%, propamidine isethionate was clearly cysticidal even in low dilution. This was confirmed by the retreatment experiments using a larger, standardized cyst population.


CONCLUSIONS
The authors propose that DMSO is acting as a "carrier" for the propamidine isethionate and increases its penetration into the normally drug-resistant cyst form of the organism. Because DMSO has been used topically in the past and shown to be quite safe, this may be a viable new therapy for this difficult condition.
Saunders
P P
PP
Department of Ophthalmology, University of British Columbia, Vancouver, Canada.
Proctor
E M
EM
Rollins
D F
DF
Richards
J S
JS
D000048:Acanthamoeba / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001550:Benzamidines / Q000493:pharmacokinetics / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004337:Drug Carriers; D066298:In Vitro Techniques; D008825:Miconazole / Q000493:pharmacokinetics / Q000494:pharmacology; D009355:Neomycin / Q000493:pharmacokinetics / Q000494:pharmacology
D000981:Antiprotozoal Agents; D001550:Benzamidines; D004337:Drug Carriers; D008825:Miconazole; C046651:propamidine isethionate; D009355:Neomycin; D004121:Dimethyl Sulfoxide