title: In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues.
abstract: Effective chemotherapy for Acanthamoeba keratitis has been hampered because of the marked resistance of the parasites to a variety of antimicrobial agents. In view of the fact that topical Brolene (propamidine isethionate) and neosporin are currently considered to be the medical treatment of choice in Europe, we sought to determine whether pentamidine may be equally effective, because the drug is more readily available to ophthalmologists in the United States. In this study, we compared the amoebicidal activity of the Brolene (commercial product), propamidine isethionate and pentamidine isethionate (Pentam) in vitro against three different species of Acanthamoeba, and the drugs' corresponding biocompatibility with rabbit corneal epithelial and endothelial cell cultures. The results indicated that there were significant species differences in drug sensitivity. Propamidine (> 1,000 micrograms/ml) was clearly less effective than pentamidine (> 125 micrograms/ml) against A. castellanii, although equivalent potency (> 250 micrograms/ml) was observed against A. polyphaga. On the other hand, propamidine (> 31.25 micrograms/ml) was slightly more effective than pentamidine (> 62.5 micrograms/ml) against A. hatchetti. Both drugs were also relatively nontoxic after short-term contact with cell cultures, even though the highest concentration of pentamidine caused low-grade injury to the superficial epithelium and reversible membrane damage to the endothelium. Steady-state levels of propamidine at effective amoebicidal concentrations, however, were much more toxic than pentamidine, which indicated that the drug has a much lower therapeutic index. Our data suggest that pentamidine may be an effective therapeutic option because of its potency and low toxicity.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, USA.
authors.forename: H
authors.initials: H
authors.lastname: Alizadeh
authors.forename: R E
authors.initials: RE
authors.lastname: Silvany
authors.forename: D R
authors.initials: DR
authors.lastname: Meyer
authors.forename: J M
authors.initials: JM
authors.lastname: Dougherty
authors.forename: J P
authors.initials: JP
authors.lastname: McCulley
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects* / Q000502:physiology; D000563:Amebicides / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology* / Q000633:toxicity; D018929:Cell Culture Techniques; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D010419:Pentamidine / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits
chemical_list: D000563:Amebicides; D001550:Benzamidines; D010419:Pentamidine; C005555:propamidine