Abstract
The first medical cure of Acanthamoeba keratitis was obtained by use of propamidine isethionate. Since then, it has been the basic drug recommended for use in treatment. Because some Acanthamoeba strains have been reported to be resistant to propamidine and propamidine was found to be only weakly cysticidal, superior homologs such as butamidine, pentamidine, hexamidine, heptamidine, octamidine, and nonamidine were tested for their amoebicidal effects on two Acanthamoeba strains isolated from patients with keratitis. Trophozoicidal and cysticidal efficiencies were found to be increased from propamidine to nonamidine; i.e., when the alkyl chain connecting the two benzene rings in their molecular structures was elongated, in comparison with propamidine, hexamidine and octamidine were the most amoebicidal molecules. As a result of these data, a kinetic study carried out on propamidine, hexamidine, and octamidine demonstrated that the amoebicidal effects resulted from two events: the diffusion of molecules through the plasma membrane or the double wall of trophozoites or cysts, respectively, and the lethal effects of molecules on amoebic protoplasm. The diffusion kinetics were increased when the alkyl chain was elongated, i.e., with an increase in the lipophilic properties of molecules. In contrast, the lethal effect kinetics were found to be unchanged by this elongation, indicating that they originated from the cationic surface-active properties induced by the protonated amidine groups attached to each benzene ring, which themselves remained unchanged from one molecule to the other. These results strongly advocate the immediate replacement of propamidine by hexamidine in the medical treatment of Acanthamoeba keratitis; in France, 0.1% hexamidine eyedrops are available (Desomedine). The results also advocate clinical investigations on the efficiency and toxicity of octamidine, which appears to be the most amoebicidal diamidine in vitro.
Full Text
The Full Text of this article is available as a PDF (181.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Berger S. T., Mondino B. J., Hoft R. H., Donzis P. B., Holland G. N., Farley M. K., Levenson J. E. Successful medical management of Acanthamoeba keratitis. Am J Ophthalmol. 1990 Oct 15;110(4):395–403. doi: 10.1016/s0002-9394(14)77020-5. [DOI] [PubMed] [Google Scholar]
- Brasseur G., Favennec L., Perrine D., Chenu J. P., Brasseur P. Successful treatment of Acanthamoeba keratitis by hexamidine. Cornea. 1994 Sep;13(5):459–462. doi: 10.1097/00003226-199409000-00015. [DOI] [PubMed] [Google Scholar]
- Driebe W. T., Jr, Stern G. A., Epstein R. J., Visvesvara G. S., Adi M., Komadina T. Acanthamoeba keratitis. Potential role for topical clotrimazole in combination chemotherapy. Arch Ophthalmol. 1988 Sep;106(9):1196–1201. doi: 10.1001/archopht.1988.01060140356031. [DOI] [PubMed] [Google Scholar]
- Ficker L., Seal D., Warhurst D., Wright P. Acanthamoeba keratitis--resistance to medical therapy. Eye (Lond) 1990;4(Pt 6):835–838. doi: 10.1038/eye.1990.132. [DOI] [PubMed] [Google Scholar]
- Ishibashi Y., Matsumoto Y., Kabata T., Watanabe R., Hommura S., Yasuraoka K., Ishii K. Oral itraconazole and topical miconazole with débridement for Acanthamoeba keratitis. Am J Ophthalmol. 1990 Feb 15;109(2):121–126. doi: 10.1016/s0002-9394(14)75974-4. [DOI] [PubMed] [Google Scholar]
- Moore M. B., McCulley J. P. Acanthamoeba keratitis associated with contact lenses: six consecutive cases of successful management. Br J Ophthalmol. 1989 Apr;73(4):271–275. doi: 10.1136/bjo.73.4.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paniagua-Crespo E., Hasle D. P., Aouizerate F., Volant A., Simitzis-Le Flohic A. M. Etude in vitro de l'iséthionate de propamidine: intérêt dans le suivi des kératites amibiennes à Acanthamoeba. J Fr Ophtalmol. 1989;12(6-7):489–491. [PubMed] [Google Scholar]
- Saunders P. P., Proctor E. M., Rollins D. F., Richards J. S. Enhanced killing of Acanthamoeba cysts in vitro using dimethylsulfoxide. Ophthalmology. 1992 Aug;99(8):1197–1200. doi: 10.1016/s0161-6420(92)31823-8. [DOI] [PubMed] [Google Scholar]
- TOMLINSON G., JONES E. A. Isolation of cellulose from the cyst wall of a soil amoeba. Biochim Biophys Acta. 1962 Sep 10;63:194–200. doi: 10.1016/0006-3002(62)90353-0. [DOI] [PubMed] [Google Scholar]
- Upadhyay J. M., Crow S., Cox A. The cyst wall composition of Hartmannella glebae. Proc Soc Exp Biol Med. 1984 Apr;175(4):424–428. doi: 10.3181/00379727-175-41815. [DOI] [PubMed] [Google Scholar]
- Varga J. H., Wolf T. C., Jensen H. G., Parmley V. C., Rowsey J. J. Combined treatment of Acanthamoeba keratitis with propamidine, neomycin, and polyhexamethylene biguanide. Am J Ophthalmol. 1993 Apr 15;115(4):466–470. doi: 10.1016/s0002-9394(14)74448-4. [DOI] [PubMed] [Google Scholar]
- Wright P., Warhurst D., Jones B. R. Acanthamoeba keratitis successfully treated medically. Br J Ophthalmol. 1985 Oct;69(10):778–782. doi: 10.1136/bjo.69.10.778. [DOI] [PMC free article] [PubMed] [Google Scholar]