title: Miltefosine and polyhexamethylene biguanide: a new drug combination for the treatment of Acanthamoeba keratitis.
abstract: BACKGROUND
  In this study, a series of compounds - miltefosine, polyhexamethylene biguanide, chlorhexidine and propamidine isethionate - and combinations of the latter three agents with miltefosine were prepared and used in a rat model for the topical treatment of Acanthamoeba keratitis.
  
  
  METHODS
  The corneas of rats were infected with Acanthamoeba hatchetti. On the fifth day, all corneas were microscopically examined in order to determine the grade of infections. Nine groups were then prepared: miltefosine (65.12 μg/mL); chlorhexidine (0.02%); polyhexamethylene biguanide (0.02%), propamidine isethionate (0.1%), miltefosine plus chlorhexidine, miltefosine plus polyhexamethylene biguanide; miltefosine plus propamidine isethionate; infected control; and a non-infected control group. The treatment was continued for 28 days. After the treatment, the corneas were excised and used for Acanthamoeba culture to investigate the presence of Acanthamoeba growth. For the determination of cytotoxicity of the drugs on L929 cells, colorimetric assays were performed.
  
  
  RESULTS
  The best treatment results were obtained from the polyhexamethylene biguanide plus miltefosine group; the ratio of fully recovered eyes was 28.4%. It was proven that the miltefosine-polyhexamethylene biguanide combination yielded the highest anti-acanthamoebal activity in that approximately 86% of the eyes were cleared from amoebae. The cytotoxicity values of the miltefosine and the control groups were compared with other groups and found to be statistically different (P < 0.05).
  
  
  CONCLUSIONS
  This in vivo study demonstrates that a miltefosine-polyhexamethylene biguanide combination is highly effective for the treatment of Acanthamoeba keratitis.
authors.affiliation: Department of Medical Parasitology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Zubeyde A
authors.initials: ZA
authors.lastname: Polat
authors.forename: Julia
authors.initials: J
authors.lastname: Walochnik
authors.forename: Andreas
authors.initials: A
authors.lastname: Obwaller
authors.forename: Ayse
authors.initials: A
authors.lastname: Vural
authors.forename: Ayhan
authors.initials: A
authors.lastname: Dursun
authors.forename: Mustafa K
authors.initials: MK
authors.lastname: Arici
mesh_terms: D000048:Acanthamoeba / Q000302:isolation & purification; D015823:Acanthamoeba Keratitis / Q000188:drug therapy* / Q000469:parasitology; D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use* / Q000633:toxicity; D001645:Biguanides / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004202:Disinfectants / Q000627:therapeutic use* / Q000633:toxicity; D004359:Drug Therapy, Combination; D005347:Fibroblasts / Q000187:drug effects; D008297:Male; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000981:Antiprotozoal Agents; D001645:Biguanides; D004202:Disinfectants; D010767:Phosphorylcholine; C031233:polihexanide; C039128:miltefosine
keywords: Acanthamoeba; keratitis; miltefosine; polyhexamethylene biguanide; rat keratitis model