Miltefosine and polyhexamethylene biguanide, a new drug combination for the treatment of Acanthamoeba keratitis. Results from in‐vivo toxicological and efficacy studies

Abstract

AbstractPurpose Miltefosine (MLT) and combinations of Miltefosine and polyhexamethylene biguanide (PHMB), chlorhexidine (CHX), and propamidine isethionate (PI), respectively, have been tested in a rat efficacy model for treatment of Acanthamoeba keratitis. In a second step, the most promising treatment regimens from efficacy studies have been tested for local tolerance in a fully GLP‐compliant toxicological study in pigmented rabbits.Methods The cornea of rats were infected with Acanthamoeba hatchetti. Cornea infections were graded microscopically. Nine groups were treated with varous treatment regimens for 28 days (8 times per day during the first week, and 3 times per day for the last three weeks). Efficacy of treatment was examined by determination of the degree of infection and culturing of excised eyes after the end of the treatment period. On day 28 the eyes were inspected under the microscope, re‐graded and were then compered with the grades before starting the therapy.Results Best treatment results were obtained from PHMB‐MLT group. The ratio of fully recovered eyes was 28.4%. The highets therapeutic activity was yielded by the combination MLT‐PHMB (86%), followed by MLT, CHX, or PI (72%) and the combination MLT–PI (70%. The fully GLP‐compliant study in pigmented rabbits (28 days, 8 treatments per day) showed excellent local tolerance.Conclusion Thus the combination of Miltefosine and PHMB can be seen as a highly effective and save option for treatment of AK.