EVALUATION OF IN-VITRO AND IN-VIVO ANTIMICROBIAL ACTIVITY OF A NEW TOPICAL ANTIINFECTIVE AGENT

ST 1103 (Undecyl -trimethylammonium-(R)-3-isovaleroyloxy]-butanoate me thane-sulfonate) is a novel compound endowed with a broad antimicrobia l spectrum. ST 1103 is able to inhibit the in vitro growth of Gram-pos itive bacteria (mean MIC Value of 2.60 mu g/ml), Gram-negative bacteri a (mean MIC value of 27.00 mu g/ml), yeasts and yeast-like fungi (mean MIC Value of 3.76 mu g/ml), filamentous and dermatophytic fungi (mean MIC Value of 18.33 mu g/ml). Since indirect evidence indicates a poor oral absorbtion, ST 1103 was topically administered to mice with skin infections caused by mixed inocula. in these conditions, ST 1103 was able to cure mice infected with T. quinckeanum, S. aureus as well as i mmunodepressed mice infected with T. quinckeanum, S, aureus and C. alb icans. Conversely, miconazole (reference compound) appeared inadequate , in our experimental conditions, for a definitive therapy of the skin mycosis superinfected by staphylococcus. By using an in vitro 3D-huma n skin model, ST 1103 was fairly well tolerated in terms of both cell Viability and release of inflammatory mediators. In a dermal tolerance study in mice, ST 1103 at a concentration of 1% did not show any sign of local irritation on both intact and abraded skin after an 8-day to pical treatment. in conclusion, ST 1103 appears to be a promising cand idate for treatment of cutaneous infections caused by mixed microbial pathogens.