In vitroactivity of the lipopeptide derivative (Pal-lys-lys-NH2), alone and in combination with antifungal agents, against clinical isolates of dermatophytes

Autor: Wojciech Kamysz, E. Gabrielli, Elżbieta Kamysz, Francesco Barchiesi, A. M. Offidani, Sefora Castelletti, Giulia Ganzetti, Oscar Cirioni, D. Arzeni, Giorgio Scalise, Oriana Simonetti, Carmela Silvestri
Rok vydání: 2009
Předmět:
Zdroj: British Journal of Dermatology. 161:249-252
ISSN: 1365-2133
0007-0963
DOI: 10.1111/j.1365-2133.2009.09166.x
Popis: Summary Background An increasing number of antimycotics have become available for the treatment of dermatophytoses; however, there are reports suggesting recalcitrance to therapy or resistance of a dermatophyte against conventional treatment. Lipopeptides represent novel therapeutic drugs with a new mode of action. Objectives The aim of this study was to investigate the in vitro effects of the lipopeptide Pal-Lys-Lys-NH2 (PAL) alone and in combination with standard antifungal agents, such as fluconazole (FLU), itraconazole (ITRA) and terbinafine (TER) against 24 clinical isolates of dermatophytes belonging to four species. Methods A broth microdilution method following the Clinical and Laboratory Standards Institute recommendations (M38-A) was used for testing drugs alone and in combination. Results PAL minimum inhibitory concentrations (MICs) ranged from ≤ 0·25 to > 16 μg mL−1 and they were similar to those of FLU and higher than those of either ITRA or TER. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤ 0·50, was observed in 67%, 52% and 15% of PAL/ITRA, PAL/TER and PAL/FLU interactions, respectively. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. Conclusions Our study demonstrates that PAL has potential activity against dermatophytes. In addition, the in vitro activity of PAL can be enhanced upon combination with standard drugs. This lipopeptide applied in the form of lacquer, spray or ointment, could represent an interesting new therapy, particularly when combined with conventional treatment in recalcitrant or resistant dermatophyte infections.
Databáze: OpenAIRE
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