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In vitro activity of the lipopeptide derivative (Pal‐lys‐lys‐NH 2 ), alone and in combination with antifungal agents, against clinical isolates of dermatophytes
Author(s) -
Simonetti O.,
Arzeni D.,
Ganzetti G.,
Silvestri C.,
Cirioni O.,
Gabrielli E.,
Castelletti S.,
Kamysz W.,
Kamysz E.,
Scalise G.,
Offidani A.,
Barchiesi F.
Publication year - 2009
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2009.09166.x
Subject(s) - public health , humanities , pharmacy , library science , medicine , art , family medicine , computer science , nursing
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‐NH 2 (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.

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