In vitro activity of Tachyplesin III alone and in combination with terbinafine against clinical isolates of dermatophytes.
Aim of our study was to investigate the in vitro effects of Tachyplesin III (TP), a potent disulfide-linked peptide, in dermatophytes infections, with respect to or in combination with terbinafine (TERB), against 20 clinical isolates of dermatophytes belonging to four species. A broth microdilution method following the CLSI recommendations (M38-A) was used for testing drugs alone and in combination. TERB MICs were significantly lower than those observed for TP (p<0.001). Testing for antifungal agents in combination was performed for TERB with TP for all the 20 isolates. TERB activity in combination with TP showed indifferent activity for 14 of the 20 isolates (70%); synergic activity for 6 of the 20 isolates (30%); no antagonistic activity was observed. Further experiments were conducted with Microsporum canis 133, Trichophyton rubrum 62 and Trichophyton mentagrophytes 91 for fungal biomass. TP and TERB did not show a significant growth reduction compared to the control against T. mentagrophytes and T. rubrum. A significant difference of growth reduction both for TP and TERB compared to controls was observed for M. canis (p<0.01). In conclusion our study demonstrated that Tachyplesin III has potential activity against dermatophytes. In addition, we observed that the in vitro activity of Tachyplesin III can be enhanced upon combination with terbinafine. Synergy could permit lower doses of the individual antifungal agents to be used more effectively and/or safely.
Simonetti
O
O
Dermatological Clinic, Università Politecnica delle Marche, Ancona, Italy. o.simonetti@univpm.it
Ganzetti
G
G
Arzeni
D
D
Campanati
A
A
Marconi
B
B
Silvestri
C
C
Cirioni
O
O
Gabrielli
E
E
Lenci
I
I
Kamysz
W
W
Kamysz
E
E
Giacometti
A
A
Scalise
G
G
Barchiesi
F
F
Offidani
A
A
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D003883:Arthrodermataceae / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D003881:Dermatomycoses / Q000188:drug therapy; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D000077291:Terbinafine
D000890:Anti-Infective Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D009281:Naphthalenes; D010456:Peptides, Cyclic; C057636:tachyplesin peptide, Tachypleus tridentatus; D000077291:Terbinafine