title: Potential of Ergosterol synthesis inhibitors to cause resistance or cross-resistance in Trichophyton rubrum.
abstract: Superficial mycoses caused by Trichophyton rubrum are among the most common infections worldwide. T. rubrum infections are difficult to treat and are often associated with recurrences after interruption of the antifungal therapy. Nevertheless, reports on T. rubrum resistance to commonly used antifungal drugs are rare. In this study, we compared the in vitro resistance frequencies and development of resistance to terbinafine, itraconazole, amorolfine, and ciclopirox in T. rubrum. Results demonstrated that naturally occurring mutants were isolated at a frequency of 10(-7) for itraconazole and 10(-9) for terbinafine and amorolfine. To mimic conditions of body sites in which low drug levels are reached during therapy, T. rubrum was propagated for 10 transfers in media containing subinhibitory drug concentrations. Resistance to itraconazole, terbinafine, and amorolfine emerged at a higher frequency than was seen with spontaneous mutation. Itraconazole-resistant mutants also showed decreased susceptibility to amorolfine as well as to terbinafine, and amorolfine-resistant mutants were also less susceptible to terbinafine. No mutant resistant to ciclopirox was isolated, suggesting no propensity of T. rubrum to develop resistance to this drug. How different drug mechanisms of action can influence the onset of resistance is discussed.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Ghelardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Celandroni
authors.forename: Sokhna Aissatou
authors.initials: SA
authors.lastname: Gueye
authors.forename: Sara
authors.initials: S
authors.lastname: Salvetti
authors.forename: Sonia
authors.initials: S
authors.lastname: Senesi
authors.forename: Anna
authors.initials: A
authors.lastname: Bulgheroni
authors.forename: Federico
authors.initials: F
authors.lastname: Mailland
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D000077768:Ciclopirox; D025141:Drug Resistance, Fungal; D004875:Ergosterol / Q000378:metabolism*; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D000077291:Terbinafine; D014249:Trichophyton / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D009025:Morpholines; D009281:Naphthalenes; D011728:Pyridones; D000077768:Ciclopirox; D017964:Itraconazole; C038974:amorolfine; D000077291:Terbinafine; D004875:Ergosterol