title: Susceptibility testing of amorolfine, bifonazole and ciclopiroxolamine against Trichophyton rubrum in an in vitro model of dermatophyte nail infection.
abstract: Antimycotic nail lacquers are effective and safe for the treatment of onychomycosis. To assess the efficacy of three topical agents we studied the minimum inhibitory and fungicidal concentration of amorolfine, bifonazole and ciclopiroxolamine. Amorolfine showed the most effective fungistatic and fungicidal activity in vitro against seven clinical Trichophyton rubrum nail isolates, followed in descending order by ciclopiroxolamine and bifonazole. To mimic a nail infection more appropriately, the nail minimum fungicidal concentration (Nail-MFC) was determined in an onychomycosis model. Amorolfine and ciclopiroxolamine had Nail-MFCs ranging from 2-32 microg/ml and 16-32 microg/ml, respectively. In contrast, bifonazole was unable to kill T. rubrum in this model. Statistical analyses of the results show a significant difference between the two treatments with amorolfine and ciclopiroxolamine (P<0.001). For amorolfine a mean concentration of 12.28 microg/ml (95%-CI=[8.66, 17.41]) was sufficient to kill all strains, while for ciclopiroxolamine about twice that concentration was needed, i.e., 24.13 microg/ml (95%-CI=[17.06, 34.13]). The individual sensitivity of six of the seven T. rubrum strains was higher for amorolfine. These data demonstrate that both amorolfine and ciclopiroxolamine effectively kill T. rubrum growing on nail powder and suggest a better cidal action for amorolfine. Further investigation would be required to determine if these in vitro data can partially explain the clinical observation of significantly higher cure rates in onychomycosis following a therapy with an amorolfine-containing nail lacquer formulation.
authors.affiliation: Department of Dermatology, University of Tuebingen, 72076 Tuebingen, Germany. Martin.Schaller@med.uni-tuebingen.de
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Claudia
authors.initials: C
authors.lastname: Borelli
authors.forename: Ursula
authors.initials: U
authors.lastname: Berger
authors.forename: Birgit
authors.initials: B
authors.lastname: Walker
authors.forename: Sybille
authors.initials: S
authors.lastname: Schmidt
authors.forename: Günther
authors.initials: G
authors.lastname: Weindl
authors.forename: Andreas
authors.initials: A
authors.lastname: Jäckel
mesh_terms: D000287:Administration, Topical; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077768:Ciclopirox; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests / Q000379:methods; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D014009:Onychomycosis / Q000188:drug therapy*; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use; D014249:Trichophyton / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D009025:Morpholines; D011728:Pyridones; D000077768:Ciclopirox; C038974:amorolfine; C036596:bifonazole