Potential of Ergosterol synthesis inhibitors to cause resistance or cross-resistance in Trichophyton rubrum.

نویسندگان

  • Emilia Ghelardi
  • Francesco Celandroni
  • Sokhna Aissatou Gueye
  • Sara Salvetti
  • Sonia Senesi
  • Anna Bulgheroni
  • Federico Mailland
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Biochemical characterization of terbinafine-resistant Trichophyton rubrum isolates.

We investigated the biochemical basis for resistance in six sequential clinical isolates of Trichophyton rubrum, from the same patient, which exhibited high-level primary resistance to terbinafine. Cellular ergosterol biosynthesis was measured by incorporation of [14C]acetate, and microsomal squalene epoxidase was assayed by conversion of [3H]squalene to squalene epoxide and lanosterol. Direct ...

متن کامل

Calcofluor White Combination Antifungal Treatments for Trichophyton rubrum and Candida albicans

Superficial mycoses caused by dermatophyte fungi are among the most common infections worldwide, yet treatment is restricted by limited effective drugs available, drug toxicity, and emergence of drug resistance. The stilbene fluorescent brightener calcofluor white (CFW) inhibits fungi by binding chitin in the cell wall, disrupting cell wall integrity, and thus entails a different mechanism of i...

متن کامل

Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine.

There has only been one clinically confirmed case of terbinafine resistance in dermatophytes, where six sequential Trichophyton rubrum isolates from the same patient were found to be resistant to terbinafine and cross-resistant to other squalene epoxidase (SE) inhibitors. Microsomal SE activity from these resistant isolates was insensitive to terbinafine, suggesting a target-based mechanism of ...

متن کامل

PCR Typing of Trichophyton Rubrum Isolates by Specific Amplification of Subrepeat Elements in Ribosomal DNA Nontranscribed Spacer

Background: Trichophyton rubrum (T. rubrum) is the most common cause of dermatophytosis of skin and nail tissue. Strain identification in Trichophyton rubrum is important for identification of strain-related differences in infectivity potential or transmissibility and epidemiological studies. PCR typing could determine whether the original isolate is responsible for re-infection or a new strain...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Antimicrobial agents and chemotherapy

دوره 58 5  شماره 

صفحات  -

تاریخ انتشار 2014