OSBORNE CC, FAVRE B, RYDER NN; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. M-215.

Novartis Research Institute, Vienna, Austria

Background Little is known about antifungal resistance in dermatophytes despite the widespread use of oral drugs to treat patients suffering from onychomycosis. In this study we have analyzed the spontaneous resistance frequency to terbinafine of T. rubrum strains and their capacity to develop resistance to the drug in vitro. Methods To determine resistance frequency, about 1 X 10[9] CFU of 5 strains were plated on potato dextrose agar (PDA) medium containing 0.06 microg/ml terbinafine (cidal concentration) and incubated for 3 weeks at 30 degrees C. To investigate resistance induction, four strains were serially passaged at 30 degrees C either on PDA plates or in RPMI 1640 liquid medium containing increasing concentrations of terbinafine, starting at 0.002 microg/ml. In both cases, MIC values were determined before and after treatments, using microdilution assay in RPMI 1640 medium. Results The resistance frequency of the 5 strains was /= 0.5 microg/ml terbinafine for the resistant isolates versus 0.016 microg/ml (0.06 microg/ml, while the initial MICs were /= 0.03 microg/ml. The isolate able to grow in 0.125 microg/ml terbinafine was also less susceptible (>/= 16X) to other squalene epoxidase inhibitors and azoles. Conclusion Naturally occurring mutant resistants to terbinafine in a population of T. rubrum are very rare. Their selective cross-resistance to other squalene epoxidase inhibitors suggests an alteration of the target. T. rubrum does not appear to be able to develop either rapid or extensive resistance to terbinafine in vitro.

Publication Types:

• Meeting Abstracts

Keywords:

• Antifungal Agents
• Arthrodermataceae
• Azoles
• Fluconazole
• Humans
• In Vitro
• Itraconazole
• Miconazole
• Microbial Sensitivity Tests
• Naphthalenes
• Onychomycosis
• Trichophyton
• terbinafine

Other ID:

• GWAIDS0027954

UI: 102267578

From Meeting Abstracts