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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.

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Bacterial vaginosis is characterized by a shift of the physiological flora to a diverse spectrum of bacteria, where Gardnerella vaginalis and Atopobium vaginae are the most important markers. In this study, the antimicrobial activity of nifuratel against G. vaginalis, A. vaginae, and lactobacilli was compared with that of the two currently used antibiotics metronidazole and clindamycin. Results suggest that nifuratel has a better spectrum of activity, being highly active against G. vaginalis and A. vaginae without affecting lactobacilli.The microbial flora of the vagina contains high concentrations of a composite population of bacteria (11,21). It is dominated mainly by lactobacilli that maintain an acidic pH by H 2 O 2 and lactic acid production (14). Alterations in this ecosystem can lead to bacterial vaginosis (BV) and Candida vaginitis, which account for 90% of vaginal infections (10).BV is a polymicrobial syndrome characterized by alteration of the vaginal flora, where the normally occurring Lactobacillus species are overgrown by endogenous bacteria (24). In particular, high concentrations of Gardnerella vaginalis and Atopobium vaginae have been shown to be important microbiological markers (1,18,27). The association between the presence of A. vaginae and BV has been highlighted only recently (8), thanks to its detection by molecular techniques. Although its exact role is not yet fully understood, the association between A. vaginae and BV is well established (1,17,18,27), as is its involvement, together with G. vaginalis, in the biofilm present on the vaginal epithelium during BV (25).The therapies of choice for BV are systemic or topical metronidazole and clindamycin. Previous studies reported cure rates of 70 to 96% for both antibiotics, with recurrence rates of 49 to 66%, following 7 days of therapy (2, 13, 16).Inadequate diagnosis (23), pharmacologic resistance (20), and persistence of an adherent bacterial biofilm after treatment (26) seem to be the main reasons for failures of BV treatment and eradication, as well as the presence of a complex microbial population with putative resistance to antimicrobials.Nifuratel is a nitrofuran derivative with strong activity against Trichomonas vaginalis (4, 7) and a broad spectrum of antibacterial action (7,19,22). The purpose of this study was to investigate the potential of nifuratel in the treatment of BV and compare it with metronidazole and clindamycin against G. vaginalis, A. vaginae, and lactobacilli.The bacterial strains tested were both clinical isolates and reference strains. Clinical isolates from vaginal swabs (provided by Maditest, Vevey, Switzerland) were grown and identified following standard protocols. In addition, Lactobacillus strains were identified by DNA amplification and sequencing Stock solutions of nifuratel (Polichem, Lugano-Pazzallo, Switzerland) and metronidazole (Sigma-Aldrich, Munich, Germany) were prepared in dimethyl sulfoxide (DMSO; SigmaAldrich) to a concentration of 51.2 mg/ml. Clindamycin (SigmaAldrich) was dissolved in water t...