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Background Approval of topical onychomycosis drugs by regulatory agencies may be negatively impacted by an overly stringent definition of complete cure, which includes nail clearing plus mycological cure. Objectives In this position paper, we discuss interpretation of mycological outcome and clinical trial length. Methods We reviewed data from seven international onychomycosis trials that enrolled subjects with positive KOH and dermatophyte-positive culture at screening followed by 48 weeks of treatment. Further, we examined 94 KOH-positive/culture-negative week 52 follow-up samples for morphological hyphal damage. Results From 3054 samples collected at week 52 follow-up visits, 2360 were culture-negative. However, a significant percentage (78·7%) of these subungual samples ( n = 1857) remained KOH-positive. From the subset of follow-up samples examined for morphological changes, we identified hyphal breakage or distortion in 56 direct smears (60%), which may indicate nonviability. Conclusions Reassessment of the definition of onychomycosis cure is critical. For clinical trials of topical agents, length of treatment should be re-examined. Further, in our experience, a high rate of subungual debris samples remained direct smear-positive while converting to negative culture. Evidence of morphological hyphal damage suggests that late-visit microscopic results may be false-positives. Therefore, the absence of clinical signs following an adequate washout period, coupled with a negative culture, with or without negative microscopy, should be considered the definition of onychomycosis cure. [ABSTRACT FROM AUTHOR]

Dear Editor, I Trichophyton rubrum i is the most common organism causing cutaneous fungal infections of the skin, hair and nails. Repeat testing for I T. rubrum i susceptibility revealed resistance to fluconazole (MIC > 16 µg mL SP -1 sp ), itraconazole (MIC > 8 µg mL SP -1 sp ) and terbinafine (MIC > 0-5 µg mL SP -1 sp ). Given that our patient was resistant to itraconazole, posaconazole - an antifungal typically reserved to treat invasive fungal infection in immunocompromised patients - was chosen as the subsequent therapy. [Extracted from the article]

The effects of voriconazole on the growth, morphology and lipids of Candida glabrata were studied. MIC data showed that voriconazole was up to 32- to 64-fold more active than fluconazole in its ability to inhibit various C. glabrata strains. Voriconazole inhibited the growth of C. glabrata in a dose-dependent fashion. Electron microscope examination showed that voriconazole treatment affected the external and internal morphology of C. glabrata. Treatment of C. glabrata with voriconazole inhibited ergosterol synthesis and led to accumulation of methylated sterols. In contrast, no significant difference in phospholipid composition was observed between treated and untreated cells. [ABSTRACT FROM AUTHOR]

The effects of voriconazole on the growth, morphology and lipids of Candida glabrata were studied. MIC data showed that voriconazole was up to 32- to 64-fold more active than fluconazole in its ability to inhibit various C. glabrata strains. Voriconazole inhibited the growth of C. glabrata in a dose-dependent fashion. Electron microscope examination showed that voriconazole treatment affected the external and internal morphology of C. glabrata. Treatment of C. glabrata with voriconazole inhibited ergosterol synthesis and led to accumulation of methylated sterols. In contrast, no significant difference in phospholipid composition was observed between treated and untreated cells. [ABSTRACT FROM PUBLISHER]

The effects of octenidine and pirtenidine on yeasts (in particular Candida albicans) have been studied. MIC and MCC values have been established as well as the inhibitory effects on growth, budding and germ tube formation. The drugs were shown to cause extensive leakage of cytoplasmic contents from the cells which was correlated with morphological and ultrastructural changes in the yeast. [ABSTRACT FROM AUTHOR]

Background Our group, in collaboration with seven other laboratories, has recently developed a method to determine the susceptibility of dermatophytes. Objectives The objective of this study was to determine the terbinafine susceptibility profile of dermatophyte isolates obtained from patients with tinea capitis enrolled in two large worldwide clinical trials and to investigate whether these susceptibilities differ by geographical location. Methods Susceptibilities were determined according to the Clinical and Laboratory Standards Institute M38-A2 standard. Results From a total of 978 baseline dermatophyte isolates, we selected 301 isolates at random. These included: Trichophyton tonsurans ( n = 125) , Microsporum canis ( n = 94), T. violaceum ( n = 63) and M. audouinii ( n = 19) . The terbinafine minimum inhibitory concentration (MIC) range was 0·001–0·25 μg mL−1, while MIC50 and MIC90 ranged between 0·002 and 0·125 μg mL−1 and 0·03 and 0·25 μg mL−1, respectively, for all species tested. MIC50 and MIC90 varied by individual species; however, there was no difference in terbinafine MIC among the different species isolated from U.S. and non-U.S. sites. Conclusion Terbinafine demonstrates potent antifungal activity against dermatophyte isolates obtained from patients with tinea capitis worldwide. [ABSTRACT FROM AUTHOR]