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As onychomycosis is unsightly, this study clinically evaluated whether the antifungal efficacy of amorolfine 5% nail lacquer (NL) was affected by a masking, natural-coloured, cosmetic nail varnish applied 24 h later; in vitro investigations were also performed. Subjects with mild-to-moderate distal subungual toenail onychomycosis were randomised to receive amorolfine 5% NL once weekly with or without cosmetic nail varnish applied 24 h later. After 12-week treatment, antifungal activity of affected toenail clippings was assessed by measurement of zones of inhibition (ZOIs) on Trichophyton mentagrophytes seeded agar plates. Mean diameters were 53.5 mm for the amorolfine 5% NL-alone group (n = 23) and 53.6 mm for amorolfine 5% NL plus cosmetic nail varnish group (n = 25). Also, mycological cultures of subungual debris at week 12 were negative for all subjects in both groups. Most subjects (88%) reported that cosmetic nail varnish masked their infected toenails. Additionally, cadaver human nails coated in vitro with or without cosmetic nail varnish 10 min or 24 h post amorolfine NL application all gave ZOIs on Trichophyton rubrum agar plates representing potent antifungal activity. In conclusion, cosmetic nail varnish applied post amorolfine had no effect on the subungual antifungal activity of amorolfine 5% NL or its penetration through toenails., (© 2016 The Authors Mycoses published by Blackwell Verlag GmbH.)

Oropharyngeal candidiasis (OPC) is a common infection among the immuno-compromised population. Treatments include both systemic azoles, most commonly fluconazole (FLU), and topical agents such as miconazole (MICON). However, resistance to FLU has been reported with a greater frequency. The aim of this study was to determine the potential for development of resistance following repeated exposure of Candida spp. to MICON. Two clinical isolates each of Candida albicans, C. glabrata, and C. tropicalis were tested. Fifteen passages of each strain were performed in concentrations of MICON at 0.5 minimum inhibitory concentration (MIC), 1 MIC, 2 MIC and 4 MIC, with MIC determinations performed on growth obtained following each passage. There was no increase in the MIC of four of the six strains following fifteen passages in MICON. One C. albicans strain demonstrated a four-five dilution increase in MICON MIC at all concentrations and one C. glabrata strain showed a fivefold MICON MIC increase when exposed to 4 MIC. Although an increase in MIC was noted in these two isolates, the MICON MIC was still very low (0.5 μg ml(-1)). In general, there was no increase in MIC demonstrated by repeated exposure to MICON in this study., (© 2010 Blackwell Verlag GmbH.)

Miconazole (MICON) has long been used for the topical treatment of mucosal candidiasis. However, the preponderance of MICON susceptibility data was generated before standard methodology was established, and prior to the emergence of fluconazole (FLU)-resistant strains. The objective of this study was to determine the antifungal activity of MICON and comparators against recent clinical isolates of Candida spp. using standard Clinical and Laboratory Standards Institute methodology. One hundred and fifty isolates, consisting of 25 strains each of Candida albicans, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis and C. dubliniensis, were tested. Of these, twenty-two strains were known to be FLU-resistant. Minimum inhibitory concentrations (MICs) were determined for MICON, amphotericin B (AM), caspofungin (CAS), clotrimazole (CLOT), FLU, itraconazole (ITRA), nystatin (NYS) and voriconazole (VOR). MICON demonstrated potent inhibitory activity against all of the strains tested. The MIC(90) for MICON was 0.12 microg ml(-1) against FLU-susceptible strains, which was comparable to that of AM, CAS, CLOT, ITRA and VOR. The MICON MIC(90) against FLU-resistant strains was 0.5 microg ml(-1), which was 12-fold lower than the FLU MIC(90). Our study showed that MICON possesses potent activity against all of the Candida isolates tested, including those with known FLU resistance. This indicates that recent clinical isolates remain susceptible to this antifungal and that MICON could be used as first-line treatment for oropharyngeal candidiasis.

The objective of this study was to compare the antifungal activity of terbinafine (TERB) with that of lanoconazole (LAN). Test isolates, which were clinical isolates of Japanese origin, included 10 strains each of Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum. The minimum inhibitory concentration (MIC) of TERB and LAN against each dermatophyte isolate was determined according to the Clinical and Laboratory Standards Institute microbroth methodology, M38-A2. Minimum fungicidal concentrations were determined by subculturing the contents of each visibly clear well from the MIC assay for colony count. All LAN MICs were

Biofilm formation plays an integral role in catheter-associated bloodstream infections caused by Candida albicans. Biofilms formed on catheters placed intravenously are exposed to shear stress caused by blood flow. In this study, we investigated whether shear stress affects the ability of C. albicans to form biofilms. Candida biofilms were formed on catheter discs and exposed to physiological levels of shear stress using a rotating disc system (RDS). Control biofilms were grown under conditions of no flow. Tetrazolium (XTT) assay and dry weight (DW) measurements were used to quantify metabolic activity and biofilm mass respectively. Confocal scanning laser microscopy (CSLM) was used to evaluate architecture and biofilm thickness. After 90 min, cells attached under no-flow exhibited significantly greater XTT activity and DW than those under shear. However, by 24 h, biofilms formed under both conditions had similar XTT activities and DW. Interestingly, thickness of biofilms formed under no-flow was significantly greater after 24 h than of those formed under shear stress, demonstrating that shear exposure results in thinner, but denser biofilms. These studies suggest that biofilm architecture is modulated by shear in a phase-dependent manner.

Currently available topical antifungals are often not satisfactory for the treatment of nail infections, because of the inability to penetrate the nail plate. Terbinafine HCl nail solution is a novel antifungal formulation containing a nail penetration enhancer dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP HCl, trade name NexACT-88). In this study, we used a guinea pig model of Trichophyton mentagrophytes dermatophytosis and evaluated the clinical and mycological efficacy of different terbinafine HCl nail solutions (TNS) formulated with or without DDAIP HCl. Ciclopirox (8%) nail lacquer (Penlac), the only Food and Drug Administration approved topical treatment for onychomycosis, was used as a comparator. Following the IACUC Guidelines, the skin of male albino guinea pigs was abraded under anaesthesia. Each animal was infected with T. mentagrophytes ATCC 24953 (cell suspension containing 1 x 10(7) conidia). The experimental animals were divided into 11 groups (five animals per group) and tested with the following formulations: vehicle control, 0.5% DDAIP HCl, 1%, 5% and 10% TNS (without DDAIP HCl), 1% TNS with 0.5%, 2.5% and 5.0% DDAIP HCl, 5% and 10% TNS with 0.5% DDAIP HCl, 8% ciclopirox nail lacquer and an untreated control group. Evaluation of clinical and mycological efficacy was performed 72 h after completion of a 7-day treatment regimen. Skin biopsy samples were processed for histopathological examination. The infected untreated control guinea pigs showed patches of hair loss and ulcerated or scaly skin and fungal invasion of hair roots. The vehicle and 0.5% DDAIP HCl treated groups showed minimal clinical efficacy (only 11% and 5%, respectively). In contrast, all three concentrations of TNS (1%, 5% and 10% terbinafine HCl) formulated with or without 0.5% DDAIP HCl showed 100% mycological efficacy by the hair root invasion test. Clinical efficacy of the 5% and 10% TNS improved with addition of 0.5% DDAIP HCl (47.4% and 73.8% vs. 68.4% and 89.5%, respectively). In addition, no fungal elements were detected in the treated guinea pig skin. All formulations of TNS resulted in a higher clinical and mycological efficacy compared with the 8% ciclopirox nail lacquer (P = 0.0444). In conclusion, TNS containing 1%, 5% and 10% terbinafine HCl formulated with and without DDAIP HCl demonstrated high antifungal efficacy in experimental dermatophytosis. Addition of 0.5% DDAIP HCl to 5% and 10% TNS significantly enhanced the clinical and mycological efficacy of these formulations which were superior compared with the 8% ciclopirox nail lacquer. Evaluation of the 1%, 5% and 10% TNS in clinical trials for the treatment of dermatophytosis and onychomycosis is warranted.

Onychomycosis is a common fungal disease infecting up to 20% of the population over age 40. The major causative agent of onychomycosis is Trichophyton rubrum. Uncontrolled infection may eventually lead to penetration of the newly forming nail plate. In spite of the encouraging cure rate with recent antifungal agents such as the allylamines (terbinafine) and azoles (itraconazole and fluconazole) some patients inevitably fail therapy. In this investigation, a group of patients from a multi-center study designed to assess the efficacy of terbinafine with known cases of onychomycosis were selected for evaluation. Nail samples from this patient group were colonized with T. rubrum throughout the terbinafine therapy. Antifungal susceptibility testing was performed on these T. rubrum isolates to detect change in MIC values. Strain relatedness was examined using random amplified polymorphic DNA (RAPD) technique. Our results revealed failure of patients to clear T. rubrum is not related to the development of resistance to the drug. While species determination was possible, we were not able to identify differences that would indicate reinfection with a new strain. Analysis of patient demographic data revealed that 70% of patients were over 45 years old, 56.6% were previously treated with antifungals, 60% came from family history with onychomycosis and 13 % were diabetic. In conclusion, our data indicate that patients' failure to clear onychomycosis was not associated with resistant development. Failure of terbinafine therapy may be dependent on host-related factors., (1999 Blackwell Science Ltd.)

Onychomycosis is a common fungal disease infecting up to 20% of the population over age 40. The major causative agent of onychomycosis is Trichophyton rubrum. Uncontrolled infection may eventually lead to penetration of the newly forming nail plate. In spite of the encouraging cure rate with recent antifungal agents such as the allylamines (terbinafine) and azoles (itraconazole and fluconazole) some patients inevitably fail therapy. In this investigation, a group of patients from a multi-center study designed to assess the efficacy of terbinafine with known cases of onychomycosis were selected for evaluation. Nail samples from this patient group were colonized with T. rubrum throughout the terbinafine therapy. Antifungal susceptibility testing was performed on these T. rubrum isolates to detect change in MIC values. Strain relatedness was examined using random amplified polymorphic DNA (RAPD) technique. Our results revealed failure of patients to clear T. rubrum is not related to the development of resistance to the drug. While species determination was possible, we were not able to identify differences that would indicate reinfection with a new strain. Analysis of patient demographic data revealed that 70% of patients were over 45 years old, 56.6% were previously treated with antifungals, 60% came from family history with onychomycosis and 13% were diabetic. In conclusion, our data indicate that patients' failure to clear onychomycosis was not associated with resistant development. Failure of terbinafine therapy may be dependent on host-related factors.

In search of adhesion-variant strains of Candida albicans the adherence of a number of polyenes and/or azole-resistant strains of this yeast was studied (C. albicans 6406, 6406/8 and 799-XL, -XS, -YS, -R and YL). For comparison C. albicans KCCC 14172, known for its high adhesion and proteinase production, was also used. All isolates showed significantly lower adhesion (P < 0.001) compared with KCCC 14172. The exception was 6406/8 which showed superior adherability to all strains tested (2.5-4.8 times more adherent). This superiority prompted us to study the possible variation between this strain and the others in parameters that contribute to pathogenicity. Strain 6406/8 had the smallest average cell size (0.5-0.75 the size of cells from other strains). Variation in proteinase production and germ-tube formation existed among strains, with strain 6406/8 producing the lowest levels of inducible proteinase (2-4-fold less than the others), as well as being the least germ-tube former (10 times less than other strains). Ultrastructural comparisons between strain 6406/8 and its parent showed that the mutant strain had a thinner cell wall with a dense floccular layer throughout the cell wall compared to the parent strain. The cytoplasmic membrane of the mutant was more conspicuous than that of the parent strain. Comparison of the pathogenicity of strain 6406/8 and its parent (6406) revealed that although the mutant strain initially showed higher colonization than the parent strain, it was cleared much faster.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of infections due to Candida albicans and other related species has increased in recent years. A number of factors have contributed to this, e.g. the use of a wide range of potent antibacterial and immunosuppressive therapeutic agents and the increased incidence of immune-deficiency diseases such as AIDS. Pathogenicity determinants which confer virulence on C. albicans, and other Candida species to a lesser extent, have been reviewed. These include factors related to species and strains, adherence, dimorphism, toxin and enzyme production and cell surface composition. This review clearly shows that C. albicans virulence is a function of a multiplicity of factors working jointly to overcome the host defences. A lack or debility in any of these parameters will reflect negatively on its infectivity and make it difficult for Candida to establish itself, particularly in a healthy individual.