Experimental guinea pig model of dermatophytosis: a simple and useful tool for the evaluation of new diagnostics and antifungals.

The aim of this study was to establish a simple guinea pig model for the purpose of evaluating diagnostic principles and treatment modalities for dermatophytic infections. The following variables were evaluated; pre-treatment of the skin by shaving versus tape stripping, Microsporum canis or Trichophyton mentagrophytes test strains as etiologic agents, differences in inoculum concentrations, and inoculation with and without occlusion. The course of infection was evaluated clinically by redness and lesion scores and mycologically by microscopy, culture, and histopathology. The applicability of the model was evaluated with a recently developed diagnostic pan-dermatophyte PCR and antifungal treatment was tested with an oral solution of itraconazole, 10 mg/kg, once daily during days 3-14 of the test period. Pre-treatment of the skin with a manual razor was for practical reasons preferable to tape stripping. Inoculation under occlusion showed no advantage in the establishment of experimental infections. Infection severity showed some association with the inoculum concentration and subtype of T. mentagrophytes but not in studies involving M. canis. The establishment of dermatophytosis was confirmed by histopathology. Surprisingly, microscopy was found to be less sensitive than culture and the latter was as sensitive as pan-dermatophyte PCR. Itraconazole significantly reduced lesion and redness score, with M. canis infections responding better to itraconazole treatment than those caused by T. mentagrophytes. In conclusion, we established a dermatophytosis animal model, which was proven useful for evaluating diagnostic methods and antifungal susceptibility testing.

In vivo efficacy and pharmacokinetics of voriconazole in an animal model of dermatophytosis.

The standard treatment for tinea capitis caused by Microsporum species for many years has been oral griseofulvin, which is no longer universally marketed. Voriconazole has been demonstrated to inhibit growth of Microsporum canis in vitro. We evaluated the efficacy and tissue pharmacokinetics of oral voriconazole in a guinea pig model of dermatophytosis. Guinea pigs (n = 16) were inoculated with M. canis conidia on razed skin. Voriconazole was dosed orally at 20 mg/kg/day for 12 days (days 3 to 14). The guinea pigs were scored clinically (redness and lesion severity) and mycologically (microscopy and culture) until day 17. Voriconazole concentrations were measured day 14 in blood, skin biopsy specimens, and interstitial fluid obtained by microdialysis in selected animals. Clinically, the voriconazole-treated animals had significantly less redness and lower lesion scores than untreated animals from days 7 and 10, respectively (P < 0.05). Skin scrapings from seven of eight animals in the voriconazole-treated group were microscopy and culture negative in contrast to zero of eight animals from the untreated group at day 14. The colony counts per specimen were significantly higher in samples from untreated animals (mean colony count of 28) than in the voriconazole-treated animals (<1 in the voriconazole group [P < 0.0001]). The voriconazole concentration in microdialysate (unbound) ranged from 0.9 to 2.0 microg/ml and in the skin biopsy specimens total from 9.1 to 35.9 microg/g. In conclusion, orally administered voriconazole leads to skin concentrations greater than the necessary MICs for Microsporum and was shown to be highly efficacious in an animal model of dermatophytosis. Voriconazole may be a future alternative for treatment of tinea capitis in humans.

Treatment of head and neck dermatitis comparing itraconazole 200 mg and 400 mg daily for 1 week with placebo.

BACKGROUND: Head and neck dermatitis (HND) is a variant of atopic dermatitis often seen in young adults. A hypersensitivity to Malassezi antigens is considered to be of pathogenic importance. Previous mostly uncontrolled studies have shown that oral antimycotics might be of use in this condition. OBJECTIVE: To evaluate the efficacy of itraconazole in the treatment of HND in a randomized, double-blind, placebo-controlled trial. PATIENTS: Adult patients with HND were included. Systemic steroids and oral/topical antimycotics were avoided 1 and 2 months prior to the trial. Topical steroids were not allowed in the head and neck area within 2 weeks. Patients in generally good health were included and female patients had to have had a negative urine pregnancy test. The patients signed an informed consent. STUDY DESIGN: The study included a 7-day treatment period and a follow-up period of 105 days. Control visits were carried out on days 3, 7 and 14 and after 15 weeks. METHODS: The SCORAD index (one for the head and neck area and one for the remaining surface area) and global evaluations by patient and investigator were used for clinical evaluation at each visit. Prick tests with Malassezia antigens and Candida albicans antigen were carried out at the start of the trial and included positive and negative controls. The patients were randomized into three groups, which were treated with 400 mg itraconazole daily, 200 mg itraconazole daily or placebo, respectively, for 7 days. RESULTS: The number of patients included was 53: 18 had 200 mg itraconazole daily, 17 had 400 mg itraconazole daily and 18 placebo. At days 7 and 14, significant improvement was seen in the SCORAD of the head and neck area for the groups given 400 mg itraconazole daily (P = 0.0385 and P = 0.0134), and 200 mg daily (P = 0.0104 and P = 0.0006). Patients in the placebo group improved slightly (P = 0.0785). At day 14, comparison of improvement of SCORAD of the head and neck area between all three groups showed a significant difference in favour of the 200 mg itraconazole group compared to the placebo group (P = 0.0318). The prick test was positive for Pityrosporum ovale in 37% and negative for C. albicans in all patients. CONCLUSIONS: One week of treatment with 200 or 400 mg itraconazole as a single treatment has a significant effect on the head and neck area. Compared to placebo there was a significant improvement in SCORAD of the head and neck area in favour of the 200 mg itraconazole group after 14 days. The important observation seems to be that antifungal systemic treatment has a significant SCORAD reduction of atopic dermatitis, irrespective of the presence of allergy.

Onychomycosis in Denmark: prevalence of fungal nail infection in general practice.

The study was initiated in order to get knowledge of the frequency of onychomycosis in patients visiting general practitioners in Denmark. A study design was using a display showing photos of abnormal nails including fungal infection, a clinical examination and a questionnaire. The practitioners obtained nail material. Direct microscopy and culture as well as histopathology, were carried out blindly in two different mycological laboratories. A number of 8546 patients were seen during the 6 months of the study, 5755 (67.3%) took part in the investigation. Clinical abnormal nails were observed in 948 (16.5%) patients, 52% males and 48% females, aged 18-92, mean 55 years old. Onychomycosis caused by dermatophytes were found in 238 (4.1%) and by Candida albicans in 45 (0.8%). Trichosporon cutaneum and Scopulariopsis brevicaulis were isolated each in 15 cases as single cultures. Onychomycosis, was typically seen in toenails as the distal-lateral type in males more than 40 years old. Predisposing factors were familiar dermatophytosis (22%), trauma (16.9%), diabetes mellitus (6.7%) and peripheral circulatory insufficiency (5.9%).

Tinea pedis and onychomycosis in Danish soldiers before and after service in ex-Yugoslavia.

Seventy-three 1-year-experienced Danish soldiers were examined for tinea pedis as well as onychomycoses before and after a duty period of 6 months in ex-Yugoslavia. The incidence of fungal infections was 16.4% before and 32.3% after their duty period abroad. At first investigation Trichophyton rubrum and T. mentagrophytes were dominant but onychomycosis and tinea pedis were found as well. In contrast, Candida albicans was the predominant pathogen in the second investigation. We explain this by means of the more aggressive nature that yeasts can show when host-parasite relations are disturbed or compromised. Twelve soldiers with positive mycology were offered treatment and the final investigation showed a cure rate of 50%. This result is satisfactory in view of the difficult sanitary conditions.

Oral terbinafine in toenail dermatophytosis. A double-blind, placebo-controlled multicenter study with 12 months' follow-up.

The treatment of onychomycosis has previously often been protracted and unsuccessful. Terbinafine has been shown to be effective in short-term regimens. In this double-blind, placebo-controlled study, 148 patients with toenail dermatophytosis were randomized to treatment with either 250 mg terbinafine daily or placebo for 3 months. An additional treatment was given for 3 months to patients whose infection had not responded. The patients were followed clinically and mycologically through 12 months. After 3 months 82% of the terbinafine-treated group, versus 5% of the placebo group, showed significant improvement, i.e. negative culture and growth of unaffected nail more than 2 mm (p = < 0.0001). After 12 months clinical and mycological cure was seen in 40% of the patients treated with terbinafine for 3 or 6 months, while 67-81% were clinically cured, but with positive microscopy. Side-effects occurred in 13.5% of the terbinafine group, versus 5.4% of the placebo group, and were mild. 250 mg terbinafine daily for 3 months was significantly more effective than placebo. The efficacy did not appear to improve with additional treatment for 3 months.