Yvonne M. Clayton

An evaluation of itraconazole in the management of onychomycosis

At present the reported use of itraconazole, a new oral triazole antifungal, has been confined to short‐term treatments. This investigation is an appraisal of itraconazole in the treatment of three different forms of onychomycosis. Six patients with nail infections due to Candida albicans not associated with paronychia affecting a total of 20 nails received itraconazole (too mg daily) for a mean period of 5.9 months. Complete remission was achieved in all cases. Twenty six patients with dermatophyte onychomycosis affecting a total of 45 finger and 80 toe‐nails were treated with itraconazole (100–200 mg daily). In 24 cases the causative organism was Trichophyton rubrum. Remission was achieved in 64% of finger and 73% of toe‐nails in 5 and 9.4 months, respectively. Treatment failures were experienced in patients with finger‐nail infections due to T. violaceum (i) and those concurrently receiving phenytoin and phenobarbi‐tone (3). Three patients with infections due to Hendersonula toruloidea failed to respond to treatment. Adverse effects were experienced by four patients (abdominal discomfort 3, diarrhoea I), but none were serious enough to lead to abandonment of treatment. No persistent changes were seen in serum biochemical values. This study suggests that itraconazole is potentially effective in the long‐term treatment of superficial fungal infections such as onychomycosis, and comparative studies with alternatives such as griseofulvin should now be carried out.

Tioconazole nail solution—an open study of its efficacy in onychomycosis

In view of the problems encountered in the treatment of onychomycosis with orally administered antifungal drugs, alternative forms of therapy arc needed. Tioconazole (28%) nail solution is a new topical preparation for use on infected nails. In this study 27 patients received treatment with tioconazole (28%) for up to 12 months. Six patients (22%) achieved complete clinical remission and were free of infection at follow‐up, 3 months after therapy. They included infections caused by Trichophyton rubruni (4), Hendersonula toruloidea (1) and Acremonium (1). Apart from the latter, all infections responding to treatment were in the finger nails, even though three patients had active infection in the toe nails as well which did not respond to therapy. Significant improvements were recorded in a further 11 patients. They did not, however, achieve complete clinical and mycological recovery. The results indicate that cures of onychomycosis are possible after topical therapy, and further methods of using this form of treatment such as combined surgical and topical therapy are discussed.

A comparison of tioconazole 28% nail solution versus base as an adjunct to oral griseofulvin in patients with onychomycosis

While topical treatment of onychomycosis has proved largely unsuccessful, a nail solution containing 28% tioconazole has been effective in 22% of those treated. This study compared tioconazole 28% with placebo solution containing base only in patients receiving 1 g daily oral griseofulvin over a 1-year period. All patients had bilateral toe-nail infections caused by Trichophyton rubrum. Seventy nails were treated: in each patient, nails on one side received active compound and, on the other side, base only. Sixty-nine percent of nails treated with griseofulvin plus tioconazole achieved clinical and mycological remission, compared to 41% of those receiving oral drug plus placebo solution only. In addition, the mean percentage re-growth of infected nails was greater on the side receiving active compound at Months 1, 3, 6 and 9, but not at Month 12. These results suggest that combined oral griseofulvin and topical therapy with 28% tioconazole nail solution is an effective method of managing onychomycosis. No side-effects attributable to the treatment were observed during the study.

A comparative double blind study of ketoconazole and griseofulvin in dermatophytosis

The merits of oral ketoconazole and griseofulvin in dermatophytosis have been compared in a double blind study on 74 patients with 152 infected sites. The initial daily doses were 200 mg and 500 mg respectively, but these were doubled after 3 months if there was an inadequate clinical response. Treatment was continued either until clinical and mycological remission was achieved or a year of therapy had been given. Seventy‐five percent (total 80) and 74% (total 72) of all infected sites treated with ketoconazole and griseofulvin respectively were cleared of infection. However, in toe nail infections the respective cure rates were only 21% and 17%. Ketoconazole appeared to act more rapidly in curing tinea corporis or tinea cruris due to Trichophyton rubrum, whereas griseofulvin was superior in T. interdigitale infections. No serious side‐effects were encountered in either treatment group. In view of the slight risk of drug‐induced hepatitis, ketoconazole is best reserved as a second‐line drug for toe nail infections unless there are specific indications, such as griseofulvin intolerance. In these cases liver function tests should be monitored regularly throughout therapy.

Comparison of clotrimazole cream, Whitfield's ointment and Nystatin ointment for the topical treatment of ringworm infections, pityriasis versicolor, erythrasma and candidiasis

A double‐blind trial was used to compare the efficacy and acceptability of topical treatment with clotrimazole cream or Whitfields ointment for ringworm, pityriasis versicolor, and erythrasma infections, and that of clotrimazole cream or Nystatin ointment for Candida infections. Clotrimazole was found to be as effective and acceptable as Whitfields ointment and Nystatin ointment.

Antibiotic Production by Dermatophyte Fungi

Thirty-two clinical isolates of anthropophlic dermatophytes were examined for their capacity to produce antibiotics in liquid culture and on human stratum corneum in vitro. Antibiotics were detected and classified using agar diffusion bioassays and chromatographic analysis. Twenty-four isolates produced antibiotic substances in liquid culture filtrates; some strains produced more than one antibiotic. Only four isolates produced detectable levels of antibiotics when grown on stratum corneum unless an artificial sweat mixture was used as a nutrient supplement, when the number rose 11. Respresentatives of all species studied produced benzyl penicillin-like substances. Some Trichophyton isolates also produced streptomycin-like antibiotics, a characteristic previously unrecorded for eukaryotic organisms. Other antibiotics, which apart from azalomycin F could not be properly classified, were produced by Epidermophyton floccosum. Antibiotic production occurred over the normal skin temperature range but sometimes the type of antibiotic produced and the frequency of detection appeared to be influenced by the incubation temperature.

The treatment of patients with chronic mucocutaneous candidosis and Candida onychomycosis with ketoconazole

Twenty patients with chronic mucocutaneous candidosis (CMCC) and eleven patients with Candida onychomycosis (CO) were treated with oral ketoconazole. Twenty‐seven patients completed therapy after a mean treatment duration of 7‐6 months and were both clinically and mycologically free from infection. Clinical and mycological relapse was seen in five CMCC and one CO patient during follow up post treatment (8‐4 months mean). All the patients with CMCC who relapsed after ketoconazole presented with recurrent oral candidosis. During treatment, side effects such as nausea, headache and dizziness were seen in seven patients. The mean blood level of the drug i h after 200 mg of ketoconazole was 2–2 mg/1, although some patients showed persistently low levels, below 0‐4 mg/1. The use of ketoconazole is a significant advance in the management of chronic Candida infections of the nails. The relapse rate is low and there is a prompt response to retreatment.

Distribution of dermatophytes and Candida spores in the environment.

Summary.— The dispersal into the environment of spores of dermatophytes and Candida albicans from patients with mycotic skin infections is demonstrated by the culture of samples from the air and from normal areas of the body. C. albicans is found to be recovered more frequently than dermatophytes. The recovery of these fungi is also recorded from sweep plates of bedding and brush samples of the scalps of normal children in communities which harbour cases of scalp ringworm.

The treatment of fungus and yeast infections of nails by the method of‘chemical removal’

Experience with a‘chemical removal’ technique using a urea paste is described for treating dystrophic nails infected by fungus or yeasts. The method seems to be most useful in treating cases infected by organisms resistant to griseofulvin or ketoconazole.

A clinical double‐blind trial of topical miconazole* and clotrimazole† against superficial fungal infections and erythrasma

A clinical double‐blind trial of topical miconazole and clotrimazole creams was carried out against superficial fungal infections of the skin. The trial showed both compounds to be very effective against dermatophytes, pityriasis versicolor, Candida and erythrasma infections. Patient acceptability was equally good for both compounds.