[Dermatomycoses. 4: Onychomycoses--therapy--pathogens].
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Administration, Oral↗
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[Comparative evaluation of fluconazole 50 mg and 100 mg versus itraconazole 100 mg in the treatment of dermatomycoses].
In the above double-blind multicenter study the efficacy and tolerability of 50 and 100 mg doses of fluconazole were compared with 100 mg itraconazole in 178 patients with T. corporis, T. cruris, and T. pedis infections. All patients were submitted to clinical and mycological examination before starting, at weekly intervals during treatment, and 4 and 8 weeks after its conclusion. Duration of the three therapeutic regimes was 15 days for T. corporis and T. cruris, and 30 days for T. pedis infection. The percentage of symptomatic cure was 85% and 86.5%, respectively for 50 and 100 mg fluconazole, and 83% for itraconazole. Mycologic cure was achieved in 81.4% of patients treated with 50 mg fluconazole, 83.3% in those treated with 100 mg fluconazole, and 67.9% in those treated with 100 mg itraconazole. None of the groups showed changes in laboratory parameters. It is concluded that all three treatment schemes had high antimycotic activity, but fluconazole both 50 and 100 mg daily was superior. Both drugs were well tolerated and compliance was good.
Adolescent↗
[Dermatomycoses. 12: Mycoses of the genital region--clinical picture and differential diagnosis].
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Adult↗
[Dermatomycoses. 13: Mycoses of the genital region--therapy and follow-up].
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Antifungal Agents↗
[Zoonotic dermatomycoses in urban populations].
The authors analyzed epidemiologically two cases of trichophytosis caused by zoophilic dermatophytes in persons living in the city. The first case was a male aged 43, suffering from trichophytosis on the right side of his neck. The patient was infected at work from guinea pigs. Trichophyton mentagrophytes varietas granulosum was the etiological agent. The second case occurred in a female aged 29, suffering from trichophytosis on her left arm. Trichophyton verrucosum was the causal agent. A horse was the source of infection.
Adult↗
Oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis : case reports and review of the literature.
Inflammatory flare-up reactions of some dermatomycoses, particularly those caused by zoophilic fungi, are typical and potentially severe adverse effects following the intake of some oral antifungals. However, this condition has not previously been reported with the most frequently used antifungals in dermatology, namely fluconazole, itraconazole, and terbinafine. In this report, we describe five patients, observed over a 10-year period, who presented with inflammatory exacerbations following oral antifungal therapy for dermatomycoses. We also review the literature on inflammatory reactions exacerbated by oral antifungal agents. Details of the patients' age, sex, occupation, and atopic background; the site of the lesion, its clinical and histologic features, and any systemic signs; the identity of the fungal pathogen; the antifungal agent taken by the patient; the time between drug intake and occurrence of the flare-up; the approach to management; and the outcome were documented for each patient. A PubMed literature search was also conducted, focusing on inflammatory exacerbations induced by griseofulvin, ketoconazole, itraconazole, fluconazole, and terbinafine. The patients were four farmers and one veterinarian (all male). All primary lesions were inflammatory dermatophytoses, including one kerion. Inflammatory exacerbation of the skin lesions started 12-24 hours after the intake of oral antifungals. Mild systemic changes, including slight fever and malaise, occurred in two cases. Itraconazole 400 mg/day was implicated as the causative agent in four cases and terbinafine 250 mg/day in one case. Mycologic cultures grew Trichophytonverrucosum in four cases. Antifungal treatment was discontinued in all patients. Oral and topical corticosteroids were administered to the two patients with systemic changes; the other three patients were treated with topical corticosteroids only. Two days after the onset of corticosteroids, lower doses of itraconazole (100 mg/day) and terbinafine (125 mg/day) were reintroduced. All lesions healed after 4-5 weeks. The PubMed search did not identify any articles that described inflammatory exacerbations of dermatomycoses induced by oral antifungals. Inflammatory flare-up of dermatomycoses is a rare but potentially severe cutaneous complication of oral antifungal use. Occupational contact with animals, inflammatory dermatomycoses, and zoophilic fungi represent common features in these patients. Although evidence-based data are not available, clinical experience shows that, in addition to antifungal therapy, topical and/or systemic corticosteroids are helpful to reduce the inflammatory reactions. The cases described in this article represent the first published report of oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis in patients taking itraconazole or terbinafine.
Administration, Oral↗
Topical pharmacology of imidazole antifungals.
Four imidazole derivatives have now undergone extensive open and comparative trials as topical agents in dermatomycoses and vaginal candidosis. They are chlormidazole (Chemie Grünenthal), clotrimazole (Bayer), miconazole (Janssen) and econazole (Janssen, Cilag-Chemie); all also have some antibacterial activity. Many other imidazoles have been marketed, usually as antiprotozoal or anthelminthic agents, and some of these have some antimycotic activity as well as other miscellaneous therapeutic properties. The mode of action of imidazole antimycotic agents is discussed; after prolonged topical application to animals and human subjects, systemic absorption is negligible. All four agents which are available as cream, powder, lotion or vaginal tablets have many sucessful studies to their credit, often with clinical and mycological cure rates of over 80% in a variety of dermatomycoses and in vaginal candidosis. The relative value of these topical agents is discussed, and it is suggested that in severe and extensive dermatomycoses consideration should be given to the systemic use of miconazole in support of topical therapy.
Administration, Topical↗
Fungal infections of the skin: infection process and antimycotic therapy.
Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. These typically nonfatal conditions are difficult to treat, especially infections of the nail. Dermatomycoses are caused by filamentous fungi such as Trichophyton, Microsporum or Epidermophyton species. These filamentous fungi have a high affinity for keratin, an important component of hair, skin and nails, which are the primary areas of infection by dermatophytes. The antifungal agents currently marketed for dermatomycoses are mainly inhibitors of ergosterol biosynthesis, except for griseofulvin, which interferes with the cytoplasmic and nuclear microtubular system. Three different types of inhibitors of the ergosterol biosynthetic pathway have been proven to be effective in clinic: the azoles (e.g. topical miconazole and topical/oral ketoconazole, itraconazole and fluconazole), the allylamines (e.g. terbinafine) and morpholines (amorolfine). Even today more effective antifungal azoles with less adverse effects and short-term therapy are deemed necessary to treat dermatophytosis. A promising novel triazole compound in this respect is R126638, which showed potent in vitro and in vivo activity.
Allylamine↗
A multi-center, double-blind comparison of ketoconazole and griseofulvin in the treatment of infections due to dermatophytes.
The efficacy and safety of daily doses of 200 mg of ketoconazole or 250 mg of griseofulvin (Fulvicin-P/G, Schering, Kenilworth, N.J.) in the treatment of patients with infections due to dermatophytes are being evaluated in a three-center study. Patients with chronic dermatomycoses resistant to topical treatment or with infections that involve large areas of the body, a condition that indicates oral therapy, are being treated for a minimum of four weeks. Eleven (38%) of 29 patients treated with ketoconazole for four weeks and five (24%) of 21 patients treated with grisofulvin for the same amount of time were rated as cured. At completion of therapy (four to eight weeks), 24 (83%) of 29 patients treated with ketoconazole and six (32%) of 19 patients treated with griseofulvin were rated as cured (P = < 0.001). One (7%) of 14 patients treated with ketoconazole and four (80%) of five patients treated with griseofulvin were rated as relapsed within 28 days after completion of therapy (P = 0.006). No significant adverse effects have been reported for either treatment group. The preliminary results of this study have shown ketoconazole to be more effective than griseofulvin in the treatment of dermatomycoses.
Dermatomycoses↗
Safety of itraconazole in diabetic patients.
BACKGROUND: Onychomycosis and dermatomycoses can result in serious complications in patients with underlying chronic diseases such as diabetes. To avoid these complications, these dermatological disorders need to be treated efficiently, for example with the triazole antifungal itraconazole. Itraconazole can inhibit the metabolism of drugs by CYP 3A4 and therefore might affect the efficacy of antidiabetic agents. OBJECTIVE: To investigate this, we assessed the safety of itraconazole in diabetic patients with onychomycosis or dermatomycoses. METHODS: We reviewed pharmacokinetic and safety data from clinical trials and postmarketing surveillance over the past 10 years. RESULTS: Postmarketing surveillance (a review of all adverse-event reports in patients receiving itraconazole concomitantly with insulin or an oral antidiabetic agent) revealed 15 reports suggestive of hyperglycemia and 9 reports suggestive of hypoglycemia; in most patients, no change in antidiabetic effect was reported. From clinical trials including a total of 189 diabetic patients treated with itraconazole for various infections (mainly systemic infections and vaginal candidiasis), only one itraconazole-related adverse event was recorded; this was a case of aggravated diabetes in a renal transplant recipient who was also receiving cyclosporine. Adverse effects due to drug-drug interactions are not expected in diabetic patients receiving oral antidiabetic agents that are not metabolized through the CYP 3A4 system (e.g. tolbutamide, gliclazide, glibenclamide, glipizide and metformin). CONCLUSION: Itraconazole can be used safely and efficiently for the treatment of dermatological disorders in diabetic patients.
Antifungal Agents↗
The use of itraconazole to treat cutaneous fungal infections in children.
BACKGROUND: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. OBJECTIVE: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. METHODS: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). RESULTS: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. CONCLUSIONS: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.
Antifungal Agents↗
Ciclopirox olamine 1% cream. A preliminary review of its antimicrobial activity and therapeutic use.
Ciclopirox olamine is a substituted pyridone antimycotic, unrelated to the imidazole derivatives, with activity against a broad spectrum of dermatophytes, yeasts, actinomycetes, molds, other fungi, and a variety of Gram-positive and Gram-negative bacteria. The efficacy of ciclopirox olamine cream has been demonstrated in open and placebo-controlled studies in patients with superficial dermatophyte or yeast infections, and in double-blind comparative trials in patients with dermatomycoses, topical ciclopirox olamine was comparable to or better than clotrimazole in efficacy and caused a similar number of side effects. Ciclopirox olamine penetrates through fingernails and in preliminary studies has been successfully used in onychomycoses. However, further studies are needed to establish the role of ciclopirox in the treatment of onychomycoses and dermatomycoses relative to that of the more recently introduced antigungal agents.
Animals↗
[Statistical study of dermatomycosis for 30 years (1968-1997) in sendai national hospital].
A statistical study on dermatomycoses for the 30 years from 1968 to 1997 in the dermatologic section of Sendai National Hospital was carried out with the following results. The total number of dermatomycosis patients was 14,259 and accounted for 9.59% of all new outpatients during this period. These cases of dermatomycoses were composed of the following: dermatophytoses 10,656, candidiasis 3,287, malassezia infection 566, sporothrichosis 20, aspergillosis 7, and chromomycosis 1. Annual changes in number of dermatophytoses varied in each clinical type: tinea corporis and tinea cruris had increased by the end of the 1970s, and there after decreased gradually until recent years. Tinea pedis and tinea unguium, on the contrary, increased after the 1980s. Age distribution of all clinical forms of dermatophytoses changed gradually, and its peak of the distribution curve shifted to an older site each year, while the number of younger generation patients decreased. Mycologically Trichophyton (T.) rubrum was mainly isolated from all types of dermatophytoses, and T. mentagrophytes followed. The ratio of these two species (R/M) in tinea pedis was 1.25, and the ratio of T. mentagrophytes was relatively high. Epidermophyton floccosum was continuously isolated, but its frequency in recent years has decreased. Microsporum canis infection increased from the middle period of this research, but after 1990 decreased gradually. The other dermatophytes were found sporadically. In recent years the species isolated have become more simplified. Among candidiasis, infantile candidiasis increased dramatically in the 1970s but soon decreased. Intertrigo type also increased in the same period and then decreased to an intermediate level. Paronychia, onychia and erosio interdigitale were constantly found in small numbers, while malassezia infection remained at a constant level and was found more in male patients.
Adolescent↗
Oral itraconazole therapy for superficial, subcutaneous, and systemic infections. A panoramic view.
The availability of the oral triazole agents itraconazole and fluconazole has revolutionized antifungal therapy. Although there are still some limitations and treatment failures, these agents have allowed for improved efficacy, increased safety, reduced morbidity, decreased mortality from systemic fungal disease, and a shift toward increased outpatient therapy for fungal infections that are not life-threatening. The treatment of superficial infections also has been enhanced by the development of effective intermittent and short-course regimens. Itraconazole exhibits broad-spectrum in vitro activity against several fungal organisms, including Trichophyton species, Candida albicans, Pityrosporum species, Aspergillus flavus, Aspergillus fumigatus, Blastomyces dermatitidis, Histoplasma capsulatum, Histoplasma capsulatum var duboisii, Sporothrix schenckii, and Cryptococcus neoformans. Animal model studies have confirmed the broad-spectrum in vivo activity of itraconazole. Multiple clinical studies and extensive clinical experience have substantiated the versatility of itraconazole, with good efficacy demonstrated in a wide variety of infections in humans. Itraconazole is approved for use in several countries for dermatomycoses, onychomycosis, oral-esophageal candidiasis, vaginal candidiasis, histoplasmosis, blastomycosis, aspergillosis, and fungal keratitis. Pulse therapy regimens for dermatomycoses and onychomycosis of the toenails or fingernails have been approved in several countries.
Administration, Oral↗
[Multicenter study of superficial mycoses in Argentina. EMMS Group].
Dermatomycoses are an important sanitary problem. Our country counts with partial epidemiological data only referred to a few geographical areas. The aim of our work was to perform a multicenter study with the participation of 15 medical centers located at the Capital City and in 11 Provinces of Argentina with different socioeconomical and cultural characteristics. Between October and December 1998, 851 ambulatory patients of both sexes (58% female, 42% male) with lesions compatible with mycoses in skin, nails or scalp were studied. Only 51.6% of the patients had mycoses confirmed by direct microscopic examination and/ or culture. Dermatophytes caused 69.3% of the diagnosticated infections, yeast 12.2% and Malassezia furfur 13.3%. Agents of dermatomycoses most frequently isolated were T. rubrum (52.7%), T. mentagrophytes (19.2%) and M. canis (14.2%). C. albicans was the predominant causative agent of yeast infections (44.4%). In children below 11 years old, the most frequent infections were tinea capitis 55.4% (M. canis 60%, T. tonsurans and M. gypseum 8.3%) and tinea corporis 20% (M. canis 46%, T. mentagrophytes 30%). The most frequent localizations in adult were toenail and feet (63%) (T. rubrum 47.3% and 45.7%, T. mentagrophytes 9.5% and 23.4%, respectively), fingernail 15.6% (C. albicans 25% and T. rubrum 8.3%) and trunk and extremities 12.2% (M. furfur 57.5% and T. mentagrophytes 14.9%). Direct examination allowed the diagnosis of 94.66% of all positive samples and 91.74% of the cases with positive isolation.
Adolescent↗
[Therapeutic experience with 5-chloro-8-hydroxyquinoline].
This paper reports on the clinical trials of an antimycoticum using 5-chlorine-8-hydroxychinolin as an antimycotic agent. 142 patients with surface dermatomycoses were treated locally with the preparation for 5 to 6 weeks. Clinical and mycological healing was achieved in 68% of the cases. The results of the treatment, the epicutaneous tests and the additional UV exposition are discussed. The best results of treatment were obtained in the case of superficial dermatomycoses, in particular Trichophytia inguinalis.
1-Propanol↗
Croconazole: a new broad spectrum agent in the treatment of fungal skin infections.
Croconazole hydrochloride (1%) cream is a new antifungal agent for the treatment of dermatomycoses. In vitro, croconazole has a broad spectrum of activity against dermatophytes, moulds, yeasts, dimorphic fungi and some skin-relevant bacteria. Therapeutic results obtained in 277 patients (mean age 43.0 +/- 14.8 years; 158 male and 119 female) who had mycoses at various locations and were treated with 1% croconazole cream are reported. The types of fungal infection in these patients were: pityriasis versicolor (94), candidiasis (43) and trichophytosis (140). One topical application per day was administered for a period of up to three weeks. Clinical improvement and mycology were assessed at one-week intervals, and after a two-week treatment-free follow-up. In all three infection groups the criteria of mycosis, particularly fungal microscopy findings and itching, showed rapid improvement. At the end of the observation period, clinical and mycological cure was observed in the majority of patients. The physicians' global efficacy rating of the medication was "good" or "very good" in 92.6% of the cases with pityriasis versicolor, 97.7% of the patients with candidiasis and 82.9% of the trichophytosis patients. The medication was well tolerated: only one patient reported an adverse reaction (pruritus) at the site of application. It is concluded that croconazole cream is effective and well tolerated in dermatomycoses. The once-a-day use of croconazole cream may be a positive factor in patient compliance.
Adult↗
An investigation of the pharmacokinetics of topical terbinafine (Lamisil) 1% cream.
Twenty human volunteers were entered into a study to investigate the pharmacokinetics of terbinafine 1% cream. Subjects were randomized to receive terbinafine 1% cream applied to the back on 1 day, or on 3, 5 or 7 consecutive days. Up to five sequential skin surface biopsies were taken at a site on the upper back at various time-points both during treatment, and following cessation of treatment. Terbinafine levels in these biopsies were analysed using HPLC. The study showed that increasing the number of applications from one to seven did not significantly increase the peak concentration (Cmax) in the stratum corneum. It did, however, increase the total amount of terbinafine found in the stratum corneum, resulting in terbinafine being detected for longer periods after cessation of therapy. Treatment for 7 days resulted in terbinafine still being detectable 7 days after cessation of therapy, when the terbinafine concentration was significantly higher than the known cidal concentrations for the common causative organisms of superficial dermatomycoses. This study indicates a significant potential for short-duration treatment with terbinafine (Lamisil) 1% cream in superficial dermatomycoses.
Administration, Topical↗