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Immunochemical characterization of somatic and metabolic antigens of 4 species of Aphanoascus: preliminary results.

Aphanoascus spp. are keratinophylic fungi occasionally described as etiological agents of tinea-like dermatomycoses. The goal of this work was to immunochemically characterize somatic and metabolic soluble antigens prepared from 4 species of Aphanoascus. Electrophoresis in SDS-PAGE gel and immunoblotting with sera from rabbits experimentally immunized with both somatic and metabolic antigens have shown a similar pattern among the species analyzed. However, some differences were noted between the species of Aphanoascus. These results suggest the existence of species-specific antigens.

Animals↗

Skin infections in renal transplant recipients.

BACKGROUND: Skin infection is a frequent complication in renal transplant recipients. The purpose of the study was to acquire long-term, period-specific incidence data on the most commonly occurring skin infections in renal transplant recipients. METHODS: A retrospective analysis was performed using medical records of 134 patients, covering a period between 10 and 29 yr. Cumulative incidences of the skin infections were calculated by counting the infections per patient for different time periods and were expressed as a percentage of the total group of patients. The incidence of the skin infections was determined for different post-transplant time periods. RESULTS: A total of 340 skin infections in 105 out of 134 patients were recorded. Some infections, such as candidal infection, herpes simplex infection, and impetigo were most prominent during the first post-transplant year and did not affect many new patients after the first year. Other infections, such as dermatomycoses, herpes zoster, and folliculitis were also affecting a substantial number of new patients after the first post-transplant year. CONCLUSIONS: This study confirms that skin infections among renal transplant recipients are very common and that the spectrum of skin infections differs according to the post-transplant time period.

Adult↗

Cutaneous adverse effects associated with terbinafine therapy: 10 case reports and a review of the literature.

Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions associated with terbinafine therapy which required discontinuation of the antifungal agent: erythema multiforme (five patients), erythroderma (one), severe urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis (two patients). The spectrum of cutaneous adverse effects associated with terbinafine therapy is reviewed. Patients should be counselled about discontinuing terbinafine at the onset of a cutaneous eruption and about seeking medical advice about further management.

Adult↗

Drug interactions of the newer oral antifungal agents.

The newer oral antifungal agents, such as fluconazole, itraconazole and terbinafine, are generally both effective and well tolerated in the management of widespread or resistant dermatomycoses such as onychomycosis. However, these agents differ markedly in their potential to cause clinically significant drug interactions. Triazoles such as fluconazole and itraconazole have been responsible for a greater number of clinically significant drug interactions than terbinafine. For example, itraconazole, and to a lesser extent fluconazole (in high doses) are inhibitors of CYP3A4. Therefore certain agents that are substrates of this enzyme, such as some of the new generation of H1-antihistamines, several HMG-CoA reductase inhibitors and certain benzodiazepines, are contraindicated. Other drugs like cyclosporine and quinidine need careful monitoring if administered concurrently with these triazoles. In contrast, there are no drug-drug contraindications with terbinafine. Indeed, in a postmarketing surveillance study, in which 42.8% of the 25,884 participating patients were taking a variety of concomitant therapies, no new drug-drug interactions were revealed. Physicians should be aware of the potential for interaction of the medications that they prescribe, in order to prevent or reduce the burden of adverse events. Terbinafine may be the most rational choice of oral antifungal agent in patients receiving concomitant medications that may adversely affect or be affected by either fluconazole or itraconazole.

Administration, Oral↗

Inhibition of sterol 14 alpha-demethylation of Candida albicans with NND-502, a novel optically active imidazole antimycotic agent.

To investigate the mode of action of the newly synthesized optically active imidazole compound, NND-502, (-)-(E)-[4-(2, 4-dichlorophenyl)-1,3-dithiolan-2-ylidene]-1-imidazolylacetonit rile, its effect on ergosterol biosynthesis in cell-free extracts of Candida albicans was examined and compared with that of the (S)-enantiomer of NND-502 in addition to lanoconazole and bifonazole, both of which are clinically used for the treatment of dermatomycoses. NND-502 was found to interfere with ergosterol biosynthesis by inhibition of sterol 14alpha-demethylase, while no interference due to the (S)-enantiomer of NND-502 was found, indicating that the stereochemical orientation of the 2, 4-dichlorophenyl group plays an important role in the interaction with the enzyme. In terms of drug concentration exerting 50% inhibition of ergosterol biosynthesis, NND-502 was 2.5 and 28 times more effective than that of lanoconazole and bifonazole, respectively.

Antifungal Agents↗

Incidence and distribution of Candida species isolated from human skin in Jordan.

In the period between December 1992 and September 1993 a total of 1060 clinically suspected cases of dermatomycoses were examined for causative fungi. Of these 330 (31%) were suspected as cutaneous candidosis. A higher incidence was observed in adults (62.9%) than in children (36.2%) and infants (19.5%). The infected patients that were adults were divided into four categories: diabetics; those receiving steroid; those receiving antibiotic therapy; and a non-risk control group. Analysis of the data revealed that the incidence rate appears to be approximately doubled in diabetes (49.3%), steroid therapy (33.8%) and antibiotic therapy (27.4%) than in the control group (15.7%). Candida albicans was the most frequent isolate (57.6%) followed by Candida tropicalis (16.5%).

Adolescent↗

A review of the epidemiology of tinea unguium in the community.

Tinea unguium is a common, chronic fungal infection of the nails. Many epidemiological studies have looked at the frequency with which this condition is seen in hospital outpatients clinics or mycological laboratories along with other dermatomycoses. Only recently have studies begun to emerge looking at the prevalence of this condition in populations. Hospital and mycological laboratory-based studies give valuable information about tinea unguium prevalence in a particular clinic, but cannot be compared with other studies due to confounding factors inherent in the different people attending individual clinics. From population-based studies the prevalence of tinea unguium lies between 2 and 8%. Tinea unguium increases steadily with age. It is infrequent but definitely found in children. With the increasing life expectancy in the Western world the prevalence of tinea unguium is likely to increase further without adequate prevention and treatment.

Adolescent↗

Etiology of ringworm of the scalp, beard and body in Rome, Italy.

From 1972 to 1977 the authors examined 1,311 patients in Rome affected by ringworm of the scalp, beard and body, comparing their findings with a study made in Milan between 1969 to 1973 and with earlier Italian studies from 1900 to date. It appears that at the beginning of the century scalp ringworm was usually caused by Trichophyton violaceum and T. tonsurans, whereas Microsporum canis was rarely found. Today the Trichophyton species are rarely isolated, whereas Microsporum species, particularly M. canis (88.9% of the cases in Rome, 74.6% in Milan), predominate in the etiology of scalp ringworm. Ringworm of the beard in Rome is mainly caused by T. mentagrophytes (50% of the cases) and T. verrucosum (25%). In Milan the frequency of T. verrucosum is 51.2% and of T. mentagrophytes 38.5%. Ringworm of the body today is mainly due to M. canis (47.8% of the cases in Rome and 65.7% of those in Milan). These ringworms in Rome and Milan are caused mostly by the zoophilic dermatophytes that have supplanted the anthropophilic dermatophytes, which were the main cause of dermatomycoses in the early years of this century. This change, particularly evident after World War II, appears to result from improved socio-economic and hygienic conditions, with resulting decrease of infections through interhuman contacts, and from increased numbers of pet animals and consequent increase of stray cats and dogs, which result in increase of infections of animal origin.

Epidermophyton↗

Open clinical study of the efficacy and safety of terbinafine cream 1% in children with tinea corporis and tinea cruris.

BACKGROUND: Topical application of antifungal agents is considered the treatment of choice for dermatomycoses. Most of the available drugs are fungistatic, requiring long term treatment to prevent relapses. Terbinafine is a synthetic antifungal agent that, because of its fungicidal action, provides high cure rates and low relapse rates after short periods of treatment. METHODS: Ninety-seven children ages 2 to 15 years with a suspected diagnosis of tinea corporis and/or tinea cruris were enrolled in this open trial. After mycologic assessment to confirm diagnosis (culture and direct microscopy) terbinafine 1% cream was applied once daily during 1 week. Clinical and mycologic assessments were made at the baseline visit and on Days 7, 14 and 21. Efficacy assessment was based on 88 children (9 patients excluded by protocol violation). RESULTS: Therapy was considered effective in 92.0% (81 of 88) of patients (complete clinical and mycologic cure or mycologic cure with minimum signs and symptoms or clinical improvement, > or = 50%). Tolerability was assessed in 97 patients on an intention-to-treat basis. Adverse reactions were itching 3% (3 of 97), itching associated with erythema exacerbation 1% (1 of 97) and contact dermatitis 1% (1 of 97). CONCLUSION: Terbinafine 1% cream appears to be an effective and well-tolerated treatment for tinea corporis and tinea cruris in children.

Administration, Topical↗

Comparative efficacy and safety of amorolfine nail lacquer 5% in onychomycosis, once-weekly versus twice-weekly.

Amorolfine is a new topical antifungal of the phenylpropyl morpholine class which is highly active both in vitro and in vivo against yeasts, dermatophytes and moulds responsible for superficial fungal infections. Human pharmacological studies have established that amorolfine has a persistent antifungal effect in the nail bed and in the skin without being systemically absorbed. This has been confirmed by clinical work showing that amorolfine is effective in treating dermatomycoses and onychomycoses when administered as cream or nail lacquer. It is ineffective when given orally for systemic mycoses or bacterial infections in animals. In earlier studies a 5% concentration of amorolfine nail lacquer was found to produce a better cure rate in onychomycosis than a lower concentration of 2%. From data available on the penetration of amorolfine and on the persistence of mycologically relevant tissue concentrations, it appeared likely that once- or twice-weekly application of nail lacquer should suffice to produce a satisfactory therapeutic effect in onychomycosis. The aim of this investigation was to assess the efficacy and tolerability of 5% amorolfine nail lacquer given once versus twice weekly to patients with onychomycosis of finger nails and toe nails.

Administration, Topical↗

Langerhans cell accumulation in chronic tinea pedis and pityriasis versicolor.

Persistence of chronic tinea pedis (CTP) and pityriasis (tinea) versicolor (PIVE) has been tentatively attributed to an impaired cellular immune response. Therefore immunophenotyping of the inflammatory infiltrates in both disorders was performed in order to detect possible defects in cellular defence. The results of the present study show a dominance of memory T cells, an accumulation of macrophages and lack of B cells. A very prominent feature in CTP and especially PIVE was a marked accumulation of Langerhans cells (LCs) in the epidermis, mostly without expression of CD4. Furthermore, reduced expression of cellular activation markers and the presence of suppressor T cells was noted. In general, the cellular response in PIVE appeared to be slightly stronger than in CTP. This composition of the inflammatory infiltrates in chronic dermatomycoses is similar to previous findings in a variety of dermatoses. However, in PIVE and CTP local reduction of delayed-type hypersensitivity may occur. The function of LCs in these infections is therefore of special interest.

Chronic Disease↗

Treatment of Microsporum spp. tinea capitis with pulsed oral terbinafine.

Oral terbinafine is widely used in the treatment of superficial dermatomycoses as well as subcutaneous and systemic mycoses. It is also useful in treating tinea capitis, although for Microsporum canis and some ectothrix organisms, the effectiveness of the drug may be less than for some endothrix infections. In this study, we undertook a double-blind randomized trial comparing standard and double doses of terbinafine given in a pulsed protocol (1 week on, 3 weeks off) in treating Microsporum spp. tinea capitis in 42 individuals. We found that pulsed terbinafine at a higher dose did not improve treatment efficacy. However, our data clearly demonstrated that the duration of treatment is an important factor in determining clinical outcome and cure. Two pulses of standard dose terbinafine were found to be sufficient for treating most cases of Microsporum spp. tinea capitis, although additional treatment (a third pulse) may be needed if clinical improvement is not evident at 8 weeks after initiating therapy.

Administration, Oral↗

Fungal infection as a cause of skin disease in the eastern province of Saudi Arabia: tinea pedis and tinea manuum.

In the period between April 1984 and April 1988 a total of 4294 clinically suspected cases of dermatomycoses were examined for causative fungi. Of these cases 680 were suspected as tinea pedis and tinea manuum. These cases belonged to 21 different nationalities. Both sexes were represented and 649 cases (95.4%) were adults while 31 (4.6%) were prepubertals. Clinical diagnosis was confirmed by direct microscopy in 505 cases or 74.4% (485 adults and 20 prepubertal children). Out of these, 504 cases were positive on culture and yielded 516 isolates. Candida species and other yeasts were responsible for 88.9% and dermatophytes for 11.1% of these infections. The interdigital type of lesions was the most common type (91.9% of all infections) followed by the hyperkeratotic scaling type (6.9%) while the acute inflammatory type was only 1.2% of infections. Treatment showed satisfactory results in most of the cases.

Adult↗

Fungal infection as a cause of skin disease in the eastern province of Saudi Arabia: cutaneous candidosis.

In the period between April 1984 and April 1988 a total of 4,294 clinically suspected cases of dermatomycoses were examined for causative fungi. Of these cases 174 (4.1%) were suspected as cutaneous candidosis. These cases belonged to 15 different nationalities. Both sexes were involved (122 males and 52 females). Thirty four cases were prepubertal children while 140 were adults. Of these cases 163 had their clinical diagnosis confirmed by direct microscopy and on culture yielded 164 isolates (Candida albicans 161, C. stellatoidea 1 and Trichophyton rubrum 1).

Adolescent↗

Frequency of Trichophyton rubrum in tinea capitis.

Trichophyton rubrum has led to unprecedented worldwide suppression of other dermatophytes which had been predominant earlier as a causative agent of superficial dermatomycoses. In tinea capitis on the other hand, several other species of Trichophyton or Microsporum are dominant depending on the region or continent. Tinea capitis caused by T. rubrum is a rare event worldwide. Occasional concentrations may be explained by several cases occurring by chance in one family or community. The relative frequency of this causative agent in tinea capitis in children is under 1%. In adults, however, where tinea capitis occurs very infrequently indeed, the incidence of T. rubrum appears to exceed 10%. Apart from two studies from India, one from Iran, two from Portugal and observations from Germany, which in the first country report of around 30% of all cases published, while the others document some 10% each, there are not only any conspicuous, unequivocal concentrations at all. Increased frequency of T. rubrum in this clinical picture has not been easily recognizable over the last decades due to low absolute case numbers.

Humans↗

Hypersensitivity syndrome reaction to oral terbinafine.

Terbinafine is used extensively to treat onychomycosis and other dermatomycoses. The case of a patient who developed a hypersensitivity syndrome reaction to oral terbinafine is discussed. A 66-year-old male was placed on terbinafine (250 mg/day) for the treatment of onychomycosis. After 4.5 weeks of therapy, the patient developed a cutaneous eruption, pyrexia, lymph-adenopathy and hepatic dysfunction. No infectious or other cause was found for the symptoms and signs, which resolved within 6 weeks of stopping terbinafine. The patient had been on prednisone, doxazosin mesylate and aspirin for several months prior to starting terbinafine. These medications were continued during the episode and subsequently afterwards, with adjustment to the prednisone dosage only. The hypersensitivity syndrome reaction in this case involved multiple systems and was idiosyncratic in nature with no apparent predisposing factors. With the increasing use of oral terbinafine, it is likely that rare adverse events will occur more frequently. It is, therefore, important for physicians to be aware of the possible development of a hypersensitivity syndrome reaction in a patient on terbinafine who experiences an adverse event with multisystem involvement. Prompt recognition and determination of the extent of systemic involvement is important for the proper management of the patient.

Administration, Oral↗

Multiple-dose pharmacokinetics and distribution in tissue of terbinafine and metabolites.

The pharmacokinetics of terbinafine and its inactive metabolites SDZ 86-621 (the N-demethyl form), SDZ 280-027 (the carboxybutyl form), and SDZ 280-047 (N-demethyl- carboxybutyl form) in plasma were characterized for 10 healthy male subjects receiving 250 mg of terbinafine orally once a day for 4 weeks and in the subsequent 8-week washout phase. Terbinafine concentrations were also measured in sebum, hair, nail, and stratum corneum samples. Concentrations of the parent compound and metabolites were determined by validated high-performance liquid chromatography methods. Terbinafine was rapidly absorbed, with peak concentrations in plasma of 1.70 +/- 0.77 micrograms/ml occurring 1.2 +/- 0.3 h postdose. Concentrations subsequently exhibited a triphasic decline, with a terminal deposition half-life of 16.5 +/- 2.8 days. Terbinafine accumulated approximately twofold over the 4-week dosing phase. The predominant metabolite in plasma samples was SDZ 280-027; specifically, the ratios of metabolite area under the curve to terbinafine area under the curve following the last dose were 1.25, 1.38, and 1.08 for metabolites SDZ 86-621, SDZ 280-027, and SDZ 280-047. Measurable concentrations of terbinafine were achieved in sebum and hair samples within the first week of administration and by week 3 in stratum corneum and nail samples. Fungicidal concentrations persisted in plasma and peripheral tissue samples for prolonged periods (weeks to months) after administration of the last dose. These pharmacokinetic properties are likely an underlying factor in the shorter treatment times and good clinical cure rates which have been reported for terbinafine in the therapy of onychomycoses and dermatomycoses.

Adult↗