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Levels of fluconazole in serum, stratum corneum, epidermis-dermis (without stratum corneum) and eccrine sweat.

The distribution in the skin of orally active antifungals and other drugs claimed to be active in the treatment of skin diseases is of major importance, but to date has been studied only rarely. In the present study the distribution of fluconazole in stratum corneum, epidermis-dermis (without stratum corneum), eccrine sweat and serum was studied in human male volunteers after dosages of 50 mg daily for 12 days and 150 mg once weekly for 2 weeks. In the present study high levels of fluconazole were found especially in the stratum corneum. At a dose of 50 mg once daily the concentration of fluconazole after 12 days was 73.0 micrograms/g and 7 days after cessation of treatment the concentration was still 5.8 micrograms/g. At the 150 mg once a week dose the concentration 7 days after the second dose was still 7.1 micrograms/g in stratum corneum indicating that medication once a week may be effective in the treatment of dermatomycoses. High concentrations, all above the serum concentrations, were also seen in sweat and epidermis/dermis. These results indicate that fluconazole is delivered to the stratum corneum, where it is accumulated, through sweat and by direct diffusion through the dermis-epidermis. These pharmacokinetic results indicate that the drug should be very effective in the treatment of dermatomycoses. An extremely high concentration of the drug in the stratum corneum combined with concentrations from 2.93 to 4.62 micrograms/g in the rest of the epidermis and dermis is important in the treatment of these diseases.

Adult↗

Otomycosis in Turkey: predisposing factors, aetiology and therapy.

Otomycosis usually requires long-term treatment and tends to recur. This study was performed on 87 patients with the clinical diagnosis of otomycosis and 20 controls in order to determine the pathogenic agents, predisposing factors and a cost-effective treatment. The predisposing factors included wearing head clothes (74.7 per cent), presence of dermatomycoses (34.5 per cent) and swimming (27.6 per cent). The most common pathogenic fungus was Aspergillus niger (44.8 per cent) in the otomycosis group. The only isolate was Candida albicans in the control group (2.5 per cent). We concluded that administration of four per cent boric acid solution in alcohol and frequent suction cleaning of the ear canal might be a cost-effective treatment for otomycosis since 77 per cent of the patients were treated effectively this way. Eighty per cent of the resistant cases had mixed fungal-bacterial infections, and 50 per cent of them had dermatomycoses. These resistant cases were treated by administration of tioconazole ointment.

Adolescent↗

Econazole: a review of its antifungal activity and therapeutic efficacy.

Econazole1 is a recently introduced imidazole antifungal agent which is very closely related structurally to another imidazole derivative, miconazole. For local application the nitrate salt of econazole is used, while in preliminary investigations of systemic use in a few patients econazole base has been administered orally or intravenously. In uncontrolled studies in large numbers of patients, econazole nitrate has been administered topically in the treatment of dermatomycoses due to a wide variety of fungi, and vaginally in the treatment of vaginal candidosis; but it has not been compared with any other antifungal drug in controlled therapeutic trials in mycoses of the skin and has only been compared with nystatin in a few patients with vaginal candidosis. Until adequate comparative studies are done the relative place of econazole in the treatment of dermatomycoses and vaginal condidosis, compared with traditional antifungal agents and with other imidazole derivatives such as miconazole or clotrimazole, cannot be clearly stated. Nevertheless, econazole nitrate is an effective antifungal drug. In dermatological studies about 90% of a large number of patients were cured, often after a relatively short treatment period (2 to 6 weeks, as occurs with other imidazole antifungal agents). The cure rate was only slightly lower (about 85%) in patients with severe mycoses of many years' duration than in those whose infections were of more recent onset. In vaginal candidosis a 3-day treatment regimen using a 150mg suppository once daily was only slightly less effective (85% mycological cure rate) than a 15-day regimen using a 50mg dose (suppository or cream) once daily (90% cure rate). A 3 to 5 day 'higher' dose regimen was slightly more effective than a standard 15-day regimen of nystatin vaginal inserts in a small group of patients with vaginal candidosis. The convenience of the higher-dose shorter term regimen would likely be an important advantage to most patients. Whether other agents useful in vaginal candidosis would be as effective as econazole were they to be used in this way, has not been determined. Topical or intravaginal econazole nitrate has usually been well tolerated, side effects being limited to local irritation in about 1 to 4% of patients in most studies.

Adult↗

[Comparison of the efficacy of 1% flutrimazole cream twice a day with 1% flutrimazole cream once a day for the treatment of superficial dermatophytoses].

Different clinical studies have demonstrated flutrimazole's efficacy in the treatment of superficial dermatomycoses when administered either twice daily or once daily for four weeks. The aim of the present study was to compare both dosing schedules for the treatment of superficial dermatomycoses. In this randomized, controlled, double blind study, we included 84 patients suffering superficial dermatophytosis (confirmed by microscopic examination (KOH) and culture) susceptible for topical monotherapy. Forty-one patients received flutrimazole 1% twice daily (TD) and forty-three once daily (OD) for four weeks. The efficacy of treatment was evaluated by clinical and mycological criteria at the end of treatment (D28) and after four weeks without treatment (D58). Clinical and mycological cure rates on D28 were 50% with TD and 65% with OD treatment. Only considering clinical evaluation, clinical cure rates on D28 were 63% (TD) and 70% (OD). Also, clinical and mycological cure rates on D56 were 65% with TD and 72% with OD treatment. Only considering clinical evaluation, clinical cure rates on D56 were of 68% (TD) and 72% (OD). The overall tolerability was similar in both treatment groups. The efficacy assessment at the end of treatment (D28) and four weeks after treatment discontinuation (D56) showed that the OD treatment is not inferior to the TD treatment, with similar clinical and mycological cure rates and clinical cure rates in both cases. The OD administration of flutrimazole cream 1% is the most appropriate dosing schedule as it provides the same efficacy, it improves patient's compliance and the cost per day of treatment.

Clinical Trial↗

[Significance of skin changes in diabetes mellitus].

500 patients of a dispensaire of diabetes were inspected dermatologically. 335 patients had a duration of the glucose metabolism intoleration less than 10 years and 165 patients more than 10 years. 215 patients stated a striking family case history according diabetes. 54 per cent (273) of the cases showed an adiposity, 418 patients (83.6 percent) had pathological changes of the skin and mucosal changes. It is clear that dermatomycoses, eczema and pyodermias occur more often with acute metabolic disorder and adiposity. Neurovascular changes of the skin occur with long persistent glucose metabolism intoleration. Bad healing tendencles of wounds, pruritus, intensive dermatomycoses, balanitis, vulvitis, furunculosis and pyodermias are important references to a glucose metabolism intoleration. They should give rise to look for a diabetes irrespective of the age of the patient.

Adolescent↗

Prevalence of superficial mycoses in the Aosta Valley region of Italy from 1984 to 1989.

This report represents the results of the culture tests for fungi carried out in the Aosta Valley region of Italy from 1984 to 1989. The pathological material consisted of cutaneous scales, hair and nails. It was possible to identify 91.8% of the isolates: out of these, 36.1% were dermatophytes, 21% were Aspergillus spp, 15.6% Deuteromycetes, 15% yeasts and 4.1% members of the family Mucoraceae. The resulting data indicate that Microsporum canis was the most wide-spread species (73.7%) among the isolated dermatophytes and keratinophilic fungi (Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum and Scopulariopsis brevicaulis): 87.5% were isolated from hair and 65.9% from the glabrous skin. The high prevalence of M. canis as the cause of dermatomycoses is discussed. Lastly the use made of the Regional Hospital's Mycology Department by health workers is discussed.

Arthrodermataceae↗

In vitro antifungal activity of luliconazole (NND-502), a novel imidazole antifungal agent.

The in vitro activity of luliconazole (NND-502), a novel imidazole antifungal agent, against dermatophytes and several other groups of medically important fungi including the rare causative agents of dermatomycoses, was studied. The luliconazole susceptibility tests were performed with a total of 58 fungal strains of 23 species of fungi grouped into dermatophytes, dematiaceous fungi, hyaline hyphomycetes, yeastlike fungi, and zygomycetes using a broth microdilution method with RPMI 1640 medium. The minimum inhibitory concentration (MIC) values for luliconazole were compared with those of three reference drugs, lanoconazole (LCZ), bifonazole (BFZ), and terbinafine (TBF), all of which have been popular for the topical treatment of dermatophytosis, cutaneous candidiasis, and other superficial fungal infections in Japan. Luliconazole inhibited growth of all filamentous fungi except zygomycetes at low concentrations (MIC, < or =0.004-0.125 microg/ml), with dermatophytes being most susceptible (MIC, < or =0.004-0.008 microg/ml). The susceptibility of these filamentous fungi to luliconazole was almost equal to that to LCZ, and surpassed TBF and BFZ, although to a lesser extent; yeastlike fungi were also susceptible to luliconazole (MIC, 0.125-4 microg/ml). Again the anti-yeastlike fungi activity of luliconazole was at the same level as LCZ and was greater than that of BFZ and TBF. In contrast to BFZ and TBF, however, luliconazole and LCZ were virtually inactive against zygomycetes.

Antifungal Agents↗

Seasonal change and its effect on the prevalence of infectious skin disease in a Gambian village.

A longitudinal dermatological study was carried out to determine the effect of seasonal change on the prevalence of skin diseases, particularly infectious skin diseases. This study was performed at the end of the rainy season and at the end of the subsequent dry season at Keneba, The Gambia. The surveys provide a profile of the influence of climate on the prevalence of certain skin diseases, both in terms of the susceptible diseases and who in the community was most affected. These surveys also provided an appreciation of the magnitude of skin disease in the community. The greatest effect of climatic change was on the prevalence of the dermatomycoses and pyoderma in children under 10. No seasonal influences were detected with other forms of skin disease. Some unusual aspects of scabies were noted in the surveys, particularly the low prevalence and the unusual age distribution pattern with no higher prevalence amongst children.

Child↗

Bovine leucocyte adhesion deficiency: a review of a modern disease and its implications.

Bovine leucocyte adhesion deficiency (BLAD) is a genetic disease of cattle which affects the hematopoietic system. In the last decade BLAD has become a disease of economic importance in the dairy industry. This review describes the chronological developments and thinking that led to the elucidation of BLAD as a disease distinct from previous models in canine and human populations. All species affected show signs of chronic and recurrent infections. Necrotic and/or gangrenous infections of soft tissues are prevalent, in addition to secondary infections with bacteria or fungi. Low birthweight and unthriftiness are key signs in all species affected by leucocyte adhesion deficiency (LAD). Dermatomycoses and impaired pus formation are also common findings. The physiological basis for BLAD is a deficiency in the chemotactic and phagocytic properties of leucocytes and particularly neutrophils. The inhibition of diapedesis in the inflammatory response prevents normal immune reactions to invading pathogens. Chronic infections are a consequence of the faulty immune mechanisms. The biochemical aetiology of BLAD involves cell surface glycoprotein molecules known as integrins. These are responsible for the cell-cell interactions necessary for neutrophils to adhere to vascular endothelium in a normal individual. Experiments with monoclonal antibodies to block LFA-1, Mac-1, and p150,95 (three integrins vital for cell-cell interactions) mimic BLAD symptomatology and have led to the discovery of the reciprocal intercellular adhesion molecule (ICAM). Through pedigree analysis and biochemical detection with restrictive endonucleases, BLAD has been isolated genetically to a single gene locus. The economic significance and prophylaxis of the disease are briefly discussed. In addition, the beneficial aspects of the study of BLAD are considered. There are advantages in producing a BLAD-like state for preventing transplant rejection, ischaemia-reperfusion injury and other problems arising from the deleterious effects of the inflammatory response.

Animals↗

Terbinafine: an update.

Oral terbinafine was first introduced in the United Kingdom in February 1991 and was approved for the treatment of onychomycosis in the United States in May 1996. It is estimated that 4 million patients worldwide have been treated with oral terbinafine as of December 1996. The efficacy of terbinafine in the treatment of onychomycosis and other dermatomycoses is reviewed. The adverse-effects profile of oral terbinafine is evaluated.

Adult↗

Cutaneous infections dermatophytosis, onychomycosis, and tinea versicolor.

Cutaneous fungal infections cause significant morbidity for healthy and ill patients. The incidence of some dermatomycoses is increasing, despite availability of newer and better topical and systemic treatments. Fungal remnants last months to years under the ideal conditions, allowing continued spread of infection. Mycoses treated in one area may recur because of organism travel from concomitant areas of infection. Failure of patients and physicians to recognize a fungal etiology early may lead to more extensive, severe, or difficult-to-treat infections. Finally, a patient's concurrent illnesses may play a part in susceptibility and ability to manage fungal infections. For these reasons, scientists have studied and developed newer antifungal agents with better efficacy and greater convenience in dosing. These drugs, however, still have side effects and medication interactions that may limit their use in some patients. Better efforts to educate patients and physicians alike may aid in faster recognition and treatment of dermatophytoses. More research is needed to continue to develop drugs suitable for use in a broader range of patients and diagnostic tests that may be quicker or more specific than conventional ones.

Administration, Oral↗

Comparison of in vitro antifungal activities of topical antimycotics launched in 1990s in Japan.

In vitro anti-dermatophyte, anti-Candida albicans and anti-Malassezia furfur activities of amorolfine hydrochloride (AMF), terbinafine hydrochloride (TBF), butenafine hydrochloride (BTF), neticonazole hydrochloride (NCZ) and ketoconazole (KCZ), all of which were introduced for the treatment of dermatomycoses in the 1990s in Japan, were compared. Although all of the test drugs are classified as an ergosterol biosynthesis inhibitor, the antifungal properties were found to be different. TBF and BTF exerted extremely potent antifungal activity against Trichophyton spp. but not against C. albicans and M. furfur, whilst KCZ and NCZ showed potent antifungal activity against C. albicans and M. furfur rather than Trichophyton spp. AMF exhibited potent antifungal activity against all of the fungal species tested. Fungicidal activities of these antifungal agents against T. rubrum were determined by using neutral red staining. The fungicidal potentialities correlated with those obtained in the in vitro susceptibility test as determined by MICs against dermatophytes. TBF, BTF and AMF exerted more potent fungicidal action than NCZ and KCZ.

Administration, Topical↗

Ecological effects of antibiotic production by dermatophyte fungi.

Antibiotic production by dermatophyte fungi has been demonstrated in vivo in the lesions of patients with dermatomycoses. Patients infected with antibiotic-producing strains more frequently carried cocci resistant to penicillin and other antibiotics than did patients infected with non-producer strains. The total bacterial load was less in lesions caused by producer fungi. In vitro studies demonstrated the selection of penicillin-resistant S. aureus from mixed populations of resistant and sensitive cells.

Anti-Bacterial Agents↗

Prevalence of dermatophytoses in the Zarqa district of Jordan.

A total of 350 clinically suspected cases of dermatomycoses were examined for causative fungi during July 1997 to September 1998. Mycotic infection was demonstrable by microscopy and culture in 199 (56.8%) cases. The most common superficial mycotic infections were tinea pedis (35.2%) followed by tinea capitis (23.1%), tinea unguium (21.6%) and tinea corporis (10.6%). Most of the infected patients were 1-9, 20-29 and 30-39 years old. Men were mainly infected with tinea cruris and tinea pedis, while women were infected with tinea pedis, tinea unguium and tinea capitis. The frequencies of etiological agents isolated from patients were as follows: Trichophyton mentagrophytes var. interdigitale (32.7%), T. rubrum (28.6%), Epidermophyton floccosum (20.1%), Microsporum canis (11.1%), T. schoenleinii (4%), T. verrucosum (2%), T. violaceum (1%), and M. gypseum (0.5%). The number of infections varied with the seasons. The highest number of cases of tinea pedis and tinea cruris occurred in the summer months, while tinea capitis, tinea corporis and tinea unguium occurred in the spring and winter months.

Adult↗

Fast, simple and highly sensitive double-rounded polymerase chain reaction assay to detect medically relevant fungi in dermatological specimens.

BACKGROUND: Early detection of fungal infection is essential for beginning of prompt and specific therapy. In this study we describe a rapid and sensitive procedure to detect, by polymerase chain reaction (PCR) assays, a wide range of medically important opportunistic and pathogenic fungi in dermal specimens from dermatomycoses-affected patients. MATERIALS AND METHODS: Three primer pairs, amplifying fragments of the highly conserved gene coding for small ribosomal RNA (18S rDNA) and the adjacent internal transcribed spacer (ITS) rDNA, previously published by others, were probed on DNA from pure cultures of medically relevant human and animal fungal species. In order to evaluate the specificity of the assay, amplifications of control DNAs from other eukaryotes and prokaryotes were also carried out, and they gave negative results. RESULTS: These primer sets, in single amplification or double-rounded PCR assays, allowed specific amplification when applied to a wide number of fungal DNA from human and animal tissue specimens, including dermatophytes (genera Trichophyton, Microsporum), several yeast species (Candida, Saccharomyces, Cryptococcus, Malassezia) and moulds (Aspergillus, Penicillium). The PCR assay was able to detect as little as 10 pg of fungal DNA, corresponding to approximately 25 fungal genomes per sample specimen. A small-scale DNA extraction method was also developed. This simple, time-saving and sensitive procedure was successfully applied to 40 human and veterinary specimens, and the diagnosis was confirmed with cultural techniques, being shown to work even in the presence of other lesions or contaminating organisms. CONCLUSIONS: This method allows early recognition of fungal pathogen cells in clinical samples as an alternative tool to conventional detection techniques.

Animals↗

Characteristics of superficial mycoses in Malta.

BACKGROUND: A study was conducted to determine the chief agents of superficial mycoses in Malta. Data were collected over a 5-year period from mycologic investigations carried out on all dermatologic specimens sent to the Mycology Laboratory at St. Luke's Hospital in Malta. METHODS: In the period between January 1995 and December 1999, a total of 1271 specimens from skin, nails, or hair were collected from 1200 clinically suspected cases of dermatomycoses. RESULTS: The fungi cultivated included dermatophytes (n = 371), yeasts (n = 33), and nondermatophyte filamentous fungi (n = 12). Trichophyton rubrum (n = 121) was the most prevalent, followed by Microsporum canis (n = 109), T. mentagrophytes (n = 80), M. gypseum (n = 27), Epidermophyton floccosum (n = 17), T. soudanense (n = 10), T. tonsurans (n = 2), T. verrucosum (n = 2), M. persicolor (n = 1), and T. violaceum (n = 1). Candida species were also cultivated, with C. parapsilosis (n = 14) being the most common, followed by C. albicans (n = 12) and C. tropicalis (n = 6). Nondermatophyte filamentous fungi were isolated from nail specimens only. CONCLUSIONS: In this study, superficial fungal infections were reported more commonly in female (n = 207) than in male (n = 182) patients. M. canis was the chief agent of tinea capitis and tinea corporis, whilst T. rubrum was the main causative agent of tinea pedis, tinea manuum, and tinea unguium. Onychomycosis due to Candida species was more common in female than in male patients.

Adolescent↗

Isolates of fungi from symptomatic carthorses in Awassa, Ethiopia.

Samples were collected from clinically infected carthorses in Awassa. Fungus species affecting the carthorses were identified. Eight genera of fungal groups were isolated from swabs and skin scrapes taken from symptomatic horses. These included Aspergillus spp., Histoplasma spp., Penicillium spp., Microsporum spp., Trichophyton spp., yeast cells of Candida spp., Cryptococcus spp. and Geotrichum spp. The most frequent isolates were from the genera Aspergillus (48%), Penicillium (39.2%) and Trichophyton (31.6%). Clinical findings are reported, the economic, zoonotic and pathogenetic importance of fungi causing dermatomycoses is discussed, and further studies are recommended.

Animals↗

Dermatophytoses in Prague, Czech Republic, between 1987 and 1998.

Over a 12-year period, from 1987 to 1998, the spectrum of aetiological agents isolated from 11208 patients (6265 females and 4943 males) suspected of having dermatomycosis was analysed in the mycological laboratory of the Department of Dermatology, Charles University, Prague. The most frequently examined locations were toenails (34.9%), feet (15.6%), fingernails (12.8%), toe webs (11%), trunk (10%) and hands (8.7%). Dermatophytes were isolated from 5605 (30.2%) of all 18528 samples examined. Among dermatophytes, the most common infectious agent was Trichophyton rubrum (90.2%) followed by Trichophyton mentagrophytes (6.6%), Microsporum canis (1.8%) and Epidermophyton floccosum (1.4%). Trichophyton verrucosum, Microsporum persicolor and Microsporum gypseum were rare. During this 12-year period the pattern of aetiological agents of dermatomycoses in Prague was relatively stable.

Czech Republic↗