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The various agents of the superficial mycoses have been recognized for more than a century as causes of mild diseases affecting humankind. Two of these, Malassezia furfur and Trichosporon beigelii, are ubiquitous organisms now known to be opportunistic pathogens in susceptible patient populations. The clinical manifestation, pathogenesis, and treatment of the common skin presentation of these and the other superficial mycoses are reviewed.
The frequency of respiratory mycosal infections has increased over recent Years. Diagnosis has been improved by recent epidemiological data and advances in radiological and mycological diagnostic methods. Two new antifungal agents have recently received marketing approval: voriconazole and caspofungine. Voriconazole belongs to the echinocandin family of antifungals. Sites of action of antifungals have become more diversified: amphotericins act on ergosterol directly, azolated agents act on the synthesis of ergosterol, flucytosine affects synthesis of nucleic acids, and echinocandins alter the fungal wall. Synergetic or additive combinations, such as amphotericin-caspofungine, or voriconazole-caspofungine, can be proposed for advanced disease. Thus both first intention and secondary treatments, particularly for systemic candidiasis and aspergillosis, have been modified. These new protocols take into consideration the severity of the mycosal infection, co-morbidity, and drug combinations as well as cost.
We carried out a retrospective study on the infection rate--in episodes per 100 person months at risk (p/m/r)--of septicaemia and invasive mycoses in children with solid tumours treated at a single institution between 1985 and 1996. Among 982 patients, accounting for 8108 p/m/r, 257 infectious episodes were documented, for an infection rate of 3.2. The infection rate for "intensive" treatment was greater than that for "less intensive" treatments, 3.7 compared with 0.5, respectively; P<0.001. 58% of infectious episodes were associated with neutropenia, 22% were megatherapy-related, and 39% were related to central venous catheter (CVC), while in 13% of the episodes no risk factor was identified. Of the episodes, single organism Gram-positive bacteraemias accounted for 62%, single organism Gram-negative for 23%, multiple organism bacteraemias for 7%, invasive mycoses for 4%, and isolated fungaemias for 4%. The infection rate for Gram-positive organisms decreased significantly over time (-5.9% per year; P<0.01), but increased for the Gram-negative organisms (+3.4% per year; P=0.4). This study demonstrates that the risk of bacteraemia increases in parallel with the treatment intensity, and that a considerable number of children with solid tumours develop bacteraemia in the absence of an identifiable risk factor.
High incidence of mycoses were found in the guts and malpighian tubes of Phlebotomus papatasi from the Jordan Valley and P. tobbi from Zakinthos, Greece. Infections with several different bacteria were also found in the guts of female P. tobbi. Fungi cultured from guts of laboratory reared P. papatasi that had similar mycoses were identified as Aspergillus sclerotiorum and Saccharomyces cerevisiae. Fungi-infected laboratory reared P. papatasi were refractory to artificial infections with a Leishmania major strain specific to them. The crop contents of P. papatasi, where sugar meals are stored, demonstrated antibacterial activity against the following bacterial species in culture: Escherichia coli, Staphylococcus aureus, Shigella sonnei, Streptococcus group A and Pseudomonas aeruginosa. It is postulated that the bacteria-free gut normal to sandflies is effected by the bacterial inhibitor present in the crop.
Mycotic infections of paranasal sinuses are frequently reported in southern Asia. Aspergillus and Mucor species are the predominant ones. Intracranial extension of paranasal sinus mycoses is a difficult problem to manage. We report 18 cases of paranasal sinus mycoses with intracranial extensions. The commonest manifestations were nasal discharge (67%), nasal obstruction (50%), ocular symptoms such as proptosis (44%), telecanthus (39%) and ophthalmoplegia. Computerized tomography scans were found to be quite informative regarding the nature and extent of the disease (100% sensitivity and 78% specificity). A combined intracranial-extracranial approach (six cases) gave a distinct advantage over only adopting an extracranial approach (12 cases). A 17% incidence of CSF leak was noted by adopting only an extracranial approach as well as a recurrence in four cases out of the 12 that were treated using this method (P < 0.05). A slight increase in morbidity was associated with the combined intracranial-extracranial treatment, but no recurrence or significant complications were noted in this approach.
Forty patients with superficial mycoses were treated with itraconazole, a new triazole derivative, in an open study. In 29 cases the diagnosis was dermatophytosis; in five, candidosis; and in six, pityriasis versicolor. Each patient received 50 mg of itraconazole orally once a day for 30-60 days. Thirty-three patients completed therapy; at the end of therapy, 21.2% were considered clinically cured and 57.6% were considered mycologically cured. Results of direct microscopic examination were negative at 30 days for the patients with pityriasis versicolor; none of the patients with candidosis responded to therapy. Pruritus and other symptoms or signs of infection improved after the 15th day, but even after 60 days of therapy, nine of the 10 patients who finished the trial at that time had residual lesions. The drug was well tolerated. It appears that a dosage of 50 mg of itraconazole daily is not adequate for the treatment of these mycoses.
Twenty-five years ago many of the topical remedies for superficial mycoses were irritating, toxic, or allergenic. Total x-ray depilation of the scalp was the accepted mode of therapy for tinea capitis. The introduction of topical nystatin for candidiasis and tolnaftate for dermatophytosis were major advances, but tinea capitis, onychomycosis, and chronic tinea pedis still presented problems. Soon after its introduction in 1958, griseofulvin became the definitive form of therapy for all types of dermatophytosis and played a major role in abolishing large-scale epidemics of tinea capitis in some countries. Recently, haloprogin and the imidazole derivatives, miconazole and clotrimazole, which are topically active against dermatophytes and Candida albicans, have become available. Selective indicator media for isolating dermatophytes are useful diagnostic tools, but quicker methods of diagnosis which require little interpretation are still lacking. Epidemiologic studies in Vietnam again revealed the effects of climate and occlusion on the prevalence, incidence, and severity of superficial mycoses and led to renewed interest in host susceptibility, environment, and prevention of infections.
This article describes common cutaneous mycoses in children: mucocutaneous candidiasis, pityriasis versicolor, tinea corporis, tinea pedis, onychomycosis and tinea capitis. Topical therapy is effective in tinea corporis and pedis, pityriasis versicolor and cutaneous candidiasis. It is ineffective in tinea capitis, in immunocompromised children and onychomycosis. Griseofulvin has been the main treatment until now in children, but it is only fungistatic, may cause interactions and has to be given for long periods. Ketoconazole has not been widely accepted for use in children because of hepatotoxicity and it is not an effective as griseofulvin. There are few data on paediatric use of fluconazole, although it is available in liquid form, has an excellent safety profile and may become important for treating paediatric mycoses. Similarly, there are only limited data on itraconazole in this area, with most experience in tinea capitis. There is only a 100-mg capsule available, which is not easy to administer in paediatric dosages. All azoles have the potential for drug interaction. Most experience in the treatment of children with the allylamine, terbinafine, has been in tinea capitis. A treatment time of 4 weeks with terbinafine and 8 weeks with griseofulvin has produced similar results at 12 weeks. There are also limited data on the use of terbinafine in paediatric onychomycosis. Terbinafine has the best safety profile, least risk of drug interactions and may be the most suitable alternative to griseofulvin in children. The lack of a liquid formulation may preclude its use. Itraconazole and fluconazole are also potential replacement drugs for griseofulvin.
Patients with deep mycoses diagnosed in dermatologic clinics of Manaus (state of Amazonas, Brazil) were studied from November 1973 to December 1983. They came from the Brazilian states of Amazonas, Pará, Acre, and Rondônia and the Federal Territory of Roraima. All of these regions, with the exception of Pará, are situated in the western part of the Amazon Basin. The climatic conditions in this region are almost the same: tropical forest, high rainfall, and mean annual temperature of 26C. The deep mycoses diagnosed, in order of frequency, were Jorge Lobo's disease, paracoccidioidomycosis, chromomycosis, sporotrichosis, mycetoma, cryptococcosis, zygomycosis, and histoplasmosis.
In a 2-year period, 30 patients with culture-proven mycoses (chromoblastomycosis, sporotrichosis, and paracoccidioidomycosis) were treated with the new orally administered triazole, saperconazole (SPZ) (R66905). The daily dose varied from 100 to 200 mg. All patients responded to treatment; the mean time required to heal the lesions and convert the cultures to negative was 3.5 months for sporotrichosis, 4.6 for paracoccidioidomycosis, and 9.0 for chromoblastomycosis. Evaluation by a scoring system indicated that 36.6% of the patients achieved complete resolution of the pretherapy abnormalities, while the remaining (63.3%) experienced major improvement. No collateral effects were reported; there were no bone-marrow or liver toxicities. SPZ is an effective drug for the treatment of the above-mentioned mycoses and appears to be suitable for the control of chromoblastomycosis.
Cinnamic aldehyde has been identified as the active fungitoxic constituent of cinnamon (Cinnamomum zeylanicum) bark oil. The fungitoxic properties of the vapours of the oil/active constituent against fungi involved in respiratory tract mycoses, i.e., Aspergillus niger, A. fumigatus, A. nidulans A. flavus, Candida albicans, C. tropicalis, C. pseudotropicalis, and Histoplasma capsulatum, were determined in vitro as minimum inhibitory concentration (MIC), minimum lethal concentration (MLC), inoculum density sustained, and exposure duration for fungicidal action at MIC and higher doses, as well as effect of incubation temperatures on fungitoxicity. It is concluded that these inhalable vapours appear to approach the ideal chemotherapy for respiratory tract mycoses.
The incidence of superficial infections in patients with human immunodeficiency virus (HIV) is increasing in Yaounde. To determine the prevalence of superficial mycoses in HIV-positive subjects, a study was carried out in different hospital settings in Yaounde over a period of 18 months. Clinical observations were followed by the culture of samples on Sabouraud's glucose agar. Of the 148 HIVab-positive patients examined, 79 (44 males and 35 females) had at least one superficial mycosis (53%). The clinical presentations and the causative organisms did not differ from those found in immunocompetent individuals. The main lesions were oral candidiasis (77%), tinea corporis (21%), tinea versicolor (15%), tinea pedis (13%) and tinea inguium (12%). Trichophyton rubrum and Candida albicans were the organisms most commonly isolated. These results indicate the benefit of studying superficial mycoses for optimal management of HIV patients.
AIM: To test a total of 15 strains belonging to four species of yeasts by different in vitro methods against propolis and itraconazole (ITC). METHODS AND RESULTS: Three methods were compared for susceptibility testing of yeast isolates to propolis: disc diffusion method, agar dilution method and National Committee for Clinical Laboratory Standards (NCCLS, M27A) broth microdilution method. ITC was selected as the antifungal agent for comparison study. Using the broth microdilution method, the geometric mean for MIC (microg ml(-1)) with regard to all isolates was < or =0.06 for propolis and < or =0.35 for ITC. The broth microdilution and the agar dilution methods were in good agreement (75%) for propolis against yeasts isolated from patients with superficial mycoses. Using the diffusion method, all strains showed a broad zone of inhibition at the first available reading time (24 or 48 h). An increase of MIC values was accompanied by a decrease of growth inhibition zone diameter. A favourable correlation was found between MIC and inhibition zone around the disc for propolis sample and the correlation coefficient was: r = -0.626 (P < 0.01). CONCLUSIONS: This study suggests the potential value of the agar dilution and disc diffusion method as a convenient alternative method for testing of yeasts to propolis. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that propolis and ITC were very active against yeasts from patients with superficial mycoses. The other prominent finding in this study is that RPMI 1640 with L-glutamine was the available broth for the in vitro susceptibility testing of yeasts.
BACKGROUND: Scalpel blade sampling of a lesion with clinical suspicion of superficial mycosis may eventually harm the patient, especially anxious children, and when sampled from areas such as the neck and the genitals. In these cases--provided that an acceptable level of confidence in results can be warranted--vinyl tape skin strippings, or strip cultures, could be preferable. PATIENTS AND METHODS: Eighty-five patients presenting with scaly lesions clinically suspected of superficial mycoses were randomly included in this study. Thin, crystal clear vinyl tape strips were firmly applied to lesions, pulled up, and then attached glue-face down to glass slides, on which a drop of 10% potassium hydroxide/40% dimethyl sulfoxide solution had previously been placed. Once scales were cleared, microscopic examination was performed. For specimens yielding negative results, further scales were scraped from lesions, cleared, and examined in the conventional manner. Patients with proven negative results in both techniques have been considered a control group. RESULTS: Sixty cases of superficial mycoses were confirmed (dermatophytosis, 38; candidiasis, 12; tinea versicolor, 10). Of these, 59 (98.33%) yielded positive results on vinyl tape preparations, with clear visualization of organisms' structures. The technique failed to demonstrate fungal elements in a single case, subsequently diagnosed as tinea capitis. The additional 25 patients were regarded as our control group. CONCLUSIONS: In addition to improved patient compliance, ease of performance, and low cost, the technique seems appropriate for using in an office environment during a routine medical visit. Whenever vinyl tape specimens yield negative results, a scraping-sampled preparation should be provided.
Yeasts isolated from patients with superficial mycoses were tested against propolis samples collected from different regions and honeybee races. The minimum inhibitory concentration (MIC) values obtained using the agar dilution methods were compared to the diameters of growth inhibition zones by using the disk diffusion method. The results showed that Candida albicans, C. glabrata, Trichosporon spp., and Rhodotorula sp. were susceptible to low concentrations of propolis, the latter showing a higher susceptibility. Relative to the other propolis tested, the propolis sample collected by Apis mellifera caucasica possessed the highest antifungal activity against all of the superficial mycoses. In contrast, the propolis samples collected by A.m. carnica and A.m. anatolica were the least active samples. Also, the propolis sample from the Adana region is more active than samples from other regions. An increase of MIC values was accompanied by a decrease of growth inhibition zone diameters.
UNLABELLED: Terbinafine is an allylamine antifungal agent which has fungicidal activity against a wide variety of dermatophytes, moulds and certain dimorphic fungi, and fungistatic activity against Candida albicans. Oral terbinafine 250 mg/day is effective in the treatment of superficial dermatophyte infections such as onychomycosis, tinea pedis and tinea corporis/cruris, generally achieving mycological cure in > 80% of patients. The drug is also effective in children with tinea capitis when administered orally in the dosage range 62.5 to 250 mg/day for 4 weeks. Comparative data indicate that oral terbinafine is more effective than continuous or intermittent intraconazole in dermatophyte onychomycosis, and is as effective as itraconazole 400 mg/day in tinea pedis. The drug has shown greater efficacy than griseofulvin in dermatophyte onychomycosis, tinea pedis and tinea corporis/cruris, and comparable efficacy in children with tinea capitis. Additionally, oral terbinafine is more effective than ketoconazole 200 mg/day in tinea corporis/cruris. Topical terbinafine 1% formulations are effective when applied once or twice daily for up to 2 weeks, achieving mycological cure in > 80% of patients with tinea pedis, tinea corporis/cruris, cutaneous candidiasis and pityriasis versicolor. Its formulations are at least as effective as miconazole 2% cream and naftifine 1% gel in tinea pedis, and more effective than clotrimazole 1% cream, bifonazole 1% cream and oxiconazole 1% lotion. Mycological cure rates achieved with terbinafine generally improve after treatment cessation, reflecting the drug's fungicidal mechanism of action and its residual effect in tissue. Terbinafine is well tolerated after oral or topical administration and has a relatively low potential for drug interactions. Pharmacoeconomic data support the use of terbinafine in dermatophyte infections of the skin or nails. CONCLUSIONS: Evidence suggests that oral terbinafine is the treatment of choice for dermatophyte onychomycosis, as it achieves high rates of mycological and clinical cure, is generally well tolerated and has a relatively low potential for drug interactions. It must also be considered a first-line treatment option, along with itraconazole, in cutaneous mycoses which warrant systemic treatment; topical terbinafine is a treatment of choice in less extensive mycoses. The use of terbinafine in non-dermatophyte or mixed infections has not been fully defined.
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.
In the field of cutaneous mycoses, some are cosmopolitan and others keep a geographical territory of predilection. Such a fact is bound to the fungus identity and natural biotope, and to the overall quality of public health in the region under consideration. Some of the tropical mycoses of cutaneous origin remain superficial in extension. Others are semi invasive or are even at risk of systemic dissemination.