Mycoses

To mycologists, each fungal infection has something specific, either in its symptomatology or its etiology. However, this is less obvious to practitioners. The incidence and the severity of the pathology are sometimes underestimated. Mycoses may be classified as follows ... 

Oral treatment offers the advantage of bringing all the lesions at all sites under control, in addition to the absence of unpleasant cosmetic effects. In certain cases, it may be preferable to use oral treatment for C. albicans vaginitis and for extensive and persistent pityriasis versicolor, a skin disorder caused by Pityrosporum orbiculare. In the case of onychomycosis, a combination treatment, topical plus systemic, is required. It is preferable to use oral treatment for deep and systemic mycoses, though intravenous or intrathecal treatment is sometimes required. 

Because of their limited, activity, small spectmm, and side effects, the older topical antimycotics have generally been surpassed by newer antimycotic chemotherapeutic agents. These newer antimycotics for topical use iaclude the imida2ole derivatives clotrimazole, miconazole, econazole, isoconazole, sulconazole, fenticonazole, oxiconazole, bifonazole, butoconazole, ziaoconazole, tioconazole, and the triazole derivative, terconazole (Table 2) (5—7). The iatroduction of the azole derivatives represents a milestone ia the treatment of mycoses. 

Clotrimazole. The imidazole derivative clotrimazole (6) was iatroducedia 1969. Clotrimazole [23593-75-1] or l-((9-chloro-a,a-diphenylbenzyl)imidazole is a water-iasoluble antimycotic for topical appHcation, with a broad-spectmm activity against mycoses of the skin and the vagiaa. 

Naftifine. Nafdfine (8) belongs to the aHylamines, a new class of antimycotics (14). It is used to treat superficial mycoses and is particularly active against dermatophytes. 

The biochemical basis for its action in fungi has not been totally elucidated. Giclopiroxolamine [41621 -49-2] is used mainly in the treatment of mycoses of the skin and nails. 

Ketoconazole. Initial observations indicating that oral administration of ketocona2ole (10) produced good results in seborrheic ec2ema and dandruff, led to the development of a 2% cream and a 2% shampoo (scalp gel) of this antimycotic (17,18). Naturally, these two topical forms of ketocona2ole [65277-42-1] are highly active against superficial mycoses. 

Indications are mycoses of the skin, hair, and nails due to species of Trichophyton Tpidermophyton floccosum and Microsporum. Yeasts and bacteria are not sensitive. Griseofulvin has a very weak effect against Side effects may include headaches and gastrointestinal disorders, but they are usually only... 

Miconazole. Miconazole (Fig. 2, 7a) is also available as a sterile solution for intravenous infusion. Miconazole has a therapeutic effect on systemic mycoses due to C albicans A.spergillusfumigatus Cyptococcus neoformans Blastomyces dermatitidis Histoplasma capsulatum Coccidioides immitis Paracoccidioides brasiliensis and Petriellidum boydii. 

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

Due to the divergence of fungal diseases, there is neither single best treatment nor a superior drug for all diseases. However, a superior drug does exist for dermatomycoses caused by dermatophytes, namely the allylamine terbinafine (TER). For the treatment of deep mycoses in immunosuppressed patients the most efficacious drug is the polyene Amph B. 

Three fungal infections - Madura feet (mycetoma), chromomycosis and sporotrichosis - fall into the category of subcutaneous mycoses, their distribution is mainly in tropical and subtropical areas. The ideal treatment for madura feet caused by fungi is not yet established the azoles are of some benefit, however, neither the optimal drug, dose, nor the treatment schedules are known. Chromomycosis responds well to ITRA monotherapy or the combination of 5FC plus ITRA. ITRA has been set up as standard therapy for cutaneous and lymphatic sporotrichosis. 

Systemic mycoses are caused either by true pathogenic fungi (endemic in distinct areas of USA/South America) or by opportunistic fungi that induce severe infections in immunosuppressed patients. The arsenal for the treatment of deep organ mycoses is relatively small Amph B, 5FC, azoles (FLU, ITRA, voriconazole (NBA filing)) and CAS. 

Korting HC, Grundmann-Kollmann M (1997) The hydro-xypyridones. Mycoses 40 243-247... 

All three of these are dermatophytes, i.e. filamentous fungi which can utilize keratin for their nutrition. Keratin is the chief protein in skin, hair and nail. Hence, all of these organisms are responsible for superficial mycoses in mammals. It is often stated that dermatophytes are the only fungi to have evolved which rely upon infection for then-own survival. This mistaken belief results from a view which is too human-centred and neglects, for example, the presence of symbiotic fungi in the stomachs of ruminants. 

Secondary prophylaxis or suppressive therapy is recommended for endemic mycoses in immunocompromised patients, especially in hosts with pronounced defects in T-cell-mediated immunity (i.e., AIDS). 

Commensal or environmental fungi that are typically harmless can become invasive mycoses when the host immune defenses are impaired. Host immune suppression and risk for opportunistic mycoses can be broadly classified into three categories (1) quantitative or qualitative deficits in neutrophil function, (2) deficits in cell-mediated immunity, and (3) disruption of mechanical/and or microbiologic barriers. 

Clinical trials performed by the National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group showed that 2 weeks of induction antifungal therapy with combination amphotericin B (0.7 mg/kg per day) plus... 

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