Mycoses systemic

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. 

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. 

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. 

Younger than 2 years of age) - Daily dosage has not been established. Minimum treatment is 1 or 2 weeks for candidiasis and 6 months for the other indicated systemic mycoses. Chronic mucocutaneous candidiasis usually requires maintenance therapy. 

Amphotericin-B, an amphoteric polyene macrolide remains the most effective for severe systemic mycoses. It is indicated for systemic mycoses such as disseminated candidiasis, cryptococcosis, aspergillosis, mucormycosis, coccidioidomycosis, histoplasmosis, extracutaneous sporotrichosis and blastomycosis. It is a fungicidal antibiotic without antibacterial activity. It binds to ergosterol in the... 

Vomiting and diarrhea have occurred with large doses in the treatment of systemic mycoses. 

It is indicated in dermatophytoses, tinea versicolor, onychomycoses, oropharyngeal candidiasis, cutaneous candidiasis, chronic mucocutaneous candidiasis, oculomycoses systemic mycoses like cryptococcosis, candidiasis and aspergillosis subcutaneous mycoses like sporotrichosis and chromomycosis. 

Nystatin and amphotericin are useful in the topical therapy of C albicans infections but ineffective against dermatophytes. Nystatin is limited to topical treatment of cutaneous and mucosal Candida infections because of its narrow spectrum and negligible absorption from the gastrointestinal tract following oral administration. Amphotericin has a broader antifungal spectrum and is used intravenously in the treatment of many systemic mycoses (see Chapter 48) and to a lesser extent in the treatment of cutaneous Candida infections. 

Amphotericin B, a polyene antibiotic, is the most suitable remedy, despite the nephrotoxicity that may occur, for treating systemic mycoses such as coccidio-mycoses, histoplasmosis, and blastomycosis in animals. It is not effective against dermatophytes and has no activity against bacteria. It is only available in form of a colloidal dispersion for intravenous injection since its poor absorption from the gastrointestinal tract obviates oral administration. 

Ketoconazole was the first imidazole derivative used for oral treatment of systemic mycoses. Patients with chronic mucocutaneous candidiasis respond well to a once-daily dose of 200 mg of ketoconazole, with a median clearing time of 16 weeks. Most patients require long-term maintenance therapy. Variable results have been reported in treatment of chromomycosis. 

The drugs used in the treatment of subcutaneous and systemic mycoses are amphotericin B, flucytosine, and the new group of azoles, ketoconazole, fluconazole and itraconazole. 

Amphotericin B [am foe TER i sin] is a naturally occurring polyene macrolide antibiotic, produced by Streptomyces nodosus. In spite of its toxic potential, amphotericin B is the drug of choice used in the treatment of the systemic mycoses. It is sometimes used in combination with flucytosine so that lower (less toxic) levels of amphotericin are possible. 

Flucytosine [floo SYE toe seen] (5-FC) is a synthetic pyrimidine anti metabolite used only in combination with amphotericin for the treatment of systemic mycoses and meningitis caused by Cryptococcus neoformans and Candida. 

Ketoconazole [kee toe KON a zole], a substituted imidazole, is one of a family of azoles useful in treating systemic mycoses. In addition to its antifungal activity, ketoconazole also inhibits gonadal and adrenal steroid synthesis in humans by blocking C17-20 lyase, Up-hydroxylase, and cholesterol side-chain cleavage thus, it suppresses testosterone and cortisol synthesis. 

Caspofungin is a cyclic polypeptide that inhibits synthesis of the fungal cell wall. It can be used in systemic mycoses due to as-pergillus fungi when amphotericin B or itroconazole cannot be employed. It is given by infusion and causes various adverse effects. 

One compound that has been associated with distal tubular injury is amphotericin B, a polyene antifungal agent used in the treatment of systemic mycoses caused by opportunistic fungi. Clinical utility of amphotericin B is limited by its nephrotoxicity, characterized functionally by polyuria resistant to antidiuretic hormone administration, hyposthenuria, hypokalemia, and mild renal tubular acidosis. 

Flucytosin i.v., 0. ind. systemic mycoses, given in combination with amphotericin B resistance when used as monotherapy bone marrow toxicity, nephrotoxicity, hepatotoxicity avoid other nephrotoxic drugs cytarabin as antagonist... 

Body BA Cutaneous manifestations of systemic mycoses. Dermatol Clin 1996 14 125-135. 

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