Mycoses systemic, treatment

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. 

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. 

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

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. 

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. 

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. 

Antoniskis et al reported four cases of reversible acute kidney injury in patient with AIDS who received both intravenous pentamidine (for PCP) and amphotericin B (for systemic mycoses). Of note, nephrotoxicity did not develop in three AIDS patients treated with both TMP-SMZ and amphotericin B or in two patients who concomitantly received inhaled pentamidine and amphotericin B [160]. Reports of renal damage in patients receiving parenteral pentamidine for the treatment of non-HIV diseases continue. Reversible acute kidney injury and nephrotic syndrome were documented in a young child given pentamidine mesylate and an antimonial salt for the treatment of visceral leishmaniasis [161]. In Africa (Kenya) patients with visceral leishmaniasis have developed renal toxicity during prolonged treatment (1 to 10 months) with pentamidine [162]. 

Polyene Antibiotics—This class of compounds is of considerable usefulness, primarily for the treatment of systemic mycoses and conditions caused by various species of Candida. 

Hamycin, used for the treatment of 30 patients with proven vaginal moniliasis, produced cxires in 29 patients and was considered to be an outstanding drug for the treatment of this disease.29 in contrast to this its use in 10 cases of systemic mycoses resulted in improvement in only two cases.30 A question has been raised as to the possible identity, or at least close similarity of hamycin, trichomycin and candicidin. 

For many years, fungal infections were classified as either superficial nuisance diseases, such as athlete s foot or vulvovaginal candidiasis, or as relatively rare infections confined primarily to endemic areas of the country. When invasive fungal infections were encountered, amphotericin B was the only consistently effective, systemi-cally active agent available for the treatment of systemic mycoses. 

The physician must decide whether to opt for systemic or topical treatment and which arguments will convince the patient to use one or both forms for the minimum period recommended. It is typical for mycoses that the period of treatment generally exceeds one week and may even last a few months. There is still a strong tendency to treat the organ or the part of the organ affected by the pathogenic microorganism. This is justifiable in the case of localized unifocal mycoses of the skin caused by dermatophytes. 

Any plans to make new therapeutics for Chagas disease need to bear in mind the characteristics of a drug that would allow it to succeed in clinical use. Essentially all the data in animal models and the clinical experience with humans indicate that long courses of treatment are required to produce cures. The situation is analogous to tuberculosis infection and systemic mycoses in which extended periods of drug pressure are necessary to kill off all the organisms. 

Anon. New possibilities in the treatment of systemic mycoses. Reports on the e q)erimental and clinical evaluation of miconazole. Round table discussion and Chairman s summing up. ProcR SocMed Sm), 70 (Sxtppl 1), 51. ... 

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