Ketoconazole resistance

C. glabrata is intrinsically more resistant than C. albicans to ketoconazole. Several strains of C. glabrata have been well characterized in terms of the mechanism of ketoconazole resistance. 

Because of the outbreak of antimony-resistant leishmania sis and the need to develop an oraky-adrninistered therapy, the use of many other compounds has been considered. Those that appear to have clinical utility ate aHoputinol (62), ketoconazole (63), and both systemicaHy and topically applied paromomycin (8) (see Antiparasitic agents, antimycotics). 

Treat nipple candidiasis by applying topical ketoconazole, nystatin, or miconazole to the nipples after each feeding and by administering oral nystatin drops to the breast-feeding infant12 (Table 44-5). In severe or recurrent cases, the mother may be treated with oral fluconazole.12,14 Although messy, gentian violet applied topically to both the nipples and the infant s mouth is also effective for resistant cases.12... 

Disseminated histoplasmosis Acute (Infantile) Subacute Progressive histoplasmosis (immunocompetent patients and immunosuppressed patients without AIDS) 0.02-0.05 Disseminated histoplasmosis Untreated mortality 83% to 93% relapse 5% to 23% in non-AIDS patients therapy is recommended tor all patients Nonimmunosuppressedpatients Ketoconazole 400 mj day orally x 6-12 months or amphotericin B 35 mg/kg IV Immunosuppressed patients (non-AIDS) or endocarditis or CNS disease Amphotericin B >35 mg/kg x 3 months followed by fluconazole or itraconazole 200 mg orally twice daily x 12 months Life-threatening disease Amphotericin B 0.7-1 mg/kg/day IV for a total dosage of 35 mj kg over 2-4 months once the patient is afebrile, able to take oral medications, and no longer requires blood pressure or ventilatory support therapy can be changed to itraconazole 200 mg orally twice daily for 6-18 months Non-life-threatening disease Itraconazole 200-400 mg orally daily for 6-18 months fluconazole therapy 400-800 mg daily should be reserved for patients intolerant to itraconazole, and the development of resistance can lead to relapses... 

Management Prolonged and repeated systemic therapy with fluconazole, itraconazole or ketoconazole - always with the risk of development of resistance - is crucial, treatment of an underlying endocrine disorder has no effect on candidiasis. Genetic counseling is indicated. 

Flucytosine has been successfully used in combination with ketoconazole, fluconazole, and itraconazole. Flucytosine and ketoconazole were synergistic in about 40% of yeast isolates resistant to flucytosine alone. The synergistic action of flucytosine with the triazoles against Candida species was seen both in vitro and in vivo (3-6). 

An AIDS patient who is being treated with multiple drugs, including AZT, lamivudine, indinavir, ketoconazole, and TMP-SMX, develops breast hypertrophy, central adiposity, hyperlipidemia, insulin resistance, and nephrolithiasis. If these changes are related to his drug treatment, the most likely cause is... 

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