Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia

The Effect of Ketoconazole on Amphotericin B in a Model of Disseminated Aspergillosis

“…Other studies show a high rate of breakthrough infection under ketoconazole prophylaxis [12,30] in addition to a high-failure rate of amphotericin B in such patients [12]. 909 In consideration of the available clinical experience with ketoconazole prophylaxis, our data (1) show that ketoconazole might significantly interfere with subsequent therapy of aspergillosis with amphotericin B, making this form of prophylaxis unsuitable for centers in which aspergilli are important pathogens; (2) indicate that ketoconazole prophylaxis, which has few side effects on the patient, might have an important, undesired effect of reducing the susceptibility of fungi to the only antimycotic agent shown to be effective in most invasive opportunistic mycoses; and (3) point out that future clinical evaluation of imidazoles for fungal prophylaxis should include analysis of the efficacy of amphotericin B therapy in patients with breakthrough mycosis.…”

“…Opportunistic fungal infections have emerged as a major threat to patients undergoing intensive chemotherapy for malignancies such as acute myelogenous leukemia [1][2][3][4][5][6][7][8]. Thus the question of prevention of fungal infection in such patients has become an important concern.…”

“…Thus two different approaches have been proposed to study the problem of opportunistic fungal infections in cancer patients; on one hand, chemoprophylaxis with ketoconazole [12,18,19]-an oral systemic antifungal agent with few side effectsand on the other hand, in bacterial infections, early empirical therapy with amphotericin B in neutropenic patients with febrile episodes not responding to antibacterial agents [1,26].…”

“…The study design for the in vivo chemotherapeutic trials are shown in figure 1.Ketoconazole (100-200 mg/kg per day) suspended in 0.2 ml of carboxymethylcellulose with 0.01% Tween 80 was given by gavage. Amphotericin B-deoxycholate (Squibb), in a dose of 2 mg of amphotericin B/kg per day, was injected iv in a volume of 0.5 ml of 5OJo glucose.…”

Suporte de terapia intensiva no paciente oncológico

“…Amphotericin is the drug of choice. 15 The liposomal formulation should be reserved for renal insufficiency cases. This drug can be utilized in itraconazole -sensitive (fluconazole) and in localized infections (fungal cystitis).…”