Antifungal Therapy Timing of antifungal therapy

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Early studies have shown that the risk of occult fungal infection increases sharply when the neutropenic patient has been febrile on broad-spectrum antibiotics for 5-7 days or more. Traditionally, i.v. amphotericin B has been added at this time.1 The patient with pulmonary infiltrates is also more likely to have occult fungal infection.9 However, toxicities of amphotericin B have been problematic, including renal insufficiency, electrolyte abnormalities, and infusion-related chills and dyspnea. The availability of newer antifungals has expanded the choices available to the clinician. Interpretation of the literature is complicated by the multiplicity of studies and issues in clinical trial design.20,21

Lipid formulations of amphotericin, including amphotericin B lipid complex (ABLC) and liposomal amphotericin, are less nephrotoxic than conventional amphotericin, but are costly; infusion-related reactions may still occur (less so with liposomal amphotericin). Fluconazole is primarily useful for prevention of infection with sensitive Candida species, and does not have activity against Aspergillus. Centers with extensive flu-conazole use may see a rise in fluconazole-resistant yeast, including C. glabrata and C. krusei. Itraconazole has activity against Aspergillus and is sometimes used as antifungal prophylaxis. However, oral tolerability is decreased in patients with chemotherapy-induced nausea, and the i.v. formulation cannot be used in patients with renal dysfunction.

Caspofungin and micafungin are echinocandin antifungals with broad activity against yeasts and molds including Aspergillus (not Cryptococcus). They are generally well tolerated and available only in an i.v. formulation. Liver function tests should be monitored with their use.

Voriconazole is a broad-spectrum antifungal agent with both i.v. and oral formulations. It covers many Candida species resistant to other azoles, has excellent activity against Aspergillus, and also a number of emerging fungal pathogens, but not mucormycetes. As with itraconazole, the i.v. formulation cannot be used in patients with renal insufficiency. Visual symptoms occur in many patients, especially early in therapy. Patients should be warned in advance that these symptoms may occur.

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