Cutaneous Cryptococcus Medication
- Author: David G Moskowitz, MD; Chief Editor: Dirk M Elston, MD more...
The duration of treatment and the combination of agents depend on the patient's immune status and whether the infection is disseminated. For primary cutaneous Cryptococcus infection, treat with oral fluconazole at 200 mg/d for 10 days and then 100 mg/d for 8 weeks.
For non-CNS disseminated Cryptococcus infection, treat with fluconazole at 200-400 mg/d for 3-6 months. An alternative is itraconazole at 200-400 mg/d for 6-12 months. For more severe involvement, amphotericin B is recommended at 0.5 mg/kg/d for 6-10 weeks.
For CNS disease, use amphotericin B at 0.7-1 mg/kg/d plus flucytosine at 100 mg/kg/d for 6-10 weeks. Alternatively, use amphotericin B/flucytosine for 2 weeks, followed by fluconazole at 400 mg/d for 10 weeks. This is then followed by fluconazole for 6-12 months. Voriconazole is another possible treatment but its use is not well reported for CC.
Posaconazole, the newest triazole antifungal agent, is structurally similar to itraconazole and possesses activity against Cryptococcus neoformans. Randomized, double-blind trials demonstrated that posaconazole to be at least as effective as fluconazole for the prevention of invasive fungal infections in immunocompromised patients. The dose of posaconazole is 200 mg orally 3 times daily for the prevention of invasive fungal infections and 800 mg/d in 2-4 divided doses for the treatment of invasive fungal infections refractory to other antifungal treatment.
For non-CNS disseminated Cryptococcus infection, use fluconazole or itraconazole as dosed above. Maintenance fluconazole therapy is recommended for life. Studies have shown that treatment can be discontinued after 1-2 years if the patient is receiving highly active antiretroviral therapy (HAART) and has had a CD4 count greater than 200/µL for at least 6 months, a nondetectable viral load, and a negative serum Cryptococcus antigen test result.
For CNS disease, use amphotericin B at 0.7-1 mg/kg/d plus flucytosine at 100-150 mg/kg/d for 2 weeks, fluconazole at 400 mg/d for at least 10 weeks, and then, in some cases, maintenance fluconazole for life. Studies have shown that treatment can be discontinued after 1-2 years if the patient is receiving HAART and has had a CD4 count greater than 200/µL for at least 6 months, a nondetectable viral load, and a negative serum Cryptococcus antigen test result.
Liposomal formulations of amphotericin B may be used as needed. Newer azoles, such as voriconazole, appear to have good activity against Cryptococcus and may be used more frequently in the future. Caspofungin lacks significant activity against Cryptococcus and is not recommended.
Antifungal Agent, Systemic
Antifungal agents are used in the management of infectious diseases caused by fungi.
Fluconazole is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. It has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Fluconazole is available as a tablet for oral administration, as powder for oral suspension, and as sterile solution for intravenous use. It has fewer adverse effects and better tissue distribution than older systemic imidazoles. Fluconazole is active against many yeast and dimorphic fungi. In general, it has poor activity against molds and filamentous fungi.
Itraconazole has fungistatic activity. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Amphotericin B deoxycholate is produced from a strain of Streptomyces nodosus. Its antifungal activity results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, its main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, 40- to 105-nm pores are produced in the cytoplasmic membrane, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. The main fungicidal activity of amphotericin B may reside in its ability to cause auto-oxidation of cell membranes.
If therapy is supplemented by oral flucytosine, therapy can be used until the patient is afebrile and alert and spinal fluid cultures are negative for 6 weeks; then, the patient can begin fluconazole therapy.
Although the exact mode of action is unknown, flucytosine may act directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism, where it is converted to 5-fluorouracil after penetrating fungal cells. It inhibits RNA and protein synthesis. Flucytosine is active against candidal and cryptococcal species and generally used in combination with amphotericin B.
Use it in combination with another agent because acquired resistance develops frequently when administered alone. Flucytosine is well absorbed orally but should be administered intravenously to critically ill patients.
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