Pediatric Blastomycosis Medication

Amphotericin B remains the antifungal agent with the most success against B dermatitidis. Cumulative doses less than 1 g have resulted in cure without relapse in 70-91% of adult cases of blastomycosis. A retrospective study of blastomycosis cases in Mississippi reported a cure rate of 86.5% and a relapse rate of only 3.9% for patients treated with amphotericin.^[10]

Toxicity often necessitates interruption of therapy. Cutaneous and noncavitary lung disease should be treated for approximately 8-10 weeks. Cavitary lung disease or infection that extends beyond the lung and skin should be treated for about 10-12 weeks with a cumulative dose of 2.5 g or more of amphotericin B.

Amphotericin B is the drug of choice for treating children with life-threatening and central nervous system infections caused by blastomycosis. Most experts recommend a total cumulative dose of 30 mg/kg or higher of amphotericin B. Human trials of lipid formulations of amphotericin B in the treatment of blastomycosis have not been performed. However, limited clinical data suggest that these preparations may be used for selected patients intolerant to standard amphotericin B therapy.

The azoles are an equally effective and less toxic alternative to amphotericin B for treating adult immunocompetent patients with mild-to-moderate pulmonary or extrapulmonary disease, excluding CNS disease. In a multicenter clinical trial involving adult patients, itraconazole was found to be more effective and associated with fewer adverse effects than ketoconazole.^[7]

Most experts recommend a minimum of 6 months of oral azole therapy for mild-to-moderate pulmonary or nonmeningeal disseminated blastomycosis. Safety and efficacy data using oral azole therapy in children are limited. Itraconazole has been used successfully as treatment in a small number of pediatric patients with non–life-threatening non-CNS disease. Short courses of amphotericin B (5-10 mg/kg total dose) followed by oral itraconazole for 6 months may be used to treat extrapulmonary blastomycosis.

The oral azoles are not beneficial in treating CNS blastomycosis. If oral azole antifungal agents are used for non–life-threatening cases, patients should be closely monitored. Amphotericin B should be substituted for the oral azole agent if clinical deterioration is noted or serum levels of medications are not adequate.

Acute pneumonia complicated by acute respiratory distress syndrome and extrapulmonary disease may need treatment with moderate doses of amphotericin B (>1.5 g total dose) or short courses of amphotericin B (500 mg total dose) followed by 6 months of oral itraconazole. In pregnant women with blastomycosis, amphotericin B is the drug of choice because the oral azoles are contraindicated due to their embryotoxic and teratogenic effects.

Although unusual, in recent years, an increased number of cases of blastomycosis have been reported in compromised hosts, including patients with AIDS, bone marrow and solid organ transplant recipients, and patients receiving cytotoxic or long-term immunosuppressive therapy. Early and aggressive therapy with amphotericin B therapy is warranted because multiple organ and CNS involvement with resultant mortality is relatively common in this population. Furthermore, response to antifungal therapy may be suboptimal, and relapses are common.

Most experts recommend treating blastomycosis in children with AIDS with 30 mg/kg of amphotericin B over 4-6 weeks, followed by itraconazole for at least 6 months in those who have responded to a primary course of amphotericin B. Until more data are available, primary therapy with itraconazole should be used with caution in compromised patients with blastomycosis and considered only in mild illness without CNS infection and stable or improving disease.

Long-term suppressive therapy may be needed in immunocompromised patients. Some experts recommend itraconazole as probably the best secondary prophylaxis for AIDS patients with blastomycosis.

Class Summary

Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Amphotericin B (Amphocin, Fungizone)

Initial DOC for blastomycosis in patients with severe illness (eg, rapidly progressive infections, CNS disease), immunocompromised hosts, and special circumstances (eg, pregnancy, childhood disease).

Itraconazole (Sporanox)

PO itraconazole (at a dosage of 200-400 mg/d) is now the azole of choice in adult patients with indolent nonmeningeal blastomycosis of mild-to-moderate severity, whether given as primary therapy to stable patients or following a course of amphotericin B. Compared with other PO azoles, itraconazole is better absorbed and has enhanced antimycotic activity with fewer adverse effects. In a prospective phase 2 clinical trial involving adult patients, itraconazole was effective in 90% of cases receiving 200-400 mg/d. In a cohort study of 42 patients, similar success rates were noted for patients treated with 200 mg of itraconazole.

Ketoconazole (Nizoral)

An effective alternative agent in the treatment of immunocompetent patients with mild-to-moderate blastomycosis. In prospective randomized clinical trials conducted by the Mycoses Study Group, cure rates of 70-85% have been documented in patients treated with 400-800 mg/d. Relapse rates of 10-14% have been reported, and close follow-up monitoring is warranted for 1-2 years after therapy with ketoconazole.

Fluconazole (Diflucan)

The role of fluconazole therapy in blastomycosis is limited. In a small pilot study involving 23 patients, a successful outcome was noted in only 15 (65%) of cases. Better results were reported recently using higher dosages of fluconazole (400-800 mg/d). A successful outcome was noted for 34 (87%) of 39 patients treated for a mean duration of 8.9 mo. Although fluconazole demonstrates excellent CNS penetration, its role in the treatment of blastomycotic meningitis and cerebral abscesses is anecdotal.