eMedicine Specialties > Pulmonology > Infectious Lung Diseases
Blastomycosis: Treatment & Medication
Updated: May 21, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
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Treatment
Medical Care
Patients with a subclinical disease (presence of serologic or other markers without symptoms) can be observed but not given antifungal treatment. Some experts advise that patients with resolving symptoms of mild disease limited to the lung also may be managed without antifungal treatment. However, many other experts, including these authors, disagree with this approach.
Patients with cutaneous dissemination must be treated. Spontaneous resolution does not occur, and irreversible scarring results.
Consultations
Since blastomycosis is rarely encountered, it is advisable for primary care physicians to seek consultation from a physician more experienced with this disease. In cases with extrapulmonary involvement, consult a specialist (pulmonologist or infectious disease) for diagnosis and treatment recommendations.
- Consult a pulmonologist or an intensivist for blastomycosis that presents with or develops ARDS.
- Surgical consultation may be needed for a tissue biopsy, but only rarely for adjunctive surgical treatment (eg, evacuation of a joint abscess, pleural empyema). Alert the microbiologist to the possibility of blastomycosis before sending any specimen to the laboratory.
- Consultation with a dermatologist may facilitate making the diagnosis by recognition of typical skin lesions, aspiration or expression of microbiologically diagnostic pus, or skin biopsy.
Medication
Choice of medication used to treat blastomycosis should be based on type, extent, and severity of disease; the immune status of the patient; and the toxicity of the drug.
Newer drugs such as voriconazole and posaconazole have shown significant in vitro and in vivo (murine model) activity against blastomycosis,6 but experience in humans is limited. Caspofungin and micafungin have variable in vitro activity.
Amphotericin B and itraconazole continue to be the main drugs of choice.
Patients with life-threatening disease, pulmonary (eg, ARDS) or extrapulmonary, should be treated with amphotericin B at a high dose of 0.7-1 mg/kg/d to a total dose of 1.5-2 g. However, amphotericin is associated with several toxic effects, most notably renal impairment. Infusion of saline before, during, and after amphotericin reduces renal toxicity. Other effects include thrombophlebitis at the injection site, chills, fever, nausea, hypokalemia, and anemia. Lipid formulations of amphotericin are less likely to cause renal impairment, and these agents are alternatives in persons who cannot tolerate amphotericin B.
It is reasonable to consider initial treatment with amphotericin B to a minimum cumulative dose of 500 mg followed by itraconazole 200-400 mg for 6 months. This approach, however, has not yet been validated in large clinical studies.
Itraconazole is the drug of choice in mild-to-moderate pulmonary blastomycosis. The appropriate dose is 200 mg/d for 6 months. The value of a higher dose is uncertain. Gastric acidity is required for absorption of itraconazole. Itraconazole provides the ease of oral administration, low toxicity, and high efficacy. Other azoles (eg, ketoconazole, fluconazole) at 400-800 mg/d for 6 months may also be considered. If disease progresses while on any azole, change to amphotericin B. Azoles are contraindicated in pregnancy.
In disseminated (extrapulmonary) disease, treatment decision hinges on CNS involvement. Patients with CNS blastomycosis should be treated with amphotericin B (dose schedule as in life-threatening disease). Azoles are not appropriate drugs for CNS disease with the exception of fluconazole. Fluconazole has good cerebrospinal fluid penetration and the dose recommended is a minimum of 800 mg/d.
Patients with mild-to-moderate disseminated blastomycosis without CNS involvement should be treated with itraconazole 200-400 mg/d for 6 months. Treatment period should be extended to 12 months in patients with bone involvement (osteomyelitis).
Immunocompromised patients should be treated early and aggressively with amphotericin B as in life-threatening disease. After the amphotericin B course, chronic suppressive therapy with itraconazole may be needed in some cases.
Antifungal agents
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 (AmBisome)
Alters fungal cell membrane permeability by binding with ergosterol, resulting in cell component leakage and death.
Administered IV and must be mixed with dextrose in water.
Adult
1 mg IV over 2 h, titrate up by 10 mg/d to 40-50 mg/d (0.4-0.6 mg/kg) infused IV over 4-6 h
If clinically stable, dose can be administered qod
Total cumulative dose: 2 g; <1.5 g increases risk of relapse
Critically ill: 0.6 mg/kg IV on first d, may increase dose
Pediatric
0.25-1.5 mg/kg/d IV qd over 2-6 h; 1-1.5 mg/kg IV qod; total cumulative dose 30 mg/kg
Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Infusing saline 500 mL IV before and after administration reduces nephrotoxicity; aspirin/diphenhydramine prior to drug infusion decreases chills and fever; using central vein or changing peripheral IV site reduces occurrence of phlebitis; monitor serum K+ level; discontinue for 2 d if serum creatinine of 3 mg/dL or less; not all pregnant women and newborns suffer complications
Itraconazole (Sporanox)
Synthetic thiazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Adult
200 mg PO qd for 6 mo; not to exceed 400 mg/d
Pediatric
Not established; adjust dosage to child's weight
Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered)
Documented hypersensitivity; concurrent use of simvastatin, lovastatin, midazolam, triazolam
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not indicated for CNS blastomycosis; compliance in completing course of therapy necessary; caution in hepatic insufficiencies
More on Blastomycosis |
| Overview: Blastomycosis |
| Differential Diagnoses & Workup: Blastomycosis |
 Treatment & Medication: Blastomycosis |
| Follow-up: Blastomycosis |
| Multimedia: Blastomycosis |
| References |
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References
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Chapman SW, Bradsher RW Jr, Campbell GD Jr, Pappas PG, Kauffman CA. Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America. Clin Infect Dis. Apr 2000;30(4):679-83. [Medline].
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Further Reading
Keywords
blastomycosis, Gilchrist disease, Gilchrist's disease, fungal infection, fungus infection, Blastomyces dermatitidis, B dermatitidis, pulmonary infection, adult respiratory syndrome, ARDS, antifungal treatment
