What is the treatment for Blastomyces infections?

Treatment of Blastomyces Infections

Yes, Blastomyces infections (not "trophozoites"—the correct term is yeast form) are treated with antifungal medications, primarily itraconazole for mild-to-moderate disease and amphotericin B for severe or life-threatening infections. 1

Clarification on Terminology

Blastomyces exists as a yeast form in human tissue, not as trophozoites (which is a term used for protozoan parasites). 2 The organism transforms from its mold phase in the environment to its yeast phase at body temperature after inhalation. 2

Treatment Algorithm Based on Disease Severity

Mild to Moderate Disease

Oral itraconazole is the first-line treatment for non-life-threatening blastomycosis. 1

• Dosing regimen: 200 mg three times daily for 3 days (loading dose), then 200 mg once or twice daily for 6-12 months 1
• Success rate: Approximately 95% in compliant patients who complete at least 2 months of therapy 1
• Serum level monitoring: Measure itraconazole levels after 2 weeks of therapy to ensure adequate drug exposure (target >1.0 μg/mL) 1, 3

Moderately Severe to Severe Disease

Initial treatment with amphotericin B followed by step-down to itraconazole is the standard approach. 1, 3

• Initial therapy: Lipid formulation amphotericin B at 3-5 mg/kg/day OR amphotericin B deoxycholate at 0.7-1 mg/kg/day for 1-2 weeks or until clinical improvement 1, 3
• Step-down therapy: Switch to itraconazole 200 mg twice daily to complete a total of 6-12 months of treatment 1, 3
• Lipid formulations are strongly preferred over deoxycholate due to significantly reduced nephrotoxicity while maintaining equivalent efficacy 1, 3

CNS Blastomycosis

CNS involvement requires prolonged high-dose amphotericin B followed by extended azole therapy. 1

• Initial therapy: Lipid formulation amphotericin B at 5 mg/kg/day for 4-6 weeks 1, 3
• Step-down options: Fluconazole 800 mg daily, itraconazole 200 mg 2-3 times daily, or voriconazole 200-400 mg twice daily for at least 12 months 1
• Duration: Continue until resolution of CSF abnormalities 1

Immunocompromised Patients

Immunosuppressed patients require aggressive initial therapy and prolonged treatment. 1

• Initial therapy: Amphotericin B (lipid formulation 3-5 mg/kg/day or deoxycholate 0.7-1 mg/kg/day) for 1-2 weeks 1
• Step-down therapy: Itraconazole 200 mg three times daily for 3 days, then twice daily to complete at least 12 months total therapy 1
• Lifelong suppressive therapy with itraconazole 200 mg daily may be required if immunosuppression cannot be reversed 1
• Mortality rates of 30-40% have been reported, with most deaths occurring in the first few weeks, emphasizing the need for early aggressive treatment 3

Osteoarticular Disease

Bone and joint involvement requires extended treatment duration. 1

• Treat for a minimum of 12 months regardless of initial severity 1

Special Populations

Pregnant Women

Lipid formulation amphotericin B is the only safe option during pregnancy. 1

• Dosing: 3-5 mg/kg/day 1, 3
• Azoles are absolutely contraindicated due to teratogenic effects 1, 3

Children

Pediatric dosing is weight-based with similar treatment principles. 1

• Severe disease: Amphotericin B deoxycholate 0.7-1.0 mg/kg/day or lipid formulation 3-5 mg/kg/day, followed by itraconazole 10 mg/kg/day (maximum 400 mg/day) for 12 months 1
• Mild to moderate disease: Itraconazole 10 mg/kg/day (maximum 400 mg/day) for 6-12 months 1
• Children generally tolerate amphotericin B deoxycholate better than adults 1

Alternative Agents

Fluconazole

Fluconazole is less effective than itraconazole but useful in specific situations. 1, 4

• Higher doses (400-800 mg daily) achieve 87% success rates 1, 4, 5
• Preferred for patients on proton pump inhibitors since absorption is not pH-dependent 4
• Particularly useful for CNS disease due to excellent CSF penetration 1

Ketoconazole

Ketoconazole is rarely used due to higher toxicity and inferior efficacy. 1

• Historical cure rates of 70-85% with relapse rates of 10-14% 1
• Replaced by itraconazole as first-line azole therapy 1, 6

Voriconazole and Posaconazole

These newer azoles may be effective but have limited data. 1

• Can be considered for patients intolerant of itraconazole 1, 2
• Voriconazole has good CSF penetration and may be useful for CNS disease 1

Critical Monitoring Requirements

Itraconazole-Specific Considerations

Absorption varies significantly and requires monitoring. 1, 7

• Capsule formulation: Requires gastric acidity; take with food; avoid proton pump inhibitors 7, 4
• Solution formulation: Take on empty stomach; does not require gastric acidity 1
• Serum level monitoring: Check after 2 weeks to ensure levels >1.0 μg/mL 1, 3, 7

Laboratory Monitoring

Regular monitoring is essential to detect toxicity. 7, 4

• Hepatic enzymes: Check before starting therapy, at 2 and 4 weeks, then every 3 months 7, 4
• Renal function: Monitor frequently during amphotericin B therapy 8
• Electrolytes: Particularly magnesium and potassium during amphotericin B treatment 8

Important Clinical Pitfalls

When NOT to Treat

Very select cases of mild, self-limited acute pulmonary blastomycosis may not require treatment if clinical resolution occurs before diagnosis is established. 1 However, most clinicians now treat even these patients with itraconazole to prevent extrapulmonary dissemination. 1

Drug Interactions

Amphotericin B-induced hypokalemia can potentiate digitalis toxicity and enhance effects of skeletal muscle relaxants. 8 Monitor electrolytes closely and correct deficits promptly. 8

Acute Respiratory Distress Syndrome

ARDS carries mortality rates of 50-89% despite treatment. 1 Overwhelming pulmonary disease is the most common cause of death, often occurring within the first few days of therapy. 1