What is the recommended treatment for blastomycosis using Amphotericin B (Antifungal medication)?

Treatment of Blastomycosis with Amphotericin B

Amphotericin B is the mandatory first-line treatment for severe/life-threatening blastomycosis, CNS disease, immunocompromised patients, and pregnant women, with lipid formulations preferred over deoxycholate due to reduced toxicity. 1

Clinical Scenarios Requiring Amphotericin B

Absolute Indications (Must Use Amphotericin B)

• CNS blastomycosis: Lipid amphotericin B 5 mg/kg/day for 4-6 weeks, followed by step-down azole therapy for at least 1 year 1

  • Deoxycholate formulation: 0.7-1 mg/kg/day (total dose ≥2 g) if lipid formulations unavailable 1
  • Azoles should never be used as primary therapy for CNS disease 1

• Moderately severe to severe pulmonary disease: Lipid amphotericin B 3-5 mg/kg/day OR deoxycholate 0.7-1 mg/kg/day for 1-2 weeks, then switch to itraconazole 200 mg twice daily for 6-12 months 1

• Life-threatening disseminated disease: Same dosing as severe pulmonary disease, with step-down to itraconazole after clinical stabilization 1

• Immunocompromised patients (AIDS, transplant recipients, those on immunosuppressive therapy): Amphotericin B 0.7-1 mg/kg/day initially, followed by itraconazole 200 mg three times daily for 3 days, then twice daily to complete ≥12 months total therapy 1

  • Mortality rates of 30-40% reported in this population, with most deaths occurring in first few weeks—early aggressive treatment is critical 1
  • Lifelong suppressive therapy with itraconazole 200 mg/day may be required if immunosuppression cannot be reversed 1

• Pregnancy: Lipid amphotericin B 3-5 mg/kg/day is the only acceptable treatment 1

  • Azoles are absolutely contraindicated due to embryotoxic and teratogenic effects 1

• Children with severe disease: Amphotericin B deoxycholate or lipid formulation, as children generally tolerate deoxycholate better than adults 1

Relative Indications

• Azole treatment failure: Switch to amphotericin B 0.5-0.7 mg/kg/day (total dose 1.5-2.5 g) 1

• Azole intolerance: Same dosing as azole failure 1

Formulation Selection

Lipid formulations (liposomal, lipid complex) are strongly preferred over amphotericin B deoxycholate due to significantly fewer adverse effects, particularly nephrotoxicity. 1

• Lipid formulations: 3-5 mg/kg/day 1
• Deoxycholate formulation: 0.7-1 mg/kg/day 1
• Both formulations achieve cure rates of 77-97% when adequate total doses administered 1

Critical Caveat for ECMO Patients

In patients on extracorporeal membrane oxygenation (ECMO) with concurrent continuous renal replacement therapy (CRRT), amphotericin B deoxycholate should be used preferentially over liposomal formulations. 2 Liposomal amphotericin B may be significantly removed by ECMO circuits, leading to undetectable drug levels and circuit failure. Serum drug levels should be monitored when possible in this setting. 2

Step-Down Therapy Strategy

Most clinicians prefer step-down therapy rather than completing the entire course with amphotericin B: 1

• Continue amphotericin B for 1-2 weeks (or until clinical improvement) 1
• Switch to itraconazole 200 mg twice daily 1
• Complete 6-12 months total therapy for pulmonary disease 1
• Complete ≥12 months for disseminated disease 1
• Osteoarticular disease requires 12 months of treatment 1

Monitoring Requirements

• Serum itraconazole levels after 2 weeks of step-down therapy (target >1.0 μg/mL) 1, 3
• Hepatic enzymes before starting azole therapy, at 2 and 4 weeks, then every 3 months during prolonged treatment 3

Mild-to-Moderate Disease (Itraconazole Preferred)

For immunocompetent patients with mild-to-moderate pulmonary or non-CNS disseminated disease, itraconazole 200 mg once or twice daily for 6-12 months is first-line therapy. 1 Amphotericin B is reserved for the severe presentations outlined above. 1