IV Amphotericin B is Essential and Life-Saving for Severe Blastomycosis
Intravenous amphotericin B is not just helpful but mandatory for severe, life-threatening, CNS, and immunocompromised blastomycosis cases, with cure rates of 77-97% when adequate doses are administered. 1, 2
When IV Amphotericin B is Required
Absolute Indications (Must Use)
- Moderately severe to severe pulmonary blastomycosis: Lipid amphotericin B 3-5 mg/kg/day or deoxycholate 0.7-1 mg/kg/day for 1-2 weeks, followed by step-down to itraconazole 200 mg twice daily for 6-12 months 1, 2
- CNS involvement: Lipid amphotericin B 5 mg/kg/day for 4-6 weeks, then oral azole for at least 1 year 1, 2
- Life-threatening disseminated disease: Same dosing as severe pulmonary disease, with step-down after clinical stabilization 1
- Immunocompromised patients (AIDS, transplant recipients, chemotherapy): Amphotericin B 0.7-1 mg/kg/day initially, as mortality rates reach 30-40% with most deaths in the first few weeks 1, 2
- Pregnancy: Lipid amphotericin B 3-5 mg/kg/day is the only safe option, as azoles are absolutely contraindicated due to teratogenic effects 1, 2
- Pediatric patients with life-threatening or CNS disease 1
When Oral Therapy is Appropriate
- Mild to moderate pulmonary or disseminated disease (excluding CNS) in immunocompetent patients: Itraconazole 200 mg once or twice daily for 6-12 months is preferred 1
Formulation Selection
Lipid formulations of amphotericin B are strongly preferred over deoxycholate due to significantly fewer adverse effects, particularly nephrotoxicity, while maintaining equivalent efficacy. 1, 2
Critical Exception
One recent case report demonstrated successful treatment of severe blastomycosis with ARDS using continuous infusion amphotericin B deoxycholate after poor response to liposomal amphotericin B, suggesting deoxycholate may be considered when lipid formulations fail 3
Treatment Strategy and Monitoring
Step-Down Approach
- Continue IV amphotericin B for 1-2 weeks until clinical stabilization 1, 2
- Switch to itraconazole 200 mg twice daily to complete total therapy duration 1, 2
- For CNS disease: Continue amphotericin B for 4-6 weeks before step-down 1, 2
- For immunocompromised patients: Consider itraconazole 200 mg three times daily for 3 days, then twice daily for ≥12 months total 2
Essential Monitoring
- Check serum itraconazole levels after 2 weeks of step-down therapy, targeting >1.0 μg/mL 2
- Monitor for relapse, especially in immunocompromised patients who may require chronic suppressive therapy 1
Common Pitfalls to Avoid
- Never use azoles as primary therapy for CNS blastomycosis - amphotericin B is mandatory despite fluconazole's excellent CSF penetration 1
- Do not undertreat bone disease - requires at least 12 months of therapy due to higher relapse rates 1
- Avoid premature step-down - ensure clinical stabilization before switching to oral therapy, particularly in immunocompromised patients 1
- Do not use ketoconazole for chronic suppression - higher relapse rates compared to itraconazole 1
FDA Approval Context
Amphotericin B is FDA-approved specifically for potentially life-threatening fungal infections including North American blastomycosis, confirming its role as definitive therapy for severe disease 4