Antifungal therapy - mild to moderate disseminated disease
›Itraconazole oral therapy
›Loading dose 200 mg three times daily for 3 days
›Then 200 mg once to twice daily
›Duration 6-12 months for non-CNS disease
›Formulation considerations
›Oral solution preferred over capsules for better bioavailability
›Take capsules with fatty meal or acidic beverage
›Monitoring
›Serum level check at minimum 2 weeks
›LFTs every 1-3 months
›Drug interactions with CYP3A4 inhibitors and inducers
Antifungal therapy - CNS disease
›Liposomal amphotericin B induction
›Dose 5 mg/kg/day IV
›Duration 4-6 weeks
›Higher dose than non-CNS disease
›Step-down after induction
›Fluconazole 800 mg/day orally
›Or voriconazole 200-400 mg twice daily orally
›Or itraconazole 200 mg twice to three times daily
›Voriconazole preferred for step-down
›Superior CNS penetration compared to itraconazole
›Intrinsic activity against Blastomyces
›Monitor for visual disturbances, hepatotoxicity, QTc prolongation
›Duration minimum 12 months
›Continue until CSF normalization
›Longer in immunocompromised patients
Alternative antifungal agents
›Alternatives for itraconazole intolerance
›Fluconazole 400-800 mg/day orally
›Less effective than itraconazole
›Acceptable alternative for non-CNS disease
›Voriconazole
›Effective across disease severity
›QTc monitoring required
›Posaconazole and isavuconazole
›Limited data for blastomycosis
›Consider for refractory or intolerant cases
›Agents to avoid
›Ketoconazole: more toxic, rarely used
›Replaced by safer azoles
›Amphotericin B deoxycholate
›Higher nephrotoxicity than liposomal formulation
›Reserved for resource-limited settings or poor response to liposomal formulation
Refractory and severe ARDS management
›Adjunctive measures for ARDS
›Corticosteroids
›Used at some centers but no proven mortality benefit
›Clinical judgment should guide use
›ECMO for refractory ARDS
›All 4 patients treated with ECMO survived in one case series
›Consider at ECMO-capable center for refractory cases
›Amphotericin B deoxycholate continuous infusion
›Consider if poor response to liposomal amphotericin B
›Immunocompromised host management
›Liposomal amphotericin B induction regardless of severity
›IDSA recommendation for SOT recipients
›Higher mortality justifies aggressive initial therapy
›Prolonged azole suppressive therapy
›Minimum 12 months; consider lifelong suppression while immunosuppression persists
›ART optimization for HIV-positive patients
›Immunosuppression reduction if clinically feasible
›Balance rejection risk versus infection severity in SOT recipients