Table 4. Therapeutic recommendations for commonly encountered IFIs in lung transplant recipients.

IFIs	Recommended dose	Alternative therapy	Comments
Commonly encountered IFIs
Invasive aspergillosis (IA)	Voriconazole 6 mg/kg IV. q12h ×2 doses, then 4 mg/kg IV q12h × at least 7 days; convert to PO when stable and trough level is adequate: 200 mg PO q12h (>40 kg) and 100 mg PO q12h (<40 kg)	Isavuconazole 372 mg IV every 8 h for 6 doses, then 372 mg IV/PO once daily. Lipid formulations of Amphotericin B (AmB): liposomal AmB 3–5 mg IV daily, or; AmB lipid complex 5 mg/kg IV daily. Other agents: itraconazole 200 mg PO q8h ×9 doses, then 200 mg BID (need TDM). Posaconazole 300 mg (IV or PO delayed-release tablet) q12h ×2 doses, then 300 mg IV/PO daily	Avoid using voriconazole in severe cirrhosis. Therapeutic drug monitoring of voriconazole with ideal targeted therapeutic voriconazole level between 1–5 µg/mL. For severe or disseminated IA, combination with an echinocandin can be considered (caspofungin 70 mg IV load then 50 mg IV daily; micafungin 100–150 mg IV daily; or anidulafungin 200 mg IV load then 100 mg IV daily). Echinocandin alone is not recommended for initial treatment of IA
Invasive candidiasis (empyema, candidemia, surgical site and intra-abdominal infections) are the most common manifestations of IC among LTR. Invasive pulmonary candida infection is very rare	Echinocandin: caspofungin 70 mg IV load then 50 mg IV daily, or micafungin 100–150 mg IV daily, or anidulafungin 200 mg IV load then 100 mg IV daily. Transition to fluconazole after 5–7 days after clinically stable	Fluconazole. Voriconazole or posaconazole for Candida isolates susceptible to these agents, but resistant to fluconazole	Therapeutic drug monitoring is recommended if voriconazole is used
Less common IFIs in LTR: yeast infections
Cryptococcus (pulmonary and extra-CNS disease)	Severe: Liposomal AmB 5 mg/kg IV q24h until improved, then fluconazole 400 mg PO daily. Mild to moderate: fluconazole 400 mg PO daily	Mild to moderate: itraconazole 200–400 mg daily	Low threshold to perform lumbar puncture for CSF cryptococcal antigen to rule out CNS involvement
Cryptococcus (CNS infection)	Ambisome 6 mg/kg IV q24h and flucytosine 25 mg/kg PO qid for ≥2 weeks, then fluconazole. 400–800 mg/d ×8 weeks, then fluconazole 200–400 mg PO daily for 6–12 months as maintenance		Serum flucytosine levels should be measured after 3 to 5 days of therapy, with a target 2-hour post dose level of 30–80 µg/mL; flucytosine levels >100 mcg/mL should be avoided. Fluconazole dose should be adjusted for renal function
Dimorphic fungi
Blastomycosis (pulmonary and extra-CNS disease)	Severe: ambisome 5 mg/kg IV q24h, until stable/improved then itraconazole 200 mg PO q8h ×3 days, then 200–400 mg PO daily. Mild-moderate: itraconazale 200 mg PO q8h ×3 days, then 200–400 mg PO daily	Mild-moderate: fluconazole 400–800 mg PO daily
Blastomycosis (CNS disease)	Ambisome 5 mg/kg IV q24h
Coccidioidomycosis (pulmonary and extra-CNS disease)	Severe: ambisome 5 mg/kg IV q24h until stable/improved, then fluconazole, 800 mg or itraconazole 200 mg PO q8h ×3 days then 200 mg PO BID. Moderate to severe: itraconazole 200 mg PO q8h ×3 days, then 200 mg PO BID or fluconazole 400 mg PO daily	Moderate to severe: ambisome 5 mg/kg, IV q24h
Coccidioidomycosis (CNS disease)	Fluconazole 400–1,200 mg IV/PO daily until improved then fluconazole 400 mg daily PO lifelong	Intrathecal AmB deoxycholate 0.1–1.5 mg, itraconazole 200 mg, PO q8h ×3 days, then 400–600 mg q24h
Histoplasmosis (pulmonary and disseminated)	Severe: ambisome 5 mg/kg IV q24h then itraconazole 200 mg PO q8h ×3 days, then 200 PO mg BID. Mild to moderate: itraconazole 200 mg PO q8h ×3 days, then 200 mg PO BID
Less common molds in LTR
Mucormycosis	Ambisome 5 mg/kg IV q24h	Ambisome IV q24h up to 10 mg/kg for severe, CNS involvement, or worsening infection. Or posaconazole IV or PO delayed release tablets 300 mg q12h on day 1, then 300 mg daily thereafter	Check posaconazole trough level ~1 week after initiation. Treatment efficacy is associated with level >1 μg/mL

IFI, invasive fungal infection; LTR, lung transplant recipient.