Chapter 37  ·  Module 7
Clinical Syndromes
Candidiasis, Aspergillosis, Cryptococcosis, Mucormycosis, and Endemic Mycoses — drug of choice by syndrome
L-AmB = liposomal amphotericin B  ·  TDM = therapeutic drug monitoring  ·  HIV = human immunodeficiency virus  ·  ART = antiretroviral therapy  ·  IRIS = immune reconstitution inflammatory syndrome  ·  DKA = diabetic ketoacidosis
Drug of Choice by Syndrome
Syndrome First-Line Alternative Key Rules
Candidemia Echinocandin (any) Fluconazole (low-risk only) Remove catheter; step down to fluconazole when stable and susceptible; 14 days from negative culture
Invasive aspergillosis Voriconazole or isavuconazole L-AmB TDM mandatory for voriconazole; test isolates for azole resistance; minimum 6 weeks
Cryptococcal meningitis (induction) L-AmB + flucytosine + fluconazole (1 week) AmB deoxycholate + flucytosine (1 week) Manage intracranial pressure; defer ART 2–4 weeks to prevent IRIS
Cryptococcal meningitis (consolidation) Fluconazole 400 mg daily (8 weeks) — Followed by maintenance: fluconazole 200 mg daily until CD4 above 200 on ART x 6 months
Mucormycosis L-AmB 5 mg/kg/day + surgery Posaconazole or isavuconazole (step-down) Surgery essential — cannot omit. Voriconazole: NO activity. Reverse DKA, reduce steroids
Histoplasmosis (mild-moderate) Itraconazole Fluconazole (inferior) Severe or disseminated: L-AmB induction then itraconazole x 12 months
Coccidioidomycosis Fluconazole (including meningitis) Itraconazole (bone/joint) Meningitis: lifelong fluconazole suppression required
Blastomycosis (mild-moderate) Itraconazole — Severe or CNS: L-AmB induction then itraconazole x 12 months
High-Yield Clinical Distinctions
Aspergillosis vs. Mucormycosis
Critical Distinction at the Bedside
  • Both: mold infection in immunocompromised host; similar CT findings
  • Aspergillosis: voriconazole first-line — effective
  • Mucormycosis: voriconazole has NO activity — must use L-AmB
  • Mucormycosis: palatal/nasal eschar, periorbital swelling, DKA clues
  • Breakthrough mucormycosis on voriconazole: switch immediately to L-AmB
Cryptococcal Meningitis
ART Timing Is Critical
  • Defer ART 2–4 weeks after starting antifungals
  • Early ART (within 2 weeks) dramatically worsens mortality via IRIS
  • Manage elevated intracranial pressure with serial lumbar punctures
  • Consolidation fluconazole: 400 mg x 8 weeks
  • Maintenance fluconazole: 200 mg daily until immune reconstitution
Endemic Mycoses — Host and Geographic Clues
Histoplasmosis
Ohio / Mississippi River Valleys
  • Soil with bird or bat droppings
  • Fever, hepatosplenomegaly, cytopenias in HIV patient
  • Urine antigen: most sensitive for disseminated disease
  • Mild-moderate: itraconazole. Severe: L-AmB then itraconazole
Coccidioidomycosis
Desert Southwest / Valley Fever
  • Desert Southwest US, northern Mexico
  • Erythema nodosum, erythema multiforme clues
  • Meningitis: lifelong fluconazole — cannot be cured
  • Bone/joint: itraconazole preferred
Blastomycosis
Ohio / Mississippi / Great Lakes
  • Ohio/Mississippi valleys + Great Lakes + Canada
  • Verrucous or ulcerative skin lesions (disseminated)
  • Disseminates even in immunocompetent hosts
  • Mild-moderate: itraconazole. Severe/CNS: L-AmB then itraconazole
The Overarching Rule — Antifungal Class by Severity

Superficial / mucosal disease: topical agents or oral azoles (fluconazole, itraconazole). Mild to moderate invasive disease (most endemic mycoses): itraconazole or fluconazole. Severe or life-threatening invasive disease: liposomal amphotericin B induction followed by azole step-down. Exception — invasive aspergillosis: voriconazole or isavuconazole first-line (not amphotericin B). Exception — mucormycosis: liposomal amphotericin B always (voriconazole contraindicated).