invasive fungal infections
in review
3 min read
Updated 2026-09-29
invasive fungal infections
Yeasts (Candida, Cryptococcus), moulds (Aspergillus, Mucorales), and dimorphic fungi (Blastomyces, Histoplasma, Coccidioides). Invasive aspergillosis: neutropaenia/transplant, nodules with halo sign, galactomannan → voriconazole (or isavuconazole). Mucormycosis: DKA, neutropaenia, iron overload; black necrotic eschar → emergency debridement + liposomal amphotericin B. Blastomycosis is endemic around the Great Lakes, St Lawrence, and northwestern Ontario/Manitoba → itraconazole (amphotericin first if severe). Candidaemia: echinocandin, remove lines, eye exam.
do not miss
- rhino-orbital-cerebral mucormycosis — palatal/nasal black eschar, facial pain, proptosis in DKA → same-day surgery; voriconazole does not cover Mucorales
- Candida in blood is never a contaminant
classification
| group | organisms | form in tissue |
|---|---|---|
| yeasts | Candida, Cryptococcus | budding yeast ± pseudohyphae |
| moulds | Aspergillus (acute-angle septate hyphae), Mucorales (broad, ribbon-like, pauci-septate, right-angle branching) | hyphae with angioinvasion |
| dimorphic | Blastomyces, Histoplasma, Coccidioides, Sporothrix | mould in the environment, yeast in the body (“mould in the cold, yeast in the beast”) |
invasive aspergillosis
- risk: prolonged neutropaenia, allogeneic HSCT, GVHD on steroids, solid organ transplant, severe influenza/COVID in ICU, high-dose steroids
- CT chest: nodules with halo sign (early), air-crescent/cavitation (neutrophil recovery)
- serum/BAL galactomannan (false positives: pip-tazo historically, some IVIG; reduced sensitivity on mould-active prophylaxis); β-D-glucan non-specific
- voriconazole 6 mg/kg IV q12h × 2 then 4 mg/kg q12h (TDM trough 1–5.5 mg/L) — or isavuconazole (fewer visual/hepatic effects, no QT prolongation); liposomal amphotericin B if azoles contraindicated
- ≥6–12 weeks, until lesions resolve and immunosuppression reversed
- voriconazole toxicity: visual disturbance, hallucinations, hepatotoxicity, photosensitivity/skin cancer, periostitis (fluoride), CYP interactions (tacrolimus, sirolimus contraindicated)
- chronic pulmonary aspergillosis/aspergilloma (prior cavity, e.g. TB) and ABPA (asthma, eosinophilia, IgE) are separate entities
mucormycosis
- risk: DKA, neutropaenia, HSCT, deferoxamine, high-dose steroids
- rhino-orbital-cerebral (sinusitis → palate/nasal eschar, proptosis, cranial nerve palsies), pulmonary, cutaneous, GI
- urgent surgical debridement + liposomal amphotericin B 5–10 mg/kg/day; correct acidosis/hyperglycaemia; reduce immunosuppression
- step-down: isavuconazole or posaconazole (not voriconazole, not fluconazole)
endemic (dimorphic) mycoses
| fungus | geography | clues | treatment |
|---|---|---|---|
| Blastomyces | Great Lakes, St Lawrence, northwestern Ontario, Manitoba; soil/waterways | pneumonia mimicking CAP/cancer not responding to antibiotics; verrucous skin lesions; bone, GU (prostate) | mild–moderate: itraconazole 200 mg TID × 3 days → 200 mg BID × 6–12 months; severe/CNS: liposomal amphotericin B 1–2 weeks → itraconazole |
| Histoplasma | Ohio/Mississippi valleys, St Lawrence; bird/bat guano, caves | mediastinal nodes, calcified granulomas; disseminated in HIV (pancytopaenia, hepatosplenomegaly, oral ulcers); urine antigen | mild: itraconazole; disseminated/severe: liposomal amphotericin B → itraconazole |
| Coccidioides | southwestern US, Mexico (snowbirds) | valley fever: pneumonia, erythema nodosum, arthralgia; meningitis | many resolve untreated; fluconazole or itraconazole if risk/severe; lifelong fluconazole for meningitis |
- itraconazole: check levels (capsules need food and acid; solution better absorbed); negative inotrope — avoid in heart failure; CYP3A4 inhibitor
- culture/histology diagnose; Blastomyces broad-based budding yeast; Histoplasma urine/serum antigen
yeasts
- candidaemia and species-specific therapy — see targeted antibiotic therapy by pathogen
- Candida in urine or sputum → usually colonisation
- cryptococcal meningitis (HIV and non-HIV: transplant, steroids, cirrhosis) — see HIV opportunistic infections; C. gattii in immunocompetent hosts (British Columbia)
antifungal spectrum
| agent | covers | misses | notes |
|---|---|---|---|
| fluconazole | most Candida, Cryptococcus, Coccidioides | moulds, C. krusei, often C. glabrata | renally dosed; QT |
| voriconazole | Aspergillus, Candida | Mucorales | TDM; many interactions |
| posaconazole / isavuconazole | Aspergillus, Mucorales, Candida | — | prophylaxis (posaconazole) in AML/GVHD |
| echinocandins | Candida (incl. glabrata, krusei, auris) | Cryptococcus, Mucorales; poor urine/CNS/eye levels | first-line candidaemia |
| amphotericin B (liposomal) | broadest — moulds incl. Mucorales, yeasts, dimorphic | Candida lusitaniae, Aspergillus terreus | nephrotoxicity, hypokalaemia, hypomagnesaemia, infusion reactions |
traps
- voriconazole for suspected mucormycosis (or breakthrough mucormycosis on voriconazole prophylaxis)
- treating Candida in sputum
- blastomycosis treated as recurrent CAP with repeated antibiotic courses
- itraconazole capsules with a PPI — poor absorption; check a level
- voriconazole with sirolimus, or unadjusted tacrolimus