Phys · infectious
Invasive and Mucocutaneous Fungal Infections
Also known as invasive candidiasis · candidaemia · invasive aspergillosis · cryptococcal meningitis · Pneumocystis pneumonia · PJP · PCP · mucormycosis · zygomycosis · rhinocerebral mucormycosis · histoplasmosis · coccidioidomycosis · Valley fever · blastomycosis · galactomannan · halo sign · echinocandin · voriconazole · amphotericin B · liposomal amphotericin
Consultant-physician-depth guide to fungal infections in the immunocompromised and critically ill host — the central principle that the type of immune defect predicts the fungus, with systematic coverage of candidiasis (mucocutaneous and invasive, including candidaemia risk factors, empiric echinocandin for the unstable patient, and mandatory line removal), invasive pulmonary aspergillosis (halo sign, galactomannan, voriconazole first-line and isavuconazole alternative), cryptococcal meningitis (amphotericin B plus flucytosine induction, fluconazole consolidation, and the manage-raised-ICP principle with serial LPs), the endemic mycoses (Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, Talaromyces), Pneumocystis jirovecii pneumonia (CD4 below 200, co-trimoxazole, adjunctive steroids), and rhinocerebral mucormycosis (ketoacidosis, black necrotic eschar, amphotericin plus debridement) — structured for FRACP DWE and DCE preparation.
Checked against its sources on 3 Sept 2026
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- Persistent fever in neutropenia beyond 3 to 5 days despite broad-spectrum antibacterials mandates a chest CT, serum galactomannan, and empiric antifungal therapy — invasive aspergillosis carries 50 to 60 per cent mortality despite treatment
- A neutropenic or transplant patient with new pleuritic chest pain, haemoptysis, or a pulmonary nodule on CT has invasive pulmonary aspergillosis until proven otherwise — voriconazole (or isavuconazole) is first-line, not amphotericin B
- Any patient with candidaemia must have the central venous catheter removed and a dilated fundoscopy performed — ocular candidiasis is present in 10.7 per cent (sight-threatening concordant endophthalmitis 1.8 per cent) and source control (line removal) is as important as the antifungal choice
- A diabetic patient in ketoacidosis with facial or sinus pain, black necrotic eschar on the palate or turbinate, or cranial nerve palsy has rhinocerebral mucormycosis until proven otherwise — this is a surgical emergency requiring immediate high-dose liposomal amphotericin B and aggressive debridement; mortality exceeds 50 per cent
- An HIV-positive patient with CD4 below 100 and subacute headache has cryptococcal meningitis until proven otherwise — raised intracranial pressure is the single most important determinant of early mortality; measure the opening pressure at LP and manage with daily therapeutic LPs
- An immunocompromised patient with dry cough and exertional dyspnoea has PJP until proven otherwise, even if the CXR looks near-normal — hypoxia disproportionate to radiology is the hallmark; check the A-a gradient and send induced sputum or BAL
- Voriconazole has no activity against Mucorales — do not use it for mucormycosis; the correct agent is high-dose liposomal amphotericin B plus surgical debridement
Invasive and Mucocutaneous Fungal Infections
[1]The one-minute consultant answer
A fungal infection in the immunocompromised or critically ill patient is a different disease from a fungal infection in the normal host, because the type of immune defect predicts the organism, diagnostic test, empiric therapy, and the prophylaxis. The single most important question at the bedside is what is the type and depth of immunocompromise? — and the answer divides every patient into one of five categories that drive the rest of the encounter. [1]
Prolonged neutropenia (post-chemotherapy, AML induction, above 10 to 14 days) opens the door to the angioinvasive moulds — Aspergillus and the Mucorales — because the neutrophil is the primary defence against hyphal organisms. Cellular immunodeficiency (HIV with CD4 below 100 to 200; transplant at 1 to 6 months) is the home of Cryptococcus, the endemic mycoses (Histoplasma, Coccidioides, Talaromyces), and Pneumocystis jirovecii. Broad-spectrum antibiotics, central venous catheters, total parenteral nutrition, and ICU stay together create the substrate for Candida, the most common healthcare-associated fungal pathogen. Diabetic ketoacidosis and iron overload uniquely predispose to Mucorales (Rhizopus), because the acidotic, ketotic, iron-rich environment is the one in which these organisms thrive. And severe immunosuppression with neutropenia or graft-versus-host disease is where mould-active prophylaxis (posaconazole, voriconazole) shifts the epidemiology and where breakthrough infection demands a different empiric approach. [1]
The non-negotiable principles: identify the host, image early, and treat on the basis of the most likely organism — never wait for definitive confirmation in a deteriorating patient. In candidaemia, the echinocandins (caspofungin, micafungin, anidulafungin) are first-line for the unstable or critically ill patient and the central line MUST be removed [1]. In invasive aspergillosis, voriconazole is first-line because the Herbrecht randomised trial showed a survival benefit over amphotericin B deoxycholate [4], and isavuconazole is a non-inferior alternative with a cleaner safety profile [5]. In cryptococcal meningitis the three-phase regimen (amphotericin B plus flucytosine induction, fluconazole consolidation and maintenance) is the framework, but the single most important determinant of early survival is management of raised intracranial pressure with serial therapeutic lumbar punctures [3]. In Pneumocystis pneumonia the treatment is high-dose co-trimoxazole with adjunctive corticosteroids when the PaO2 is below 60 mmHg or the A-a gradient is above 35 mmHg. In mucormycosis the answer is high-dose liposomal amphotericin B plus aggressive surgical debridement — voriconazole and the echinocandins are inactive, and delay is fatal [10].
References11ShowHide
- [1]Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America Clin Infect Dis, 2016.PMID 26679628
- [2]Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America Clin Infect Dis, 2016.PMID 27365388
- [3]Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america Clin Infect Dis, 2010.PMID 20047480
- [4]Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis N Engl J Med, 2002.PMID 12167683
- [5]Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial Lancet, 2016.PMID 26684607
- [6]Jarvis JN, Lawrence DS, Meya DB, et al. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis N Engl J Med, 2022.PMID 35320642
- [7]Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versus fluconazole for invasive candidiasis N Engl J Med, 2007.PMID 17568028
- [8]Molloy SF, Kanyama C, Heyderman RS, et al. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa N Engl J Med, 2018.PMID 29539274
- [9]Ewald H, Raatz H, Boscacci R, et al. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection Cochrane Database Syst Rev, 2015.PMID 25835432
- [10]Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium Lancet Infect Dis, 2019.PMID 31699664
- [11]Phongkhun K, Pothikamjorn T, Srisurapanont K, et al. Prevalence of Ocular Candidiasis and Candida Endophthalmitis in Patients with Candidemia: A Systematic Review and Meta-Analysis Clin Infect Dis, 2023.PMID 36750934