Candidiasis — mucocutaneous vs invasive, diagnosis and antifungal choice viva

Interpretation

The examiner presents a clinical scenario: "A 72-year-old in ICU for 12 days after a perforated diverticulum, central line, broad-spectrum antibiotics, TPN, persistent fever despite 5 days of antibacterials. Blood cultures grow Candida. Talk me through your diagnosis and management."

• Diagnosis: invasive candidiasis — candidaemia in a high-risk ICU host (central line, TPN, broad-spectrum antibiotics, abdominal surgery — the CANDIDA mnemonic).^[1][3]
• Clinical message: clinically indistinguishable from bacterial sepsis; persistent fever on appropriate antibacterials is the cardinal clue in the high-risk patient. Blood culture is the gold standard.

Key points

The examiner will probe each of these; be ready to defend them at viva depth:

1. Spectrum of disease — mucocutaneous (thrush, vulvovaginal, oesophageal AIDS-defining, intertrigo, chronic mucocutaneous) vs invasive (candidaemia, acute disseminated, chronic disseminated/hepatosplenic, endophthalmitis, endocarditis, CNS, osteomyelitis, peritonitis, candiduria).^[3]
2. Risk profile (mnemonic CANDIDA) — Catheter, Antibiotics, Neutropenia, Diabetes/Drugs, Immunosuppression, Digestive breach (abdominal surgery/TPN), Age extremes. The Candida score (León, score at least 3) guides empirical therapy in ICU.^[3]
3. Pathophysiology — two portals into the bloodstream: gut translocation (mucositis, neutropenia, GI perforation) and biofilm on central venous catheters. Neutrophils/macrophages (Dectin-1, Th17/IL-17) are the principal defence — neutropenia drives invasive disease; Th17 defects drive chronic mucocutaneous candidiasis.^[1]
4. Diagnosis — blood cultures (gold standard); (1→3)-beta-D-glucan (pan-fungal; positive in Candida/Aspergillus/Pneumocystis; NOT Cryptococcus or Mucorales; cut-off at least 80 pg/mL; false positives from haemodialysis, IVIG, gauze, severe bacteraemia, amoxicillin-clavulanate); T2Candida (rapid, high NPV, no susceptibility); MALDI-TOF for rapid species ID; susceptibility testing.^[1][3]
5. First-line therapy — echinocandin (caspofungin 70 mg load then 50 mg/day; micafungin 100 mg/day; anidulafungin 200 mg then 100 mg/day; rezafungin 400 mg weekly, non-inferior to caspofungin in ReSTORE). Mechanism: inhibit beta-1,3-glucan synthesis (cell wall).^[2][3]
6. Step-down to fluconazole once stable, cultures negative, isolate fluconazole-susceptible (C. albicans, parapsilosis, tropicalis). C. glabrata/krusei → continue echinocandin/voriconazole; C. parapsilosis → fluconazole preferred (reduced echinocandin susceptibility); C. krusei intrinsically fluconazole-resistant; C. lusitaniae amphotericin-resistant.^[3]
7. Source control + surveillance — remove central line (biofilm causes persistence); ophthalmology dilated exam within first week (endophthalmitis in up to a quarter); echocardiography if persistent. Duration: 2 weeks AFTER FIRST NEGATIVE blood culture.^[3]
8. Candida auris — multidrug-resistant outbreak pathogen; susceptibility-guided therapy; isolation, contact precautions, screen contacts, terminal sporicidal disinfection.^[1]

References

1. Lass-Flörl C, et al. Invasive candidiasis. Nat Rev Dis Primers 2024.^[1]
2. Thompson GR 3rd, et al. ReSTORE (rezafungin vs caspofungin). Lancet 2023.^[2]
3. Pappas PG, et al. IDSA 2016 candidiasis guideline. Clin Infect Dis 2016.^[3]

References3ShowHide

1. [1]Lass-Flörl C, Kanj SS, Govender NP, et al. Invasive candidiasis. Nature Reviews Disease Primers, 2024.PMID 38514673
2. [2]Thompson GR 3rd, et al. Rezafungin versus caspofungin for candidaemia and invasive candidiasis (ReSTORE). Lancet, 2023.PMID 36442484
3. [3]Pappas PG, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update (IDSA). Clinical Infectious Diseases, 2016.PMID 26679628