Fungal Infections

Patient: 58M in the MICU after abdominal surgery for perforated diverticulitis. Day 12 postop. On pip-tazo + vancomycin. Receiving TPN via PICC. New fever to 39.2°C, WBC 18K.

Labs: 2/2 blood cultures (PICC and peripheral draw) grow Candida albicans. Creatinine 1.4 (baseline 0.9).

Key Decision Points:

• Start micafungin 100 mg IV daily, echinocandin is first-line for candidemia in critically ill patients (superior tolerability, unknown susceptibility)
• Remove the PICC line immediately, Candida forms biofilm on catheters; antifungals cannot penetrate biofilm. New access at a different site.
• Ophthalmology consult within 24 hours, endophthalmitis in 2-4% of candidemia; can cause blindness if missed
• Echocardiogram, candidal endocarditis is rare but devastating; prosthetic valves at especially high risk
• Blood cultures every 48 hours until two consecutive negatives. Duration: 14 days from first negative culture.
• Step-down to fluconazole PO once stable, cultures clear, and susceptibilities confirm sensitivity

Teaching point: Candidemia risk = central line + TPN + broad-spectrum antibiotics + abdominal surgery + ICU days. All four present here = start antifungals without delay once blood cultures return positive.

Patient: 45M with AML, day 18 post-induction chemotherapy. ANC 80. New persistent fever despite broad-spectrum antibiotics × 5 days. Dry cough, mild hemoptysis.

Imaging: CT chest: 2.3 cm right lower lobe nodule with surrounding ground-glass halo ("halo sign").

Labs: Serum galactomannan 1.8 (positive; threshold ≥0.5). Beta-D-glucan positive. BAL galactomannan 3.2.

Management:

• Start voriconazole IV: 6 mg/kg q12h × 2 loading doses, then 4 mg/kg q12h. Switch to oral voriconazole once tolerating PO (excellent bioavailability).
• Check voriconazole trough at day 5-7, target 1–5.5 mcg/mL. Below threshold = treatment failure. Above = hepatotoxicity, QTc, neurotoxicity.
• Duration: 6–12 weeks minimum, continue until ANC recovery and CT improvement
• Alternative if voriconazole fails: isavuconazole (fewer drug interactions, no QTc) or liposomal amphotericin B
• Bronchoscopic biopsy not required when galactomannan + CT are diagnostic in high-risk neutropenic host

Teaching point: Aspergillus does NOT grow from routine blood cultures, serum galactomannan and CT findings are your diagnosis. The halo sign is most sensitive early; cavitation with air-crescent sign appears later as the infarct liquefies.

Patient: 34F with HIV (not on ART), CD4 42. Three weeks of worsening headache, photophobia, mild confusion. Temperature 38.5°C. No focal deficits.

LP results: Opening pressure 42 cmH₂O. CSF: 35 WBC (lymphocytic), protein 89, glucose 32 (serum 110). India ink: budding yeast with thick capsule. Serum CrAg titer 1:1024. CSF CrAg positive.

Management steps:

• Immediate therapeutic LP: Drain CSF to opening pressure <20 cmH₂O (remove 20–30 mL now). Elevated ICP is the leading cause of early death, this is urgent.
• Induction: Liposomal amphotericin B 3–4 mg/kg IV daily + flucytosine 25 mg/kg PO q6h × 2 weeks
• Consolidation: Fluconazole 400 mg daily × 8 weeks
• Maintenance: Fluconazole 200 mg daily × 1 year (until CD4 >100 + suppressed viral load on ART)
• Daily LPs until two consecutive normal pressures. If >4 LPs needed, place lumbar drain or VP shunt.
• Delay ART 5–10 weeks, starting ART immediately risks IRIS (cryptococcal-IRIS can be fatal)

Teaching point: CrAg is far more sensitive than India ink or culture, use it for screening and diagnosis. Elevated ICP management (LP drainage) is as critical as antifungal therapy. Do NOT use acetazolamide or steroids for ICP in cryptococcal meningitis.