322.1 🎓 醫孞生版

322.1.0.1 📌 䞀頁重點

322.1.0.1.1 Opportunistic Fungal Infections
322.1.0.1.1.1 Pneumocystis jirovecii Pneumonia (PCP)

Epidemiology: - Most common opportunistic fungal infection - HIV CD4 < 200 (especially < 100) - Other: solid organ transplant, hematologic malignancy, steroid use (≥ 20 mg prednisone × 4 wk), TNF-α inhibitor, severe protein-calorie malnutrition

Clinical: - Subacute (weeks) - Dyspnea (insidious, progressive) - Dry cough - Fever - Hypoxemia with exertion (clinical pearl)

Diagnosis: - HRCT: bilateral ground-glass opacities (perihilar, sparing periphery) - LDH: often elevated - β-D-glucan: serum biomarker (also positive for other fungi) - Induced sputum or BAL: cytology (silver stain, immunofluorescence) or PCR - PCR (now standard): more sensitive than smear

Treatment: - TMP-SMX (cotrimoxazole) 15-20 mg/kg (TMP component) IV/PO divided q6-8h × 21 days - Alternative for sulfa allergy: - Pentamidine IV - Atovaquone (mild-moderate) - Clindamycin + primaquine - Trimethoprim + dapsone (mild) - Adjunctive corticosteroids (in HIV + PaO2 ≀ 70 OR A-a gradient ≥ 35): - Prednisone 40 mg BID × 5 d → 40 mg daily × 5 d → 20 mg daily × 11 d - Reduces mortality + respiratory failure - HIV ART: start within 2 weeks - Watch for IRIS

Prophylaxis: - HIV with CD4 < 200: TMP-SMX (preferred) - Alternatives: dapsone, atovaquone, pentamidine inhaled - Discontinue if CD4 > 200 × 3 months on ART - Solid organ transplant + hematologic malignancy: case-by-case

322.1.0.1.1.2 Invasive Pulmonary Aspergillosis (IPA)

Epidemiology: - Severely immunocompromised (neutropenia, transplant, AML, hematologic malignancy, steroid use) - COVID-19 associated (CAPA) - Influenza associated (IAPA) - A. fumigatus most common; also A. flavus, A. niger, A. terreus, A. lentulus

Clinical: - Fever despite antibiotics - Cough, hemoptysis, pleuritic chest pain - Variable severity

HRCT: - Halo sign (early; ground-glass around nodule) - Air crescent sign (later; cavitation as neutrophils return) - Wedge-shaped peripheral lesions - Macronodules (≥ 1 cm)

Diagnosis: - Serum + BAL galactomannan: cell wall component - β-D-glucan: less specific - BAL + biopsy: Aspergillus on culture / histopathology (septate hyphae 45°) - PCR: emerging

Treatment: - Isavuconazole (Cresemba) — first-line per IDSA 2016 (SECURE trial 2016) - Voriconazole — alternative first-line (long-standing standard) - Amphotericin B (liposomal preferred) — for refractory or severe - Combination (voriconazole + echinocandin) — for severe - Duration: minimum 6-12 weeks - Reverse immunosuppression if possible (e.g., neutrophil recovery) - Surgical resection: for cavitary, hemoptysis, refractory

Aspergilloma (Fungus Ball): - Pre-existing cavity (post-TB, COPD bullae) - Mass of hyphae - Treatment: surgical if hemoptysis; antifungals less effective alone - Bronchial artery embolization for massive hemoptysis

Chronic Pulmonary Aspergillosis: - Less acutely immunocompromised - COPD, bronchiectasis, post-TB - Cavitary + nodules + fibrosis - Long-term itraconazole or voriconazole

ABPA (Allergic Bronchopulmonary Aspergillosis): - See Ch305 - Hypersensitivity, not invasive - Itraconazole + steroids + dupilumab

322.1.0.1.1.3 Mucormycosis (Zygomycosis)

Epidemiology: - Rhinocerebral most common, pulmonary 2nd - Risk factors: DM ketoacidosis, iron overload (hemochromatosis, deferoxamine), neutropenia, transplant, COVID-19 (CAM — COVID-associated mucormycosis epidemic in India 2021) - Rapid progression

Clinical: - Aggressive vascular invasion → infarction - Cavitation, hemoptysis - Rapid lung destruction

HRCT: - Multiple nodules - Reverse halo sign - Cavitation - Vascular invasion

Diagnosis: - Tissue biopsy: broad non-septate hyphae 90° - Culture (often negative) - PCR

Treatment: - Liposomal amphotericin B (high-dose, first-line) + surgical debridement - Isavuconazole or posaconazole (alternative or step-down) - Reverse DKA, iron overload - Aggressive multidisciplinary

322.1.0.1.1.4 Candida Pulmonary Infections
  • Often colonization, not true infection
  • Disseminated candidiasis can involve lungs
  • Treatment: echinocandin (caspofungin, micafungin) for severe; fluconazole for susceptible
322.1.0.1.1.5 Cryptococcus

Cryptococcus neoformans (most common in HIV) + C. gattii (immunocompetent)

Clinical: - Pulmonary: nodules, masses, infiltrates, often asymptomatic - Disseminated: meningitis (most common), CNS, skin

Diagnosis: - Serum cryptococcal antigen (CrAg) - BAL India ink or culture - Lumbar puncture if disseminated/CNS

Treatment: - Pulmonary alone (immunocompetent): fluconazole × 6-12 months - Pulmonary in HIV: amphotericin + flucytosine × 2 wk → fluconazole consolidation + maintenance - CNS / disseminated: amphotericin + flucytosine × 2 wk → fluconazole consolidation × 8 wk → maintenance × ≥ 1 year

322.1.0.1.1.6 Scedosporium / Lomentospora
  • Severely immunocompromised
  • Drug-resistant (limited options)
  • Voriconazole, posaconazole, isavuconazole
  • New: olorofim emerging
322.1.0.1.2 Endemic / Geographic Mycoses
322.1.0.1.2.1 Histoplasmosis (Histoplasma capsulatum)

Geography: Ohio + Mississippi River valleys (US), Central + South America, parts of Africa, Asia Source: Bird + bat droppings; soil disturbance Clinical: - Acute pulmonary (self-limited usually) - Chronic cavitary (mimics TB) - Disseminated (HIV) - Mediastinal LAD, fibrosing mediastinitis (chronic)

Diagnosis: - Urine + serum Histoplasma antigen - Histopathology: yeast in macrophages - Culture (slow)

Treatment: - Mild: observation or itraconazole - Moderate-severe: liposomal amphotericin → itraconazole 12 months - Disseminated: amphotericin → itraconazole

322.1.0.1.2.2 Coccidioidomycosis (Coccidioides immitis / posadasii)

Geography: Southwest US (Arizona, California, New Mexico, Texas), Mexico, Central + South America Source: Soil Clinical: - “Valley fever” — acute febrile illness + cough + arthralgia + erythema nodosum - Pulmonary nodules + cavities - Disseminated: skin, meningitis, bone (severe in immunocompromised + pregnancy + African American)

Diagnosis: - Serology (IgM + IgG) - Culture / histopathology (spherules with endospores) - Cocci urinary antigen

Treatment: - Mild: observation or fluconazole - Severe / disseminated: amphotericin → fluconazole or itraconazole - Meningitis: fluconazole high-dose lifelong

322.1.0.1.2.3 Blastomycosis (Blastomyces dermatitidis)

Geography: Mississippi + Ohio River valleys, Great Lakes, Central + Southern US Source: Soil with decaying organic matter Clinical: - Pulmonary (most common) - Cutaneous (verrucous skin lesions) - Bone, GU, CNS

Diagnosis: - Urinary antigen - Culture / histopathology (broad-based budding yeast)

Treatment: - Mild: itraconazole 6-12 months - Severe: liposomal amphotericin → itraconazole

322.1.0.1.2.4 Paracoccidioidomycosis
  • Latin America (Brazil)
  • Soil exposure
  • Itraconazole + amphotericin for severe
322.1.0.1.2.5 Talaromyces marneffei (formerly Penicillium marneffei)
  • Southeast Asia (Vietnam, Thailand, India, southern China)
  • HIV-associated disseminated
  • Bamboo rats as reservoir
  • Clinical: fever + skin papules (umbilicated, like molluscum) + LAD + hepatosplenomegaly + cytopenias + pulmonary
  • Treatment: liposomal amphotericin → itraconazole × 10 weeks
  • HIV ART
  • Common in Taiwan returning travelers + immigrants from SE Asia

322.1.0.2 🩺 床邊速查

  • PCP: HIV CD4 < 200; bilateral ground-glass; TMP-SMX + steroids (PaO2 ≀ 70)
  • Aspergillus IPA: neutropenia, transplant; halo + air crescent; isavuconazole / voriconazole
  • CAPA + IAPA: COVID/influenza + ICU + steroids → consider aspergillosis
  • Mucormycosis: DM DKA, iron overload, COVID-19; amphotericin + surgery
  • Cryptococcus: HIV + CNS most; amphotericin + flucytosine → fluconazole
  • Endemic mycoses: histoplasmosis (Ohio/Mississippi), coccidioidomycosis (SW US), blastomycosis (river valleys), talaromyces (SE Asia)
  • PCP prophylaxis: HIV CD4 < 200 → TMP-SMX