251.1 🎓 醫孞生版

251.1.0.1 📌 䞀頁重點

251.1.0.1.1 Pathogen
  • Pneumocystis jirovecii (renamed 2002 from P. carinii)
  • Fungus (reclassified from protozoan based on rRNA studies)
  • Cyst + trophozoite forms
  • Strict tropism for alveolar epithelium (intra-alveolar)
251.1.0.1.2 Risk Factors
  • HIV CD4 < 200 (especially < 100)
  • Solid organ transplant (especially lung, heart, kidney)
  • HSCT (early phase)
  • High-dose corticosteroids (≥ 20 mg prednisone × 4+ weeks)
  • Chemotherapy (especially for cancer)
  • Anti-CD20 therapy (rituximab, ocrelizumab)
  • Anti-TNF therapy
  • Hematologic malignancy
  • Primary immunodeficiencies
  • Severe malnutrition
251.1.0.1.3 Clinical
  • Insidious onset over weeks
  • Dry cough (non-productive typically)
  • Progressive dyspnea
  • Hypoxia (exercise desaturation early; rest desaturation later)
  • Low-grade fever
  • Tachypnea
  • CXR: bilateral perihilar interstitial / “ground-glass” infiltrates (can be normal early)
  • HRCT: bilateral ground-glass + cystic changes
  • Severe: ARDS, pneumothorax (from cysts rupturing), respiratory failure
251.1.0.1.4 Laboratory
  • β-D-glucan elevated > 200 pg/mL (sens > 90%)
  • Elevated LDH
  • Normal WBC (or mildly elevated)
  • Lymphopenia in HIV
  • A-a gradient elevated
  • Pulse oximetry: hypoxia + exercise desaturation
251.1.0.1.5 Diagnosis
  • Induced sputum + immunofluorescence (sens 70-80%; less sensitive in non-HIV)
  • BAL + immunofluorescence / DFA / silver stain (GMS) (gold standard; sens > 95%)
  • PCR (BAL or sputum) — emerging, sensitive but also detects colonization
  • β-D-glucan ≥ 200 pg/mL supports diagnosis
  • CXR / HRCT characteristic
  • Lung biopsy rare (open or VATS)
251.1.0.1.6 Treatment
251.1.0.1.6.1 First-Line
  • TMP-SMX 15-20 mg/kg/day (TMP component) IV/PO × 21 days
  • Divided q6h (4-5 daily doses)
  • HIV: 21 days
  • Non-HIV: 14-21 days
251.1.0.1.6.2 Steroid Adjunct (Critical)
  • For: A-a gradient > 35 mmHg OR PaO2 < 70 mmHg on room air
  • Prednisone: 40 mg PO bid × 5 days → 40 mg qd × 5 days → 20 mg qd × 11 days
  • IV methylprednisolone equivalent if PO not tolerated
  • Significantly reduces mortality + need for ventilation
  • Start within 72 hours of antibiotic
  • Especially in HIV-PJP
251.1.0.1.6.3 Alternatives (TMP-SMX Intolerance / Failure)
  • Clindamycin + Primaquine (G6PD screen — primaquine causes hemolysis in G6PD deficiency)
  • Pentamidine IV (toxic — nephro + hypoglycemia + arrhythmia; reserved)
  • Atovaquone PO (mild-moderate only)
  • TMP + Dapsone (G6PD screen)
  • Salvage: combinations (TMP-SMX + caspofungin in trial settings)
251.1.0.1.7 Prophylaxis
251.1.0.1.7.1 Primary Prophylaxis
  • HIV + CD4 < 200: TMP-SMX 1 DS PO qd (or 1 SS qd) — also Toxo coverage
  • Solid organ transplant: TMP-SMX × 6-12 months post-transplant
  • HSCT: until immune recovery
  • Anti-CD20 + high-dose steroids + chemo regimens: case-by-case (especially with prolonged immunosuppression)
  • Pediatric leukemia: routine
251.1.0.1.7.2 Discontinuation (Secondary Prophylaxis)
  • HIV: CD4 > 200 for 3-6 months on ART (then stop)
  • Transplant: variable by center + drug + recipient
251.1.0.1.7.3 Alternatives
  • Dapsone 100 mg PO qd (G6PD screen)
  • Atovaquone 1500 mg PO qd with food
  • Pentamidine inhaled 300 mg q month (less effective)
251.1.0.1.8 Special Considerations
  • HIV-PJP: more severe; steroid critical
  • Non-HIV-PJP: higher mortality often; rapid onset; steroid use less standardized
  • Transplant: opportunistic; reduce immunosuppression
  • Pediatric: TMP-SMX prophylaxis routine in leukemia

251.1.0.2 1⃣ Microbiology + Pathogenesis

251.1.0.2.1 Taxonomy
  • Pneumocystis jirovecii — fungus (Ascomycota)
  • Renamed 2002 from P. carinii (animal species; rabbits, rodents — P. carinii for animal)
  • Cannot culture in vitro
  • DNA detection via PCR
251.1.0.2.2 Forms
  • Cyst (8-10 µm): thick wall, contains 8 sporozoites
  • Trophozoite (1-4 µm): pleomorphic, single nucleus
251.1.0.2.3 Tropism
  • Alveolar epithelium type 1 cells
  • Intra-alveolar replication
  • Doesn’t invade tissue or disseminate (extra-pulmonary rare)
251.1.0.2.4 Pathogenesis
  • Inhalation of trophic forms / cysts
  • Replication in alveolar lumen (with surfactant)
  • Inflammatory response: edema, type 2 cell hyperplasia, foamy intra-alveolar exudate
  • Impaired gas exchange → hypoxia
251.1.0.2.5 Transmission
  • Person-to-person (airborne, droplet)
  • Most asymptomatic colonization
  • Reactivation in immunocompromise
  • Colonization in healthy adults: low frequency
  • Pediatric colonization common (60%+ children seropositive by 2 yr)

251.1.0.3 2⃣ Clinical Course

251.1.0.3.1 HIV-PJP
  • Insidious onset over weeks
  • Dry cough, exertional dyspnea, low-grade fever
  • Often gradual decline
  • Less severe than non-HIV at presentation (counterintuitive)
251.1.0.3.2 Non-HIV-PJP
  • Often rapid onset (days)
  • More fulminant
  • Higher mortality (especially transplant, hematologic malignancy)
  • Lower lymphocyte counts at presentation
251.1.0.3.3 Severity Markers
  • A-a gradient > 35 mmHg
  • PaO2 < 70 mmHg on room air
  • Need for supplemental O2
  • Need for non-invasive / mechanical ventilation

251.1.0.4 3⃣ Imaging

251.1.0.4.1 CXR
  • Bilateral perihilar interstitial (“interstitial-alveolar”)
  • Reticulonodular pattern
  • “Ground-glass” early
  • Often bat-wing distribution
  • Can be normal in early disease
251.1.0.4.2 HRCT (Better Sensitivity)
  • Bilateral ground-glass opacities
  • Mosaic / patchy pattern
  • Cystic changes (cyst formation)
  • Sometimes nodules + consolidation in severe
  • Cysts can rupture → pneumothorax (atypical complication)

251.1.0.5 4⃣ Treatment Specifics

251.1.0.5.1 TMP-SMX Dose Calculation
  • TMP 15-20 mg/kg/day as 4-5 daily doses
  • E.g., 75 kg patient: TMP 1100-1500 mg/day = TMP 240-320 mg q4-6h
  • IV preferred initially in severe; PO once tolerating
251.1.0.5.2 TMP-SMX Side Effects
  • Allergic rash (10-15% HIV+, common; sometimes severe — Stevens-Johnson)
  • Marrow suppression
  • AKI (interstitial nephritis)
  • Hyperkalemia (HIV-PJP — block ENaC)
  • Hepatotoxicity
251.1.0.5.3 Steroid Indications + Mechanism
  • A-a > 35 mmHg or PaO2 < 70 — administer
  • Mechanism: reduces inflammatory response to dying P. jirovecii
  • Mortality reduction documented in HIV-PJP (Bozzette 1990)
  • Less data in non-HIV-PJP but generally used in severe
  • Start within 72 hours of antibiotic initiation
251.1.0.5.4 Alternatives Drug Profile
  • Clindamycin 600 mg IV q6h + Primaquine 30 mg PO qd: G6PD screen mandatory
  • Pentamidine IV 4 mg/kg/d: severe nephrotoxicity, hypoglycemia, arrhythmia
  • Atovaquone 750 mg PO bid with food: mild-moderate only
  • TMP + Dapsone: G6PD screen, methemoglobinemia risk
251.1.0.5.5 Failure / Refractory
  • Re-evaluate diagnosis (BAL repeat, exclude co-infection)
  • Combination (sometimes TMP-SMX + caspofungin off-label)
  • Reduce immunosuppression
  • Supportive ICU
  • ECMO for severe ARDS
251.1.0.5.6 When to Start ART (HIV-PJP)
  • Early ART (within 2 weeks) in HIV-PJP improves outcomes
  • IRIS less of an issue than other OIs (e.g., cryptococcal)

251.1.0.6 5⃣ Prophylaxis Detail

251.1.0.6.1 HIV
  • CD4 < 200: TMP-SMX 1 DS qd (or 1 SS qd)
  • Discontinue: CD4 > 200 for 3-6 months on ART
  • Restart if CD4 falls below
251.1.0.6.2 Solid Organ Transplant
  • TMP-SMX × 6-12 months post-transplant
  • Lifelong if HIV+ recipient + immunosuppression
  • Different protocols by organ + center
251.1.0.6.3 HSCT
  • Allogeneic: 6 months minimum
  • Autologous: 3-6 months
  • Reactivation possible up to 1 year
251.1.0.6.4 Anti-CD20 (Rituximab)
  • Long depletion period
  • Some guidelines recommend prophylaxis × duration of B cell recovery
  • Case-by-case
251.1.0.6.5 Pediatric Leukemia
  • Routine TMP-SMX prophylaxis
  • Continued during chemotherapy