148.1 🎓 醫孞生版

148.1.0.1 📌 䞀頁重點

  • Timeline of infections (Fishman æš¡åž‹):
    • < 1 mo: Nosocomial / donor-derived / surgical — bacterial (HAI), Candida, HSV reactivation
    • 1-6 mo (peak immune suppression): Opportunistic — CMV, BK virus, EBV, Pneumocystis jirovecii (PJP), fungi (Aspergillus, Mucor), TB, Nocardia, Listeria, Toxoplasma
    • > 6 mo: Community + opportunistic; CMV reactivation, late EBV-PTLD, chronic viral hepatitis, latent TB reactivation
  • Prophylaxis 必懂:
    • PJP: TMP-SMX 1 SS daily × 6-12 mo (or lifelong if continued immune-sup)
    • CMV: valganciclovir / letermovir (high-risk D+/R-)
    • HBV reactivation (if HBcAb+): entecavir / tenofovir
    • Strongyloides (endemic): ivermectin pre-transplant
  • Workup of fever in tx pt: lower threshold for broad workup; don’t miss CMV, fungi, PJP

148.1.0.2 1⃣ Timeline + Pathogens (Fishman Model)

148.1.0.2.1 Phase 1: < 1 Month (Nosocomial / Donor-Derived)
  • Bacterial wound, line, UTI, pneumonia — similar to non-tx surgery patients
  • Donor-derived (rare but devastating): HIV, HCV, WNV, rabies, Cryptococcus, MTB, lymphoma
  • HSV reactivation (mucocutaneous)
  • Candida (BSI, CRBSI from line)
148.1.0.2.2 Phase 2: 1-6 Months (Opportunistic Peak)
  • CMV (major!) — Pneumonia, colitis, retinitis, hepatitis, encephalitis
  • EBV → PTLD (post-transplant lymphoproliferative disorder)
  • BK virus (kidney transplant) — nephropathy
  • HHV-6, HHV-8: fever, cytopenias, encephalitis
  • PJP (without prophy)
  • Aspergillus: invasive pulmonary, sinus, CNS
  • Mucormycosis: rhino-cerebral (DM transplant), pulmonary
  • Cryptococcus: pneumonia, meningitis
  • Endemic mycoses: Histo, Cocci, Blasto
  • TB / NTM: reactivation, donor-derived
  • Nocardia: pulmonary, CNS, skin
  • Listeria: meningitis, bacteremia
  • Toxoplasma: encephalitis (D+/R−)
  • Strongyloides hyperinfection (if endemic exposure)
148.1.0.2.3 Phase 3: > 6 Months
  • Community-acquired infections more like general population (flu, CAP, UTI, etc.)
  • Late CMV reactivation (if prophy stopped)
  • EBV-PTLD (late)
  • Chronic viral hepatitis (HBV, HCV) progression
  • JC virus → PML

148.1.0.3 2⃣ CMV (#1 Killer of Transplant)

148.1.0.3.1 Risk Stratification
  • High risk: D+/R− (donor positive, recipient negative — never seen CMV) → primary infection
  • Intermediate: R+ — reactivation
  • Low: D−/R−
148.1.0.3.2 Manifestations
  • CMV syndrome: fever + leukopenia + transaminase ↑ + thrombocytopenia
  • CMV pneumonia (more in lung tx, BMT) — bilateral interstitial infiltrates
  • CMV colitis (more in renal tx, intestinal tx) — diarrhea, ulcers
  • CMV retinitis (also HIV) — fluffy retinal infiltrates with hemorrhage
  • CMV hepatitis
  • CMV encephalitis (rare)
148.1.0.3.3 Diagnosis
  • CMV PCR quantitative (blood) — primary screen + monitor
  • Tissue biopsy + immunohistochemistry (owl-eye inclusions) — for organ-specific disease
148.1.0.3.4 Treatment
  • IV Ganciclovir 5 mg/kg q12h × 2 wks → then PO valganciclovir 900 mg BID × 4-6 wks total (mild-mod)
  • Foscarnet if ganciclovir-resistant (UL97 mutation)
  • Letermovir (Prevymis) — newer, FDA 2017: prophylaxis in CMV-seropositive HSCT
  • Maribavir (Livtencity) — FDA 2021: refractory CMV; UL97 inhibitor
148.1.0.3.5 Prophylaxis
  • D+/R−: Valganciclovir 900 mg/day × 3-6 mo (longer in lung tx)
  • HSCT seropositive: Letermovir 480 mg/day × 100 d post-HSCT (CMV prevention)
  • Preemptive monitoring: PCR weekly; treat when threshold exceeded
  • Vaccine: in development (Moderna mRNA candidate in phase 3)

148.1.0.4 3⃣ PJP (Pneumocystis jirovecii Pneumonia)

148.1.0.4.1 Risk Factors
  • All transplant types, especially: lung, kidney + chronic high-dose immunosuppression
  • HIV with CD4 < 200
  • Steroid + biologic
  • Chemotherapy
148.1.0.4.2 Clinical
  • Subacute (weeks): dyspnea, hypoxia disproportionate to CXR, dry cough, fever
  • DLCO ↓ + LDH ↑ + Beta-D-glucan ↑
148.1.0.4.3 Diagnosis
  • PCR on BAL / induced sputum (gold)
  • Direct fluorescent antibody on BAL
  • Serum Beta-D-glucan (supportive, non-specific)
148.1.0.4.4 Treatment
  • TMP-SMX 15-20 mg/kg/day (TMP component) IV / PO × 21 days
  • Adjunctive steroid (HIV: PaO2 ≀ 70 or A-a gradient ≥ 35; non-HIV less clear)
  • Alternative if intolerance: Atovaquone (mild), Pentamidine IV (severe), Clindamycin + Primaquine, Dapsone + Trimethoprim, TMP-Dapsone
148.1.0.4.5 Prophylaxis
  • TMP-SMX 1 SS daily OR 1 DS 3x/wk
  • 4-6 mo minimum; longer if continued immunosuppression
  • Alternative: dapsone, atovaquone, pentamidine inhaled

148.1.0.5 4⃣ BK Virus (Kidney Transplant)

148.1.0.5.1 Clinical
  • BK nephropathy → graft loss
  • Mostly in kidney transplant (immunosuppression)
148.1.0.5.2 Diagnosis
  • BK viruria (urine cytology — “decoy cells”)
  • BK PCR (plasma) > 10,000 copies/mL → active infection
  • Renal biopsy: SV40 + immunostain, intranuclear inclusions
148.1.0.5.3 Treatment
  • Reduce immunosuppression (first-line, mainstay)
  • No specific antiviral (cidofovir, leflunomide, IVIG — limited evidence)
  • Monitor BK PCR

148.1.0.6 5⃣ EBV / PTLD

148.1.0.6.1 Risk
  • D+/R−: highest
  • Pediatric heart/lung tx
  • Intense T-cell immunosuppression
148.1.0.6.2 Clinical
  • Mass lesions (lymph nodes, GI, CNS), B-symptoms, organ-specific dysfunction
  • Spectrum: polyclonal hyperplasia → polymorphic PTLD → monomorphic (DLBCL-like) → classical Hodgkin’s-like
148.1.0.6.3 Diagnosis
  • EBV PCR (plasma) elevated
  • Biopsy mandatory — histology + EBER-ISH
148.1.0.6.4 Treatment
  • Reduce immunosuppression (first step)
  • Rituximab (anti-CD20) if B-cell PTLD
  • Chemotherapy (R-CHOP) if aggressive
  • EBV-specific cytotoxic T cells (CTL) — emerging