What is the management of infection post bone marrow transplant (BMT)?

Management of Infections Post Bone Marrow Transplantation

Antimicrobial prophylaxis with fluoroquinolones is strongly recommended during the early post-transplant period to prevent bacterial infections in BMT recipients. 1

Understanding Infection Risk by Phase

Infection management after BMT must be tailored to the three distinct phases of immune recovery:

Phase I: Pre-engraftment (<30 days post-BMT)

• Primary risks: Neutropenia and mucocutaneous barrier breakdown

• Common pathogens:

  • Gram-negative bacteria (gut translocation)
  • Gram-positive bacteria (skin, mucosa, catheters)
  • Candida species
  • Aspergillus species (after prolonged neutropenia)
  • HSV reactivation

• Management strategies:

  • Fluoroquinolone prophylaxis (AI recommendation) 1
  • Empiric broad-spectrum antibiotics for febrile neutropenia
  • Acyclovir prophylaxis for HSV-seropositive patients 1
  • Consider growth factors to decrease neutropenia duration 1
  • Strict hand hygiene to prevent pathogen transmission 1

Phase II: Post-engraftment (30-100 days post-BMT)

• Primary risk: Impaired cell-mediated immunity

• Common pathogens:

  • CMV (pneumonia, hepatitis, colitis)
  • Pneumocystis jiroveci (carinii)
  • Aspergillus species

• Management strategies:

  • CMV prevention: Either prophylactic ganciclovir or preemptive strategy with routine screening and treatment when positive (A-I) 1
  • For CMV-seronegative recipients with CMV-seropositive donors, preemptive strategy is preferred (B-II) 1
  • Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole

Phase III: Late phase (>100 days post-BMT)

• Primary risks: Impaired cellular and humoral immunity, especially with chronic GVHD

• Common pathogens:

  • Encapsulated bacteria (S. pneumoniae, H. influenzae)
  • CMV
  • Varicella-zoster virus
  • EBV (post-transplant lymphoproliferative disease)
  • Respiratory viruses
  • Aspergillus (with chronic GVHD)

• Management strategies:

  • Penicillin or erythromycin prophylaxis for encapsulated bacteria in patients with chronic GVHD 2
  • Consider pneumococcal, influenza, and HiB vaccines after 6-12 months in patients without GVHD 2
  • Extended antifungal prophylaxis in high-risk patients with chronic GVHD 3

Specific Antimicrobial Recommendations

Bacterial Prophylaxis

• Fluoroquinolones are preferred over trimethoprim-sulfamethoxazole for bacterial prophylaxis during neutropenia (AI) 1
• Additional Gram-positive prophylaxis is generally not recommended (DIII) except in high-risk patients 1

Viral Prophylaxis

• CMV prevention: Begin at engraftment and continue to day 100 (A-I) 1
  • Option 1: Universal ganciclovir prophylaxis
  • Option 2: Preemptive strategy with regular screening and treatment when positive
• HSV prevention: Acyclovir starting with conditioning therapy until engraftment or mucositis resolution (B-III) 1

Fungal Prophylaxis

• Fluconazole plus oral amphotericin B is commonly used 4
• Consider extended antifungal prophylaxis in patients with chronic GVHD or corticosteroid therapy ≥21 days at ≥1mg/kg/day 3

Pneumocystis Prophylaxis

• Trimethoprim-sulfamethoxazole or pentamidine 4

Special Considerations

Allogeneic vs. Autologous Transplants

• Autologous recipients primarily at risk during Phase I, with more rapid immune recovery 1
• Allogeneic recipients, especially with GVHD or mismatched/unrelated donors, have prolonged risk through all phases 1
• Mortality from infection: 11.2% after allogeneic vs. 0.8% after autologous transplantation 4

GVHD Impact

• GVHD significantly increases infection risk through delayed immune recovery 1
• Corticosteroid therapy ≥21 days at ≥1mg/kg/day is a major risk factor for invasive aspergillosis 3
• CMV infection is linked to corticosteroid use and increases fungal infection risk 3

Pitfalls and Caveats

• Fungal infections (especially Aspergillus) have shifted to later occurrence post-transplant, requiring prolonged surveillance 3
• Routine IVIG administration is not recommended for all patients (D-II) 1
• Consider IVIG only for severe hypogammaglobulinemia (IgG <400 mg/dL) (C-III) 1
• Gram-positive prophylaxis must be balanced against the risk of selecting for resistant organisms 1
• Empirical antifungal therapy should be considered in persistently febrile patients not responding to antibacterial therapy 5

By following these phase-specific strategies, infection-related morbidity and mortality in BMT recipients can be significantly reduced, improving overall transplant outcomes.