Question 7

College answer

Aim: To display a general awareness of post-transplant ID issues and principles of immunosuppression.

Key sources include: T Oh., All chapters on solid organ transplants. CanMEDS Medical Expert.

Discussion: A lack of depth and understanding of the different stages of immunosuppression was demonstrated by most candidates. The better answers highlighted the differences in infections at different stages of immunosuppression (early, intermediate, and late as stipulated in the stem.) and provided a rationale.

The expert answer detailed the risk of infections as being highest in the early post operative and intermediate stage and then falls as the immunosuppression requirements reduce and provided reasons why. The detailed answer outlined the common post operative infections including transplant-related and early hospital related infections and gave examples of likely pathogens at this time.
Opportunistic infectious aetiologies common to immunosuppressed patients were outlined in the successful answer.
 

Discussion

The Oh's Manual chapters on solid organ transplantation referenced by the examiners consist of Chapter 101 (Liver transplantation) and Chapter 102 (Heart and lung transplantation) in the 8th edition. Unfortunately, they do not seem to contain enough information to answer this question. There is only this table in the liver chapter, as well as some scattered ideas, which would be difficult to knit together into a coherent answer. Fortunately, there is an excellent UpToDate entry on this subject, which spares the reader an hour of digging through Oh's. It is tempting to tabulate this answer, and perhaps the better candidates did so, but the 800 pixel width of Deranged Physiology does not lend itself very well to tables with multiple columns, and so the reader is treated to an unordered bullet list instead. 

Relative risk of infection in the transplant recipient, and reasons:

• Early: high risk because:
  • infectious complications of surgery and ICU stay (anastomotic leaks, line site infections, VAP, etc)
  • donor-dreived infections (eg. hepatitis viruses)
  • Reactivation of CMV and TB
  • However: there are also protective factors:
    • The patient retains some residual humoral immunity
    • There are usually post-op antibiotics in use
    • The patient is usually in a controlled environment (i.e. ICU or hospital), carefully monitored and protected from transmission by reverse barrier practices
• Intermediate:  greatest risk, because:
  • During this period the immunosuppression is maximal:
  • Residual humoral immunity has dissipated
  • Opportunistic pathogens with long incubation periods have had time to emerge 
  • Pathogens picked up during the stay in hospital (eg. resistant organisms, C.difficile, etc) now re-emerge as problematic
  • Graft rejection may be occurring, requiring higher levels of immunosuppression
• Late:  lowest risk, because during this period the immunosuppression is minimised:
  • Satisfactory graft function will at this stage permit a decrease in the dose of immunosuppression
  • The recipients will mostly be exposed to community acquired pathogens, which are lower in virulence

Potential pathogens and sites of infection:

• Early
  • From the donor: viruses (eg. HIV), toxoplasmosis, hepatitis
  • From the recipient: HSV, TB, CMV reactivation
  • From the surgery: anastomotic leaks, surgical wound infections
  • Hospital acquired: VRE, MRSA, VAP, Aspergillus, bloodstream infections (eg. CLABSI)
• Intermediate
  • Opportunistic pathogens 
    • Bacteria: TB (lung, brain)
    • Fungi: Pneumocystis (lung), Cryptococcus (lung, brain)
    • Parasites: strongyloidiasis, toxoplasmosis
    • Viruses: HSV, CMV, EBV, BK virus, hepatitis viruses
  • Community-acquired pathogens
    • viruses (influenza, RSV, etc)
    • urinary tract infections
• Late
  • ​​​​​​​Community-acquired pathogens
    • Standard viruses (influenza, RSV, etc)
    • Listeria (meningitis)
    • Legionella and S.pneumoniae

Prophylaxis 

• Early
  • ​​​​​​​Bactrim (covers PJP Listeria and toxoplasmosis)
  • Fluconazole or posaconazole (covers Aspergillus and Candida)
  • Valganciclovir or letermovir (if seropositive)
  • Perioperative surgical site prophylaxis (cephazolin, vancomycin or clindamycin if MRSA-colonised)
• Intermediate
  • ​​​​​​​​​​​​​​Bactrim (covers PJP Listeria and toxoplasmosis)
  • Valganciclovir or letermovir (if seropositive)
  • Antifungals only for at-risk patients (eg. graft rejection)
• Late
  • ​​​​​​​Vaccination vs. influenza, pneumococcus, other community-based pathogens
  • Bactrim continues