Infections in Solid Organ Transplant Recipients

Pearls:

• Inflammatory responses are often blunted by immunosuppression, therefore clinical and radiograph findings may be more subtle
• Choice of abx is often complicated by drug interactions with transplant medications
• The risk of infection is determined by two factors: the epidemiologic exposures of the individual and the total degree of immunosuppression (which incorporates time post transplant, see below)
• The timing post-transplant is important in the ddx of possible infections.  You can generally divide up post-transplant infections based on these 3 time periods:
  • <1 month post transplant
  • 1-6 months post-transplant
  • >6 months post-transplant
  • <1 month post-transplant:
    • either infections derived from the donor (or reactivation in recipient) OR infectious complications of the transplant surgery and hospitalization
    • major effects of exogenous immunosuppression are not yet evident
    • at risk for nosocomial infections with resistant organisms (wound infxns, catheter infections, aspiration pna, anastomotic leak):
      • MRSA
      • VRE
      • Candida (non-alibcans)
      • C. Diff
    • Recipient derived reactivation (colonization) infections include:
      • Aspergillus
      • Pseudomonas
    • Donor-derived infections that are latent or unappreciated at the time of procurement ; although donors are screened prior to transplant, this can be limited in the deceased-donor population due to urgency of transplant
      • §  Viruses:  Herpes viruses (CMV, EBV, HSV, HHV-6, VZV), HTLV 1&2, HIV, West Nile, LCMV
      • §  Bacteria: bacteremia, TB, meningococcus, syphilis, non-TB mycobacterium
      • §  Fungi: candida, aspergillus, endemic mycoses, cryptococcus
      • §  Parasites: toxoplasma, malaria, strongyloides, babesia,trypanosoma cruzi
  • 1-6 months post-transplant:
    • Period of time with greatest immunosuppression (induction therapy to prevent acute rejection)
    • Most at risk for opportunistic infections (post-surgical infections can still occur)
    • DDx includes:
      • Pneumocystis jirovecii pneumonia (PCP)
      • Latent protozoal infections (toxo, Chagas’)
      • Viral pathogens, including HBV and HCV, polyomavirus BK/JC, respiratory viruses
      • TB
      • GI parasites (cryptosporidium, microsporidium) and viruses (CMV, rotavirus)
    • Solid organ transplant recipients should be on prophylaxis for: PCP, CMV, +/- toxoplasmosis (esp in cardiac tx with donor-/recipient +),  +/- endemic fungi,  HSV and VZV if h/o prior infections (latent), HBV if h/o prior infection, + several vaccines (pneumococcal, HBV etc)
  • >6 months post-transplant:
  • More at risk for community-acquired pathogens as they are generally on stable, lower dose immunosuppression
  • Patients with failing graft function may be on higher doses of immunosuppresants and therefore at greater risk of developing OIs and more severe community-acquired infections
  • Ddx inclues:
    • CAP PNA, UTIs
    • Aspergillus, atypical molds
    • Norcardia
    • Late viral infections (CMV colitis, retinitis, HBV, HCV, PTLD, etc.)

Specific viral pathogens (key associations for board review):

• CMV: 
  • CMV occurs most frequently within the 1-6 month post-transplant period
  • CMV infection occurs most often in the setting of a CMV-negative transplant recipient with an organ from a CMV-positive donor (rare if both are negative)
  • Infection vs. Disease
    • Infection is defined by a positive CMV culture, PCR, CMV antigen, or serology,
    • Disease is the presence of infection plus typical findings, such as fever, leukopenia, hepatitis, pneumonitis, pancreatitis, colitis, or meningoencephalitis
  • CMV infection often develops in organs concurrently with various other pathogens, such as with bacterial pneumonia or polyomavirus BK and appears to cause increased risk of coinfections
  • Prophylaxis with ganciclovir, valganciclovir, or high-dose acyclovir is generally indicated in transplant recipients for the first 6 months
• EBV: can cause a self-limited infectious mononucleosis, but also found in almost all patients with posttransplantation lymphoproliferative disease (PTLD), and it is believed to be pathogenic
  • Treatment of PTLD involves decreasing or discontinuing immunosuppressive therapy and often leads to organ or graft failure
• BK polyomavirus:  virus is generally acquired during childhood and remains dormant; reactivation is associated with infection of renal allografts  and can cause hemorrhagic cystitis, ureteral obstruction, AKI and AIN in renal transplant recipients
  • Experimental treatments, but only proven one is discontinuing immunosuppression.
• JC polyomavirus is another virus commonly acquired in childhood and remains dormant; if reactivation occurs post transplant, it can cause progressive multifocal leukoencephalopathy.
  • Generally fatal; only proven treatment involves discontinuing all immunosuppression
    

(Victoria Kelly MD, 6/9/11)