1.

Prophylactic Therapy
a. Three methods
i. Immunization
1. Assess need for vaccination before txp
2. Live vaccines are CI after transplant
3. Pneumococcal vaccine every 3-5 years
ii. Universal Prophylaxis
1. Routine surgical ppx
a. Liver: skin flora, biliary enterococcus, anaerobes,
Enterobaceriaceae
b. Important to consider known colonization patterns (MRSA,
VRE, fungi)
2. Antifungal: based on risk and epidemiologic factors
a. Most infections caused by non-candida albicans and
aspergillus
i. Aspergillus at tracheal anastomosis post lung txp
ii. Candida post liver or pancreatic txp
b. More common in ICU pts, surgical exp sx,
retransplantation, large amounts of blood products, liver
recipient with metabolic dysfunction, respiratory failure,
CMV/HCV infection, broad-spectrum abx tx
3. PCP Ppx: Bactrim ppx 3mo to lifetime
a. PCP PNA, T. gondii, Isospora bellli, Cyclospora cayetanensis,
nocardia, listeria and common UTI, respiratory, GI
pathogens
b. Alternate agents for PCP are dapsone, atovaquone,
pentamidine but narrowed protection
4. CMV Ppx
a. CMV and most herpes virsus infections
i. Universal ppx = all pts for a defined period
ii. Preemptive ppx = sensitive quantitative assays and
Ag detection monitor pt at pre-determined intervals
to determine infection status
b. Duration based on institutional protocols
c. Crude risk of infection is lower in seropositive pts
compared to seronegative pt with seropositive donor
iii. Preemptive Therapy
2. Changing Infection Patterns
a. Devo of better immunosuppressive regimens and prophylaxis have changed
rate of graft rejection and the timeline of infectious complications
i. Steroid sparing regimens + ppx have greatly decreased PCP PNA risk
ii. Herpes virus infections are greatly decreased while on antiviral ppx
iii. Sirolimus can induce noninfections pneumonitis PNA or viral PNA
iv. T-lymphocyte depleting Ab are associated with profound, durable
lymphopenia and subsequently an increased risk of CMV, EBV and HIV
re-activation

1. Late onset due to durable suppression past antiviral ppx period

a. CMV, JC polyomavirus
v. Timeline is reset with each treatment for acute rejection or
immunosuppression intensification
3. Cytomegalovirus Infection
a. Can cause invasive dz direct effects
i. Generally during 1st year after completion of immunosuppression; can
manifest as F&N
ii. CMV Syndrome
1. Fever, weakness, myalgia, arthralgia, myelosuppression
iii. End organ disease
1. Nephritis, hepatitis, colitis, pneumonitis, retinitis, encephalitis
b. Cellular effects
i. Allograft injury and rejection
1. Atherosclerosis, bronchiolitis obliterans, vanishing bile duct
syndrome
ii. Increased risk of infection
1. EBV-associated PTLD
c. Seropositivity associated w/ cellular immunity
d. Primary infection = sero(-) recipient w/ no previous immunotherapy receiving
allograft from sero(+) donor
i. Seroconversion generally happens within 1st year and w/o ppx can
have asx viremia (while some develop invasive dz)
1. 25% do not seroconvert and benefit from prolonged ppx
e. Universal CMV ppx
i. Generally first 3-6mo after txp using acyclovir, valacyclovir,
ganciclovir, valganciclovir, CMV IgG
ii. Protects against CMV, HSV, HHV-6, HHV-7, VZV, EBV and reduces risk
of fungal infections, bacterial infections and viral complications
(accelerated HCV)
iii. May reduce early and late acute rejection (not shown in studies)
iv. Sero(+) heart/lung recipients or D-/R+ combos generally benefit from
prolonged 6-12mo ppx, ? longer if no evidence of immunity or require
greater duration of sustained immunosuppression
1. Marrow suppression of tx dose ganciclovir and valcyte requiring ?
longer ppx
2. Ganciclovir resistance presents as slow or relapsing infection
a. More prevalent in D-/R+ patients, prolonged doses of oral
ganciclovir or valcyte (especially tx during active infxn),
lung tx
b. No difference with universal or preemptive ppx
f. Treatment warrents IV ganciclovir usually, though a positive benefit has been
seen with PO valcyte
4. Epstein-Barr Virus
a. Responsible for B-cell predominant PTLD

i. 3-10% of adult txp recipients with 40-60% mortality rate; 50% of

malignancies in post-txp pedi SOT recipients
ii. Varies from benign infectious polycolonal B-cell mononucleosis to
monocolonal malignant lymphoma
iii. Risk factors = primary EBV infection, allograft rejection, CMV coinfection
iv. Usually CD20+ and B-cell in origin
1. T cell, NK cell PTLD generally has worse prognosis
a. EBV not as heavily implicated as cause
v. May infiltrate organ and cause allograft rejection
vi. Evidence of relapsing-remitting EBV reflecting relationship between
immunity and immunosuppression
vii. Treatment: reduce immunosuppression (w/ increased rejection risk)
and chemotx, radiation and rituxan for progressive dz
viii. Adopotive immunotherapy under investigation for PTLD
5. Polyomavirus BK and JC
a. BK virus associated nephropathy
b. JC virus Progressive multifocal leukoencephalopathy
c. No effective antiviral for polyomavirus exists!
i. Reduction in immunosuppression
ii. Cidofovir (nephrotoxicity)
iii. Leflunomide
iv. IVIG
v. Retransplant after immunosuppressive reversal to allow antiviral
immune activity