Infections in Transplant recipients
phagocytes and immune cells (T&B
Infections following transplantation are
complicated by the use of drugs that
are necessary to enhance likelihood of
survival of the transplanted organ but
also cause the host to be
immunocompromised.
Variety of organisms have been
transmitted by organ transplantation
(see table 117-1)
From 2% to >20% of donor kidneys are
contaminated with bacteria – in most
cases, with the organisms that colonize
the skin or grow in the tissue culture
medium used to bathe the donor
kidney while it awaits implantation.
Use of enrichment columns and
monoclonal-antibody depletion
procedures results in higher incidence
of contamination.
Approx 2% of cryopreserved and
peripheral blood stem cells transfused
as part of treatment for cancer are
contaminated.
Results of cultures performed at the
time of cryopreservation and at the
time of thawing were helpful in guiding
therapy for the recipient.
In many transplantation centers,
transmission of infections that may be
latent or clinically inapparent in the
donor organ has resulted in the
development of specific-donor
screening protocols.
Serologic testing focusing on such
viruses such as HSV 1 and HSV 2; VZV,
CMV, HHV 6, EBV, HHV-8, hepaB and C,
HIV, HTLV -1 and on parasites such as
Toxoplasma gondii, skin testing for M.
tuberculosis. Investigation of patients
dietary habits (consumption of raw
meat or fish or unpasteurized
products) , occupations or avocations
(gardening or spelunking), and travel
history (travel to areas with endemic
fungi) is mandatory. It is expected that
the recipient will have been likewise
assessed.
INFECTIONS IN BONE MARROW
AND HEMATOPIETIC STEM CELL
TRANSPLANT RECIPIENTS
BM or hematopoeitic stem cell
transplantation for either
immunodeficiency or cancer patients
results in a transient state of complete
immune incompetence.
Immediately after transplantation, both
cells) are absent, and the host is
extremely susceptible to infection.
BACTERIAL INFECTIONS.
1st month  bm or hematopoietic stem
cell transplantation, infectious
complications are similar to those in
granulocytopenic patients receiving
chemotherapy for acute leukemia.
1-4 week – due to anticipated
neutropenia and high rate of bacterial
infection in this population, many
centers give prohyplactic antibitiocs to
patients upon initiation of
chemotherapy.
LEVOFLOXACIN – decrease the
incidence of gram- negative
bacteremia among these patients
Bacterial infections are common in first
few days after BM transplant.
Predominantly aerobic bacteria
found in the bowel
( Pseudomonas, E.coli,
Klebsiella) and those found in
the skin or in intravenous
catheters (S. aureus and
coagulase-negative staph)
Filamentous bacteria (Nocardia and
organisms that cause actinomycosis)
 beyond 1st few days of neutropenia
Episodes of bacteremia due to
encapsulated organisms  marked the
late post transplantation period (>6
months after BM reconstitution).
FUNGAL INFECTIONS  beyond 1st
week after transplantation, become
increasingly common.
Candida albicans  most common in
granulocytopenic patients
Candida glabrata & aspergillus 
increased used of prophylactic
fluconazole; resistant fungi
Candida % aspergillus  in patients
with GVHD who required prolonged or
indefinite coursed of glucocoticoids
and immunospressive agents, high risk
even after engraftment and resolution
of neutropenia. High risk of
reactivation of fungal infection
(Histoplasmosis, Blastomycosis,
Coccidiodomycosis) – endemic areas.
PARASITIC INFECTIONS
Pneumocystis pneumonia (especially
among patients being treated for
hematologic malignancies)  most
patients receive maintenance
prophylaxis TMP-SMX (trimethroprim-
sulfamethoxazole starting 1 month
after engraftment and continuing for at
least 1 year.
TMP-SMX- may also protect patients
seropositive fo T. gondii which may
cause pneumonia & CNS lesion
- advantage on maintenance
daily for 1 yr after
transplanatation include
protection against Listeria
monocytogenes and
Nocardial disease as well as
late infections with S.
pneumoniae & H. influenzae
which are consequence of
the inability of immature BM
to respond to
polysaccharide antigens
VIRAL INFECTIONS
BMT/HSCT reciepents are
susceptible to infection with variety of
viruses, including reactivation
syndrome caused by mist HHVS (Table
117-3) and infections caused by
viruses that circulate in the
community.
HSV – Within 1st 2 weeks after
transplantation
- HSV-1 from oropharynx
- prophylactic ACYCLOVIR (or
VALACYCLOVIR) to
seropositive BMT/HSCT
recipients reduce mucositis
and HSV pneumonia ( a rare
condition reported
exclusively in BMT
recipients).
- Esophagitis due HSV-1 &
anogenital disease HSV2
may be prevented with
acyclovir prophylaxis
VZV – Reactivation may occur in 1st
month but more commonly after
several months after transplantation.
- 40% in allogeneic patients
and 25% for autlogous
recipients.
- Disseminated disease could
be controlled by ACYCLOVIR
( given prophylactic) to
prevent sever disease. Low
dose (400mg orally, TID)
appear to be effective in
preventing reactivation.
- However, it may also inhibit
the dev’t of VZV-specific
immunity. Thus
administration for only 6
months after transplantation
does not prevent zoster
from occurring when
treatment is stopped.
- Low dose for 1 year may be
effective
CMV – onset of CMV
disease(interstitial pneumonia, BM
suppression, or graft failure) usually
comes betweedn 30 days and 90 days
after transplantation, when
granulocyte count is adequate but
immunologic reconstitution has not
occurred.
- it develops earlier than 14
days after transplantation
may be evident as late as 4
months after the procedure.
- Great concern in the 2nd
month after transplantation,
particularly in BMT/HSCT
recipients.
- In donor marrow is depleted
of T cells – disease is
manifested earlier
- aCD52 antibody
(alentuzumab)  prevent
GVHD in nonmeloablative
transplantation
- patients who receive
gancyclovir (for prophylaxis,
preemptive treatment, or
treatment) may develop
infection even later than 4
months after transplantation
- although CMV disease may
present isolated fever,
granulocyotpenia, or gi
disease, the foremost cause
of death from CMV infection
in this setting is PNEUMONIA
- with the std use of
CMV0negative filtered blood
products, primary CMV infxn
should be a risk in allogenic
transplantation only when
the donor is CMV-
seropositive and the
recipient is CMV-
seronegative.
- Reactivation or
superinfection is common in
CMV seropositive recipients
and seropositice patients
who undergo BM
transplantation excrete
CMV, with or without clinical
findings
- Serious CMV disease is
common among allogenic
than autologous recipients
and is often associated with
GVHD.
- Finding of CMVin liver of a
patient with GVHD does not
necessarily mean that CMV
iis responsible for hepatic
enzyme abnormalities.
 - MANAGEMENT: Prophylaxis
 Ganciclovir (or
valganciclovir) abort CMV
disease during the period of
maximal vulnerability (from
engraftment to day 120
after transplantation).
Adverse effects: dose-
related BM suppression
(thrombocytopenia,
leucopenia, anemia, and
pancytopenia).
- Suppressive treatment –
PCR evidence of CMV or
urine cultures positive for
CMV, entails unnecessary
treatment of many
individuals (on the basis of a
lab test that is not highly
predictive of disease) with
drugs that have adverse
effects.
- Treatment of CMV
pneumonia in BMT/HSCT
recipient requires both IVIg
and ganciclovir.
- Foscarnet, for patients who
cant tolerate ganciclovir,
although it may produce
nephrotoxicity and
electroloyte imbalance.
- Transfusion of CMV-specific
T-cells from the donor
decreased viral load in small
series of patients.
HHV-6&7 - HHV-6 , cause of roseola
in children, is a ubiquitous herpesvirus
that reactivates (as determined by
culture of the virus from the blood) in
50% of transplant patients between 2
and 4 weeks after surgery
- appears to be asso with
neutropenia, since, like
CMV, this can be found in
marrow cells
- although encephalitis
developing after
transplantation has been
asso with HHV-6 in CSF,the
causality of the association
is not well defined.
- May be found in lung
samples after
transplantation
- susceptible to foscarnet
( and possibly to
ganciclovir)
EBV - Primary EBV infection can be
fatal to transplant recipients
- EBV reactivation can cause
EBV-B cell
lymphoproliferative disease
(LPD), which may be fatal in
patients taking
immunospuppressive drugs.
- Marrow ablation that occurs
as part of BMT/HSCT
procedure may eliminate
latent EBV from the host.
- Infection may be reacquired
immediately after
transplantation by transfer if
infected donor B cells.
- Reactivation can occur in T-
cell depleted autologous
recipients (patients being
given antibioses to T cells
for treatment of a T-cell
lymphoma with marrow
depletion).
- EBV-LPD, becomes apparent
as soon as 1 to 3 months
after engraftment, causes
high fever, and cervical
lymphadenopathy
resembling the symptoms of
infectious mononucleosis
but more commonly
presents as an extranodal
mass..
- In all cases, EBV-LPD is more
likely to occur with
continued
immnosuppression
(especially that caused by
the use of antibodies to T-
cell and cyclosporine or
other T-cell suppressive
agents).
- 1st line treatment:
Monoclonal anibody to CD20
(rituximab) for treatment of
B cell lymphomas
- Ganciclovir has been
postulated to have activity
on the basis of its ability to
inhibit proliferation of B
cells, but is asso with high
toxicity.
- High-dose Ziduvidine –
shows a promising effect for
treatment of EBV positive
CNS lymphomas
- Both interferon alpha and
retinoic acid have been
used
- As has IVIg
HHV – 8 – EBV related gamma
herpesvirus which is usually asso with
Kaposi’s sarcoma, with primary
effusion lymphoma, and sometimes
with multicentric Castleman;s disease,
has rarely resulted in disease in
BMT/HSCT recipients.
Other (nonherpes) virus –
- Both RSV and parainfluenza
particularly type 3, can
cause severe or fatal
 pneumonia in BMT
recipients.
- Therapy with aerosolized
ribavirin as well as RSV Ig or
monoclonal ab to
RSV(palivizumab) has been
reported to lessen severity
of RSV disease
- Influenza also occurs in BMT
recipients and generally
mirrors the presene of
infection in the community.
(amantadine/rimantadine,
ribavirin?), but have limited
effects, primarily reducing
symptoms and shortening
the duration of illness.
Neuraminidase inhibitors
(oseltamivir and zanamivir)
are active against Influenza
Typa A and B and are a
reasonable treatment
option.
- Adenovirus occurs in 1st or
2nd month after
transplantation., is often
asymptomatic.
- Parvovirus B19 (presenting
as anemia, or occasionally
as pancytopenia) can be
treated with IVIg and
enterovirus can occur and
being treated with
Pleconaril, a capsid binding
agent.
- Rotavirus are common
cause of gastroenteritis in
BMT/HSCT recipients.
- Polyomavirus BK is found at
high titers in the urine of
patients who are highly
immunosuppressed.
- BK viruria may be asso with
hemorrhagic cystitis.
- PML by JC virus is rare
among BMT/HSCT recipients
compared with the rate
among patients with
impaired T cell function due
to HIV infection.
INFECTIONS IN SOLID ORGAN
TRANSPLANT RECIPIENTS
Organisms that cause infections in
recipients of solid organt transplant
recipients are different from those that
infect BMTHSCT because solid organ
recipients do not go through
neutropenia.
As the transplantation procedure
involves surgery, however, solid organ
recipients are subject to infections at
anastomotic sites and to wound
infections.
Compared with BMT/HSCT, organ
transplant patients are
immunosuppressed for longer periods
(often permanently). Thus they are
susceptible to organisms as patients
with chronic impaired T cell immunity.
Early period (< 1month after
transplantation),infections are most
commonly due to extracellular bacteria
( staph, strep, e. coli and other gram-
neg bacteria), which often originate in
surgical wound or anastomotic sites.
In subsequent weeks, consequences
of the administration of agents that
suppress cell-mediated immunity and
of the acquisition or reactivation of
virus and parasites become apparent.
CMV infection – first 6 months
HHV-6 reactivation – occurs within the
1st 2 to 4 weeks and may be asso with
fever and granulocytopneia
HHV6&7 – exacerbate CMV disease
CMV – asso not only with generalized
immunosuppression but also with
organ specific, rejection-related
syndromes, glomerulopathy in kidney
transplant patients, bronchitis
obliterans in lung transplant ,
vasculopathy in heart transplant, and
vanishing bile duct in liver transplant.
Beyond 6 months, infections
characteristic of patients with defects
in cell-mediated immunity – L.
monocytogenes, Nocardia, various
fungi and intracellular parasites.
May be susceptible to EBV-LPD from as
early as 2 months to many years after
transplantation.
The prevalence of this complication is
increased by potent and prolonged
used of T-cell suppressive drugs.
Among organ transplant patients,
those with heart and lung transplants-
who receive most intensive
immunosuppressive regimens- are
most likely to develop EBV-LPD.
KIDNEY TRANSPLANT
Early infections
- often caused by bacteria
asso with skin or wound
infections.
- There is a role for
perioperative antibiotic
prophylaxis
- Cephalosporins to decrease
risk of postoperative
complications.
 - UTI developing soon after
transplantation are usually
related to anatomical
alterations resulting from
surgery.
- UTI that occur >6 months
after transplantation do not
seem associated with high
rate of pyelonephritis or
relapse seen with infections
that occur in 1st 3 months
and may be treated in
shorter periods.
- Prophylaxis with TMP-SMX
for the 1st 4 months after
transplantation decreases
incidence of early and
middle-period infections.
Middle-Period infections
- predisposal to lung infection
characteristic of those In
patients with T-cell
deficiency with intracellular
bacteria, mycobacteria,
nocardiae, fungi, viruses
and parasites.
- 50% of all renal transplant
recipients with fever in 1 to
4 months after
transplantation has
evidence of CMV disease.
- CMV may also present with
athralgias or myalgias
- During this period, this
infection may present as
primary disease, or may
present as reactivation or
superinfection.
- Px may have atypical
lmphocytosis. Unlike
immunocompetent patients,
however, they often do not
have lyphadenopathy or
splenomegaly.
- CMV may also cause
glomerulopathy.
- Ig enriched with ab to CMV
decreases incidence in
group at higher risk
(seronegative recipient of
seropositive kidneys)
- Ganciclovir – useful
prophylaxis and treatment
of CMV disease
- Prophylacitv valacyclovir for
the first 90 days after renal
transplantations shows 50
% reduction in CMV disease
and rejection at 6 months
- Herpes group infection
become evident within 6
months of infection.
- HSV cause either oral or
anogential lesions that are
responsive to acyclovir.
- VZV may cause fatal
disseminated infection in
nonimmunie kidney
transplant recipiens, but in
imunie patients may cause
reactivation zoster usually
does not disseminate
outside dermatome.
- HHV-6 may be reactivated
and (usually asymptomatic)
may be associated with
fever, rash, suppression,
encephalitis
- EBV reactivation disease is
more serious; it may
present as extranodal
proliferation of B cells that
invade the CNS,
naspharynx, liver, small
bowel, heart and
transplanted kidneys.
- Disease may regress once
immunocompetence is
restored.
- HHV-8 asoo with
development of Kaposi’s
sarcoma often appears
within 1 year after
transplantation, although
the range is wide (1 month –
20 years)
- Papovavirus BK and JC have
been cultured from the
urine of kidney transplant
recipients. The excretion kf
BK virus is asso with
urethral strictures
- Patients may develop
pulmonary infections with
Nocardia, Aspergillus, and
Mucur as well as other
intracellular organisms.
- In patients with IV catheter,
L. monocytogenes is a
common cause of
bacteremia > 1 month after
renal transplantation and
should be seriously
considered in recipients
presenting with fever and
headache.
- Salmonella bacteremia may
lead to endovascular
infections and require a
prolonged therapy.
- Nocardia occur generally >
1 month after
transplantation and may
follow immunosuppressive
treatment episode of
rejection. May present as
skin, bones, and lungs or in
CNS in single or multiple
abscesses.
- TMP-SMX is often
efficacious.
Late infections
 6 months after kidney
transplantation include CMV
retinitis and a variety of CNS
complication.
 Patients whose
immunosuppression has been
increased, are at high risk of
Subacute meningitis due to
Cryptococcus neoformans
 Listeria meningitis, acute and fatal
 “Transplant elbow” to patients
who take glucocorticoids; a
recurrent bacterial infection in and
around the elbow that is thought
to result from a combination of
poor tensile strength of the skin of
steroid-treated patients.
 Bouts of cellulites due to S. aureus
 Susceptible to Aspergillus and
Rhizopus which may present as
superficial lesions before
dissemination
 M. marinum diagnosed by skin
examination
 Protheteca wickerhamii by skin
biopsy
 Warts caused BY HPV
HEART TRANSPLANTATION
Early infection
Sternal wound infection and
mediastinitis as early complication
Common microbes in the skin are
involved can also be due Mycoplasma
hominis can be cured with a
combination of surgical debridement
(sometimes requiring muscle flap
placement) plus clindamycin and
tetracycline.
Middle Period infections
T. gondii  TMP-SMX
CMV – 1 to months after
transplantation causes early signs and
lab abnormalities (usually with fever
and atypical lymphocytosis
orleukopenia and thrombocytopenia)
at 2 to 3 months, and produces severe
disease (pneumonia) in 3 to 4 months.
Ganciclovir is efficacious
Late infections
EBV infection usually present as a
lymphoma-like proliferation of B-cells
late after heart transplantation
especially in patients on heavy
immunosuppression.
LUNG TRANSPLANTATION
Early infection
- combination of ischemia
and resulting mucosal
damage together with
accompanying denervations
and lack of lymph drainage
probably contributes to high
rate of pneumonia.
- Prophylactic use od high
doses broad spectrum
antibiotics for first 3-5 days
after surgery decreases
incidence of pneumonia
- Gram negative organisms
(pseudomonas and
enterobacteriaceae) are
troublesome in first 2 weeks
after surgery.
- It can also be caused by
Candida, Aspergillus and
Cryptococcus.
- Mediastinitis may occur at
higher rate and most
commonly develops within 2
weeks of surgery,
- Pneumonitis due to CMV
usually present within 2
wekks and 3 months after
surgery, with primary
disease occurring later than
reactivating disease.
Middle-period infection
- 75 to 100% incidence of
CMV infection.
- More than half has CMV
pneumonia
- CMV can also cause
bronchitis obliterans
- Ganciclovir is more active
against CMV and also HSV.
Prophlaxis is recommended.
Late infections
- Incidence of
Pneumocystisinfection is
high among heart-lung
recipients.
- TMP-SMX for 12 months
after transplantation may be
sufficient for 12 months
after transplantation.
- EBV may cause either
mononucleosis-like
syndrome or LPD.
- The tendency of B cell
blasts to present on lung
appears to be greater after
lung transplantation than
after the transplantation of
other organs.
LIVER TRANSPLANTATION
Early infections
- Administratioin of systemic
broad-spectrum antibiotics
for the first 5 days after
surgery, even in the
absence of documented
infection,
 - However, despite
prophylaxis, infectious
complications are common
and are correlated with the
duration of the surgical
procedure and the type of
biliary drainage.
- Operation lasting >12 hrs is
asso with high likelihood of
infection.
- Patients who have
choledojejunostomy with
drainage of the biliary dure
to a Roux-en- Y jejunal
bowel loop have more
fungal infections thant those
whose bile is drained via a
choledochocholedochostom
y with anastomosis of the
donor common bile duct to
the recipient common bile
duct.
- Peritonitis and
intraabdominal abscesses
are common complications
of liver transplantation.
- Bacterial peritonitis may
result from biliary leaks and
primary and secondary
infection after leakage of
bile.
- Abscesses within the 1st
month after surgery may
occur not only over the liver
but also in the spleen,
pericolic area and pelvis.
- treatmentL antibiotic and
drainage as necessary
Middle Period Infections
- development of postsurgical
biliary stricture predisposes
patients to cholangitis.
These patients may lack the
characteristic signs and
symptoms of cholangitis:
fever, abdominal pain and
jaundice. Alternatively, may
be present but suggests
graft rejection.
- Invasive studies of biliary
tract (either T-tube
cholangiography or
endoscopic retrograde
cholangiopancreatography)
may lead to cholangitis. For
this reasons, prophylaxis
with antibiotics covering
gram – negative and
anaerobes is
recommeneded when these
procedures are performed in
liver transplant patients
- Reactivation of HepaB and C
- High dose Hepa B Ig to
prevent Hepa B. Long term
efficacy of lamivudive and
aefovir in inhibiting hepa b
viral replication after
transplantation is being
studied
- Combination of interferon
alpha and ribavirin is being
tested for treatment
/prophylaxis of Hepa C.
- CMV causes vanishing bile
syndrome after liver
transplantation
PANCREAS TRANSPLANTATION
To prevent contamination of the
allograft with enteric bacteria and
yeasts,some surgeons, instead of
draining the pancreas through the
bowel, drain secretions into urinary
tract or bladder.
Bladder drainage casuses a high rate
or UTI and sterile cystitis. Prophylactic
antimicrobials or transplantation of
islet cells only as alternative.
MISCELLANEOUS INFECTION
IV catheter poses a risk of local and
bloodstream infection, significant
insertion-site-infection is most
commonly caused by S. aureus.
Coaugulase-neagative Staph are the
most common isolates from the blood.
Tuberculosis
-Occurring within 12 months
after solid organ transplantation.
- It has been rarely transmitted
from the donor organ.
Virus-associated Malignancies
- transplant patients may
develop nonmelanoma skin
or lip cancers, that, in
contrast to de novo skin
cancers, have high ratio of
squamous cells to basal
cells.
- Among renal transplants,
rates of melanoma are
modestly increased and
rates of ca of kidney and
bladder are increased.
VACCINATION OF TRANSPLANT
RECIPIENTS
- recipients of allogenic BMTs
must be reimmunized if
they are to be protected
against pathogens.
- In the absence of
compelling data as to
optimal timing, it is
reasonable to administer
pneumococcal and HiB
conjugate vaccines to both
autologous and allogenic
 BMT recipients 12 months (and certainly within 96 hrs)
after transplantation and or, if this is not possible,
again 12 months later. should be started
- pneumococcal and HiB are immediately on a 10-14 day
important for patients whi couese of acyclovir therapy.
have undergone - Susceptible household
splenectomy. contacts should receive live
- N. meningitides vaccines
polysaccharide vaccibe, - Immunocompromised patients
diphtheria, tetanus, and who travel may benefit from
inactivatedpolio vaccines some but not all vaccines.
can all be given at these
same intervals (12 and 24
months after
transplantation)
- Some authorities,
recommend (12, 14 and 16
months after
transplantation)
- Because of risk of spread,
household contacts of BMT
recipients should receive
only inactivated polio
vaccine.
- Live attenuated
vaccines(MMR) can be given
to autologous BMT
recipients 24 months after
transplantation and to most
allogenic BMT recipients at
the same point if they are
receiving ,aintenance
therapy with
immunosuppressive drugs
and do not have ongoing
GVHD.
- Avoid all live-virus vaccines
in patients who have GVHD
and/or taking high
maintenance dose of
glucocorticoids.

Solid organ transplant recipients

- all the usual vaccines and of
the indicated booster doses
should be completed before
immunosuppression, if
possible, to maximize
responses.
- For taking
immunosuppressive agents,
the administration of
pneumoccocal vaccine
should be repeated every 5
years.
- H influenzae conjugate
vaccine is safe and should
be efficacious in this
population; therefore, its
administration is
recommended.
- Person exposed to measles
should receive Ig
- Seronegative for Varicella
and comes in contact with a
person who has chicken pox
should be given VZIg asap