Download Infections Post-Organ Transplant - Coram CVS Specialty Infusion

VOLUME 12
C O R A M ’ S C O N T I N U I N G E D U C AT I O N P R O G R A M
Infections Post-Organ Transplant
It has been established that for
most organ recipients, transplant is
both life-saving and life-enhancing.
Success rates support
transplantation as a therapeutic
option for many patients with
end-stage organ failure. However,
it is important to understand that
transplant does not guarantee
freedom from complications,
including infection. Due to
immunosuppression — and
significantly depending on the
degree of immunosuppression —
infection remains the second-most
common cause of death postorgan transplant. Although
the risk of infection tends to
decrease over time, it remains
an area of vigilance in terms of
prevention and timely intervention.1
Infection presents as a key cause
of morbidity and mortality after
transplant. In fact, more than half
of transplant recipients experience
at least one infectious episode
during the first year post-transplant.
Also, post-transplant patients
have a greater lifetime risk of
opportunistic infection, even as
the risk equalizes over time as
compared to that of the general
population.2
Risk Factors for
Infection
Multiple factors, alone or in
combination, impact a transplant
patient’s infection risk. These
include:
yy Co-morbidities
yy Malnourishment
yy Existing colonization (often
with resistant organisms), for
example in patients with cystic
fibrosis or cirrhosis
yy Recent and/or frequent
hospitalizations
yy Multiple exposures to broadspectrum antimicrobial agents
yy Total immunosuppressive
burden
A successful transplant depends
on modulation of the immune
system in order to weaken the
immune response and prevent
rejection of the newly transplanted
organ. A patient’s infectious risk is
directly related to the amount of
immunosuppressive agents given,
and is thus influenced by transplant
center protocols for both prevention
and treatment of a rejection
episode. Some protocols, for
example, incorporate induction
immunosuppressive therapy
(immunosuppressants given in the
operating room at the time of the
transplant), which significantly
heightens the degree of
immunosuppression.
The early post-transplant phase is
a time of high immunosuppressive
dosing. Patient response and
protocols also dictate the
maintenance dosing (the amount
of medication required to prevent
a rejection episode). Maintenance
doses are typically tapered over
time as clinically appropriate.
Should a patient experience
a rejection episode,
immunosuppressant doses
are increased and/or additional
immunosuppressive agents are
The risk of infection is
determined primarily by:
1. The state of immune
suppression
2. The intensity of exposure
to any pathogen
added, with tapering again
determined by response
and protocol. It is the total
immunosuppressive burden that
plays a major role in the patient’s
risk for and development of an
infectious episode.
Types of Infectious
Pathogens
Infections can develop from any
type of pathogen — bacterial, viral,
fungal and protozoal — and their
risk, severity and timeline are
influenced by many factors.
Potential infectious etiologies are
diverse, including common,
community-acquired bacterial and
viral diseases and uncommon
opportunistic infections.
Opportunistic infections tend to
contribute to morbidity only in
immunocompromised hosts. As
illustrated in Table 1, there is some
degree of “predictability” in
timeframes for specific risks along
the post-transplant continuum,
although host and environmental
factors influence both risk and
development.
The majority of post-transplant
infections are opportunistic.
Opportunistic infections are caused
A leading national provider of home infusion services, including alternate site of care and specialty pharmacy distribution.
12600 E Arapahoe Road, Suite A, Centennial, CO 80112 | 720.568.3401 | coramhc.com
Table 1
Changing Timeline of Infection After Organ Transplant
Donor-Derived Infection
Nosocomial, technical
(donor or recipient)
Activation of latent infection (relapsed, residual,
opportunistic)
Community-acquired
Dynamic assessment of risk of infection
Common Infections in Solid-Organ Transplant Recipients
Recipient-Derived Infection
<1 Month
1–6 Months
yy Infection with antimicrobial-resistant species:
MRSA, VRE, Candida (non-albicans)
yy Wound infection
yy Infection with PCP and antiviral (CMV,
hepatitis B virus) prophylaxis: Polyomavirus
BK infection, nephropathy, C difficile colitis,
hepatitis C virus infection, adenovirus infection,
influenza, Cryptococcus neoformans infection,
Mycobacterium tuberculosis infection
yy Anastomotic leaks and ischemia
yy Anastomotic complications
yy Clostridium difficile colitis
yy Infections without prophylaxis: Pneumocystis;
infection with herpes viruses; hepatitis B virus
infection; infection with Listeria, Nocardia,
Toxoplasma, Strongyloides, Leishmania,
T. cruzi
yy Aspiration
yy Catheter infection
yy Donor-derived infection (uncommon): HSV,
LCMV, rhabdovirus, West Nile virus,
HIV, Trypanosoma cruzi
yy Recipient-derived infection (colonization):
Aspergillus, Pseudomonas
> 6 Months
yy Community-acquired pneumonia, urinary
tract infection; infection with Aspergillus,
atypical molds, Mucor species
yy Infection with Nocardia and Rhodococcus
species
yy Late viral infections: CMV infection (colitis,
retinitis), hepatitis (B or C), HSV encephalitis,
community-acquired infection (i.e., SARS,
West Nile virus infection), JC polyomavirus
infection, skin cancer, lymphoma (PTLD)
Adapted from: Fishman J. Infection in solid-organ transplant recipients. N Engl J Med. 2007;357(25):2601–2614.
Table 2
Herpes Viruses
Herpes Virus
Clinical Presentations
Herpes simplex 1
Cold sores
Herpes simplex 2
Genital herpes
Herpes zoster
Chicken pox/shingles
Cytomegalovirus
Multi-systemic
Epstein-Barr virus
Hepatitis, lymphocytic
interstitial
pneumonitis (LIP),
meningoencephalitis,
post-transplant
lymphoproliferative
disease (PTLD)
by pathogens that are ever-present in
our environment, many of which are
colonized in the general population.
Opportunistic organisms rarely cause
infection in an immunocompetent
person, but present a serious risk in
the immunosuppressed patient.3
Infection may result from exposure to
environmental organisms, the
reactivation of latent organisms
2
|
(particularly viruses), or invasion of
colonized organisms. Of significant
concern is infection caused by
antimicrobial-resistant organisms.
Viral Infections
the reactivation of latent infection.
The viruses most responsible for
infection in transplant recipients
are herpes viruses (see Table 2),
including herpes simplex 1 and 2,
herpes zoster, CMV and EpsteinBarr virus (EBV).4,5 Viral infections are
delineated as primary or secondary.
For example, by adulthood almost
all persons have been exposed to a
herpes virus (whether or not there are
physical manifestations) and have
antibodies against the virus. Once
the immune system is compromised,
the dormant virus can reactivate. For
the small percentage of patients who
do not have antibodies, there
is significant risk for a primary
infection and its associated multisystemic involvement and morbidity
and mortality, particularly if not
caught and treated early.
Viral infections are the most
prevalent post-transplant infections,
particularly cytomegalovirus
(CMV).3 Most viral illness is due to
Most adults have been exposed to
and have antibodies to CMV. Most
healthy people who are infected with
Bacterial Infections
Bacterial infections can be caused
by both gram-negative and
gram-positive organisms. During
the first post-transplant month,
approximately two-thirds of bacterial
infections are hospital-acquired.2
As in the general population,
community-acquired respiratory
infections are the main cause of
infectious complications in patients
with good allograft function and
who are maintained on minimal
immunosuppression.2
C O R A M ’ S C O N T I N U I N G E D U C AT I O N P R O G R A M VOLUME 12
Table 3
CMV Disease
System Involved
Clinical Presentations
Pulmonary
Dyspnea, cough, fever,
infiltrates on CXR
Upper GI
Oral ulcers, esophagitis,
gastropathy, enteritis
Lower GI
Colitis, proctitis
Additional Systems
Hepatitis, encephalitis,
pancreatitis, retinitis,
nephritis, pancytopenia
CMV have no symptoms, although
some may experience a self-limiting
infectious mononucleosis/glandular
fever-like syndrome. As illustrated in
Table 3, CMV disease can affect the
GI tract, lungs, liver, pancreas and
kidneys, with significant morbidity
and mortality (the latter particularly
with a primary infection). In fact,
CMV pneumonia has an 80–85%
mortality.4,5
Also significant to CMV is its
contribution to chronic graft failure
and graft loss.6 The cytokines
released in response to CMV
replication function essentially the
same as they do for rejection, thus
creating the risk.
The Epstein-Barr virus
(EBV) infects B cells and
stimulates their proliferation. In
immunocompetent persons,
proliferation of the transformed
B cells is usually controlled and
the infection is typically resolved.
In immunosuppressed patients,
however, the B cell stimulation may
not effectively turn off, creating a
significant risk of a B cell cancer
such as non-Hodgkin’s lymphoma,
T-cell lymphoma or post-transplant
lymphoproliferative disease (PTLD).7
Patients with a history of hepatitis
B and/or hepatitis C (or those
transplanted using a hepatitispositive donor) will reactivate the
virus post-transplant, even if their
hepatitis was effectively treated
prior to transplant. Ongoing
antiviral treatment is essential
post-transplant in order to achieve
sustained virologic response.
VOLUME 12 Two types of polyomaviruses, the
BK and JC viruses, are significant
pathogens in immunosuppressed
populations. As with herpes viruses,
the polyoma viruses affect the
majority of all adults.6 BK virus
remains latent in the kidneys and
can reactivate post-transplant.
Approximately 5–10% of kidney
transplant recipients develop a
reactivated BK infection, presenting
with hematuria and progressing to
hemorrhagic cystitis if not treated
early and effectively.8 If discovered
prior to the onset of clinical signs
and symptoms, BK virus can most
often be treated without harm to
the transplanted kidney. Patients
undergo routine post-transplant
surveillance monitoring for the
presence of BK virus.
JC virus is very similar, but adds
the central nervous system (CNS)
to its latency sites. JC virus is
most often a non-aggressive viral
pathogen, even upon reactivation.
When reactivated in the kidney,
the clinical picture is typically
similar to that of BK virus. When
reactivated in the CNS, patients can
progress to progressive multifocal
leukoencephalopathy (PML), with
its serious demyelination and
resulting neurologic deficits.8 There
is no effective therapy available for
treating polyomaviruses.3
the likelihood of spread with the
administration of post-transplant
immunosuppression. Accordingly,
the first components of infection
prevention occur in the pretransplant phase. For instance, as
part of their transplant evaluation,
patients undergo dental exams to
rule out or correct any potential
or actual infection. Similarly, a
consultation with an ear, nose and
throat (ENT) specialist is often
indicated. It is essential to assess
the viral infection history of both
the recipient and the donor prior
to transplant. The results of viral
screening do not necessarily
prevent a patient from undergoing
transplant, but will influence
immunosuppressive protocols as
well as pharmacologic prophylactic
or treatment regimens.
Yearly influenza vaccinations are
recommended post-transplant for
transplant recipients and close
contacts, along with pneumococcal
vaccination every 3 to 5 years.
Routine vaccinations are restarted
approximately 6 months posttransplant; note that transplant
recipients should not receive live
vaccines.3
Prevention
Other measures for preventing
infection include avoiding potential
environmental pathogens. For
example, patients should consume
only cooked food and eggs,
and avoid non-pasteurized dairy
products and open salad bars,
particularly during the first year
post-transplantation. They should
also avoid exposure to animal
excrement. It is recommended that
transplant recipients who require
blood transfusions receive their
transfusion only from CMV-negative
blood donors. Antibiotic prophylaxis
is typically recommended for
dental visits and procedures. Each
transplant center has specific
protocols regarding avoidance of
exposure to infectious pathogens;
these are but a few examples.
The patient must be free of infection
at the time of transplant, given
Prophylactic anti-infective agents
may be prescribed, depending
Fungal and Yeast Pathogens
The most common fungal/yeast
infections are caused by Candida
albicans, Candida tropicalis,
Aspergillus aeruginosa and
Cryptococcus.9 Candida species are
being seen with increased incidence
in transplant, with a mortality rate
of approximately 30%. Aspergillus
has been linked primarily with
pneumonia; however, necrotizing
sinusitis and/or brain abscesses
can also develop. Aspergillus has a
mortality rate of approximately 80%.
C O R A M ’ S C O N T I N U I N G E D U C AT I O N P R O G R A M | 3
Infection Control Strategies
yyPre-transplant dental exams
yyIsolation precautions
yyIntravenous immune globulin
yyOther prophylactic medications
yyImmunizations
on the disease being targeted
for prevention, the time posttransplant and the patient’s unique
risks.5 For example, trimethoprimsulfamethoxazole prophylaxis is
given to all transplant recipients
(who do not have sulfa allergies)
to prevent Pneumocystis jirovecii
pneumonia. Patients
universally take an anti-candida/
anti-fungal to prevent oral
candidiasis. Targeted prophylaxis,
such as in patients who are CMVnegative and have a CMV-positive
donor, is prescribed to prevent
primary infection. Patients with
hepatitis B require ongoing viral
suppression, typically hepatitis B
immunoglobulin (HBIg), with or
without the antivirals lamivudine
or adefovir.2,3,5
Treatment
For patients who develop an
infection, anti-infective treatment
is specific to the pathogen and its
sensitivity. Protocols may include
antibiotics, antivirals or antifungal
medications. For any medications
administered, careful monitoring
for any potential adverse effects,
interactions with the patient’s
yyCMV negative blood products
yyAvoidance of unnecessary
hospital days
yySurveillance cultures
yyHandwashing
current immunosuppressive regimen
(many medications can either
raise or lower the serum level of
some immunosuppressants), and
response to treatment are crucial.
Infection treatment may require a
reduction of the immunosuppression
doses. While this will likely increase
the risk of a rejection episode
and even of graft loss, it is often
necessary again to walk that
tightrope of immunomodulation
while supporting the patient’s ability
to recover from an infection.
An essential component of infection
prevention or early identification and
treatment is responsible compliance
by the patient and family. While
each transplant center may vary
in some of the specifics about
infection prevention, it is critical that
the patient be clear on what those
instructions are. Topics incorporated
into each transplant center’s patient
teaching protocol typically include:
yy Risks of infection
yy Principles of infection
transmission
yy Exposure to and avoidance of
communicable disease
yy Care of central venous catheter
4
Self-Care Measures
yy Reportable signs and symptoms
yyPerform thorough
handwashing.
yyAvoid people with colds, flu
and other contagious illnesses.
yyDo not handle animal waste.
yyAvoid any child who
has received a live
virus vaccination.
yyAvoid yard work, or wear
gloves while doing yard work.
yy High-risk areas for infection
|
yy Temperature monitoring
yy Self-care/health promotion
practices
yy Diet, food handling and storage
Conclusion
Transplantation is a life-saving
option for many patients and
C O R A M ’ S C O N T I N U I N G E D U C AT I O N P R O G R A M typically supports a greatly
improved quality of life. However,
potential complications exist,
including the risk of infection.
Infection prevention, monitoring
and effective treatment are essential
from pre-transplant through longterm post-transplant. Patient
education, including measures for
infection prevention, is essential in
the successful transplant process. t
References
1. Snyder JJ, Israni AK, Peng Y, Zhang
L, Simon TA, Kasiske BL. Rates of first
infection following kidney transplant in the
United States: post-transplant infection.
Kidney International. February 2009;
75:317-326.
2. Clark NM and Grim SA. Management
of infectious complications in solidorgan transplant recipients. Clinical
Pharmacology & Therapeutics. Aug
2011;90(2):333-342.
3. Fishman JA. Infection in solid
organ transplant recipients. NEJM.
2007;357:2601-2614.
4. Sharma R, Dronen SC. Herpes Simplex
in Emergency Medicine. http://emedicine.
medscape.com/article/783113-overview.
Accessed January 23, 2012.
5. Razonable RR. Management of viral
infections in solid organ transplant
recipients. Expert Rev Anti Infect Ther.
2011; 9(6):685-700. www.medscape.com/
viewarticle/747419. Posted September
16, 2011. Accessed October 13, 2011.
6. Stitt NL. Infection in the transplant
recipient. www.medscape.com/
viewarticle/451788. Accessed April 23,
2012.
7. Mukherjee S, Prendergast M, Ranga
V. Post-transplant lymphoproliferative
disease. http://emedicine.medscape.
com/article/431364-overview. Updated
August 6, 2010. Accessed November 5,
2011.
8. Josephson MA, Williams JW, Chandraker
A, Randhawa PS. Polyomavirusassociated nephropathy: update on
antiviral strategies. Transpl Infect Dis.
2006:8:95.
9. Pappas PG, Alexander BD, Andes DR,
Hadley S, Kauffmann CA, Freifeld A,
et al. Invasive fungal infection among
organ transplant recipients: result of
the Transplant-Associated Infection
Surveillance Network (TRANSNET).
Clin Inf Dis. 2010;50:1101-1111.
* Do not use the information in this article to
diagnose or treat a health problem or disease
without consulting a qualified physician. Patients
should consult their physician before starting any
course of treatment or supplementation, particularly
if they are currently under medical care, and should
never disregard medical advice or delay in seeking it
because of something set forth in this publication.
VOLUME 12
Self-Assessment Quiz: Infections Post-Organ Transplant
LEARNING GOAL
LEARNING OBJECTIVES
To appreciate the risk factors for
post-transplant infection, common
infectious risks, and prevention,
treatment and self-care
recommendations.
Upon completion of this continuing education program, the reader will
be able to:
1. Identify two factors that contribute to the etiology of infection in the
organ transplant recipient.
2. Discuss a timeline for infection in the organ transplant recipient.
3. Define common organisms seen following organ transplant and treatment
strategies to manage these infectious complications.
4. Discuss strategies to prevent or minimize infection in the organ
transplant recipient.
SELF-ASSESSMENT QUESTIONS
In the Quiz Answers section on the next page, circle the correct answer for each question. To obtain two (2.0)
contact hours toward CE credit, the passing score is 100%. Return your Self-Assesment Quiz to Coram via email,
fax or mail. See the next page for details on how to return to your quiz. Please allow approximately seven days to
process your test and receive your certificate upon achieving a passing score.
1. The risk of infection is determined primarily by:
6. Herpes viral infections can be:
a.The degree of immunosuppression.
b.The intensity of exposure to a pathogen.
c.A and B.
a.Primary.
b.Secondary reactivation.
c.A and B.
2. The greatest risk for viral reactivation is:
a.The first 90 days post-transplant.
b.The first 6 months post-transplant.
c.The first 12 months post-transplant.
3. Multiple factors, alone or in combination, impact a
transplant patient’s infection risk. These include:
a.Nutritional status.
b.Existing colonization.
c.Recent hospitalization.
d.A and C.
e.All of the above.
4. The majority of post-transplant infections
are opportunistic.
a.True
b.False
5. Opportunistic pathogens are:
a.Ever-present in our environment.
b.Commonly infective in immunocompetent and
immunosuppressed patients.
c.A and B.
VOLUME 12 7. B cell cancers are a potential consequence of:
a.CMV infection.
b.EBV infection.
c.Hepatitis C infection.
8. Infection prevention begins in the pre-transplant
phase.
a.True
b.False
9. Infection treatment may require a reduction in the
patient’s immunosuppressive dosing.
a.True
b.False
10.Patient education specific to infection prevention
must include:
a.Signs and symptoms of infection.
b.Avoidance of potential pathogens.
c.Self-care measures.
d.B and C.
e.All of the above.
C O R A M ’ S C O N T I N U I N G E D U C AT I O N P R O G R A M | 5
VOLUME 12
C O R A M ’ S C O N T I N U I N G E D U C AT I O N P R O G R A M
Infections Post-Organ Transplant
QUIZ ANSWERS
Circle the correct answers
below to receive 2.0 Continuing
Education credits.*
1.
a
b
c
2.
a
b
c
3.
a
b
c
4.
a
b
5.
a
b
c
6.
a
b
c
7.
a
b
c
8.
a
b
9.
a
b
10.
a
b
To obtain Continuing Education credits, please complete this
information in full. Please print clearly.
Name: _____________________________________________________________
Address: ___________________________________________________________
City: ________________________________ State:________Zip:___________
d
e
License Number (required to receive CEs): ______________________________
 RN
 LPN

Certified Case Manager

Social Worker
Employer:__________________________________________________________
Work Phone:________________________________________________________
Coram Representative:______________________________Date: ___________
Was this material:
c
d
e
*Accreditation Information
• Provider approved by the California Board of Registered
Nursing, Provider Number 15200 for 1.0 contact hours.
• Coram CVS/specialty Infusion Services is approved
by the Delaware Board of Nursing, Provider Number
DE-14-010517.
• Coram CVS/specialty Infusion Services is approved
by The Commission for Case Manager Certification to
provide continuing education credit to CCM® board
certified case managers.
• Coram CVS/specialty Infusion Services is an approved
provider for the American Board for Transplant
Certification (ABTC). Coram CVS/specialty Infusion
Services will grant one Continuing Education Point
for Transplant Certification (CEPTC) for this offering.
Provider #147.
Coram offers other Continuing
Education opportunities on home
care topics. Contact your local Coram
Representative for more information.
Useful in your practice?
Yes

No
Comprehensive enough?

Yes

No
Well organized?

Yes

No
Certificate delivery:

I would like my certificate mailed to the address provided above.
I would like my certificate emailed to me at:________________________

(ex: [email protected])
RETURN THIS PAGE TO CORAM VIA:
Mail: Coram’s CE Department
12600 E Arapahoe Road, Suite A
Centennial, CO 80112
Fax:949.462.8990
SUBMIT FORM VIA EMAIL: [email protected]
Clear Form Fields
A leading national provider of home infusion services, including alternate site of care and specialty pharmacy distribution.
12600 E Arapahoe Road, Suite A, Centennial, CO 80112 | 720.568.3401 | coramhc.com
© 2015 Coram LLC | COR16041-1215