Surveillance and Prevention of Post-Transplant
Infections
Shree Patel, PharmD, BCPS
VA Great Lakes Healthcare System
Reviewed by Rick Ricer, MD, Adjunct Professor of Family Medicine, University of Cincinnati,
Cincinnati, Ohio
Physicians
Activity release date: December 19, 2013
Expiration date: December 20, 2014
Transplant Nurses and Coordinators
Activity release date: December 19, 2013
Expiration date: December 20, 2014
Pharmacists
Activity release date: December 19, 2013
Expiration date: December 19, 2016
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Introduction
With the development of new anti-infective agents over the past couple of decades,
significant advancements have been made in treating post-transplant infections. As
more patients are transplanted each year, clinicians also have gained additional clinical
experience and understanding regarding the complexity of infectious disease in
transplant recipients. Nonetheless, infections still cause considerable morbidity and
mortality within the solid organ transplant population. Infectious disease will remain a
major concern for the foreseeable future due to the elevated net state of
immunosuppression in transplanted individuals and the constant development of novel
immunosuppressive agents with unique mechanisms of action.
Earlier this year, the Infectious Diseases Community of Practice of the American
Society of Transplantation (AST) published an updated edition of their infectious
diseases guidelines.1 This interactive case study highlights key issues involving the risk
factors, timeline, and prevention of infections in solid organ transplant recipients, using
renal transplantation as an example.
1. The American Society of Transplantation Infectious Diseases Guidelines, 3rd Edition. Am J
Transplant. 2013;13(suppl 4):1–371.
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Learning Objectives
After completing this interactive case study, participants in this continuing education
activity should be able to:

Explain the predisposing factors for infection after solid organ transplantation

Utilize the timing of infections post transplant as a guide to the most likely
pathogens and differential diagnosis

Compare the effectiveness of methods to prevent donor-derived infections in
order to choose the most appropriate course

Describe preventative measures and strategies for immunocompromised patients
to minimize exposure to and spreading of infectious diseases
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QUESTION 1
Risk Factors
BL is a 70-year-old white male who received a renal transplant for long-standing
hypertension from a living, unrelated donor 1 week ago. There were no intraoperative
complications, and a ureteral stent was utilized. He received induction
immunosuppression with anti-thymocyte globulin. His current maintenance
immunosuppressive regimen consists of tacrolimus, mycophenolate mofetil, and
prednisone. Thus far, his postoperative course has remained uncomplicated, and the
patient will be discharged home today. Prior to discharge, BL has some concerns
regarding his risk for infection in the immediate postoperative period.
Which of the following statements regarding this patient’s risk factors for
infection is false?
a. In the acute setting, the urinary tract is the most likely site of infection
following renal transplantation.
This is not the correct answer. This statement is true. Following solid organ
transplantation, risk factors for infections can be classified as pre-transplant (recipientor donor-derived), intraoperative, and post-transplant.1 Pre-transplant risk factors
attributed to the recipient include the type of organ being transplanted, as organ type is
predictive of the most likely site of infection.2 Therefore, infections of the urinary tract
are most common within 90 days of a renal transplant. Similarly, after a heart or liver
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transplant, the chest or abdomen is the most common site of post-transplant infection,
respectively. Contamination, along with localized ischemia and bleeding, are theorized
to be potential reasons as to why the most likely acute infections are proximal to the
allograft.3
1. Green M. Introduction: infections in solid organ transplantation. Am J Transplant. 2013;13(suppl
4):3–8.
2. Dummer JS, Hardy A, Poorsattar A, et al. Early infections in kidney, heart, and liver transplant
recipients on cyclosporine. Transplantation 1983;36:259–267.
3. Ho M, Dummer JS. Risk factors and approaches to infection in transplant recipients. In: Mandell
GL, Douglas RG Jr, Bennett JE, eds. Principles and Practice of Infectious Diseases. New York,
NY: Churchill Livingstone; 1990:2294.
b. BL’s age can lead to an augmented risk of infection post transplant.
This is not the correct answer. This statement is true. Being very young or old is a
recipient-related pre-transplant risk factor that can predispose a patient to infection post
transplant. Although limited, initial evidence demonstrates that people over the age of
65 are more predisposed to infections, because they undergo a gradual deterioration of
their immune system.1,2
1. Gelson W, Hoare M, Vowler S, et al. Features of immune senescence in liver transplant
recipients with established grafts. Liver Transplant. 2010;16:577–587.
2. Meier-Kriesche H, Friedman G, Jacobs M, Mulgaonkar S, Vaghela M, Kaplan B. Infectious
complications in geriatric renal transplant recipients: Comparison of two immunosuppressive
protocols.Transplantation 1999;68:1496–1502.
c. BL has an increased likelihood of developing a urinary tract infection (UTI) as a
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result of the ureteral stent placement.
This is not the correct answer. This statement is true. Major urologic complications
are associated with significant morbidity following renal transplantation; hence, many
transplant centers have adapted routine stenting in an effort to prevent urologic
complications. A recent Cochrane review demonstrated that prophylactic stenting
significantly reduced the incidence of urologic complications, but UTIs were more
common after stenting.1 Moreover, evidence suggests that patients continue to have a
higher incidence of UTI recurrence after stent removal.2
Because the risk of UTIs increases with prolonged stent duration, ureteral stents should
be removed as soon as warranted.3 Preliminary studies suggest that, along with early
removal, the use of antibiotic prophylaxis may negate the increased infection risk
associated with prophylactic stenting.1 However, evidence to support this notion is
limited.
1. Wilson CH, Rix DA, Manas DM. Routine intraoperative ureteric stenting for kidney transplant
recipients. Cochrane Database Syst Rev. 2013;6 CD004925. doi:
10.1002/14651858.CD004925.pub3.
2. Ranganathan M, Akbar M, Ilham MA, Chavez R, Kumar N, Asderakis A. Infective complications
associated with ureteral stents in renal transplant recipients. Transplant Proc. 2009;41:162–164.
3. Tavakoli A, Surange RS, Pearson RC, Parrott NR, Augustine T, Riad HN. Impact of stents on
urological complications and health care expenditure in renal transplant recipients: results of a
prospective, randomized clinical trial. J Urol. 2007;177:2260–2264.
d. The induction immunosuppressive strategy chosen for BL (anti-thymocyte
globulin) is associated with a lower risk of infection than that associated with
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other agents that do not deplete the T-cell population.
This is the correct answer. This statement is false. Post transplant, the net state of
immunosuppression is the primary risk factor for infection after solid organ transplant.1
Additionally, the use of T cell-depleting agents, such as anti-thymocyte globulin, antilymphocyte globulin, and alemtuzumab, has been linked to an augmented risk of
infection when compared with biologic agents that do not deplete the T-cell population,
such as basiliximab or daclizumab.2–4 Accordingly, the use of additional
immunosuppression to prevent acute rejection would increase, not decrease, the
likelihood of post-transplant infection.
1. Green, M. Introduction: infections in solid organ transplantation. Am J Transplant. 2013;13(suppl
4):3–8.
2. Bowman JS, Green M, Scantlebury VP. OKT3 and viral disease in pediatric liver transplant
recipients. Clin Transplant. 1991;5:294–300.
3. Kusne S, Dummer JS, Singh N, et al. Infections after liver transplantation: an analysis of 101
consecutive cases. Medicine (Baltimore). 1988;67:132–143.
4. Koo S, Marty FM, Baden LR. Infectious complications associated with immunomodulating biologic
agents. Infect Dis Clin North Am. 2010;24:285–306.
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QUESTION 2
Infection Timeline
BL presents to the outpatient clinic for follow-up 3 weeks after transplant. His current
maintenance immunosuppressive regimen has been reduced to tacrolimus and
mycophenolate mofetil. He continues to take valganciclovir (cytomegalovirus serology,
D+/R+) and sulfamethoxazole-trimethoprim prophylactically. BL complains of a
subjective fever, abdominal pain, pain upon urination and over the graft site, and
generalized fatigue over the past couple of days. The results of all labs and cultures for
this follow-up visit are still pending.
If BL is infected, what is the most likely source of the patient’s infection?
a. As BL is in the early transplant period, he probably is infected with a bacterial
source.
This is the correct answer. The timing of infections post transplant can guide clinicians
toward identifying the most likely pathogens and making a differential diagnosis.1,2 A
relationship exists between the various stages post transplant, the potential for
epidemiologic exposure, and the immunosuppressive strategy chosen. The early posttransplant period extends from 0 to 30 days after surgery. This initial phase is
characterized by bacterial or yeast infections due to preexisting conditions or
colonization in the recipient, donor factors, or complications of surgery. Of all transplantrelated bacterial infections, more than half present in the early post-transplant stage.3,4
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1. Green, M. Introduction: infections in solid organ transplantation. Am J Transplant. 2013;13(suppl
4):3–8.
2. Fishman JA. Introduction: infection in solid organ transplant recipients. Am J Transplant.
2009;9(suppl 4):S3–S6.
3. Green M, Wald ER, Fricker FJ, et al. Infections in pediatric orthotopic heart transplant recipients.
Pediatr Infect Dis J. 1989;8:87–93.
4. Al-Hasana B, Razonableb RR, Eckel-Passowd JE, Baddourb LM. Incidence rate and outcome of
gram-negative bloodstream infections in solid organ transplant recipients. Am J Transplant.
2009;9:835–843.
b. Donor-derived cytomegalovirus (CMV) is the most likely pathogen.
This is not the correct answer. In the absence of prophylaxis, CMV typically presents
in the intermediate post-transplant period, 31–180 days after surgery.1,2 However, with
the recent trend in extending CMV prophylaxis, CMV infection is beginning to manifest
itself much later, more than 6 months post transplant.3
1. Green, M. Introduction: infections in solid organ transplantation. Am J Transplant. 2013;13:3–8.
2. Dummer JS, White LT, Ho M, et al. Morbidity of cytomegalovirus infection in recipients of heart or
heart-lung transplants who received cyclosporine. J Infect Dis. 1985;152:1182–1191.
3. Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients. Am J Transplant.
2013;13:93–106.
c. BL likely is infected with BK virus due to the use of a ureteral stent.
This is not the correct answer. Although the use of ureteral stents has been linked
with an increased incidence of polyomavirus-associated nephropathy, BK virus most
commonly presents in the intermediate post-transplant period, 31–180 days after
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surgery.1
1. Hirsch HH, Randhawac P. BK polyomavirus in solid organ transplantation. Am J Transplant.
2013;13:179–188.
d. A classic “opportunistic” pathogen, such as Pneumocystis jirovecii (PJP), is
the most probable source of BL’s infection.
This is not the correct answer. Opportunistic infections typically present in the
intermediate post-transplant period, 31–180 days after surgery.1 Additionally, BL
currently is receiving sulfamethoxazole-trimethoprim prophylaxis, which can further
delay the presentation of PJP.
1. Green, M. Introduction: infections in solid organ transplantation. Am J Transplant. 2013;13(suppl
4):3–8.
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QUESTION 3
Donor-Derived Infections
BL’s urine culture was consistent with a bacterial urinary-tract infection (UTI). He was
prescribed appropriate oral antibiotics at this visit. The patient is concerned that his UTI
was transmitted from his donor.
Which of the following statements regarding donor-derived infections is
false?
a. Although rare, donor-derived infections are often coupled with significant
morbidity and potential mortality.
This is not the correct answer. This statement is true. The estimated incidence of
donor-derived infections is 0.2% after deceased-donor transplantation, and this
incidence is even lower following living-donor transplantation, owing to the additional
time needed to perform donor risk assessments and screenings.1 However, active
infection is a relative contraindication to organ donation due to the potential for
significant repercussions for the recipient, such as rejection, allograft failure, and
death.2–5
1. Ison MG, Grossi P. Donor-derived infections in solid organ transplantation. Am J Transplant.
2013;13:22–30.
2. Len O, Gavalda J, Blanes M, et al. Donor infection and transmission to the recipient of a solid
allograft. Am J Transplant. 2008;8:2420– 2425.
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3. Wong SY, Allen DM. Transmission of disseminated histoplasmosis via cadaveric renal
transplantation: case report. Clin Infect Dis. 1992;14:232–234.
4. First MR, Linnemean CC, Munda R, et al. Transmitted streptococcal infection and hyperacute
rejection. Transplantation. 1977;25:400–404.
5. Nelson PW, Delmonico FL, Tolkoff-Rubin NA, et al. Unsuspected donor Pseudomonas infection
causing arterial disruption after renal transplantation. Transplantation. 1984;37:313–314.
b. BL’s infection likely was spread from his donor, since the transmission of
unexpected donor-derived infections is common.
This is the correct answer. This statement is false. Because of advancements in
donor screening, it is rare nowadays to see an unanticipated transmission of an
infection from a donor.1 Currently, the risk-mitigation strategies used to negate disease
transmission include obtaining an accurate medical and social history and performing a
careful physical examination of the donor. Additionally, donors undergo extensive pretransplant laboratory screening for bacterial and viral infections. The estimated
incidence of donor-derived infections is 0.2% after deceased-donor transplant.2
1. Ison MG, Grossi P. Donor-derived infections in solid organ transplantation. Am J Transplant.
2013;13:22–30.
2. Grossi PA, Costa AN, Fehily D, et al. Infections and organ transplantation: new challenges for
prevention and treatment—a colloquium. Transplantation. 2012;93(5 suppl):S4–S39.
c. Similar to deceased donors, infection screening is also performed prior to livedonor transplantation.
This is not the correct answer. This statement is true. After a recent case of HIV
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transmission, the Centers for Disease Control and Prevention released
recommendations for live-donor screenings.1 Currently, live donors should be screened
for syphilis, HIV, hepatitis B and C, and tuberculosis not more than 28 days prior to
transplant.2,3
1. Centers for Disease Control and Prevention. HIV transmitted from a living organ donor —New
York City, 2009. Morbid Mortal Wkly Rep. 2011;60:297–301.
2. Ison MG, Grossi P. Donor-derived infections in solid organ transplantation. Am J Transplant.
2013;13:22–30.
3. Fischer SA, Lub K. Screening of donor and recipient in solid organ transplantation. Am J
Transplant. 2013;13:9–21.
d. In some cases, prophylaxis against donor-derived infections can be used to
reduce the risk for transmission.
This is not the correct answer. This statement is true. Transmission of latent
organisms such as herpesviruses has been significantly mitigated with viral
prophylaxis.1 Additionally, short-term administration of hepatitis B immunoglobulin along
with maintenance nucleoside or nucleotide analogs also has been shown to be effective
in reducing transmission and recurrence of hepatitis B virus.2 When determining
whether or not to start prophylaxis against a donor-derived infections, several questions
must be considered: Is there a safe, effective prophylactic agent available? If not, the
risk of prophylaxis may outweigh the potential benefit. Are there alternatives to
pharmacologic prophylaxis, such as pre-emptive prophylaxis, and how does the
effectiveness of these alternative methods compare with that of universal prophylaxis? If
there is a population that is most at risk, then prophylaxis potentially can be limited to
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this group of recipients. Finally, duration is an area of continued debate. Is there a
period of time during which the risk for the infection is at a peak? If so, then this interval
can be used as a guide for determining the duration of prophylaxis.
1. Ison MG, Grossi P. Donor-derived infections in solid organ transplantation. Am J Transplant.
2013;13(suppl 4):22–30.
2. Levitskya J, Doucetteb K; AST Infectious Diseases Community of Practice. Viral hepatitis in solid
organ transplantation. Am J Transplant. 2013;13(suppl 4):147–168.
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QUESTION 4
Preventive Measures
As a result of his recent infections, BL is concerned that he is not taking appropriate
measures to minimize his infection risk. He asks you for strategies he can take to
prevent further infections.
Which of the following measures is the correct education point to stress
when addressing BL’s concerns?
a. BL can minimize exposure to infections by avoiding direct contact with sick
persons, adapting appropriate hand-washing techniques, and refraining from
eating specific foods associated with the transmission of infections.
This is the correct answer. All patients and family members should be educated on
techniques to prevent infectious diseases or minimize exposures after solid organ
transplant.1 Direct contact with infected family members, coworkers, and other
individuals; ingestion of contaminated foods; and inhalation of bacterial and viral
pathogens are the most common means of transmitting disease. Hence, patients and
family members must be instructed on safe practices, such as washing their hands
thoroughly and frequently, along with the need for avoiding contact with sick persons or
crowded areas. In addition, transplant recipients must be made aware of foods to avoid,
such as unpasteurized, raw, or undercooked products.
1. Avery RK, Michaels MG. Strategies for safe living after solid organ transplantation. Am J
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Transplant. 2013;13:304–310.
b. To further diminish his infection risk, BL should also avoid animals and owning
personal pets.
This is not the correct answer. Infections can be transmitted from pet animals to
transplant recipients.1 However, abstinence from pet ownership is not necessary as
long as the recipient is willing to take additional precautionary measures.2 For instance,
transplant recipients should avoid contact with pet animals that are sick, handling the
feces of pets, and cleaning their pet’s cages or litter boxes without appropriate
protective gear, such as gloves. Most importantly, transplant clinicians should stress the
importance of careful hand hygiene after handling pets. Moreover, transplant recipients
can further reduce their infection risk by maintaining the health of their pets and seeking
veterinary assistance at the first sign of illess.3
1. Kotton CN. Zoonoses in solid-organ and hematopoietic stem cell transplant recipients. Clin Infect
Dis. 2007;44:857–866.
2. Avery RK, Michaels MG. Strategies for safe living after solid organ transplantation. Am J
Transplant. 2013;13:304–310.
3. Wong SK, Feinstein LH, Heidmann P. Healthy pets, healthy people. J Am Vet Med Assoc.
1999;215:335–338.
c. As long as BL limits all travel to non-developing countries, there are no
additional precautions necessary to reduce infection risk.
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This is not the correct answer. Travel safety is key in abating the risk of infectious
diseases after solid organ transplant.1 Travel to developing countries poses the greatest
risk. However, regardless of the area of travel, infection risk is also imminent when the
net state of immunosuppression is at its peak. Therefore, recipients should discuss all
travel with their physicians at least 2 months prior to departure. Transplant clinicians
can obtain up-to-date travel advisories specific to the area of travel from the Centers for
Disease Control and Prevention website (wwwnc.cdc.gov/travel).
1. Avery RK, Michaels MG. Strategies for safe living after solid organ transplantation. Am J
Transplant. 2013;13:304–310.
d. Vaccination is ineffective because BL is immunocompromised and thus will
not be able to mount a response to a vaccine.
This is not the correct answer. The results of studies investigating antibody response
to vaccination after solid organ transplant are conflicting, but the available evidence
suggests that transplant recipients still produce a response, though not entirely
adequate. A recent review assessed the response to tetanus, diphtheria, and polio
vaccines in renal transplant recipients; hepatitis A vaccine in adult liver transplant
recipients; and mumps, measles, and rubella vaccines in pediatric liver transplant
recipients.1 The results indicated that transplant recipients mount a lower and shorterlived immune response when compared with the response of healthy, non-transplanted
individuals.
Similarly, the efficacy of the influenza vaccine has been investigated after heart, renal,
and liver transplantation.2–5 Taken as a whole, these studies demonstrate either a
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comparable or diminished ability to mount an appropriate response to vaccination
against influenza.
However, as all of this evidence demonstrates at least some portion of an antibody
response, the potential benefit gained by vaccinating far outweighs the risk and
morbidity associated with failing to vaccinate immunocompromised recipients. Thus,
vaccination remains essential post transplant for both the transplant recipient and the
people with whom the recipient will be in direct contact.6
1. Eckerle I, Rosenberger KD, Zwahlen M, Junghanss T. Serologic vaccination response after solid
organ transplantation: a systematic review. PLoS One. 2013;8(2):e56974.
2. Fraund S, Wagner D, Pethig K, et al. Influenza vaccination in heart transplant recipients. J Heart
Lung Transplant. 1999;18:220–225.
3. Scharpé J, Evenepoel P, Maes B, et al. Influenza vaccination is efficacious and safe in renal
transplant recipients. Am J Transplant. 2008;8:332–337.
4. Sanchez-Fructuoso AI, Prats D, Naranjo P, et al. Influenza virus immunization effectivity in kidney
transplant patients subjected to two different triple-drug therapy immunosuppression protocols.
Transplantation. 2000;69:436–439.
5. Duchini A, Hendry RM, Nyberg LM, et al. Immune response to influenza vaccine in adult liver
transplant recipients. Liver Transpl. 2001;7:311–313.
6. Avery RK, Michaels MG. Strategies for safe living after solid organ transplantation. Am J
Transplant. 2013;13:304–310.
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Post Test
1. Which of the following increase the risk of infection in the first 30 days following renal
transplantation?
a. Use of T cell-depleting therapies for induction immunosuppression
b. Recipient age > 65 years old
c. Placement of a urethral stent post transplant
d. All of the above
2. Bacterial or yeast infections in transplant recipients are most common:
a. From 0 to 30 days post transplant
b. From 31 to 180 days post transplant
c. From 3 to 6 months post transplant
d. More than 6 months post transplant
3. Opportunistic and BK virus infections in transplant recipients are most common:
a. From 0 to 30 days post transplant
b. From 31 to 180 days post transplant
c. From 3 to 6 months post transplant
d. More than 6 months post transplant
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4. The incidence of donor-derived infections in recipients of solid organs from
deceased donors is estimated to be:
a. 0.1%
b. 0.2%
c. 0.5%
d. 1.0%
5. Which of the following statements is false?
a. Transplant recipients should avoid contact with infected individuals.
b. Transplant recipients should avoid traveling to developing countries
c. Transplant recipients should not be vaccinated
d. Transplant recipients may safely own personal pets
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Evaluation
Your candid and thorough completion of this evaluation will help us improve the quality
of our CME/CE activities. Thank you for your participation.
1. I found the content of this educational activity …
a. Clearly written and well organized.
 Strongly agree
 Agree
 Disagree
 Agree
 Disagree
b. Accurate and timely.
 Strongly agree
c. Related to its overall objectives.
 Strongly agree
 Agree
 Disagree
d. Free from commercial bias.
 Strongly agree
 Agree
 Disagree
e. Relevant to my own clinical practice.
 Strongly agree
 Agree
 Disagree
2. Did the information you received from this CME/CE activity:
a. Confirm the way you currently manage your patients?
 Yes
 No
 Don’t know
b. Suggest new options for managing your patients that you might apply
in the future?
 Yes
 No
 Don’t know
3. I used the information in this CME/CE activity for … (check all that apply)
 Patient management
 Board review
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 CME credit
4. Approximately how long (in hours) did it take you to complete this activity, including
this evaluation?
[
] Hours
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