Infections Post-Organ Transplant

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Lewis Palmer
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1 VOLUME 12 CORAM S CONTINUING EDUCATION PROGRAM 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: y Co-morbidities y Malnourishment y Existing colonization (often with resistant organisms), for example in patients with cystic fibrosis or cirrhosis y Recent and/or frequent hospitalizations y Multiple exposures to broadspectrum antimicrobial agents y 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 E Arapahoe Road, Suite A, Centennial, CO coramhc.com

2 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 y Infection with antimicrobial-resistant species: MRSA, VRE, Candida (non-albicans) y Aspiration y Catheter infection y Wound infection y Anastomotic leaks and ischemia y Clostridium difficile colitis y Donor-derived infection (uncommon): HSV, LCMV, rhabdovirus, West Nile virus, HIV, Trypanosoma cruzi y Recipient-derived infection (colonization): Aspergillus, Pseudomonas 1 6 Months y 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 y Anastomotic complications y Infections without prophylaxis: Pneumocystis; infection with herpes viruses; hepatitis B virus infection; infection with Listeria, Nocardia, Toxoplasma, Strongyloides, Leishmania, T. cruzi > 6 Months y Community-acquired pneumonia, urinary tract infection; infection with Aspergillus, atypical molds, Mucor species y Infection with Nocardia and Rhodococcus species y 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): Table 2 Herpes Viruses Herpes Virus Herpes simplex 1 Herpes simplex 2 Herpes zoster Cytomegalovirus Epstein-Barr virus Clinical Presentations Cold sores Genital herpes Chicken pox/shingles Multi-systemic 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 (particularly viruses), or invasion of colonized organisms. Of significant concern is infection caused by antimicrobial-resistant organisms. 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 Viral Infections Viral infections are the most prevalent post-transplant infections, particularly cytomegalovirus (CMV). 3 Most viral illness is due to 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 Epstein- Barr 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. Most adults have been exposed to and have antibodies to CMV. Most healthy people who are infected with 2 CORAM S CONTINUING EDUCATION PROGRAM VOLUME 12

3 Table 3 CMV Disease System Involved Pulmonary Upper GI Lower GI Additional Systems Clinical Presentations Dyspnea, cough, fever, infiltrates on CXR Oral ulcers, esophagitis, gastropathy, enteritis Colitis, proctitis 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. 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 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%. Prevention The patient must be free of infection at the time of transplant, given 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 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. Prophylactic anti-infective agents may be prescribed, depending VOLUME 12 CORAM S CONTINUING EDUCATION PROGRAM 3

4 Infection Control Strategies ypre-transplant dental exams yisolation precautions yintravenous immune globulin yother prophylactic medications yimmunizations 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 Self-Care Measures yperform thorough handwashing. yavoid people with colds, flu and other contagious illnesses. ydo not handle animal waste. yavoid any child who has received a live virus vaccination. yavoid yard work, or wear gloves while doing yard work. ycmv negative blood products yavoidance of unnecessary hospital days ysurveillance cultures yhandwashing 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: y Risks of infection y Principles of infection transmission y Exposure to and avoidance of communicable disease y Care of central venous catheter y Reportable signs and symptoms y High-risk areas for infection y Temperature monitoring y Self-care/health promotion practices y Diet, food handling and storage Conclusion Transplantation is a life-saving option for many patients and 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: Clark NM and Grim SA. Management of infectious complications in solidorgan transplant recipients. Clinical Pharmacology & Therapeutics. Aug 2011;90(2): Fishman JA. Infection in solid organ transplant recipients. NEJM. 2007;357: Sharma R, Dronen SC. Herpes Simplex in Emergency Medicine. medscape.com/article/ overview. Accessed January 23, Razonable RR. Management of viral infections in solid organ transplant recipients. Expert Rev Anti Infect Ther. 2011; 9(6): viewarticle/ Posted September 16, Accessed October 13, Stitt NL. Infection in the transplant recipient. viewarticle/ Accessed April 23, Mukherjee S, Prendergast M, Ranga V. Post-transplant lymphoproliferative disease. com/article/ overview. Updated August 6, Accessed November 5, Josephson MA, Williams JW, Chandraker A, Randhawa PS. Polyomavirusassociated nephropathy: update on antiviral strategies. Transpl Infect Dis. 2006:8: 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: * 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. 4 CORAM S CONTINUING EDUCATION PROGRAM VOLUME 12

5 Self-Assessment Quiz: Infections Post-Organ Transplant LEARNING GOAL To appreciate the risk factors for post-transplant infection, common infectious risks, and prevention, treatment and self-care recommendations. LEARNING OBJECTIVES 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 , 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: a. The degree of immunosuppression. b. The intensity of exposure to a pathogen. 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. 6. Herpes viral infections can be: a. Primary. b. Secondary reactivation. c. A and B. 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. VOLUME 12 CORAM S CONTINUING EDUCATION PROGRAM 5

6 VOLUME 12 CORAM S CONTINUING EDUCATION PROGRAM Infections Post-Organ Transplant QUIZ ANSWERS Circle the correct answers below to receive 2.0 Continuing Education credits.* To obtain Continuing Education credits, please complete this information in full. Please print clearly. Name: Address: City: State: Zip: d e a b License Number (required to receive CEs): RN LPN Certified Case Manager Social Worker Employer: Work Phone: 8. a b Coram Representative: Date: a b d e Was this material: Useful in your practice? Yes No Comprehensive enough? Yes No *Accreditation Information Provider approved by the California Board of Registered Nursing, Provider Number for 1.0 contact hours. Coram CVS/specialty Infusion Services is approved by the Delaware Board of Nursing, Provider Number DE 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. Well organized? Yes No Certificate delivery: I would like my certificate mailed to the address provided above. I would like my certificate ed to me at: (ex: john.smith@coramhc.com) RETURN THIS PAGE TO CORAM VIA: Mail: Coram s CE Department E Arapahoe Road, Suite A Centennial, CO Fax: SUBMIT FORM VIA CEDept@coramhc.com A leading national provider of home infusion services, including alternate site of care and specialty pharmacy distribution E Arapahoe Road, Suite A, Centennial, CO coramhc.com 2015 Coram LLC COR

Potential etiologies of infection in these patients are diverse, including common and uncommon opportunistic infections.

In the name of God Principles of post Tx infections 1: Potential etiologies of infection in these patients are diverse, including common and uncommon opportunistic infections. Infection processes can progress