Transplant Complications: Infectious Diseases



Transplant Complications: Infectious Diseases


Debra Dumas-Hicks, RN, BS, CCTC, CCTN

Fawn Fitzmorris, RN, CCTC

Cynthia Cassidy, RN, BSN, CCTC

Karýn Ryan Canales, RN, BSN, CCTC



I. INTRODUCTION

A. Solid organ transplantation (SOT) has been established as an accepted therapy for end-stage disease of the kidneys, liver, heart, and lungs for nearly 30 years. When infection occurs after SOT, early and specific diagnosis and rapid and aggressive treatment are essential to good clinical outcomes.1



  • Recognition of infection is challenging in transplant recipients as presentation is often complicated by noninfectious causes of fever, such as drug interactions or graft rejection.


  • As a result of the growing population of immunosuppressed patients with prolonged survival, an increased incidence and spectrum of opportunistic infections has been observed.


  • Guidelines for the diagnosis and treatment of infection in transplant recipients have been developed.2


  • While there is general agreement on the major infections for which routine screening is performed, centers vary in the extent of infectious disease investigation and the actions taken as a result of those investigations.3


II. INFECTIOUS DISEASE EVALUATION OF THE PRETRANSPLANT CANDIDATE

A. Key Points



  • The successful outcome of SOT requires the careful selection of transplant recipients through a process of medical evaluation and screening.


  • The identification of active and latent infection, along with the optimization of treatment, is an important role of the transplant specialist.



  • Early identification of risk factors that predispose transplant candidates to infection and prompt referral to an experienced infectious diseases (ID) specialist when indicated can prevent posttransplant infections and improve patient outcomes.

B. Goals of Pretransplant Screening



  • Identify conditions that may indicate a contraindication to transplantation.


  • Treat active infection in the pretransplant phase, as clinically indicated.


  • Recognize the risk of posttransplant infection and develop strategies for prophylaxis.


  • Implement preventative measures, including updating immunizations.

C. History Review



  • Childhood infections such as measles, mumps, chickenpox, mononucleosis


  • Underlying illness causing organ failure including, but not limited to, cystic fibrosis (respiratory failure), hepatitis C virus (HCV cirrhosis/liver failure)


  • Adulthood infections that can include the following:



    • Hepatitis B virus (HBV) and hepatitis C virus (HCV)


    • Human immunodeficiency virus (HIV)


    • Tuberculosis (TB)


    • Sexually transmitted diseases


    • Endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis)


    • Recurrent infections (e.g., urinary tract, pneumonia, staphylococcal skin soft tissue infection, line-related infections)


  • Concurrent/nosocomial infections such as



    • Urinary tract infection


    • Pneumonia


    • Peritonitis


    • Wound infection


    • Occult abscess


    • Catheter/ventricular assist device-related infection


  • Immunizations


  • Travel history


  • Social risk factors such as



    • Alcohol/drug abuse


    • Incarceration


    • High-risk sexual behavior



      • Lack of contraceptive barrier use


      • Multiple sex partners


    • Tattoos


    • Body piercings


    • Socioeconomic challenges



      • Limited health care access


      • Poverty


      • Language barriers


      • Low health literacy


  • Environmental exposure such as industrial chemicals, cigarette smoke


  • Nutritional practices such as the following:



    • Unsafe source of drinking water


    • Consumption of raw/undercooked meat, unpasteurized dairy products, seafood


  • Allergies to antimicrobial agents


  • See Table 5-1 for Pretransplant Diagnostic Tests and Team Evaluations









TABLE 5-1 Infectious Disease Evaluation

















Physical examination


Nutritional status: cachexia, obesity, integumentary (skin lesions)


Eyes, ears, nose, throat


Respiratory (rales, rhonchi, breath sounds)


Cardiac (rub, murmur, endocarditis)


Gastrointestinal (diarrhea, bleeding, ulcers)


Genitourinary (prostate examination, Papanicolaou test)


Blood work


Complete blood cell count with differential leukocyte count


Complete metabolic panel


Cytomegalovirus IgG and IgM antibodies


Toxoplasma gondii IgG and IgM antibodies


Herpes simplex virus I and II IgG and IgM antibodies


Varicella zoster titers


Epstein-Barr virus IgG and IgM antibodies


Serologic screening for syphilis (rapid plasma reagin test)


Human immunodeficiency virus (HIV) 1 and 2


Hepatitis A, B, and C


Lyme titers (if indicated)


Glycosylated hemoglobin (if indicated)


Other


Chest radiograph


Computed tomography scan (if indicated)


CT scan of paranasal sinuses (particularly for patients with cystic fibrosis or a history of recurrent sinus infections)


Abdominal ultrasound


Tuberculin skin test


Quantiferon gold lab


Urinalysis and urine culture


Stool culture (if indicated)


Stool for ova and parasites (if indicated)


Dental screening


Organ-specific


Heart transplantation: Toxoplasma gondii IgG and IgM antibodies


Lung transplantation: Sputum cultures to detect colonization of respiratory tract by Aspergillus species, Burkholderia cepacia


From Fischer SA, Lu K. Screening of donor and recipient in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):9-21; Danziger-Isakov L, Kumar D. Vaccination in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):311-317; Ison MG, Grossi P. Donor-derived infections in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):22-30; Ison MG, Nalesnik MA. An update on donor-derived disease transmission in organ transplantation. Am J Transplant. 2011;11:1123-1130; Greenwald MA, Kuehnert MJ, Fishman JA. Infectious disease transmission during organ and tissue transplantation. Emerg Infect Dis. 2012;18(8):e1.



III. IMMUNIZATIONS

A. Key Points4



  • Transplant candidates and recipients are at increased risk of infectious complications due to end-organ failure and immunosuppression.


  • Every effort should be made to immunize patients in the early phase of disease because the response to many vaccines is diminished in organ failure.


  • Transplant recipients may have a suboptimal response to vaccinations due to their immunosuppressed status; therefore, it is critical to update immunizations prior to transplantation.



  • The ideal time to give vaccines following transplantation is unknown; however, most centers restart vaccinations approximately 3 to 6 months posttransplant.

B. Recommended Pretransplant Immunizations4



  • Adult Candidates



    • Influenza (administered yearly posttransplantation: inactive vaccine only)


    • Hepatitis B:



      • Assess before and monitor after transplant


      • Administer booster if titers fall below 10 IU/L5


    • Hepatitis A (liver transplant candidates or patients at high risk for exposure)


    • Tetanus


    • Pertussis (Tdap) if no tetanus booster in last 10 years


    • Inactive polio


    • Pneumococcal


    • Meningococcal, especially for



      • Military personnel


      • Travelers to high-risk areas


      • Postsplenectomy patients


      • College freshmen living on campus


    • Rabies (exposure or potential exposures due to vocations only)


    • Human papillomavirus (HPV): males and females ages 9 to 26 years


    • Measles, mumps, rubella (MMR): if seronegative (see Pediatric Candidates section)


    • Varicella—if seronegative


    • Note: Live vaccine: must avoid transplantation 4 weeks following administration


    • Bacille Calmette-Guérin (BCG)—unavoidable exposure to TB


  • Pediatric Candidates: same as adult candidates with the following exceptions:



    • Hepatitis A: all pediatric candidates.


    • N. meningitidis (MCV4): all candidates 11 to 18 years of age and as young as 9 months with special circumstances (see Adult Candidates section).


    • Varicella: vaccine should be administered after 12 months of age with second dose approximately 3 months later.


    • Measles, mumps, rubella (MMR) may be administered as early as 6 months of age and repeated after 4 weeks following the first injection.


    • Wait at least 4 weeks between administration of live vaccines and transplant procedure for all adult and pediatric candidates.


IV. DONOR-TRANSMITTED INFECTIONS

A. Key Points5



  • Donor-transmitted infection is frequently associated with significant recipient morbidity and mortality.6


  • Despite advances in surgical technique, immunosuppression, and infection prevention, unexpected transmission of infections from donor to recipient is an infrequent complication of transplantation.7

B. Donor Risk Assessment



  • Donor chart review



  • Discussion with available family, friends, and/or acquaintances for knowledge of



    • Prior infections


    • Immunizations


    • Unusual exposures to infection


    • Psychosocial history



      • Alcohol/drug abuse


      • Incarceration


      • High-risk sexual behavior/multiple sex partners


      • Tattoos


      • Body piercing


    • Socioeconomic status/challenges



      • Living conditions


      • Health care access


      • Medical adherence


      • Poverty


      • Language barriers

C. Physical Examination



  • Performed by organ procurement team and procuring surgeon


  • Evidence of active infections including abscesses, ulcers, genital/anal trauma, lymphadenopathy


  • Evidence of recent drug use such as track marks


  • Evidence of underlying disease (cirrhosis, skin lesions, or other malignancies)


  • Other abnormalities such as free spillage of intestinal contents or obvious pus or sign of infection involving specific donor organs and/or vessels

D. Laboratory Studies



  • Donor testing includes the following:



    • Complete blood cell count (CBC)


    • Microbial cultures (e.g., blood, urine)


    • Serologic assay (e.g., antibodies against HIV, hepatitis B virus [HBV]), and hepatitis C virus [HCV]) and, in certain cases, nucleic acid testing (NAT) (including assays for HIV, HCV, or HBV).7


  • Ideally, serologic testing should be performed before and after blood product administration.


  • If serologic testing is done after the donor is transfused, the number of blood product units should be recorded.

E. High-Risk Donors



  • Public Health Service (PHS) guidelines developed in 1994 provide guidance to minimize the risk of HIV transmission and to monitor recipients following the transplantation of “high-risk” organs.8


  • The intent of the PHS guideline is to improve organ transplant recipient outcomes by reducing the risk of unexpected HIV, HBV, and HCV transmission, while preserving the availability of high-quality organs using an evidence-based approach to formulate the recommendations.8


  • Transplant programs must obtain specific informed consent from the intended recipient according to the guidelines specified in the Organ Procurement and Transplant Network (OPTN) Policy 15.3 (Figure 5-1).8,9


  • Behavior/History Criteria established by the PHS as “high risk” for transmitting HIV or other infectious diseases despite negative preliminary testing:



    • People who have had sex with a person known or suspected to have HIV, HBV, or HCV infections in the preceding 12 months







      FIGURE 5-1 Organ Procurement and Transplantation Network Policy 15.3: informed consent of transmissible disease risk (available at: www.optn.transplant.hrsa.gov/ContentDocuments/OPTN_Policies.pdf).


    • Male with male (MSM) sex in the preceding 12 months


    • Women who have had sex with a man with a history of MSM behavior in the preceding 12 months.


    • People who have had sex in exchange for money or drugs in the preceding 12 months.


    • People who have had sex with a person who had sex in exchange for money or drugs in the preceding 12 months.


    • People who have had sex with a person who has injected drugs by IV, IM, or SQ route for nonmedical reasons in the preceding 12 months.



    • A child who is <18 months of age and born to a mother known to be infected with or at increased risk for HIV, HBV, or HCV infection.


    • A child who has been breast-fed within the preceding 12 months and the mother is known to be infected with or at increased risk for HIV infection.


    • People who have injected drugs by IV, IM, or SQ route for nonmedical reasons in the preceding 12 months.


    • People who have been in lockup, jail, prison, or a juvenile correction facility for more than 72 hours in the preceding 12 months.


    • People who have been newly diagnosed with or have been treated for syphilis, gonorrhea, Chlamydia, or genital ulcers for the preceding 12 months.


    • People who have been on hemodialysis in the preceding 13 months should be identified as high risk for HCV infection only.


V. POSTTRANSPLANT INFECTION10

A. Key Points



  • Early, specific diagnosis and rapid, aggressive treatment are essential in obtaining favorable outcomes when infection occurs posttransplantation.


  • Etiologies of infections are diverse and include common viral and bacterial diseases and uncommon opportunistic infections that are clinically significant only in immunocompromised hosts.


  • Immunosuppression impairs inflammatory responses normally associated with microbial invasion.

B. Exposure to Infection



  • Epidemiologic exposure


  • Latent pathogens can reactivate in the setting of immunosuppression



    • Cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV, shingles), HBV, HCV, papillomavirus, and BK polyomavirus frequently reactivate after transplantation.


    • Geographically restricted systemic mycoses (histoplasmosis, coccidioidomycosis, diseases caused by the parasite Trypanosoma cruzi) may have occurred many years pretransplantation.


    • Significance of exposure varies based upon specific immune deficit(s).


    • Bacterial (Staphylococcus spp., Streptococcus spp.) and fungal (Candida spp., Aspergillus spp.) pathogens are more significant in the setting of neutropenia.11


    • Viral (CMV) and intracellular (TB) infections are more common with T-cell immune deficits.


    • Strongyloides stercoralis may reactivate many years after exposure.


  • Community-acquired pathogens



    • Respiratory viruses such as influenza, respiratory syncytial virus (RSV), and adenovirus


    • Bacterial pathogens such as Streptococcus pneumoniae, Legionella, and Salmonella


  • Food-borne illnesses caused by organisms such as Escherichia coli, Cryptosporidium, Salmonella, Toxoplasma gondii (usually related to contact with cat feces), Vibrio vulnificus, and Campylobacter


  • Nosocomial infections



    • Prolonged hospitalization and mechanical ventilation increase vulnerability to hospital-acquired infections in the early postoperative period.



    • Gram-negative bacilli (Pseudomonas aeruginosa, Legionella)


    • Antimicrobial-resistant gram-positive organisms (vancomycin-resistant enterococci [VRE], methicillin-resistant Staphylococcus aureus [MRSA])


    • Fungi (Aspergillus spp. and nonalbicans or azole-resistant Candida species)


    • Clostridium difficile colitis12


    • See Table 5-2 for major pathogens that cause infectious disease in SOT recipients

C. Periods of Increased Risk



  • Early postoperative period when immunosuppression doses are highest


  • Increase in immunosuppressant therapy to treat acute rejection

D. Posttransplant Infection Timetable10,13



  • The posttransplant course can be divided into three time periods related to the risk of infection by specific pathogens (see Figure 5-2):



    • Early posttransplant period (days 0 to 30)



      • Infection from either donor or recipient


      • Infectious complications from surgery and/or hospitalization


    • Intermediate period (months 1 to 6)



      • Highest risk for developing opportunistic infections


      • Reflective of local epidemiology, immunosuppression, and antimicrobial prophylaxis








      TABLE 5-2 Major Pathogens that Cause Infection in Transplant Recipients









































































      Bacterial


      Viral


      Fungal


      Parasitic


      Enteric gram-negative bacteria


      Cytomegalovirus


      Candida species


      Toxoplasma gondii


      Pseudomonas aeruginosa


      Epstein-Barr virus


      Aspergillus species


      Cryptosporidium


      Legionella species


      Herpes simplex virus


      Cryptococcus neoformans


      Strongyloides stercoralis


      Nocardia asteroides


      Varicella zoster virus


      Pneumocystis carinii



      Listeria monocytogenes


      Hepatitis B virus


      Coccidioides immitis



      Salmonella species


      Hepatitis C virus


      Histoplasma capsulatum



      Mycobacterium tuberculosis


      Human herpesvirus 6


      Blastomyces dermatitidis



      Nontuberculous mycobacteria


      Papillomavirus





      Adenoviruses





      Respiratory syncytial virus





      Influenza virus





      Enterovirus





      Papovavirus


      From Green M. Introduction: infections in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):3-8; Jani AA. Infections after solid organ transplantation. Medscape. 2014. Available at emedicine.medscape.com/article.430550-overview. Accessed August 26, 2015; Fishman J. Infection in the solid organ transplant. In: Marr K, ed. Up to Date. Waltham, MA: Wolters Kluwer; 2015. Available at www.uptodate.com/contents/infection-in-the-solid-organ-transplant-recipient#H5. Accessed August 1, 2015.








      FIGURE 5-2 Infections in solid organ transplant recipients.CMV, cytomegalovirus; EBV, Epstein-Barr virus; HSV, herpes simplex virus; MRSA, methicillin-resistant Staphylococcus aureus; PML, progressive multifocal leukoencephalopathy; PTLD, posttransplant lymphoproliferative disorder; SARS, severe acute respiratory syndrome; VRE, vancomycin-resistant Enterococcus; VZV, varicella-zoster virus. (From Fishman JA; the AST Infectious Diseases Community of Practice. Introduction: infection in solid organ transplant recipients. Am J Transplant. 2009;9(suppl 4):S3. Copyright © 2009 American Society of Transplantation and the American Society of Transplant Surgeons. Reproduced with permission of John Wiley & Sons, Inc. Graphic 58770 Version 5.0.)


    • Late posttransplant period (>6 months)



      • Stable and reduced levels of immunosuppression for most patients.


      • Subject to community-acquired pneumonias and late viral infections.


      • Patients with suboptimal graft function require higher than normal levels of immunosuppression and are at highest risk for opportunistic infections (i.e., pneumocystis pneumonia [PCP], cryptococcosis, nocardiosis) and severe illness.


  • Significance of timetable



    • Common patterns of opportunistic infection are observed following solid organ transplantation based on epidemiologic exposures and the “net state of immunosuppression.”


    • The time line is altered based on the immunosuppressive regimen and prophylactic medications. The dynamic assessment of infectious risk represents assays that will measure an individual’s risk for infection due to specific pathogens or in general.


    • See Table 5-3 for posttransplant intervals for infection.10,14,15


  • Guide to develop antimicrobial strategies10,14,15



    • Develop differential diagnosis for the SOT recipient with clinical manifestations of infection.


    • Detect presence of excessive environmental risks (individual, community, nosocomial).









TABLE 5-3 Posttransplant Intervals of Infection































Time Period


Type of Infection


Example


First month


Continuation of recipient’s pretransplant infection


Pseudomonas aeruginosa infections in lung transplant candidates with cystic fibrosis



Infections related to the surgical procedure, other iatrogenic procedures, and indwelling lines and catheters


Anastomotic leaks, obstructions lymphoceles Infection related to invasive lines, catheters1



Transmission of infection by the donor allograft


Staphylococcus, Streptococcus, Pseudomonas spp., Salmonella spp., Aspergillus spp., Candida spp. CMV, EBV, HHV-6, HSV, VZV, HTLV-1 and HTLV-2, HIV, HBV, HCV, LCMV, mycobacteria, West Nile virus, rabies, Chagas’ disease, Leishmania, toxoplasmosis, respiratory viruses



Early reactivation of latent viruses


Reactivation of herpes viruses


Months 2-6


Infections caused by opportunistic organisms or immunomodulating viruses


Reactivation of latent viral infections: CMV, EBV, HSV, VZV, HBV, HCV, BK polyomavirus


CMV, cytomegalovirus; EBV, Epstein-Barr virus; HHV-6, human herpesvirus 6; HSV, herpes simplex virus; VZV, varicella zoster virus; HTLV, human T-cell lymphotropic virus; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; LCMV, lymphocytic choriomeningitis virus.


From Jani AA. Infections after solid organ transplantation. Medscape. 2014. Available at emedicine.medscape.com/article.430550-overview. Accessed August 26, 2015; Morris MI, Fischer SA, Ison MG. Infections transmitted by transplantation. Infect Dis Clin North Am. 2010;24(2):497-514; Chong PP, Razonable RR. Diagnostic and management strategies for donor-derived infections. Infect Dis Clin North Am. 2013;27(2):253-270.


E. Other Factors Associated with Posttransplant Risks



  • Donor-derived infections6,7,14



    • Latent or unappreciated active infection in donor at time of transplant (CMV or Epstein-Barr virus [EBV] infection; toxoplasmosis)


    • Bloodstream infections (Staphylococcus, Pneumococcus, E. coli, Candida); adequate therapy should be confirmed prior to organ acceptance


  • Net state of immunosuppression: determined by interaction of several factors10



    • Immunosuppressive therapies



      • Type/dose of medications, plasmapheresis, IgG


    • Comorbidities such as



      • Diabetes


      • Malnutrition


    • Graft abnormalities


    • Concurrent neutropenia or lymphopenia


    • Invasive devices—vascular access devices, urinary catheters, drains


    • Concomitant infection with immunomodulating viruses



      • CMV


      • EBV


      • HHV-6


      • HBV


      • HCV


    • See Table 5-4 regarding factors that affect the diagnosis of posttransplant infection.1,10,15









TABLE 5-4 Factors to Consider in Diagnosis of Posttransplant Infection






































Factor


Example


Pretransplant host factors


Age, nutritional status, comorbidities (e.g., diabetes mellitus), medications (e.g., steroid use), infection history (particularly infections that further suppress the immune system, such as CMV, EBV, HBV, HCV)


Preoperative factors


Invasive devices (e.g., intra-aortic balloon pump, assist devices, mechanical ventilation, hemodialysis)


Type of organ transplanted


Risk of infection greater for lung transplant recipients


Perioperative factors


Ischemic time, blood loss, transfusions


Donor factors


Donor CMV seropositive, recipient CMV seronegative


Immunosuppression regimen


Maintenance therapy (medications, doses, frequency), use of antilymphocyte therapy, net state of immunosuppression


Rejection history


Severity, treatment, and response to treatment


Current antimicrobial regimen (if any)


Use of prophylactic antiviral, antifungal, and antibiotic therapy


Posttransplant exposure to nosocomial, community, or geographic sources of infection


Any recent hospitalizations, community outbreaks of infection, exposure to endemic bacteria, virus, and fungi


Onset of symptoms


Bacterial infections usually manifest over a 24-48 h time period, but they can evolve over several (3-5) days


From Green M. Introduction: Infections in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):3-8; Jani AA. Infections after solid organ transplantation. Medscape. 2014. Available at emedicine.medscape.com/article.430550-overview. Accessed August 26, 2015; Chong PP, Razonable RR. Diagnostic and management strategies for donor-derived infections. Infect Dis Clin North Am. 2013;27(2):253-270.



VI. CLINICAL MANIFESTATIONS OF INFECTION

A. Key Points



  • Significant clinical manifestations of infection include the following10:



    • Usual signs of infection (e.g., fever, chills, generalized malaise) may be replaced by nonspecific symptoms (altered mental status, elevated liver function tests) due to immunosuppression


    • Fever without localizing findings or fever with headache


    • Central nervous system (CNS) changes, including changes in level of consciousness


    • Unexplained skin lesions


  • Important characteristics of CNS infections include the following5,7,10:



    • The signs of meningeal irritation may be masked by immunosuppression.



      • Changes in level of consciousness may be subtle.


      • The most reliable indication of a CNS infection is the simultaneous presence of unexplained fever and headache.



        • Patients presenting with these manifestations should have an immediate and complete neurologic workup (CT scan or magnetic resonance imaging [MRI] of brain; lumbar puncture [unless otherwise contraindicated]).



VII. CLASSES OF INFECTIONS

A. Key Points



  • The four classes of infection most prevalent after transplant include the following:



    • Bacterial


    • Viral


    • Fungal


    • Parasitic


  • Major infection causing pathogens



    • The major pathogens that cause infections in transplant recipients are listed in Table 5-2.1,10


VIII. PREVENTION AND SAFE LIVING AFTER TRANSPLANTATION15,16

A. Key Points



  • Leading a healthy and normal life is possible after transplantation.


  • The risk of exposure to infectious agents will always be present. Therefore, transplant recipients should be counseled on the modes of transmission and means to reduce the risk of infection.



    • Direct contact



      • Frequent and thorough hand washing is imperative and should take place



        • Before cooking and eating


        • Before and after touching wounds, even when using gloves


        • Before touching mucous membranes


        • After blowing nose or touching other secretions


        • After touching or cleaning up after pets or other animals


        • After gardening, touching soil or plants


        • After using the rest room or touching any items having contact with human or animal feces (toilets, bedpans, litter boxes)


    • Percutaneous exposures



      • Avoid intravenous and intradermal illicit drug use.


      • Tattoos and body piercings represent break in skin; all nonsterile practices should be avoided.


    • Pet safety and animal contact



      • Wash hands carefully after handling pets.


      • Avoid cleaning bird cages and feeders, litter boxes, and handling animal feces.


      • Avoid stray animals.


      • Avoid animal bites, scratches, and contact with animals having diarrhea.


      • Avoid contact with nonhuman primates (monkeys).


      • Wait approximately 6 to 12 months after transplantation before acquiring a new pet.


    • Safe sexual practices



      • Use latex condoms during periods of increased immunosuppression and/or outside of long-term monogamous relationships.


      • Avoid exposure to feces during sexual contact.


    • Inhalation



      • Avoid close contact with persons with respiratory illnesses.


      • Avoid crowded areas (elevators, subways, shopping malls) during periods of increased immunosuppression and epidemic illness circulation.



      • Avoid tobacco and marijuana smoke, which is associated with fungal spores.


      • TB exposure



        • Avoid individuals with known active disease.


        • Avoid persons with increased risk (i.e., those working in prisons, jails, homeless shelters).


      • Construction sites, excavations, and some home remodeling projects may have high concentration of dust with increased risk of mold exposure (Histoplasma, Aspergillus)


    • Ingestion



      • Water safety



        • Cryptosporidiosis may occur from drinking contaminated drinking water during recreational activities.


        • Using filters and/or drinking bottled water may reduce risk.


        • Abrasions acquired during swimming or bathing in contaminated water may pose risk to exposure to organisms such as Vibrio species, Mycobacterium marinum, or Aeromonas.


      • Food safety (items to avoid)



        • Unpasteurized milk, fruit, or vegetable juice (E. coli, Salmonella, Cryptosporidium)


        • Cheeses made with unpasteurized milk such as brie, feta (Listeria)


        • Raw or undercooked eggs (Salmonella)


        • Raw or undercooked meat, poultry, or fish (bacterial and parasitic infections such as tapeworms and Toxoplasma gondii)


        • Raw or undercooked seafood (Vibrio species, viruses that cause gastroenteritis or hepatitis, Cryptosporidium)


        • Cross-contamination of raw and cooked foods


IX. VIRAL INFECTIONS

A. Overview13,17



  • Epidemiology



    • Community exposure: influenza, adenovirus, parainfluenza, varicella


    • Allograft transmission: CMV, EBV, viral hepatitis, HSV


    • Reactivation of distant viruses: herpes simplex virus, BK virus, herpes zoster as shingles


  • Clinical



    • Direct effects: fever, neutropenia, and invasive disease (e.g., pneumonia, hepatitis, meningitis)


    • Indirect effects:



      • Alteration in the net state of immunosuppression and increased susceptibility to opportunistic infections


      • Potential allograft injury


      • Potential oncogenesis

B. Herpes viruses



  • Eight members of the herpes viruses family that can cause disease after SOT:



    • Herpes simplex virus 1 and 2


    • Varicella-zoster virus (VZV)


    • Epstein-Barr virus or HHV-4


    • Cytomegalovirus or HHV-5



    • HHV-6, HHV-7: roseola infantum18



      • Primary infection first 5 years of life and then latent.


      • In SOT, cases due to reactivation/reinfection and transient with few clinical symptoms. No antiviral therapy needed.


    • HHV-8



      • After SOT, endemic in certain regions (i.e., Saudi Arabia; South Africa) causing Kaposi’s sarcoma (KS), Castleman’s disease, and primary effusion lymphoma.


      • Treatment consists of reduction/withdrawal of immunosuppression, chemotherapy, and possible conversion to mammalian target of rapamycin (mTOR) inhibitors.


  • Can be transmitted directly but usually characterized by viral latency.


  • Replication of latent herpes viruses can be triggered by net immunosuppression in the SOT recipient.17


  • Herpes virus “infection” versus “disease”



    • The term “infection” refers to the presence of viral replication as indicated by cultures or serological testing (i.e., polymerase chain reaction [PCR] from cerebrospinal fluid, visceral tissue samples, and/or direct fluorescence antibody from vesicular lesions).


    • The term “disease” indicates that the patient has specific symptoms that are caused by a herpes virus. Viremia and/or tissue invasion are present. Tissue invasion can manifest as esophagitis, hepatitis, tracheobronchitis, and, often, disseminated disease.

C. Herpes simplex virus (HSV)13,17



  • Overview



    • Approximately 80% of adult transplant recipients are HSV seropositive.


    • Incidence highest in kidney transplant recipients.


    • Most common strains associated with mucocutaneous ulcerative infections: HSV-1 and HSV-2.


    • HSV-1 is more common with oral lesions, which may extend beyond the lip into the oral cavity and esophagus.



      • Herpes labialis is the most common clinical manifestation of HSV-1.


      • Lesions may bleed, interfere with nutritional intake, and require local analgesia to control pain.


    • HSV-2 involves the perianal and genital areas.


    • After a primary HSV infection, the virus remains latent in the sensory nerve ganglia.


    • Reactivation infection occurs in up to 40% of recipients, typically during the first posttransplant month.


  • See Table 5-5 for the clinical manifestations, prevention/prophylaxis, diagnosis, and treatment of HSV.

D. Varicella zoster virus (VZV)—Human herpesvirus 3 (HHV-3)13



  • Overview



    • VZV is a highly infectious alphaherpesvirus that is acquired through skin-to-skin contact or airborne respiratory droplets.


    • VZV causes chickenpox as a primary infection and then becomes latent in nerve root ganglia until possible reactivation later in life as shingles.


    • Most SOT recipients have developed VZV antibodies so that reactivation of the virus accounts for 90% of adult recipients.























      TABLE 5-5 Major Organisms Causing Posttransplant Infection: Clinical Manifestations, Prevention/Prophylaxis, Diagnostic Tests, and Treatment Options
































































































































































































































































































































































































































































































      Organism


      May Cause


      Clinical Manifestations


      Prophylaxis/Preemptive Therapy


      Diagnostic Tests


      Treatment Options


      CMV10,17,19,20,21


      CMV syndrome Tissue-invasive disease:


      CMV syndrome:


      CMV-negative, filtered, or leukocyte-poor blood products


      Prophylaxis: valganciclovir is first choice


      Oral ganciclovir


      IV ganciclovir


      Valacyclovir used for minimal risk recipients or if cost an issue


      Done for 3-12 mo posttransplant


      Preemptive:


      Weekly quantitative CMV-PCR assays for at least 3 mo posttransplant


      If positive, may treat


      Duration of prophylaxis: range: 3-12 mo posttransplant


      Serologic: helpful pretransplant but not diagnostic for infection


      Complement fixing assay


      Immunofluorescence ELISA


      Latex agglutination systems


      Virologic:


      IV ganciclovir


      Oral ganciclovir


      CMV hyperimmune globulin for tissue-invasive disease


      Immunoglobulin


      For ganciclovir-resistant organisms:



      Fever


      Fatigue



      Gastroenteritis


      Myocarditis


      Pneumonitis


      Retinitis (rare)


      Encephalitis (rare)


      Pancreatitis (rare)



      Malaise


      Leukopenia


      Thrombocytopenia


      Elevated LFTs


      Gastroenteritis:



      Antigenemia assay


      Quantitative PCR



      Foscarnet


      Ganciclovir + foscarnet



      Anorexia, dysphagia


      Abdominal cramping


      Nausea, vomiting, diarrhea


      Ulceration, bleeding


      Tissue culture


      Biopsy


      Antigenemia: CMV pp65 detected in leukocytes CMV DNA detected in plasma, whole blood, isolated peripheral blood leukocytes, or buffy coat specimens RNAemia: CMV RNA detected in plasma, whole blood, isolated peripheral blood leukocytes



      Foscarnet+ Cidofovir


      Intravenous immune globulin (IVIG)


      Pneumonitis:



      Fever


      Dyspnea


      Epstein-Barr virus10,17


      Mononucleosis PTLD: nodal or extranodal disease of CNS, GI tract, lungs, or bone marrow


      Mononucleosis:


      Preemptive therapy for patients at high risk (e.g., IV ganciclovir during antilymphocyte antibody therapy)


      Mononucleosis:


      Mononucleosis:



      Lymph node hyperplasia


      Splenomegaly


      Atypical mononuclear leukocytes


      Abnormal LFTs



      CBC


      EBV antibody


      LFTs


      Heterophil agglutination antibody test



      Acyclovir


      PTLD: benign polyclonal polymorphic B-cell hyperplasia:



      May consider acyclovir


      Ganciclovir



      Fever


      PTLD:



      Decreased



      Sore throat



      CT scan: Note: absence of adenopathy does not rule out PTLD; disease can be entirely extranodal


      Tissue biopsy



      immunosuppression (possibly)


      PTLD:


      PTLD: early malignant polyclonal polymorphic B-cell lymphoma:



      Mononucleosis-like syndrome



      Weight loss


      Fever of unknown origin


      Abdominal pain


      Anorexia


      Jaundice


      Bowel perforation


      GI bleeding


      Renal and hepatic dysfunction


      Pneumothorax


      Pulmonary infiltrates


      CNS findings (seizures, altered LOC)


      Allograft involvement



      Acyclovir


      Ganciclovir


      Interferon-α


      Gamma globulin


      Anti-B-cell antibodies (anti-CD20)


      Decreased immunosuppression (possibly)


      PTLD: monoclonal polymorphic B-cell lymphoma:



      Chemotherapy


      Radiation


      Resection


      Decreased immunosuppression


      Herpes simplex virus 117


      Herpes simplex virus 217


      Herpes labialis


      Herpetic esophagitis


      Anogenital lesions


      Visceral infection is rare


      HSV-1:


      Acyclovir (low-dose)


      Ganciclovir (has low oral bioavailability)


      Valacyclovir


      Famciclovir


      Duration of prophylaxis: typically 30-90 d


      Viral culture


      Direct immunofluorescence studies


      Tzanck smear


      PCR


      Acyclovir


      Ganciclovir


      Valacyclovir


      Famciclovir


      Foscarnet for resistant strains



      Crusted ulcerations


      HSV-2:


      Coalescing ulcerations without clear-cut vesicles


      Varicella zoster15,17,22


      Localized dermatomal zoster


      Disseminated infection


      Bone marrow suppression


      Encephalitis


      Interstitial pneumonitis


      Localized dermatomal zoster that involves two or three adjoining dermatomes without visceral involvement (viral reactivation)


      Primary, disseminated infection: associated with hemorrhagic pneumonia, skin lesions, encephalitis, pancreatitis, hepatitis, and disseminated intravascular coagulation


      Two noncontiguous dermatomal involvement


      Fever


      Malaise


      Rash


      Bone marrow dysfunction


      Seronegative recipients with significant exposure (same room contact with diagnosed case of chickenpox or direct contact with skin lesion of shingles)


      Varicella zoster hyperimmune globulin within 72 h of significant exposure


      IV acyclovir within 24 h of eruption of skin rash


      None at present


      Characteristic unilateral vesicular lesions


      VZV antibody titer


      Tzanck smear


      Direct immunofluorescence studies


      PCR


      Serologic testing PCR assay


      Localized infection:



      Acyclovir (oral)


      Famciclovir (oral)


      Valacyclovir (oral)


      Disseminated infection:



      Acyclovir (IV; high-dose)


      HHV-618


      VZV immune globulin for VZV-seronegative recipients within 72 h of exposure to VZV


      Ganciclovir


      Foscarnet


      Hepatitis viruses17,23,24


      Acute or chronic hepatitis


      Cirrhosis


      Recurrent HBV infection:


      HBV vaccine for nonimmune transplant candidates


      Perioperative anti-HBV immune globulin for liver transplant candidates with HBV infection


      HBV:


      HBV: Immune globulin



      + HbsAg (typically 2-6 mo posttransplant)



      Serologic testing


      Hepatocellular symptoms that can range from mild hepatitis to fulminant liver failure


      HCV: chronic hepatitis


      HCV:


      Detection of HCV-RNA by reverse transcriptase PCR


      Liver biopsy


      Polyomavirus: BK virus15,25,26


      Tubulointerstitial nephritis


      Ureteral stenosis


      Obstructive nephropathy


      Progressive graft dysfunction


      Graft loss


      Fever


      Persistent hematuria


      Elevated serum creatinine level



      Plasma and urine assays: detection of virus DNA by PCR


      Urine cytology: detection of characteristic “decoy” cells


      Immunohistochemistry


      Tissue biopsy (gold standard) May be difficult to differentiate virus infection from rejection; definitive diagnosis requires visualization of polyomavirus inclusion bodies in biopsy specimen


      Decrease immunosuppression agents under investigation



      Cidofovir


      Leflunomide


      Quinolone antibiotics


      IVIG


      Supportive care


      Polyomavirus: JC virus15,25,26


      Multifocal demyelination in brain


      Progressive demyelinating


      PML progressive multifocal leukoencephalopathy


      Progressive neurologic deficits


      May involve cerebral cortex, brain stem, or cerebellum


      Cortical syndromes:



      MRI of head


      CT scan


      EEG


      PCR analysis of spinal blood and spinal fluid


      Biopsy of brain with in situ hybridization for JC virus


      Cessation of immunosuppression


      Corticosteroid therapy


      Nucleoside analogs: interfere with DNA synthesis:



      Visual deficits (hemianopsia)


      Hemiparesis


      Frontal lobe dementia



      Cytosine arabinoside


      Adenosine arabinoside


      Iododeoxyuridine


      Brain stem lesions:



      Zidovudine



      Contralateral hemiparesis or hemisensory deficits


      Interferons: stimulate natural killer cells


      Unilateral lesions:


      Nucleoside analogs: interfere with DNA synthesis:



      Clumsiness


      Limb incoordination



      Cytosine arabinoside


      Adenosine arabinoside


      Midline lesions:



      Iododeoxyuridine


      Zidovudine



      Imbalance, falls


      Disequilibrium


      Gait disturbance


      Cerebellar lesions:



      Blurred vision


      Dysarthria


      Classic triad: dementia, hemiparesis, hemianopsia


      Respiratory syncytial virus27,28


      Upper respiratory infection


      Lower respiratory tract disease


      Organ rejection


      Bronchiolitis obliterans


      Rhinorrhea


      Sinus congestion


      Otalgia


      Nausea; abdominal pain


      Cough


      Dyspnea


      Fever >100.4°F (38°C)


      Wheezing, rales, rhonchi


      Infiltrates on chest


      radiograph


      Sinusitis on sinus radiograph


      Aggressive infection control measures


      Aerosolized ribavirin


      IVIG


      Antigen detection by immunofluorescence assay


      Antigen detection by immunoassay


      RNA detection by reverse transcription PCR


      Serology:


      Demonstration of RSV-IgM antibody (acute infection)


      Significant ↑ in RSV-IgG antibody between acute- and convalescent-stage sera


      Culture: less sensitive and specific in adult vs. pediatric population


      Aerosolized ribavirin


      IVIG


      RSV pneumonitis:



      Aerosolized ribavirin


      Palivizumab (RSV monoclonal antibody) plus aerosolized ribavirin


      Influenza virus27,28


      Influenza syndrome


      Secondary bacterial complications


      Fever


      Chills


      Rigors


      Cough (typically nonproductive)


      Sore throat


      Fatigue


      Headache


      Myalgia


      Aggressive infection control measures


      Annual vaccination of patients and household contacts (unless otherwise contraindicated)


      Annual vaccination of health care workers


      History and clinical examination


      Detection of virus-infected cells (via nasopharyngeal washing or respiratory secretions) with specific fluorescent-labeled antibody probes


      Influenza A: early administration of:



      Amantadine


      Rimantadine


      Influenza B:



      Oseltamivir


      Zanamivir


      If started within 36-48 h of symptom onset


      Parainfluenza virus27,28


      Can cause mild upper respiratory disease


      May progress to pneumonia


      May mimic influenza


      No definitive recommendations


      Viral isolation


      Viral shell assays


      Rapid antigen detection


      Ribavirin has been used for lower respiratory tract disease


      Coronavirus10,22


      Asymptomatic or mild respiratory illness that may progress to fatal respiratory failure (SARS)


      Fever >100.4°F (38°C)


      Chills


      Headache


      Myalgia


      Cough


      Shortness of breath


      Dyspnea


      Hypoxia


      Lymphopenia


      Thrombocytopenia


      Mild ↑ in transaminases


      No definitive recommendations


      Chest radiograph (evidence of pneumonia or adult respiratory distress syndrome)


      Detection of viral RNA by real-time reverse transcription-PCR


      Detection of acute and convalescent antibodies to SARS by enzyme immunoassay


      Supportive care


      Empiric antimicrobial agents


      Intravenous administration of ribavirin


      Corticosteroids


      Investigational


      Parvovirus B1910,15


      Severe, refractory anemia


      Pancytopenia


      Thrombotic microangiopathy


      Fibrosing cholestatic hepatitis


      Graft dysfunction


      Chronic anemia


      ↓ platelets


      ↓ white blood cell count


      Fever


      Malaise


      Pancytopenia


      No definitive recommendations


      Detection of parvovirus B19 DNA in serum by PCR assay


      High-dose IVIG


      ↓ in immunosuppression


      Discontinuing tacrolimus (if possible)


      Human papillomavirus10,15


      Cutaneous warts


      Anogenital warts


      Carcinoma of cervix and bladder


      Squamous cell carcinoma


      Anogenital carcinoma


      Warts


      Avoidance of excessive sun exposure and ultraviolet light


      Sun precautions


      Sunscreen with high sun protection factor (≥15)


      Tissue biopsy


      Topical keratolytic agents


      Caustic agents


      Topical retinoids


      Oral retinoids


      Podophyllin, 5-fluorouracil


      Bleomycin


      Ablation


      Carcinoma (skin, cervix, urinary tract):



      Cutaneous


      Urogenital


      Anal


      Squamous cell carcinoma that arises in beds of flat warts




      Resection


      Reduction or withdrawal of immunosuppression


      Radiation chemotherapy


      Listeria monocytogene10,22


      Bacteremia


      Meningitis


      Meningoencephalitis


      Myocarditis


      Cerebritis without meningitis


      Less common manifestations:


      Fever (1-5 d)


      Headache


      Decreased LOC


      Focal neurological deficits


      Meningismus


      Nuchal rigidity


      Spinal fluid: neutrophils, lymphocytes; glucose may be normal


      Abdominal cramps, diarrhea


      Seizures


      TMP-SMZ


      Dietary precautions regarding milk, cheeses, undercooked meats, and uncooked vegetables


      Blood, sputum cultures


      CT scan


      MRI


      CSF cell count, Gram stain, culture, and protein and sugar determination


      Note: organism may be confused with diphtheroids in Gram stain smears of pus or sputum


      Diagnosis confirmed by isolation of Listeria monocytogenes from culture of blood, CSF, or other sterile source


      Treatment of choice: ampicillin + aminoglycoside


      Meningeal doses of penicillin or ampicillin


      Gentamicin


      TMP-SMZ for penicillin-allergic patients



      Pneumonia


      Arthritis


      Endophthalmitis


      Endocarditis


      Peritonitis


      Myocarditis


      Hepatitis


      Nocardia10,29


      Pulmonary and extrapulmonary infection (CNS, skin, and bone)


      Subacute onset is typical


      Subacute symptoms:


      TMP-SMZ


      Typical pneumocystis pneumonia prophylaxis with TMP-SMZ offers some protection


      Cultures: sputum, BAL fluid


      Gram stain


      Modified acid-fast stain


      Diagnosis confirmed by the presence of Nocardia species in culture


      Sulfonamides preferred


      Sulfisoxazole


      TMP-SMZ


      Amikacin


      Imipenem


      Third-generation cephalosporins


      Minocycline


      Linezolid


      Isolated pulmonary infection: 3-6 mo of therapy


      Disseminated disease: 12 mo of therapy



      Fever


      Cough


      Chest pain


      Pulmonary nodules, abscesses, cavitating lesions, infiltrates, effusions


      Legionella22


      Pneumonia


      Fever, chills


      Focal pulmonary infiltrate


      Headache


      Confusion


      Minimally productive cough


      Diarrhea


      Chest pain


      Malaise


      Dyspnea


      Routine culture of hospital water supply


      Water treatment to control nosocomial infection


      Cultures: sputum, BAL fluid


      Direct fluorescent antibody stain of respiratory secretions


      Urinary antigen detection: can only detect serogroup 1 of Legionella pneumophila species


      Fine needle aspiration of lung


      Open lung biopsy


      Chest radiograph: dense infiltrates (unilateral or bilateral) that may → cavitation


      Diagnosis confirmed by: Legionella antigen in urine


      Direct fluorescent antibody stain (respiratory secretions or tissue biopsy)


      Culture of lower respiratory tract secretions


      Quinolones (particularly levofloxacin or ciprofloxacin)


      Rifampin (may interact with other drugs via the hepatic cytochrome p450 system)


      Macrolides (azithromycin, erythromycin) interact with immunosuppressive medications and should generally be avoided)


      TMP-SMZ (but the side effects include bone marrow suppression, hepatitis, rash)


      Mycobacteria22,30


      Pulmonary infection


      Extrapulmonary infection (intestinal, skeletal, bone, genitourinary, cutaneous, CNS)


      Disseminated disease3


      Pulmonary:


      Nonproductive cough


      Mucopurulent secretions


      Hemoptysis


      Dyspnea


      Chest pain


      Fever


      Excessive sweating


      Weight loss


      Organ-specific manifestations


      Test and treat before transplantation


      Isoniazid (controversial)


      Tuberculin test: positive in 25%-33% of recipients infected with this disease


      Chest radiograph


      Bronchoscopy with BAL


      Transbronchial biopsy


      Pleural needle biopsy


      Tuberculin test: often negative


      Smears for acid-fast bacilli and mycobacterial culture


      Organ-specific histology


      Isolates require antimicrobial susceptibility testing


      Isoniazid (hepatotoxic)


      Rifampin (hepatotoxic)


      Pyrazinamide


      Ethambutol (may → optic neuritis)


      Streptomycin (ototoxic; nephrotoxic)


      Increases catabolism of steroids and cyclosporine and tacrolimus; monitor levels of cyclosporine and tacrolimus; monitor patient for rejection


      Monitor renal and hepatic function


      Recipients with active disease: 9-12 mo of therapy with two agents to which pathogen is susceptible


      Aspergillus31,32


      Pulmonary and extrapulmonary infection


      Disseminates to:


      Depend on site(s) involved


      Pulmonary involvement:


      No definitive recommendations


      Heart, lung, heart-lung recipients: aerosolized amphotericin B


      Lung recipients: oral itraconazole for patients with airway colonization


      Epidemiologic: minimize contact with fungal spores; shield patient from nosocomial environmental hazards: high-efficiency particulate air filters; high-performance masks


      Preemptive: amphotericin B if respiratory tract is colonized


      Chest radiography


      Amphotericin B


      Itraconazole (oral or IV)


      Voriconazole: recently shown to have greater efficacy than amphotericin B for invasive disease


      Use of voriconazole with sirolimus is contraindicated


      Caspofungin: approved for refractory aspergillosis


      Absorption may be erratic, especially in patients with low gastric acidity; monitor plasma concentration of drug



      Note: may be normal



      Nonproductive cough


      Pleuritic chest pain


      BAL


      Transbronchial biopsy



      Brain


      Liver


      Spleen


      Kidneys


      Heart


      Blood vessels


      Bones


      Joints


      GI tract



      Pulmonary infiltrates or nodules


      Dyspnea


      Low-grade fever


      Open lung biopsy


      CT scan (e.g., lung, sinuses)


      Tissue biopsy


      CT or MRI for brain abscesses


      Sputum cultures


      Repeated positive cultures suggest invasive disease


      Positive sputum cultures plus cavitary lung disease suggest invasive disease


      Invasive/disseminated infection:



      Refractory fever


      Sinusitis


      Epistaxis; nasal pain


      Periorbital pain or swelling



      Cutaneous embolic lesions


      Progressive erythema or induration along tunneled venous catheter


      Focal neurologic findings


      May → nephrotoxicity in patients on calcineurin inhibitors; monitor renal function (lipid formulations are less likely to be nephrotoxic; may be preferable for chronic treatment)


      Associated with higher relapse rates than amphotericin B


      Hemoptysis: sign of invasive disease


      Candida10,33,34


      Mucocutaneous candidiasis


      Oropharyngeal thrush


      Candidal esophagitis


      Vaginitis


      Intertrigo


      Paronychia


      Onychomycosis


      Sternal wound infection; mediastinitis


      Intra-abdominal abscesses


      UTI


      Endocarditis


      Disseminated infection


      Thrush:


      Clotrimazole troches


      Oral Nystatin


      Liver transplant recipients:


      Direct fluorescent antibody stain of respiratory secretions


      Localized infection:


      Amphotericin B and lipid-based preparations


      Lipid-based preparations: less nephrotoxic


      Clotrimazole


      Mycostatin


      Fluconazole for esophagitis and refractory candidiasis


      Candidemia in unstable or critically ill patients: Amphotericin B followed by fluconazole if organism is sensitive to fluconazole


      Candidemia in stable patients: Fluconazole, if organism is sensitive to fluconazole


      Candida albicans:



      White patches or ulcers in mouth


      Vaginitis:



      Preoperative oral bowel decontamination with nystatin to ↓ gut colonization



      Cultures with Gram stain



      White or yellow vaginal discharge


      Pruritus


      Disseminated candidiasis:



      Blood cultures


      CT scan


      Intertrigo:


      Kidney and pancreas-kidney transplant recipients:



      Biopsy of skin lesions


      Tissue biopsy



      Erythematous, popular skin rash


      Paronychia:



      Preemptive therapy for asymptomatic candiduria


      Diagnosis confirmed by isolating Candida species from culture specimens



      Redness, swelling, suppuration around nail edge


      Pancreas transplant recipients:


      Onychomycosis:



      Anecdotal reports of fluconazole prophylaxis for high-risk patients:



      Thickened, discolored nails



      Intravascular catheter infections


      Fever, sepsis




      Enteric drainage



      Fluconazole


      Itraconazole



      Pretransplant peritoneal dialysis


      Candida krusei:



      Typically resistant to fluconazole




      Pancreas after kidney transplant


      Reperfusion pancreatitis


      Retransplantation



      Requires maximal doses of amphotericin B


      Newer agents: for Candida species



      Caspofungin


      Voriconazole


      Monitor renal function and cyclosporine levels; adjust dose accordingly


      Effective for most Candida species except Candida krusei and Candida glabrata


      When used with cyclosporine, may ↑ risk of hepatotoxicity; monitor liver function


      When used with tacrolimus, may → ↓ tacrolimus levels; monitor tacrolimus levels


      Cryptococcus neoformans31,35


      Predilection for CNS


      Meningitis


      Brain abscesses


      Secondary seeding of skin, CNS, eye, urinary tract, and skeletal system


      Pulmonary infection


      Pulmonary infection: cough


      Primary prophylaxis: not recommended


      Lumbar puncture


      CT scan


      MRI


      Blood culture


      CSF analysis: cell count; protein and sugar; Gram stain; acid-fast and fungal stains and cultures (fungal, bacterial, and mycobacterial)


      Cryptococcal antigen test on blood, CSF, and pleural fluid


      CSF in meningitis:


      Lymphocytic pleocytosis


      ↑ protein


      ↓ sugar


      ↑ opening pressure


      Definitive diagnosis: detection of antigen in serum and CSF


      Amphotericin B


      Amphotericin B with 5-flucytosine


      Fluconazole with 5-flucytosine


      Fluconazole


      Course of treatment: minimum of 8-10 wk


      Requires monitoring of renal function and cyclosporine levels


      Requires monitoring of 5-flucytosine levels to minimize hepatic and bone marrow toxicity


      Lung nodules


      CNS involvement:



      Progressive headache


      Memory or attention deficits


      Emotional disturbance


      Disorders of balance


      Cranial nerve dysfunction


      Fever


      Meningismus



      Confusion


      Dysphagia



      Muscle weakness, tremor



      Urinary incontinence


      Focal neurologic signs


      Seizures


      Subacute presentation:



      Low-grade fever


      Headache


      Altered mental status


      Cutaneous involvement:



      Ulcers


      Papules or pustules


      Subcutaneous swelling or tumors


      Ecchymoses


      Granulomata


      Abscesses


      Vesicles


      Palpable purpura or papules


      Necrotizing vasculitis


      Cellulitis


      Pneumocystis carinii36,37


      Pneumonitis


      Presentation typically subacute


      Fever


      Nonproductive cough


      Dyspnea


      Hypoxemia


      Tachypnea


      Diffuse pulmonary infiltrates


      TMP-SMZ (low dose for 6 mo)


      Dapsone


      Aerosolized pentamidine


      Atovaquone


      In patients with G6PD deficiency, evaluate risk of dose-dependent hemolytic anemia


      Transbronchial lung biopsy


      Needle biopsy of lung


      Bronchoalveolar lavage


      Chest radiograph (may be negative)


      Confirmatory diagnosis: direct staining of specimens: sputum, BAL lavage or lung tissue


      TMP-SMZ (high-dose) for 21 d


      Pentamidine


      Dapsone-trimethoprim


      Clindamycin-primaquine (if not G6PD deficient)


      Dose may have to be adjusted for renal dysfunction


      Histoplasma capsulatum38


      Disseminated infection (most common presentation)


      Subacute respiratory illness with either focal or disseminated interstitial or miliary infiltrates


      Fever (not always present)


      Night sweats


      Chills


      Cough


      Headache


      Arthritis, myalgias


      CNS manifestations


      Hepatosplenomegaly


      Cutaneous, intestinal, oral mucosal lesions


      No firm recommendations; some centers use itraconazole for seropositive recipients


      Methenamine-silver stain


      Peripheral blood stains


      Cultures: blood, respiratory secretions, tissue


      Serology


      Antigen detection (urine, serum, CSF, BAL fluid)


      Chest radiography (may be normal)


      Amphotericin B


      Itraconazole for maintenance therapy


      Requires monitoring of renal function and cyclosporine levels


      Absorption may be erratic, especially in patients with low gastric acidity; monitor plasma concentration of drug


      Toxoplasma gondii39


      Myocarditis


      Pericarditis


      Pneumonitis


      Encephalitis


      Hepatitis


      Retinochoroiditis


      Mononucleosis-like syndrome of fever, malaise, and lymphadenopathy


      Myocardial dysfunction that mimics rejection


      Pulmonary: fever, dyspnea, cough, hemoptysis


      CNS involvement: multiple focal neurologic deficits, altered mental status; fever with headache


      Particularly for seronegative recipient/seropositive donor:


      Pyrimethamine (for sulfa allergy)


      Pyrimethamine + sulfonamide


      Pyrimethamine + folinic acid


      Co-trimoxazole


      Atovaquone


      TMP-SMZ


      Avoid changing cat litter boxes


      Avoid raw or undercooked meat


      Endomyocardial biopsy


      Antibody titers


      Lung lavage and/or biopsy


      CT scan of head


      Chest radiograph


      Tissue and/or blood culture


      Serologic assays


      Definitive diagnosis: histological detection of trophozoites + inflammation


      Pyrimethamine with folinic acid and sulfadiazine


      Sulfa allergy: dapsone used instead of sulfadiazine


      Clindamycin and pyrimethamine with folinic acid


      Folinic acid given to prevent myelotoxicity


      Continue therapy for 2-3 wk after acute infection has resolved


      Cryptosporidium40


      Gastroenteritis


      Gallbladder infection


      Profuse, watery diarrhea


      Abdominal pain


      Nausea and vomiting


      Fever


      Myalgias


      Boil water for 5 min or use distilled or filtered water


      Avoid ice cubes in restaurants


      Avoid soda fountain drinks


      Stool testing


      Antibody detection assays


      Small or large bowel biopsy


      Replace fluid and electrolytes


      Maintain nutritional status


      Spiramycin effective for some patients; adverse effects reported (increased stool output and volume loss)


      Strongyloides stercoralis41


      Ulcerating hemorrhagic enterocolitis


      Hemorrhagic pneumonia


      Disseminated disease:


      Pulmonary


      CNS (gram-negative meningitis)


      GI:


      Consider preemptive ivermectin for transplant candidates who have traveled to or lived in endemic areas


      Screen at-risk candidates for infection


      Treat established infection before transplantation


      Stool specimen for rhabditiform larvae (may be negative)


      Papanicolaou stain of duodenal aspirates, urine, ascitic fluid, sputum, and stool


      Jejunal biopsy


      Serologic testing


      Chest radiograph (frequently inconclusive)


      Definitive diagnosis: presence of larvae in stool


      Albendazole


      Ivermectin


      Thiabendazole


      Taper immunosuppressive agents


      Systemic antibacterial therapy for bacteremia or meningitis


      Periodic retreatments may be necessary


      Hyperinfection: 7-10 d of antimicrobial therapy



      Abdominal pain and distention


      Diarrhea


      Nausea and vomiting


      Adynamic ileus


      Small bowel obstruction


      Hemorrhage


      Pulmonary:



      Tachypnea


      Dyspnea


      Bronchospasm


      Cough


      Hemoptysis CNS:



      Headache


      Fever


      Eosinophilic meningitis


      Mental status changes


      Coma


      Focal neurologic deficits


      Gram-negative meningitis


      Skin manifestations:


      Migratory, raised, linear rash that may move at a rate of 10 cm/hr


      Crops of urticarial eruptions; immediate hypersensitive reactions to migrating worms, especially on the waist and buttocks)


      BAL, bronchoalveolar lavage; CT, computed tomography; CMV, cytomegalovirus; CSF, cerebrospinal fluid; CBC, complete blood count; CNS, central nervous system; EBV, Epstein-Barr virus; ELISA, enzyme-linked immunosorbent assay; EEG, electroencephalogram; G6PD, glucose-6-phosphate dehydrogenase; GI, gastrointestinal; LFT, liver function tests; HBV, hepatitis B virus; HbsAg, hepatitis B surface antigen; HCV, hepatitis C virus; HCV-RNA, hepatitis C virus ribonucleic acid; HHV, human herpesvirus 6; HSV, herpes simplex virus; IV, intravenous; IVIG, intravenous immunoglobulin; LOC, level of consciousness; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PTLD, posttransplant lymphoproliferative disease; SARS, severe acute respiratory syndrome; TMP-SMZ, trimethoprim-sulfamethoxazole; VZV, varicella zoster virus; UTI, urinary tract infection.

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Oct 27, 2018 | Posted by in NURSING | Comments Off on Transplant Complications: Infectious Diseases
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