Donor‐derived infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation will review the current state of the art of donor‐derived infections. Specifically, the guideline will summarize standardized definitions and approaches to defining imputability, updated data on the epidemiology of donor‐derived infections, and approaches to risk mitigation against transmission of infections. This update will additionally provide guidance on the use of HIV+ donors in HIV+ recipients, the use of HCV‐viremic donors in non‐viremic recipients, donors with endemic infections, and donors with bacteremia, meningitis, and encephalitis. Lastly, the guidance will summarize an approach to recipients with a suspected donor‐derived infection.     

Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of adenovirus infections after solid organ transplantation. Adenovirus is an important cause of infectious complications in both stem cell transplant and SOT patients, causing a range of clinical syndromes including pneumonitis, colitis, and disseminated disease. The current update of the guidelines highlights that adenovirus surveillance testing should not be performed in asymptomatic recipients. Serial quantitative PCR might play a role in the decision to initiate or assess response to therapy in a symptomatic patient. The initial and most important components of therapy remain supportive care and decrease in immunosuppression. The use of antiviral therapy is not supported by prospective randomized clinical trials. However, intravenous cidofovir is considered the standard practice for treatment of severe, progressive, or disseminated adenovirus disease in most transplant centers. Intravenous immunoglobulin may be beneficial, primarily in a select group of patients with hypogammaglobulinemia. Future approaches to treatment of adenovirus disease may include administration of adenovirus‐specific T‐cell therapy.     

RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of RNA respiratory viral infections in the pre‐ and post‐transplant period. Viruses reviewed include influenza, respiratory syncytial virus (RSV), parainfluenza, rhinovirus, human metapneumovirus (hMPV), and coronavirus. Diagnosis is by nucleic acid testing due to improved sensitivity, specificity, broad range of detection of viral pathogens, automatization, and turnaround time. Respiratory viral infections may be associated with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. The cornerstone of influenza prevention is annual vaccination and in some cases antiviral prophylaxis. Treatment with neuraminidase inhibitors and other antivirals is reviewed. Prevention of RSV is limited to prophylaxis with palivizumab in select children. Therapy of RSV upper or lower tract disease is controversial but may include oral or aerosolized ribavirin in some populations. There are no approved vaccines or licensed antivirals for parainfluenza, rhinovirus, hMPV, and coronavirus. Potential management strategies for these viruses are given. Future studies should include prospective trials using contemporary molecular diagnostics to understand the true epidemiology, clinical spectrum, and long‐term consequences of respiratory viruses as well as to define preventative and therapeutic measures.     

Candida infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice provide recommendations for the diagnosis and management of Candida infections in solid organ transplant recipients. Candida infections manifest primarily as candidemia and invasive candidiasis and cause considerable morbidity and mortality. Early diagnosis and initiation of treatment are necessary to reduce mortality. For both candidemia and invasive candidiasis, an echinocandin is recommended for initial therapy. However, early transition to oral therapy is encouraged when patients are stable and the organism is susceptible. Candida prophylaxis should be targeted for high‐risk patients in liver, small bowel, and pancreas transplant recipients. Future research should address which patient groups may benefit most from preventative antifungal therapy strategies.     

Screening of donor and candidate prior to solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

This updated section of the guideline from the Infectious Diseases Community of Practice of the American Society of Transplantation reviews the screening of donor and candidate prior to solid organ transplantation. Screening of donor and candidate is vital for optimizing post‐transplant outcomes. Risk assessment based on detailed history and appropriate diagnostic evaluation is essential. Serologic screening for certain viral infections is important and aids in immunization counseling and risk mitigation of recipients. In addition to serology, nucleic acid testing for hepatitis B, hepatitis C and human immunodeficiency virus has been required for deceased and living donors. Certain endemic exposure may warrant additional evaluation beyond recommended standard testing. Diagnosed infection in the donor or recipient warrants treatment as well as additional testing and/or prophylaxis to mitigate risk for post‐transplant complications. Certain infections in the immediate pre‐transplant period may warrant delay of transplantation.     

Human T‐cell lymphotrophic virus in solid‐organ transplant recipients: Guidelines from the American society of transplantation infectious diseases community of practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Human T‐cell lymphotrophic virus 1 (HTLV)‐1 in the pre‐ and post‐transplant period. HTLV‐1 is an oncogenic human retrovirus rare in North America but endemic in the Caribbean and parts of Africa, South America, Asia, and Oceania. While most infected persons do not develop disease, <5% will develop adult T‐cell leukemia/lymphoma or neurological disease. No proven antiviral treatment for established HTLV‐1 infection is available. The effect of immunosuppression on the development of HTLV‐1‐associated disease in asymptomatically infected recipients is not well characterized, and HTLV‐1‐infected individuals should be counseled that immunosuppression may increase the risk of developing HTLV‐1‐associated disease and they should be monitored post‐transplant for HTLV‐1‐associated disease. Currently approved screening assays do not distinguish between HTLV‐1 and HTLV‐2, and routine screening of deceased donors without risk factors in low seroprevalence areas is likely to result in significant organ wastage and is not recommended. Targeted screening of donors with risk factors for HTLV‐1 infection and of living donors (as time is available to perform confirmatory tests) is reasonable.     

Cryptococcosis in solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of cryptococcosis in the pre‐ and post‐transplant period. The current update now includes a discussion of cryptococcosis, which is the third most common invasive fungal infection in SOT recipients. Infection often occurs a year after transplantation; however, early infections occur and donor‐derived infections have been described within 3 months after transplant. There are two main species that cause infection, Cryptococcus neoformans and C gattii. Clinical onset may be insidious, but headaches, fevers, and mental status changes should warrant diagnostic testing. The lateral flow cryptococcal antigen assay is now the preferred test from serum and cerebrospinal fluid due to its rapidity, accuracy, and cost. A lumbar puncture with measurement of opening pressure is recommended for patients with suspected or proven cryptococcosis. Lipid amphotericin B plus 5‐flucytosine is used as initial treatment of meningitis, disseminated infection, and moderate‐to‐severe pulmonary infection, followed by fluconazole as consolidation therapy. Fluconazole is effective for mild‐to‐moderate pulmonary infection. Immunosuppression reduction as part of management may lead to immune reconstitution syndrome that may resemble active disease.     

Strategies for safe living following solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

The present AST‐IDCOP guidelines update information on strategies for safe living after organ transplantation. While transplantation carries an increased risk for infection from the recipient's environment due to lifelong immunosuppression, the goal is for the recipient to be able to return to their home and live as normal a life as possible with a functioning graft. The current guideline provides updates to prior recommendations including additions on infections from water and food sources, exposures to animals, cannabis use as well as sexual exposures or those encountered with travel. Similar to the prior editions, many of the recommendations are based on good infection prevention standards, extrapolation from other immunocompromised hosts, and risks found from cases series in transplant patients. Enhanced education and attention to incorporating safe living strategies into daily life should help to accomplish successful transplant with recipients achieving a fulfilling life away from the hospital.     

Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Pneumocystis jiroveci fungal infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim‐sulfamethoxazole (TMP‐SMX). Without prophylaxis, PJP risk is greatest in the first 6 months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (>65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO₂ < 60 mm Hg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1 → 3) β‐d ‐glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP‐SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6‐12 months post–transplant, preferably with TMP‐SMX.     

Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of viral hepatitis in the pre‐ and post‐transplant period. The current guidelines reflect the declining need for hepatitis B immunoglobulin following liver transplant, now replaced with nucleos(t)ide analogues that effectively suppress viral replication for the long term with minimal risk for drug resistance. It describes the limitations of pegylated interferon alpha in the treatment for chronic hepatitis D. The guidelines feature the paradigm shift in the treatment arena of chronic hepatitis C, now consisting of highly effective direct‐acting antiviral (DAA) medications that effect a cure almost universally. Its safety profile and easy tolerance have permitted its use in patients with decompensated cirrhosis and/or end‐stage renal disease. The high potency of the DAA's has fueled the rapidly expanding utilization of hepatitis C‐exposed grafts in non‐hepatitis C‐infected liver, heart, or kidney recipients within structured protocols, followed by viral eradication with DAA therapy in the peri‐ or post‐transplant period. Chronic hepatitis E has become more recognized in the solid‐organ transplant recipients, and the therapeutic approach has been streamlined to start with reduction of immunosuppression, and if indicated afterward, ribavirin monotherapy.     

Serologic follow-up of solid organ transplant recipients who received organs from donors with reactive syphilis tests: A retrospective cohort study

The increased procurement of organs from donors with risk factors for blood-borne diseases and the expanding syphilis epidemic have resulted in a growing number of organs transplanted from donors with reactive syphilis serology in our center. Based on guidelines, recipients typically receive therapy shortly after the transplant, but data on outcomes are limited. The primary objective of this study was to determine syphilis seroconversion rates at three months post-transplant in recipients of solid organs procured from donors with reactive syphilis serology. Organ donors and recipients were tested for syphilis antibody; positive results were confirmed with Treponema pallidum Particle Agglutination (TPPA). Eleven donors with reactive syphilis antibody donated organs to 25 syphilis negative recipients. Three recipients seroconverted at post-transplant month 3. All of them had received therapy shortly after transplant. TPPA was negative in all 3. Despite post-transplant treatment, 3 of 25 (12%) syphilis negative recipients of organs from syphilis positive donors seroconverted at 3 months. All remained TPPA negative possibly reflecting passive antibody transfer or differing test sensitivity to low level treponemal antibodies. Further studies are needed to assess optimal syphilis transmission prevention strategies and follow up recipient testing in organ transplantation.     

Diagnosis and management of diarrhea in solid‐organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of diarrhea in the pre‐ and post‐transplant period. Diarrhea in an organ transplant recipient may result in significant morbidity including dehydration, increased toxicity of medications, and rejection. Transplant recipients are affected by a wide range of etiologies of diarrhea with the most common causes being Clostridioides (formerly Clostridium) difficile infection, cytomegalovirus, and norovirus. Other bacterial, viral, and parasitic causes can result in diarrhea but are far less common. Further, noninfectious causes including medication toxicity, inflammatory bowel disease, post‐transplant lymphoproliferative disease, and malignancy can also result in diarrhea in the transplant population. Management of diarrhea in this population is directed at the cause of the diarrhea, instituting therapy where appropriate and maintaining proper hydration. Identification of the cause to the diarrhea needs to be timely and focused.     

Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of nontuberculous mycobacterial infections in the pre‐ and post‐transplant period. NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter‐associated infection, and lymphadenitis. Diagnosis of these infections can be challenging, particularly when they are isolated from nonsterile spaces, owing to their ubiquity in nature. Consequently, diagnosis of pulmonary infections with these pathogens requires fulfillment of microbiologic, radiographic, and clinical criteria to address this concern. A combination of culture and molecular diagnostic techniques is often required to make a species‐level identification. Treatment varies depending on the species isolated and is complex, owing to drug toxicities, need for long‐term multidrug regimens, and consideration of complex drug‐drug interactions between antimicrobials and immunosuppressive agents. Given these treatment challenges, efforts should be made in both the hospital and community settings to limit exposure to these pathogens to the extent feasible.     

Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of urinary tract infections (UTI) in solid organ transplantation, focusing on kidney transplant (KT) recipients. KT recipients have unique risk factors for UTI, including indwelling stents and surgical manipulation of the genitourinary tract. KT recipients experience multi‐drug antibiotic‐resistant infections—UTI prevention and management strategies must consider risks of antimicrobial resistance. Non‐antimicrobial prevention strategies for UTI in KT recipients are reviewed. It is important to recognize that some renal transplant recipients with UTI may primarily present with fever, malaise, leukocytosis, or a non‐specific sepsis syndrome without symptoms localized to the urinary tract. However, asymptomatic bacteriuria (AB) must be distinguished from UTI because AB is not necessarily a disease state. Accumulating data indicate that there are no benefits of antibiotics for treatment of AB in KT recipients more than 2 months after post‐transplant. Further research is needed on management of AB in the early (<2 months) post‐transplant period, prophylaxis for UTI in this era of antibiotic resistance, recurrent UTI, non‐antimicrobial prevention of UTI, and uropathogens identified in donor urine and/or preservative fluid cultures.     

Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post‐operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%‐53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end‐stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug‐resistant organisms. In this guideline, we describe the epidemiology, clinical presentation, differential diagnosis, potential pathogens, and management. We also provide recommendations for the selection, dosing, and duration of peri‐operative antibiotic prophylaxis to minimize post‐operative SSIs.     

Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice

These updated guidelines of the AST IDCOP review vaccination of solid organ transplant candidates and recipients. General principles of vaccination as well as the use of specific vaccines in this population are discussed. Vaccination should be reviewed in the pre‐transplant setting and appropriate vaccines updated. Both inactivated and live vaccines can be given pre‐transplant. The timing of vaccination post‐transplant should be taken into account. In the post‐transplant setting, inactivated vaccines can be administered starting at 3 months post‐transplant with the exception of influenza which can be given as early as one month. Inactivated vaccines can be safely administered post‐transplant. There is accumulating data that live‐attenuated vaccines can also be given to select post‐transplant patients. Close contacts of transplant patients can receive most routine live vaccines. Specific vaccines including pneumococcal, influenza, hepatitis B, HPV, and meningococcal vaccines are discussed. Newer vaccines for seasonal influenza vaccine and herpes zoster are highlighted. Live‐attenuated vaccines such as measles, mumps, rubella, and varicella are also discussed. Emerging data on live‐attenuated vaccines post‐transplant are highlighted.     

Herpes simplex virus infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HSV in the pre‐ and post‐transplant period. A majority of transplant recipients are seropositive for HSV‐1 or 2. Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy. Most HSV infection is diagnosed on clinical grounds, but patients may present with atypical lesions and/or other clinical manifestations. Acquisition from the donor is rare. Polymerase chain reaction is the preferred diagnostic test unless culture is needed for resistance testing. For limited mucocutaneous lesions, oral therapy can be used; however, in severe, disseminated, visceral or CNS involvement, acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir‐resistant HSV is less common in SOT patients than in HSCT and can be treated with foscarnet, though other novel therapies are currently under investigation. HSV‐specific prophylaxis should be considered for all HSV‐1 and HSV‐2–seropositive organ recipients who are not receiving antiviral medication for CMV prevention that has activity against HSV.     

Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.     

Human papillomavirus infection in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These guidelines from the American Society of Transplantation Infectious Diseases Community of Practice update the epidemiology and management of human papillomavirus (HPV) infections in organ transplant recipients. HPV is one of the most common sexually transmitted infections and is associated with cancers of the anogenital region. Increasing evidence suggests an association with head and neck cancers as well. Solid organ transplant recipients have a higher risk of HPV infection than the general population. Infection manifests as premalignant lesions, warts, or cancer of the cervix, penis, vulva, scrotum, and anal canal. Most are asymptomatic initially, so diagnosis can be difficult without screening. A vaccine is available though not effective in preventing all cancer‐causing strains. Organ transplant recipients should be screened for HPV‐associated cancers and appropriate therapy initiated in a timely manner. Further studies are warranted to delineate the most effective screening methods and therapeutic modalities, including whether changes in immunosuppression are effective in attenuating disease.