Showing papers in "Clinical Transplantation in 2019"

Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice.

Abstract: Cytomegalovirus (CMV) is one of the most common opportunistic infections that affect the outcome of solid organ transplantation. This updated guideline from the American Society of Transplantation Infectious Diseases Community of Practice provides evidence-based and expert recommendations for screening, diagnosis, prevention, and treatment of CMV in solid organ transplant recipients. CMV serology to detect immunoglobulin G remains as the standard method for pretransplant screening of donors and transplant candidates. Antiviral prophylaxis and preemptive therapy are the mainstays of CMV prevention. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is highlighted, as a result of variability of CMV nucleic acid testing, even in the contemporary era when calibrators are standardized. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management. Strategies for managing drug-resistant CMV infection are presented. There is an increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated. Specific issues related to pediatric transplant recipients are discussed.

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

Abstract: 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.

BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

Abstract: The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non-kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV-DNAemia monthly until month 9, and then every 3 months until 2 years posttransplant. Extended screening after 2 years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV-DNAemia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL reflecting probable and presumptive BKPyV-associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy-proven BKPyV-associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV-DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine-A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV-DNAemia is definitively cleared, independent of failed allograft nephrectomy.

Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

Abstract: These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, management, and prevention of post-transplant lymphoproliferative disorders (PTLD) and other Epstein-Barr virus (EBV) syndromes after solid organ transplantation. PTLD are a heterogeneous spectrum of predominantly B-cell disorders, often extra-nodal, with complex distinct pathogeneses and variable clinical presentations determined by pathologic subtype. Recent epidemiologic studies report a decrease in early EBV-positive (+) PTLD and an increase in late EBV-negative (-) PTLD. Pre-transplant EBV-seronegativity and primary EBV infection, often from donor-transmitted infection, are an important risk factors for EBV syndromes and early EBV + PTLD. Low-quality evidence supports preemptive prevention strategies for early EBV + PTLD in EBV-seronegative recipients that involve EBV DNA measurement in peripheral blood using assays requiring further result harmonization, combined with interventions to lower viral load. Reduction in immunosuppression (RIS) is the best validated intervention. WHO pathology classification of a tissue biopsy remains the gold standard for PTLD diagnosis; optimal staging procedures are uncertain. Treatment of CD20+ PTLD with the response-dependent sequential use of RIS, rituximab, and cytotoxic chemotherapy is recommended. Evidence gaps requiring future research and alternate treatment strategies including immunotherapy are highlighted.

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

Abstract: 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.

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

Abstract: These updated AST-IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid-organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post-transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12-week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non-lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations.

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

Abstract: 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.

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

Abstract: 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.

Prehabilitation prior to kidney transplantation: Results from a pilot study.

Abstract: Prehabilitation is the process of enhancing preoperative functional capacity to improve tolerance for the upcoming stressor; it was associated with improved postoperative outcomes in a handful of studies, but never evaluated in transplantation. Kidney transplant (KT) candidates may be uniquely suited for prehabilitation because they experience a profound loss of functional capacity while waiting years on dialysis. To better understand the feasibility and effectiveness of prehabilitation in KT, we conducted a pilot study of center-based prehabilitation for candidates; this intervention consisted of weekly physical therapy sessions at an outpatient center with at-home exercises. We enrolled 24 participants; 18 participated in prehabilitation (75% of enrolled; 17% of eligible). 61% were male, 72% were African American, and mean age = 52 (SD = 12.9); 71% of participants had lower-extremity impairment, and 31% were frail. By 2 months of prehabilitation, participants improved their physical activity by 64% (P = 0.004) based on accelerometry. Participants reported high satisfaction. Among 5 prehabilitation participants who received KT during the study, length of stay was shorter than for age-, sex-, and race-matched control (5 vs 10 days; RR = 0.69; 95% CI:0.50-0.94; P = 0.02). These pilot study findings suggest that prehabilitation is feasible in pretransplant patients and may potentially be a strategy to improve post-KT outcomes.

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

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Nocardia infections after solid organ transplantation (SOT). Nocardia infections have increased in the last two decades, likely due to improved detection and identification methods and an expanding immunocompromised population. The risk of developing nocardiosis after transplantation varies with the type of organ transplanted and the immunosuppression regimen used. Nocardia infection most commonly involves the lung. Disseminated infection can occur, with spread to the bloodstream, skin, or central nervous system. Early recognition of the infection and initial appropriate treatment is important to achieve good outcomes. Species identification and antimicrobial susceptibility testing are strongly recommended, as inter‐ and intraspecies susceptibility patterns can vary. Sulfonamide is the first‐line treatment of Nocardia infections, and combination therapy with at least two antimicrobial agents should be used initially for disseminated or severe nocardiosis. Trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis may be helpful in preventing Nocardia infection after SOT.

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

Abstract: 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.

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

Abstract: 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.

Mycobacterium tuberculosis infections in solid organ transplantation: Guidelines from the infectious diseases community of practice of the American Society of Transplantation

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of tuberculosis in the pre‐ and post‐transplant period. The challenges of screening for both latent and active TB in the setting of transplantation are reviewed. The use of interferon gamma release assays for detection of latent tuberculosis is discussed and compared to tuberculin skin testing. Given the limitations of both testing modality, it is important to consider exposure history and chest imaging. The clinical manifestations of active tuberculosis in transplantation are covered. New recommendations for treatment of latent tuberculosis and active tuberculosis are included.

Endemic fungal infections in solid organ transplant recipients-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of blastomycosis, histoplasmosis, and coccidioidomycosis in the pre‐ and post‐transplant period. Though each of these endemic fungal infections has unique epidemiology and clinical manifestations, they all share a predilection for primary pulmonary infection and may cause disseminated infection, particularly in immunocompromised hosts. Culture remains the gold standard for definitive diagnosis, but more rapid diagnosis may be achieved with direct visualization of organisms from clinical specimens and antigen‐based enzyme immunoassay assays. Serology is of limited utility in transplant recipients. The mainstay of treatment for severe infections remains liposomal amphotericin followed by a step‐down azole therapy. Cases of mild to moderate severity with no CNS involvement may be treated with azole therapy alone. The newer generation azoles provide additional treatment options, but supported currently with limited clinical efficacy data. Azole therapy in transplant recipients presents a unique challenge owing to the drug‐drug interactions with immunosuppressant agents. Therapeutic drug monitoring of azole levels is an essential component of effective and safe therapy. Infection prevention centers around minimizing epidemiological exposures, early clinical recognition, and azole prophylaxis in selected individuals.

Multidrug-resistant Gram-negative bacterial infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of infections due to multidrug‐resistant (MDR) Gram‐negative bacilli in the pre‐ and post‐transplant period. MDR Gram‐negative bacilli, including carbapenem‐resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and carbapenem‐resistant Acinetobacter baumannii, remain a threat to successful organ transplantation. Clinicians now have access to at least five novel agents with activity against some of these organisms, with others in the advanced stages of clinical development. No agent, however, provides universal and predictable activity against any of these pathogens, and very little is available to treat infections with MDR nonfermenting Gram‐negative bacilli including A baumannii. Despite advances, empiric antibiotics should be tailored to local microbiology and targeted regimens should be tailored to susceptibilities. Source control remains an important part of the therapeutic armamentarium. Morbidity and mortality associated with infections due to MDR Gram‐negative organisms remain unacceptably high. Heightened infection control and antimicrobial stewardship initiatives are needed to prevent these infections, curtail their transmission, and limit the evolution of MDR Gram‐negative pathogens, especially in the setting of organ transplantation.

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

Abstract: 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.

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

Abstract: 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.

Report of National Kidney Foundation Consensus Conference to Decrease Kidney Discards.

Abstract: The organ shortage is one of the major challenges in the field of organ transplantation, yet the percentage of kidneys procured and discarded prior to transplantation has continued to rise to twenty percent. The causes of organ discard are complex, yet an urgent need exists for collaborative efforts to maximize the utilization of all potentially transplantable renal allografts. The National Kidney Foundation convened a meeting of experts to identify factors contributing to reduced organ utilization, and to propose actionable solutions to decrease the rate of kidney discards.

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

Abstract: 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.

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

Abstract: 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.

Solid organ transplantation in the HIV‐infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the management of transplantation in HIV‐infected individuals. Transplantation has become the standard of care for patients with HIV and end‐stage kidney or liver disease. Although less data exist for thoracic organ and pancreas transplantation, it is likely that transplantation is also safe and effective for these recipients as well. Despite what is typically a transient decline in CD4+ T lymphocytes, HIV remains well controlled and infection risks are similar to those of HIV‐uninfected transplant recipients. The availability of effective directly active antivirals for the treatment of Hepatitis C is likely to improve outcomes in HIV and HCV co‐infected individuals, a population previously noted to have decreased survival. Drug interactions remain an important consideration, and integrase inhibitor‐based regimens are preferred due to the absence of interactions with calcineurin and mTOR inhibitors. Additionally, despite the use of more potent immunosuppression, rejection rates exceed those found in HIV‐uninfected recipients. Ongoing research evaluating HIV‐positive organ donors may provide support for utilizing these donors for HIV‐positive patients in need of transplantation.

Intestinal parasites including Cryptosporidium, Cyclospora, Giardia, and Microsporidia, Entamoeba histolytica, Strongyloides, Schistosomiasis, and Echinococcus: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of intestinal parasites in the pre‐ and post‐transplant period. Intestinal parasites are prevalent in the developing regions of the world. With increasing travel to and from endemic regions, changing immigration patterns, and the expansion of transplant medicine in developing countries, they are increasingly recognized as a source of morbidity and mortality in solid‐organ transplant recipients. Parasitic infections may be acquired from the donor allograft, from reactivation, or from de novo acquisition post‐transplantation. Gastrointestinal multiplex assays have been developed; some of the panels include testing for Cryptosporidium, Cyclospora, Entamoeba histolytica, and Giardia, and the performance is comparable to conventional methods. A polymerase chain reaction test, not yet widely available, has also been developed to detect Strongyloides in stool samples. New recommendations have been developed to minimize the risk of Strongyloides donor‐derived events. Deceased donors with epidemiological risk factors should be screened for Strongyloides and recipients treated if positive as soon as the results are available. New therapeutic agents and studies addressing the optimal treatment regimen for solid‐organ transplant recipients are unmet needs.

Human herpesvirus 6, 7, and 8 in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HHV‐6A, HHV‐6B, HHV‐7, and HHV‐8 in the pre‐ and post‐transplant period. The majority of HHV‐6 (A and B) and HHV‐7 infections in transplant recipients are asymptomatic; symptomatic disease is reported infrequently across organs. Routine screening for HHV‐6 and 7 DNAemia is not recommended in asymptomatic patients, nor is prophylaxis or preemptive therapy. Detection of viral nucleic acid by quantitative PCR in blood or CSF is the preferred method for diagnosis of HHV‐6 and HHV‐7 infection. The possibility of chromosomally integrated HHV‐6 DNA should be considered in individuals with persistently high viral loads. Antiviral therapy should be initiated for HHV‐6 encephalitis and should be considered for other manifestations of disease. HHV‐8 causes Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease and is also associated with hemophagocytic syndrome and bone marrow failure. HHV‐8 screening and monitoring may be indicated to prevent disease. Treatment of HHV‐8 related disease centers on reduction of immunosuppression and conversion to sirolimus, while chemotherapy may be needed for unresponsive disease. The role of antiviral therapy for HHV‐8 infection has not yet been defined.

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

Abstract: 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.

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: a multidisciplinary consensus conference by the Italian GITMO, SITO and AMCLI societies

Abstract: Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain diagnostic procedures, and antiviral intervention forced the panel to use the methods of consensus for shaping some recommendations. Recommendations concerning the two types of transplant were given for the following issues: assessment of pretransplant CMV serostatus, immunological monitoring after transplant, CMV prophylaxis with antivirals, CMV preemptive strategy, and CMV prophylaxis with immunoglobulin infusion and with adoptive immunotherapy. The questions raised by and the recommendations resulting from this consensus conference project may contribute to the improvement of certain crucial aspects of the management of CMV infections in allo-HSCT and in SOT populations.

Varicella zoster virus in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

Abstract: These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, prevention, and management of varicella zoster virus (VZV) in the pre- and post-transplant period. Primary varicella is an uncommon complication post-solid-organ transplant (SOT), except among pediatric transplant patients and those seronegative for VZV. As the majority of SOT recipients are seropositive for VZV, herpes zoster (HZ) occurs frequently following SOT, particularly among recipients who are older (≥65 years of age) and those receiving more intensive immunosuppression. Transplant providers should aware of the increased risk for HZ-related complications such as dissemination, organ-specific involvement, and post-herpetic neuralgia. Treatment for localized zoster is primarily given as oral regimens, but those with more complicated presentations or those at risk for dissemination should be treated initially with IV therapy. Available antiviral prophylaxis regimens and vaccination strategies for varicella and HZ among these immunosuppressed patients remain a mainstay for prevention in the pre-and post-transplant periods. Finally, we discuss important approaches to addressing post-exposure prophylaxis and infection control practices for those SOT patients with documented VZV infections.

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

Abstract: 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.

Tissue and blood protozoa including toxoplasmosis, Chagas disease, leishmaniasis, Babesia, Acanthamoeba, Balamuthia, and Naegleria in solid organ transplant recipients- Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

Abstract: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of tissue and blood protozoal infections in the pre‐ and post‐transplant period. Significant new developments in the field have made it necessary to divide the previous single guideline published in 2013 into two sections, with the intestinal parasites separated from this guideline devoted to tissue and blood protozoa. The current update reflects the increased focus on donor screening and risk‐based recipient monitoring for parasitic infections. Increased donor testing has led to new recommendations for recipient management of Toxoplasma gondii and Trypanosoma cruzi. Molecular diagnostics have impacted the field, with access to rapid diagnostic testing for malaria and polymerase chain reaction testing for Leishmania. Changes in Babesia treatment regimens in the immunocompromised host are outlined. The risk of donor transmission of free‐living amebae infection is reviewed. Changing immigration patterns and the expansion of transplant medicine in developing countries has contributed to the recognition of parasitic infections as an important threat to transplant outcomes. Medications such as benznidazole and miltefosine are now available to US prescribers as access to treatment of tissue and blood protozoa is increasingly prioritized.

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

Abstract: 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.

Emerging fungal infections in solid organ transplant recipients: Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice

Abstract: These updated AST-IDCOP guidelines review the epidemiology, diagnosis, and management of emerging fungi after organ transplantation. Infections due to numerous generally innocuous fungi are increasingly recognized in solid organ transplant (SOT) recipients, comprising about 7%-10% of fungal infections in this setting. Such infections are collectively referred to as emerging fungal infections and include Mucormycetes, Fusarium, Scedosporium, and dematiaceous fungi among others. The causative organisms are diverse in their pathophysiology, uncommon in the clinical setting, have evolving nomenclature, and are often resistant to multiple commonly used antifungal agents. In recent years significant advances have been made in understanding of the epidemiology of these emerging fungal infections, with improved diagnosis and expanded treatment options. Still, treatment guidelines are generally informed by and limited to experience from cohorts of patients with hematological malignancies and/or solid and stem cell transplants. While multicenter randomized controlled trials are not feasible for these uncommon infections in SOT recipients, collaborative prospective studies can be valuable in providing information on the epidemiology, clinical manifestations, treatment strategies, and outcomes associated with the more commonly encountered infections.