Methicillin‐resistant Staphylococcus aureus 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 review the epidemiology, diagnosis, prevention, and management of methicillin‐resistant Staphylococcus aureus (MRSA) infections in solid organ transplantation. Despite an increasing armamentarium of antimicrobials active against MRSA, improved diagnostic tools, and overall declining rates of infection, MRSA infections remain a substantial cause of morbidity and mortality in solid organ transplant recipients. Pre‐ and post‐transplant MRSA colonization is a significant risk factor for post‐transplant MRSA infection. The preferred initial treatment of MRSA bacteremia remains vancomycin. Hand hygiene, chlorhexidine bathing in the ICU, central‐line bundles that focus on reducing unnecessary catheter use, disinfection of patient equipment, and the environment along with antimicrobial stewardship are all aspects of an infection prevention approach to prevent MRSA transmission and decrease healthcare‐associated infections.     

Etiology of increased cancer incidence after solid organ transplantation

Over the past decades, there has been an encouraging increase in survival after solid organ transplantation. However, with longer life spans, more transplant recipients are at risk of dying with functioning grafts from illnesses such as cancer and cardiovascular conditions. Malignancy has emerged as an important cause of death in transplant recipients and is expected to become the leading cause of death in transplanted patients within the next decade. While it is known that solid organ transplant recipients have a three to five-fold increased risk of developing cancer compared with the general population, the mechanisms that lead to the observed excess risk in transplant recipients are less clear. This review explores the etiology of the increased cancer incidence in solid organ transplant including the effect of immunosuppressants on immunosurveillance and activation of oncogenic viruses, and carcinogenic effects of these medications; the role of chronic stimulation of the immune system on the development of cancer; and the impact of pre-existing cancer risk factors and factors related to end-stage organ disease on the cancer excess incidence in solid organ transplant recipients.     

Hospital‐Onset Clostridium difficile Infection Among Solid Organ Transplant Recipients

Clostridium difficile infection (CDI) is a considerable health issue in the United States and represents the most common healthcare‐associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital‐onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center–affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk‐standardized CDI varied more than 3‐fold across high‐volume hospitals (infection ratio 0.54–1.82, median 1.04, interquartile range 0.78–1.28). CDI was associated with increased 30‐day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk‐standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted.     

What solid organ transplant healthcare providers should know about renin-angiotensin-aldosterone system inhibitors and COVID-19

The data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID-19) are still emerging. Kidney transplant recipients are commonly prescribed renin-angiotensin-aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin-converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS-CoV-2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID-19 pandemic. At present, there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID-19 pandemic.     

Chemotherapy and Transplantation: The Role of Immunosuppression in Malignancy and a Review of Antineoplastic Agents in Solid Organ Transplant Recipients

It is estimated that solid organ transplant recipients have a two‐ to fourfold greater overall risk of malignancy than the general population. Some of the most common malignancies after transplant include skin cancers and posttransplant lymphoproliferative disorder. In addition to known risk factors such as environmental exposures, genetics, and infection with oncogenic viruses, immunosuppression plays a large role in the development of cancer through the loss of the immunosurveillance process. The purpose of this article is to explain the role of immunosuppression in cancer and to review the classes of chemotherapeutics. The field of anticancer drugs is continually expanding and developing, with limited data on use in transplant recipients. This article aims to provide information on class review, adverse effects, dose adjustments, and drug interactions that are pertinent to the care of transplant recipients.     

Portal Hypertension and Granulomatous Liver Disease in a Lung Transplant Recipient due to Disseminated Atypical Mycobacterial Infection

The incidence of atypical mycobacterial infection among solid organ transplant recipients is increasing. While lung transplant recipients in particular are at greater risk of atypical mycobacterial infection than other solid organ transplant recipients, it is typically confined to the lung and disseminated infection remains quite rare. We describe a case of disseminated Mycobacterium avium-complex (MAC) in a lung transplant recipient presenting as granulomatous liver disease with signs of portal hypertension. After identification of the infection and institution of proper therapy, the patient had significant improvement in both clinical signs of portal hypertension and liver function tests. Current literature suggests a favorable prognosis in most cases of MAC infection in lung transplant recipients with appropriate treatment. This case highlights the need to maintain an elevated index of suspicion for atypical pathogens with unusual clinical presentations among the lung transplant population.     

Active Tuberculosis After Solid Organ Transplantation in Individuals With Negative Pretransplant QuantiFERON-TB Gold Testing: A Case Series

Active tuberculosis (TB) in solid organ transplant (SOT) recipients most commonly occurs due to reactivation of latent infection and is associated with poor clinical outcomes, including allograft loss and death. National transplant societies, including the American Society of Transplantation, recommend screening for latent TB prior to transplant, with treatment in the peritransplant setting to reduce the subsequent risk of TB reactivation. Though screening is traditionally conducted using laboratory-based assays, such as the QuantiFERON-TB Gold, false negatives may occur in SOT candidates due to anergy from end-stage organ dysfunction, highlighting the need for a multimodal diagnostic approach. In this case series, we describe the clinical characteristics and outcomes of 3 SOT recipients at the University of Pennsylvania with negative pretransplant QuantiFERON-TB Gold testing who subsequently developed active TB in the posttransplant setting, contributing to a growing body of knowledge regarding this challenging population. Each patient experienced a complicated clinical course that arose in part from the lack of diagnosis of TB prior to transplant. Because all had epidemiologic risk factors for TB, the findings of our study highlight the need for more individualized approaches to pretransplant TB screening.     

The impact of the prevention strategies on the indirect effects of CMV infection in solid organ transplant recipients

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.     

Immunosuppressive agents in transplantation: mechanisms of action and current anti-rejection strategies

Over the past century, the concept of interfering with the immune response at various sites by blocking the formation, stimulation, proliferation, and differentiation of lymphocytes has led to relentless development of new immunosuppressive drugs. These agents are associated with reduced risk of short- and long-term toxicity and have dramatically improved allograft and patient survival, especially in recipients of solid organ transplants. Current protocols in such patients are nearly all calcineurin-inhibitor based, using cyclosporine or tacrolimus, as part of dual, triple, or sequential therapy. This review focuses on agents currently in clinical use at transplant centers in United States. The drugs are described in terms of their basic mechanisms of action, therapeutic uses, clinical studies, and adverse effects. In addition, the efficacy and toxicity of a few promising new therapeutic approaches are examined. Finally, important challenges regarding pharmacological immunosuppression as it relates to solid organ and composite tissue allotransplantation are discussed.     

Biomarkers of biological aging in recipients of solid organ transplantation and clinical outcomes: A scoping review

IntroductionBiological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical outcomes of solid organ transplantation, including delayed graft function and frequency of rejection episodes. While much research has focused on the biological age of donor organs, the recipient's biological age may also influence transplantation outcomes. The aim of this scoping review was to identify and provide an overview of the existing evidence regarding biological aging in solid organ transplant recipients and the impact on patient outcomes post-transplant.MethodsLiterature searches were carried out on PubMed, Web of Science, Google Scholar, Embase and TRIP using the phrases ‘solid organ transplant’, ‘cell senescence’, ‘cell aging’ and ‘outcomes’, using boolean ‘and/or’ phrases and MeSH terms. Duplicates were removed and abstracts were reviewed by two independent reviewers. Full papers were then screened for inclusion by two reviewers. Data extraction was carried out using a standardised proforma agreed on prior to starting.Results32 studies, including data on a total of 7760 patients, were identified for inclusion in this review; 23 relating to kidney transplant recipients, three to liver transplant, five to lung transplant and one to heart transplantation. A wide range of biomarkers of biological aging have been assessed in kidney transplant recipients, whereas studies of liver, lung and heart transplant have predominantly assessed recipient telomere length. The most robust associations with clinical outcomes are observed in kidney transplant recipients, possibly influenced by the larger number of studies and the use of a wider range of biomarkers of biological aging. In kidney transplant recipients reduced thymic function and accumulation of terminally differentiated T cell populations was associated with reduced risk of acute rejection but increased risk of infection and mortality.ConclusionStudies to date on biological aging in transplant recipients have been heavily biased to kidney transplant recipients. The results from these studies suggest recipient biological age can influence clinical outcomes and future research is needed to prioritise robust biomarkers of biological aging in transplant recipients.     

Coccidioidomycosis in liver transplantation.

Coccidioidomycosis is an endemic fungal infection in the southwestern United States. It causes morbidity and mortality among solid organ transplant recipients who reside in or visit the endemic area or who receive organs from donors infected with the fungus. This paper reviews current literature addressing these infections in liver transplantation programs, including risk factors, clinical manifestations in persons with cirrhosis or who have had a liver transplantation, prophylaxis, treatment, and outcomes.     

Breast Cancer and Transplantation

Breast cancer is an important cancer among solid organ transplant recipients. While the incidence of breast cancer in solid organ transplant recipients is comparable to the age‐matched general population, the outcomes are generally poor. Interventions such as cancer screening that preclude the development of late‐stage disease through early detection are not well studied, and clinical practice guidelines for cancer screening rely solely on recommendations from the general population. Among patients with a prior breast cancer history, disease recurrence after transplantation is a rare but fearful event. Once disease recurs, the risk of death is high. The focus of this review is to present the epidemiology of breast cancer in solid organ transplant recipients, screening and preventive strategies for those who may be at risk, novel genomic profiling for determining tumor progression, and the newer targeted interventions for recipients who have developed breast cancers after solid organ transplantation.     

Donor‐derived Kaposi's sarcoma in a liver–kidney transplant recipient

Human herpes virus 8 (HHV‐8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient's latent HHV‐8 infection, or less commonly through donor‐derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor‐derived KS in the recipient of a liver–kidney transplant. The donor had multiple risk factors for HHV‐8 infection. The KS was successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)‐positive persons seeking organ transplantation and serving as organ donors for HIV‐positive recipients, HHV‐8 prevalence among donors and recipients will likely increase and with that the risk for post‐transplant KS. Predetermination of HHV‐8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV‐8 antibody screening.     

Risk factors for posttransplant diabetes mellitus: a review of the literature

The development of diabetes after solid organ transplantation is a known complication, and many published studies have examined prevalence rates and risk factors for specific categories of transplant recipients. However, fewer articles have compared rates of posttransplant diabetes and risk factors among different types of transplant recipients. This article provides an overview of the literature on this subject and compares similarities and differences related to posttransplant diabetes for different categories of organ transplant recipients. Awareness of the various risk factors for different organ transplant recipients will enhance transplant clinicians' knowledge related to this complication so that appropriate monitoring can be started.     

A prospective survey of human herpesvirus-6 primary infection in solid organ transplant recipients

Human herpesvirus 6 (HHV-6) infection is potentially life-threatening to immunosuppressed patients. There is a lack of information regarding the risk and the clinical manifestations of primary HHV-6 infection in solid-organ transplant recipients. We prospectively evaluated patients undergoing solid organ transplantation with negative immunoglobulin (Ig) G antibodies against HHV-6 by means of HHV-6 quantitative polymerase chain reaction. Among 193 recipients, seven were HHV-6 seronegative (prevalence 3.6%). We detected a positive HHV-6 viral load in only one patient, and four patients seroconverted after one year posttransplantation. The patient with a positive HHV-6 viral load developed cholestatic hepatitis without fever and did not experience severe end-organ disease. In conclusion, our findings show a low incidence of symptomatic primary HHV-6 infection among seronegative solid-organ transplant recipients.     

Impact of obesity on renal transplant outcomes

Obesity is a frequent and important consideration to be taken into account when assessing patient suitability for renal transplantation. In addition, posttransplant obesity continues to represent a significant challenge to health care professionals caring for renal transplant recipients. Despite the vast amount of evidence that exists on the effect of pretransplant obesity on renal transplant outcomes, there are still conflicting views regarding whether obese renal transplant recipients have a worse outcome, in terms of short- and long-term graft survival and patient survival, compared with their non-obese counterparts. It is well established that any association of obesity with reduced patient survival in renal transplant recipients is mediated in part by its clustering with traditional cardiovascular risk factors such as hypertension, dyslipidaemia, insulin resistance and posttransplant diabetes mellitus, but what is not understood is what mediates the association of obesity with graft failure. Whether it is the higher incidence of cardiovascular comorbidities jeopardising the graft or factors specific to obesity, such as hyperfiltration and glomerulopathy, that might be implicated, currently remains unknown. It can be concluded, however, that pre- and posttransplant obesity should be targeted as aggressively as the more well-established cardiovascular risk factors in order to optimize long-term renal transplant outcomes.     

Influenza A myocarditis developing in an adult liver transplant recipient despite vaccination: a case report and review of the literature

Solid organ transplant recipients receiving chronic immunosuppressive agents are at increased risk to acquire influenza virus despite vaccination. Myocarditis is a known but rare complication of influenza infection. We present the first adult liver transplant recipient who received prophylactic vaccination but developed influenza A myocarditis. This may occur in solid organ transplant recipients, because they have reduced response to protein vaccines, which may leave them vulnerable to infections. Studies are needed to evaluate if antiviral chemoprophylaxis in solid organ transplant recipients during influenza season would be an effective preventive therapy against influenza in this high-risk population.     

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case‐control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case‐control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5‐4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3‐3.4), and exposure to third‐ (OR 2.4, 95% CI 1.4‐4.2) or fourth‐generation (OR 2.1, 95% CI 1.2‐3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3‐0.9). Ninety‐two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1‐5.4) and third‐generation cephalosporin therapy (OR 3.9, 95% CI 1.4‐10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.     

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem‐Resistant Gram‐Negative Bacteria

Donor‐derived infections due to multidrug‐resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2‐year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem‐resistant gram‐negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor‐derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high‐risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high‐risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug‐resistant bacteria requires intra‐ and inter‐institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.