Transplantation Infectious Diseases Research Articles

Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The LT evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures (PREMs) along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into four phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care and social work selected the final set. Candidate PREMs spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures and 10 were outcome measures that focused on elements not typically measured in routine care. Among the PREMs, LT candidates rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among LT candidates. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local QI initiatives to improve access and quality of care.

Art of the Transplant Infectious Diseases Consult: Storytelling and Science

Art of the Transplant Infectious Diseases Consult: Storytelling and Science

Advanced practice providers in infectious disease: Enhancing the infectious disease team of the future.

As the infectious disease (ID) workforce encounters increasing demand for services with fewer physicians entering the field, advanced practice providers (APPs) in infectious disease offer a unique ability to enhance high-quality patient care. However, little is known about their incorporation into ID, their utilization in immunocompromised settings, or their future use. This article reviews currently known data on APPs in ID including how some groups have used APPs and provides a framework for thoughtful, deliberate steps to incorporate APPs into the ID medical team, including transplant infectious disease. Highlighted specifically are education and mentorship opportunities with ideas for curriculum development and onboarding approaches. Strategic steps must be taken for APP inclusion as the medical landscape continues to change, patient complexity increases, and the ID team of the future takes shape.

Current Landscape and Future Directions of Pediatric Transplant Infectious Diseases.

As the field of pediatric transplant infectious diseases continues to grow, new challenges are constantly arising. Advances in immunosuppressive drugs, antimicrobial development, and novel diagnostic tests add new wrinkles to the care of pediatric transplant recipients. This progress in clinical care serves as a call to direct energy toward pediatric transplant infectious diseases research, to better understand how to use these interventions in pediatric practice.

The nuts and bolts of transplant infectious disease training.

The number of transplant infectious disease (TID) fellowship programs has expanded rapidly in the past 5 years, with the creation of many new programs and the expansion of training tracks and dedicated years as the demand for TID physicians grows drastically. This editorial focuses on major factors and complexities that programs should consider in TID fellowship creation, as well as highlighting examples of formative experiences, programmatic structure, and fellow resources that trainees can use to identify their desired career path in TID.

Bring it on again: antimicrobial stewardship in transplant infectious diseases: updates and new challenges.

Advancement in solid organ transplantation and hematopoietic stem cell transplant continues to improve the health outcomes of patients and widens the number of eligible patients who can benefit from the medical progress. Preserving the effectiveness of antimicrobials remains crucial, as otherwise transplant surgeries would be unsafe due to surgical site infections, and the risk of sepsis with neutropenia would preclude stem cell transplant. In this review, we provide updates on three previously discussed stewardship challenges: febrile neutropenia, Clostridioides difficile infection, and asymptomatic bacteriuria. We also offer insight into four new stewardship challenges: the applicability of the "shorter is better" paradigm shift to antimicrobial duration; antibiotic allergy delabeling and desensitization; colonization with multidrug-resistant gram-negative organisms; and management of cytomegalovirus infections. Specifically, data are accumulating for "shorter is better" and antibiotic allergy delabeling in transplant patients, following successes in the general population. Unique to transplant patients are the impact of multidrug-resistant organism colonization on clinical decision-making of antibiotic prophylaxis in transplant procedure and the need for antiviral stewardship in cytomegalovirus. We highlighted the expansion of antimicrobial stewardship interventions as potential solutions for these challenges, as well as gaps in knowledge and opportunities for further research.

Prevention and Management of Infections in Lung Transplant Recipients.

Anti-rejection medications are essential in preventing organ rejection amongst solid organ transplant recipients; however, these agents also cause profound immunosuppression, predisposing lung transplant recipients (LTRs) to infectious complications. The timely management including prevention, diagnosis, and treatment of such infectious complications is vital to prevent significant morbidity and mortality in solid organ transplant recipients and allograft dysfunction. LTRs are inundated with microbes that may be recognized as commensals in hosts with intact immune systems. Bacterial infections are the most common ones, followed by viral pathogens. Indications of a brewing infectious process may be subtle. Hence, the importance of adapting vigilance around isolated hints through symptomatology and signs is pivotal. Signals to suggest an infectious process, such as fever and leukocytosis, may be dampened by immunosuppressive agents. One must also be vigilant about drug interactions of antibiotics and immunosuppressive agents. Treatment of infections can become challenging, as antimicrobials can interact with immunosuppressive agents, and antimicrobial resistance can surge under antimicrobial pressure. Transplant infectious disease physicians work in concert with transplant teams to obtain specimens for diagnostic testing and follow through with source control when possible. This heavily impacts medical decisions and fosters a multidisciplinary approach in management. Furthermore, the reduction of immunosuppression, although it augments the risk of allograft rejection, is as crucial as the initiation of appropriate antimicrobials when it comes to the management of infections.

485. Improved Outcome of COVID-19 in CAR T Cell Treated Patients; results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Abstract Background COVID-19 has been associated with a very high mortality in patients having received CAR T cell treatment for hematological malignancies. The aim of this study was to investigate whether the outcome has improved over time. Methods This is a retrospective analysis of prospective data collected into the EBMT registry regarding risk factors, clinical features, and outcome of patients having received CAR T cell therapy for hematological malignances diagnosed with SARS-CoV-2 infection between March 2020 and December 2022. SARS-CoV-2 was diagnosed by PCR and from January 2021 also antigen tests were accepted. All patients gave informed consent to data collection. The study was approved by the Swedish National Ethical Review Board and by local IRBs as required. Results 182 patients were included in the analysis; 39 diagnosed in 2020, 35 in 2021, and 108 were diagnosed in 2022. 152 patients were treated for B-cell lymphoma, 19 for acute lymphoblastic leukemia, and 11 for plasma-cell disorders. The median age at COVID-19 diagnosis was 58.7 ys (7.2 - 78.4). The median time from CAR T cell infusion to COVID-19 diagnosis was 7.0 months (1.0 - 42.5). 28% of the patients had lower respiratory tract disease at diagnosis. 27 (25.8%) of patients had received three or more vaccine doses and only 2.2% had received pre-exposure tix/cil. 45.1% required hospitalization, 33.4% required oxygen, and 17% was admitted to ICU. COVID-19 attributable mortality over the entire period was 18.1% with significant improvement over time (43.6% in 2020, 22.9% in 2021%, and 7.4% in 2022). Survival after COVID-19 diagnosis Conclusion Although the COVID-19 attributable mortality has decreased over time, it remains several times higher than what can be expected in an healthy population of comparable age. Therefore, preventive measures need to be maintained for this vulnerable patient group.. Disclosures Per Ljungman, MD; PhD, AlloVir: Grant/Research Support|Gilead: Honoraria|Moderna: Honoraria|MSD: Honoraria|Takeda: Honoraria Rafael de la Camara, MD, AstraZeneca: Advisor/Consultant|Moderna: Advisor/Consultant|MSD: Advisor/Consultant Marie Jose Kersten, MD, PhD, BMS: Advisor/Consultant|BMS: Honoraria|Celgene: Advisor/Consultant|Celgene: Grant/Research Support|Celgene: Honoraria|Kite/Gilead: Advisor/Consultant|Kite/Gilead: Grant/Research Support|Kite/Gilead: Honoraria|Kite/Gilead: Travel|Miltenyi Biotech: Advisor/Consultant|Miltenyi Biotech: Honoraria|Miltenyi Biotech: Travel|Novartis: Advisor/Consultant|Novartis: Honoraria|Novartis: Travel|Roche: Advisor/Consultant|Roche: Grant/Research Support|Roche: Honoraria|Takeda: Grant/Research Support Stephan Mielke, MD, PhD, BMS: Honoraria|Celgene: Honoraria|Janssen: Honoraria|Kite/Gilead: Honoraria|Mendes: Honoraria|Miltenyi: Honoraria|Pfizer: Honoraria

Routine Infectious Disease Consultation Prior to an Allogeneic Hematopoietic Cell Transplant.

A transplant infectious disease (TID) assessment is essential to select recipients for an allogeneic hematopoietic cell transplant (HCT) and tailor prophylactic and empirical treatment recommendations. We performed a retrospective single-center study to describe our model of care based on a routine TID consultation prior to an allogeneic HCT between 2018 and 2022 in 292 adult (≥18-year-old) consecutive patients. We describe the performance of a TID consultation, arbitrarily defined as major (HCT postponement, procedure, cytomegalovirus [CMV] recipient serology reinterpretation) and minor interventions. Overall, 765 interventions were observed in 257 of 292 (88%) patients: 88 of 765 (11.5%) major and 677 of 765 (88.5%) minor interventions. Among major interventions, HCT was postponed in 8 of 292 (2.7%) patients and a procedure was requested in 18 of 292 (6.2%) patients. The CMV recipient serostatus was changed from indeterminate/low-titer positive to negative in 60 of 292 (20.5%) patients. Among 677 minor interventions, there were 68 (8.8%) additional consultations with other services requested, 260 (33.7%) additional diagnostic tests requested, 102 (13.2%) additional treatments recommended, 60 (7.8%) non-CMV serology reinterpretations performed, 115 (14.9%) deviations from routine anti-infective prophylaxis, and 72 (9.3%) deviations from routine empirical antibiotic treatment recommendations in case of neutropenic fever. We are proposing a structured, clearly defined, and comprehensive pretransplant checklist for an effective assessment of infectious disease risks and complications prior to an allogeneic HCT. Further studies or experiences like ours could help to define a global strategy or new models of care to be implemented in HCT centers in the future.

Donor call simulation: A novel medical education tool to evaluate trainees' clinical decision-making in transplant infectious disease.

Evaluating organ suitability for transplantation based on infection risk is a core competency in transplant infectious disease (TID). It is unclear if trainees have opportunities to practice during training. We created a simulation curriculum to develop and evaluate this skill among infectious disease (ID) trainees. We created six simulation questions about organ suitability for transplant based on infection risk. During trainees' TID rotations, faculty texted or paged the simulation cases posing as the transplant coordinator.Trainees had 15 min to ask questions before deciding the suitability of the organ and explained their clinical reasoning in a survey. Trainees completed a post-simulation survey to evaluate its effectiveness. ID trainees, including residents and fellows on rotation, from seven centers participated. Eighty-seven percent (13/15) of trainees felt the simulation was effective in teaching them this concept, and 80% (12/15) felt prepared for clinical practice. The proportion of correct responses was generally high among the six different cases (43%-100%); correct responses increased for some cases in the post-activity survey. Of the 100 clinical reasoning decisions made during the activity, 19% were discordant, where the trainee correctly identified suitable organs for incorrect reasons. Our simulation was effective in teaching when to accept or reject an organ for transplant and was a valuable educational tool. By evaluating clinical reasoning for decisions our simulation provides educators with nuanced insight and allows for targeted coaching. This study demonstrates a critical need for further educational tools in TID.

218.5: Transplant infectious disease screening minimizes mortality across solid organ transplantation.

218.5: Transplant infectious disease screening minimizes mortality across solid organ transplantation.

Beginners guide to protocol writing in transplant infectious diseases.

Creating protocols surrounding the guidance of the prevention and treatment of infections in transplantation is an integral part of being a transplant infectious disease physician. This piece outlines the key components for success in developing a protocol, with an example protocol and protocol template available for readers. Collaborating effectively within the multi-disciplinary team to develop, implement, and assess the efficacy of a protocol is a skill that enhances the relationship with our transplantation colleagues and improves patient outcomes by standardizing the care delivered.

A review of transplant infectious diseases and pediatric transplant infectious diseases curriculum.

As the volume and complexity of solid organ and hematopoietic stem cell transplantation continue to see rapid growth, the training of a specialized transplant infectious diseases physician workforce is of increasing interest and importance. This review provides an overview of the evolution of transplant infectious diseases training programs, essential elements of training, as well as future needs. Despite the first publication of a transplant infectious diseases curriculum in 2010, more recent surveys of infectious diseases trainees have identified gaps in didactic curriculum, donor and recipient assessment, and safe living practices. This review of transplant infectious diseases training summarizes growth through the decades, the current landscape of recommend training elements, suggested areas for continued development and expansion in training as well as novel methodologies to reach a modern trainee audience.

South Asian Transplant Infectious Disease Guidelines for Solid Organ Transplant Candidates, Recipients, and Donors.

These guidelines discuss the epidemiology, screening, diagnosis, posttransplant prophylaxis, monitoring, and management of endemic infections in solid organ transplant (SOT) candidates, recipients, and donors in South Asia. The guidelines also provide recommendations for SOT recipients traveling to this region. These guidelines are based on literature review and expert opinion by transplant physicians, surgeons, and infectious diseases specialists, mostly from South Asian countries (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) as well as transplant experts from other countries. These guidelines cover relevant endemic bacterial infections (tuberculosis, leptospirosis, melioidosis, typhoid, scrub typhus), viral infections (hepatitis A, B, C, D, and E; rabies; and the arboviruses including dengue, chikungunya, Zika, Japanese encephalitis), endemic fungal infections (mucormycosis, histoplasmosis, talaromycosis, sporotrichosis), and endemic parasitic infections (malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, strongyloidiasis, and filariasis) as well as travelers' diarrhea and vaccination for SOT candidates and recipients including travelers visiting this region. These guidelines are intended to be an overview of each topic; more detailed reviews are being published as a special supplement in the Indian Journal of Transplantation .

Rapid antimicrobial resistance detection methods for bloodstream infection in solid organ transplantation: Proposed clinical guidance, unmet needs, and future directions.

Recent advances in antimicrobial resistance detection have spurred the development of multiple assays that can accurately detect the presence of bacterial resistance from positive blood cultures, resulting in faster institution of effective antimicrobial therapy. Despite these advances, there are limited data regarding the use of these assays in solid organ transplant (SOT) recipients and there is little guidance on how to select, implement, and interpret them in clinical practice. We describe a practical approach to the implementation and interpretation of these assays in SOT recipients using the best available data and expert opinion. These findings were part of a consensus conference sponsored by the American Society of Transplantation held on December 7, 2021 and represent the collaboration between experts in transplant infectious diseases, pharmacy, antimicrobial and diagnostic stewardship, and clinical microbiology. Areas of unmet need and recommendations for future investigation are also presented.

A Case of Disseminated Cryptococcus Post-Kidney Transplant

Cryptococcosis is a common invasive fungal infection in solid organ transplant recipients (SOTR) that can be challenging to manage. We discuss a case of disseminated cryptococcosis in a transplant recipient. A 26-year-old woman with a history of ESRD from C1q nephropathy, living-related kidney transplant in early 2012, and allograft nephrectomy in 2015, received a deceased donor kidney transplant (DDKT). Induction after the first transplant was anti-thymocyte globulin (ATG) and maintenance immunosuppression (IS) included tacrolimus (TAC), mycophenolate (MMF), and prednisone. In December 2014, she developed nephrotic range proteinuria due to recurrent FSGS failing plasmapheresis and Intravenous immunoglobulin leading to advanced chronic kidney disease and dialysis dependence. MMF was held due to Cytomegalovirus (CMV) DNAemia. In January 2015, she developed bilateral, painful leg ulcers. Skin biopsy, spinal fluid analysis, and culture were positive for <em>Cryptococcus neoformans.</em> She was treated with liposomal Amphotericin B (LAB) for 3 weeks and 5 doses of flucytosine (5FC) followed by maintenance oral fluconazole with recurrence requiring resumption of LAB and 5FC. The patient underwent a transplant nephrectomy in May 2015 following which IS, LAB, and 5FC were discontinued and maintenance fluconazole initiated. In 2018, another skin biopsy revealed a recurrence. Maintenance antifungal was switched to itraconazole based on fungal isolate minimum inhibitory concentration (MIC) leading to remission that persisted through subsequent DDKT in August 2022. Induction IS was ATG and maintenance included TAC, MMF, and prednisone. The post-transplant course was complicated by delayed graft function requiring dialysis for about three weeks, followed by renal recovery. She continues maintenance of itraconazole under the supervision of a transplant infectious disease specialist and <em>cryptococca</em>l disease remains in remission. IS reduction or complete withdrawal is important in managing disseminated cryptococcosis in SOTR. Management of disseminated disease may require an extended course of LAB, 5FC, and maintenance azole based on MIC.

Transplantid.net: A Pilot Crowdsourced, Living, Online Library of Resources for the Teaching and Practice of Transplant Infectious Diseases.

The field of transplant infectious diseases is rapidly evolving, presenting a challenge for clinical practice and trainee education. Here we describe the construction of transplantid.net, a free online library, crowdsourced and continuously updated for the dual purpose of point-of-care evidence-based management and teaching.

Development and implementation of "handshake rounds": An antibiotic stewardship intervention for hospitalized adult patients with hematologic malignancies.

To design and implement "handshake rounds" as an antibiotic stewardship intervention to reduce inpatient intravenous (IV) antibiotic use in patients with hematologic malignancies. Quasi-experimental analysis of antibiotic use (AU) and secondary outcomes before and and after handshake rounds were implemented. Quaternary-care, academic medical center. Hospitalized adults with hematologic malignancies receiving IV antibiotics. We performed a retrospective review of a preintervention cohort prior to the intervention. A multidisciplinary team developed criteria for de-escalation of antibiotics, logistics of handshake rounds, and outcome metrics. Eligible patients were discussed during scheduled handshake rounds between a hematology-oncology pharmacist and transplant-infectious diseases (TID) physician. Prospective data were collected over 30 days in the postintervention cohort. Due to small sample size, 2:1 matching was used to compare pre- to and postintervention AU. Total AU in days of therapy per 1,000 patient days (DOT/1,000 PD) was reported. Mean AU per patient was analyzed using Wilcoxon rank-sum test. A descriptive analysis of secondary outcomes of pre- and postintervention cohorts was performed. Total AU was substantially lower after the intervention, with 517 DOT/1,000 PD compared to 865 DOT/1,000 PD before the intervention. There was no statistically significant difference in the mean AU per patient between the 2 cohorts. There was a lower rate of 30-day mortality in the postintervention cohort and rates of ICU admissions were similar. Conducting handshake rounds is a safe and effective way to implement an antibiotic stewardship intervention among high-risk patient population such as those with hematologic malignancies.

Vision and mission of the new Editor-In-Chief

I am pleased to serve as Editor in Chief for the Indian Journal of Organ Transplantation (IJT), an official journal of the Indian Society of Organ Transplantation from January 2023 onward for 3 years. I have long regarded IJT as the foremost outlet for publishing peer-reviewed manuscripts on organ transplantation, basic sciences, transplant immunology, immunogenetics, transplant infectious diseases, and any posttransplant complications related to solid organ transplantation. I am fortunate to inherit this journal from a distinguished Editor-in-chief (EIC), Dr. Manisha Sahay, many stellar associate and subject editors and members of an impressive editorial board with a wide range of expertise. IJT has built excellent visibility as a high-quality peer-reviewed journal in the field of organ transplantation. IJT stands apart from other journals because of its inclusive focus on priorities arising out of organ transplantation in India and the adjacent Asian regions, along with the national and global perspective of organ transplantation. As a new EIC, my vision will concentrate on prioritizing the publication of research of applied relevance. There would be a rigorous review of methodological and analytic rigor with immediate downstream implications for improving the care and well-being of individuals suffering from end-stage organ disease and organ transplantation. Despite a growing number of competing journals in the field, IJT continues to receive a large number of manuscripts for publication consideration, not only from India and neighboring countries but also from authors globally now. The rigorous manuscript review by experts in the field will be ensured within the stipulated time. The Editorial team is committed to reducing the turnaround time of 6–8 weeks from the review to publication to the initial decision on acceptance or rejection. The priority of the Editorial Board will be to focus on accepting and publishing the quality manuscript rather than rejecting it. We will provide authors with detailed decision letters, a briefing about the reason in cases of rejections, and detailed comments to improve the revised manuscript for submission in this journal or any other journals. The unsuitable submission may be returned to the authors within 1 week after a quick check by the subject Editor and editorial team. The editorial staff will ensure the technical and plagiarism check of the submitted manuscript soon after the first submission. Authors will have to declare their conflict of interest, and the ethical approval, with their approval codes and number from the respective ethics board, will be the prerequisite of submission. The authors need to declare that the study was conducted as per the ethics guidelines for practice in organ donation and transplantation, laid down by the declaration of Istanbul ethical guidelines and as per the “Declaration of Helsinki” as a statement of ethical principles to guide investigators and physicians involved in human research. I am committed to ensuring that IJT remains a premier journal in the field for the members of society and reputed authors worldwide. Our goal is to consistently publish papers online soon after the acceptance of the manuscript. This goal will not only serve to improve the author’s experience but will also facilitate the dissemination of scientific clinical and basic research findings to the field. As EIC, I will strengthen the connection between the IJT and the Indian Society of Organ Transplantation. The society’s position statements and guidelines should be published in this official journal; the advantages of such publications were witnessed during the recent coronavirus disease 19 pandemics. We will actively seek input from the organization and its members about how the journal can better serve society in achieving its goals. Recent years witnessed extraordinary advances in the use of digital technologies to expand the scope and reach of evidence-based medicines and care of patients through Twitter, Facebook, and other social media dissemination of recently published articles. The visual abstract of each original and review article will be published online, ensuring the journal’s reach to the members and persons involved in organ transplantation. A few publications in crucial areas such as outreach with telehealth services, gender disparities in transplantation, and marginalized and underrepresented populations in organ transplantation will be the another goal of the editorial board. The journal will assist in narrowing the discrepancies in deceased organ transplantation in different parts of India and worldwide through sharing scientific knowledge. I will also prioritize submissions, dissemination, and implementation of research findings from researchers and will convince the researchers that the IJT is your first Go-to journal. I hope, the goals I have described will sustain and improve the journal’s reputation and entice authors to submit their work to the journal for publication. I will continue to publish editorials that describe progress toward the objectives described here and additional objectives that will be established in the coming months. Moreover, I would not be able to accomplish these objectives without the assistance and support of the editorial team and Medknow Wolter Kluwer, team India. I look forward to closely associating with the publishers to ensure that IJT is regarded as the first-choice journal.