Transplantation Infectious Diseases Research Articles

Interpreting and managing preservation fluids positive for Gram-negative bacteria.

Culturing preservation fluids of solid organs before transplantation is not a standardized procedure. In this review, we aim to describe the state-of-the-art of literature evidence in this debated setting with a special focus on Gram-negative bacteria (GNB). Contamination of preservation fluids is frequent, but preservation fluids related infections are rare and most commonly caused by high-risk pathogens, including GNB. GNB preservation fluids related infections are characterized by high morbidity and mortality. Recent studies showed improved outcomes in solid organ transplant recipients receiving antibiotic therapy tailored according to preservation fluids cultures especially when multidrug-resistant GNB are found. A robust procurement network is needed to alert recipients' centers in cases of positivity and the support of transplant infectious diseases specialists is essential to choose the best therapy. Culturing preservation fluids is a further step into preventing donor-derived infections. Interpreting and managing GNB positivity require a multidisciplinary team with specific skills. Standardized randomized trials are needed for insight into the real utility of preservation fluids cultures, the role of preservation fluids positivity, and the impact of antimicrobial therapy.

Nanotechnology-based Strategies for Molecular Imaging, Diagnosis, and Therapy of Organ Transplantation.

Organ transplantation is the preferred paradigm for patients with end-stage organ failures. Despite unprecedented successes, complications such as immune rejection, ischemia-reperfusion injury, and graft dysfunction remain significant barriers to long-term recipient survival after transplantation. Conventional immunosuppressive drugs have limited efficacy because of significant drug toxicities, high systemic immune burden, and emergence of transplant infectious disease, leading to poor quality of life for patients. Nanoparticle-based drug delivery has emerged as a promising medical technology and offers several advantages by enhancing the delivery of drug payloads to their target sites, reducing systemic toxicity, and facilitating patient compliance over free drug administration. In addition, nanotechnology-based imaging approaches provide exciting diagnostic methods for monitoring molecular and cellular changes in transplanted organs, visualizing immune responses, and assessing the severity of rejection. These noninvasive technologies are expected to help enhance the posttransplantation patient survival through real time and early diagnosis of disease progression. Here, we present a comprehensive review of nanotechnology-assisted strategies in various aspects of organ transplantation, including organ protection before transplantation, mitigation of ischemia-reperfusion injury, counteraction of immune rejection, early detection of organ dysfunction posttransplantation, and molecular imaging and diagnosis of immune rejection.

Impact of machine perfusion on transplant infectious diseases: New challenges and opportunities.

Preservation techniques that maintain the viability of an organ graft between retrieval from the donor and implantation into the recipient remain a critical aspect of solid organ transplantation. While traditionally preservation is accomplished with static cold storage, advances in ex vivo dynamic machine perfusion, both hypothermic and normothermic, have allowed for prolongation of organ viability and recovery of marginal organs effectively increasing the usable donor pool. However, the use of these novel machine perfusion technologies likely exposes the recipient to additional infectious risk either through clonal expansion of pathogens derived during organ recovery or de novo exogenous acquisition of pathogens while the organ remains on the machine perfusion circuit. There is a paucity of high-quality studies that have attempted to quantify infection risk, although it appears that prolonging the time on the machine perfusion circuit and normothermic parameters increases the risk of infection. Conversely, the use of ex vivo machine perfusion unlocks new opportunities to detect and treat donor-derived infections before implantation into the recipient. This review seeks to reveal how the use of ex vivo machine perfusion strategies may augment the risk of infection in the organ recipient as well as outline ways that this technology could be leveraged to enhance our ability to manage donor-derived infections.

Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy: Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group.

COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2-78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020-2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed.

Minimizing risk while maximizing opportunity: The infectious disease organ offer process survey.

The purpose of this study was to understand how transplant infectious disease (TID) physicians assess a potential donor with known or suspected infection and describe posttransplant management. We designed a survey of 10 organ offer scenarios and asked questions pertaining to organ acceptability for transplantation and management posttransplant. The survey was distributed to TID clinicians via transplant society listservs and email. Responses were recorded in REDCap, and descriptive statistics were employed. One hundred thirteen infectious disease physicians responded to the survey, of whom 85 completed all cases. Respondents were generally in agreement regarding organ acceptability, although some divergence was seen when evaluating lungs from donors with influenza, tuberculosis, or multidrug-resistant Acinetobacter infection. Posttransplant management showed more variation. Areas of optimization were identified: (1) Further understanding of where risk-mitigation strategies within the donor offer process may improve donor acceptability and therefore organ utilization; (2) importance of recipient considerations in assessing degree of infectious risk; and (3) gaps in evidenced-based data regarding optimal posttransplant management of recipients. Evaluation of donor offers by TID clinicians is a complex process. Although the survey does not itself serve to make recommendations regarding best practices, it highlights areas where generation of data to inform acceptance and management practices may allow for improved organ utilization and recipient management.

The pre-transplant evaluation: Considerations for trainees and early career transplant infectious diseases clinician.

Transplant infectious disease (TID) clinicians are integral to the pre-transplantation evaluation. Pre-transplant evaluations allow clinicians to assess risk factors for latent infections and relevant exposures to potential pathogens, address immunizations, and optimize patients' health and understanding of life after transplant. However, there is not a standardized approach to the pre-transplant evaluation. This article reviews the details of performing successful pre-transplant evaluations, including updated recommendations on available vaccines and contemporary opinions on marijuana use. This resource can be used for teaching with trainees or for early career TID clinicians.

Donor‐derived infections: The Swiss perspective

AbstractWhile Switzerland has not yet established a systematic approach, the small size of the country and the intensive collaboration between the transplant infectious disease teams facilitate a rapid communication once a donor‐derived infection is suspected. Critical information regarding donor infections is shared rapidly, and appropriate measures are discussed. The long‐term observational Swiss Transplant Cohort Study, which includes >92% of all solid organ recipients collects all relevant infectious disease episodes and facilitates detection of patterns of potential donor‐derived infection.

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.