Search

Infection remains a common cause of death throughout the lifespan of a lung transplant recipient. The increased susceptibility of lung transplant recipients is multifactorial including exposure of the graft to the external environment, impaired mucociliary clearance, and high levels of immunosuppression. Long-term outcomes in lung transplant recipients remain poor compared with other solid organ transplants largely due to deaths from infections and chronic allograft dysfunction. Antibacterial, antifungal, and antiviral prophylaxis may be used after lung transplantation to target a number of different opportunistic infections for varying durations of time. The first-month posttransplant is most commonly characterized by nosocomial infections and donor-derived infections. Following the first month to the first 6 months after transplant-a period of intense immunosuppression-is associated with opportunistic infections. While immunosuppression is reduced after the first year posttransplant, infection remains a risk with community-acquired and rarer infectious agents. Clinicians should be vigilant for infection at all time points after transplant. The use of patient-tailored prophylaxis and treatments help ensure graft and patient survival.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

On November 24, 2017, US lung transplant policy replaced donor service area with 250-nautical-mile radius as the first unit of allocation. Understanding this policy's economic impact is important, because the United States is poised to adopt the broadest feasible geographic organ distribution. All lung transplant recipients from January 1, 2015, to December 31, 2018, in the Scientific Registry of Transplant Recipients, were included. Recipients before and after November 24, 2017 were in the donor service area-first and 250-nautical-mile donor service area-free periods, respectively. Travel time was estimated using a Google application; mode was assigned as flying when driving time was longer than 60 min. Travel costs were estimated by mode and distance. Travel distance and time for organ procurement increased under the policy change. The estimated proportion of organs traveling by air increased from 61% to 76%. Estimated average costs increased by $14 051 if travel mode changed to flying, resulting in an average increase of $1264 for all transplants. Travel costs were highest for candidates

Patients with connective tissue disease (CTD) and advanced lung disease are often considered suboptimal candidates for lung transplantation (LTx) due to their underlying medical complexity and potential surgical risk. There is substantial variability across LTx centers regarding the evaluation and listing of these patients. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization aims to clarify definitions of each disease state included under the term CTD, to describe the extrapulmonary manifestations of each disease requiring consideration before transplantation, and to outline the absolute contraindications to transplantation allowing risk stratification during the evaluation and selection of candidates for LTx.

Efforts are underway to transition the current lung allocation system to a continuous distribution framework whereby multiple factors are simultaneously combined into a Composite Allocation Score (CAS) to prioritize candidates for lung transplant. The purpose of this study was to compare discrete CAS scenarios with the current concentric circle-based allocation system to assess their potential effects on the US lung transplantation system using the Scientific Registry of Transplant Recipients' thoracic simulated allocation model. Six alternative CAS scenarios were compared over 10 simulation runs using data from individuals on the lung transplant waiting list from January 1, 2018, through December 31, 2019. Outcome measures were transplant rate, count, waitlist deaths, posttransplant deaths within 2 years, donor-to-recipient distance, and percentage of organs predicted to have flown. Across scenarios, waitlist deaths decreased by 36% to 47%, with larger decreases in deaths at lower placement efficiency weight and higher weighting of the waitlist outcomes. When waitlist outcomes were equally weighted to posttransplant outcomes, more transplants occurred in individuals with the highest expected posttransplant survival. All CAS scenarios led to improved overall measures of equity compared with the current Lung Allocation Score system, including reduced waitlist deaths, and resulted in similar posttransplant survival.

Introduction Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. Methods We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. Results Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p = Conclusions In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment

Improved predictive models are needed in lung transplantation in the setting of a proposed allocation system that incorporates longer-term post-transplant survival in the United States. Allocation systems require accurate mortality predictions to justly allocate organs.Utilizing the United Network for Organ Sharing database (2005-2017), we fit models to predict 1-year mortality based on the Lung Allocation Score (LAS), the Chan, et al, 2019 model, a novel "clinician" model (a priori clinician selection of pre-transplant covariates), and two machine learning models (Least Absolute Shrinkage and Selection Operator; LASSO and Random Forests) for predicting 1-year and 3-year post-transplant mortality. We compared predictive accuracy among models. We evaluated the calibration of models by comparing average predicted probability vs observed outcome per decile. We repeated analyses fit for 3-year mortality, disease category, including donor covariates, and LAS era.The area under the cure for all models was low, ranging from 0.55 to 0.62. All exhibited reasonable negative predictive values (0.87-0.90), but the positive predictive value for was poor (all0.25). Evaluating LAS calibration found 1-year post-transplant estimates consistently overestimated risk of mortality, with greater differences in higher deciles. LASSO, Random Forests, and clinician models showed no improvement when evaluated by disease category or with the addition of donor covariates and performed worse for 3-year outcomes.The LAS overestimated patients' risk of post-transplant death, thus underestimating transplant benefit in the sickest candidates. Novel models based on pre-transplant recipient covariates failed to improve prediction. There should be wariness in post-transplant survival predictions from available models.

Background Studies of solid organ transplant recipients (SOTr) hospitalized for Covid-19 have focused on short-term outcomes with approximately 30 days of follow-up time. Intermediate-term mortality and associated risk factors for intermediate-term death have not previously been reported. Methods Using data from a multi-center registry, we assessed mortality by 90 days among SOTr hospitalized for Covid-19 between 3/1/2020 and 12/31/2020. Multivariable Cox-proportional hazard models were used to compare risk factors for mortality by 28 and 90 days. Covariates were selected a priori based on known predictors of death in SOTr hospitalized for Covid-19. All patients were followed for 90 days or were censored at the time of death or last clinical contact, if this occurred prior to day 90 after diagnosis. Results Among SOTr hospitalized for Covid-19, 198/979 (20%) died within 90 days of diagnosis and 37/198 (19%) of deaths occurred between days 29 and 90. Risk factors for mortality by day 90 days included age >65 years (1.8, 95% CI 1.3-2.4, P< 0.001), lung transplant (compared to non-lung) (1.6, 95% CI 1.1-2.4, P=0.02), chronic lung disease (2.2, 95% CI 1.5-3.4, P=0.002) and heart failure (1.9, 95% CI 1.2-2.9), which were similar to risk factors reported for 28-day mortality (Table 1). Diagnosis during the second half of 2020 (6/20-12/31/20) was associated with lower mortality by 28 days (aHR 0.7, 95% CI 0.5-1.0, P=0.03) compared to diagnosis during the early half of 2020 (3/1-6/19/20); however, mortality by 90 days was similar in the late and early time periods (aHR 0.9, 95% CI 0.7-1.2, P=0.54). Obesity and mTOR inhibitor use were also associated with death by 28 but not 90 days. Kaplan-Meier survival curves by time period of diagnosis are shown in Figure 1. Table 1. Multivariable Cox-Proportional Hazard Model for Mortality at 28 and 90-days Among Solid Organ Transplant Recipients Hospitalized for Covid-19 (N=979) Figure 1. Survival among SOT recipients hospitalized for Covid-19 by diagnosis time period Vertical tick marks represent censored cases. Early 2020 refers to cases diagnosed between March 1 and June 19, 2020 and late 2020 refers to cases diagnosed between June 20 and December 31, 2020. Conclusion Approximately 20% of deaths among SOTr hospitalized for Covid-19 occurred between days 29 and 90. Future investigations are required to discern the mechanism(s) for the improvement in early, but not late, mortality among SOTr with Covid-19 during the course of the pandemic. Disclosures Madeleine R. Heldman, MD, Cigna Lifesource (Other Financial or Material Support, Speaking honoraria)Thermo Fisher Scientific (Other Financial or Material Support, Speaking honoraria) Olivia S. Kates, MD, Merk (Scientific Research Study Investigator) Ajit P. Limaye, MD, astellas (Scientific Research Study Investigator)CTI (Scientific Research Study Investigator)GSK (Consultant)Johnson&Johnson (Other Financial or Material Support, Adjudication Committee)merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)moderna (Scientific Research Study Investigator)Novartis (Other Financial or Material Support, DMC member)Novo Nordisk (Consultant)