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A progressive increase in the incidence of vancomycin resistance in strains of Enterococcus faecium (VREF) has severely constrained treatment options for patients with infection caused by this emerging pathogen. Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic, is active in vitro against VREF, with an MIC90 of 1.0 mg/L. We studied the clinical efficacy and safety of quinupristin/dalfopristin in the treatment of VREF infection. Two prospective studies were conducted simultaneously the first enrolled only patients with VREF infection; the second included patients with infection caused by other Gram-positive bacterial pathogens in addition to VREF. Patients were enrolled if they had signs and symptoms of active infection and no appropriate alternative antibiotic therapy. The recommended treatment regimen of quinupristin/dalfopristin was 7.5 mg/kg iv every 8 h for a duration judged appropriate by the investigator. A total of 396 patients with VREF infection were enrolled. The most frequent indications for treatment included intra-abdominal infection, bacteraemia of unknown origin, urinary tract infection, catheter-related bacteraemia, and skin and skin structure infection. This patient population had a high prevalence of severe underlying illness, including a history of diabetes mellitus, transplantation, mechanical ventilation, dialysis, chronic liver disease with cirrhosis and oncological disorders. The mean (± S.D.) duration of treatment was 14.5 ± 10.7 days (range: 1-108). The majority of patients (82.1%) were treated every 8 h, as assessed on day 2 of treatment, while 15.9% were treated every 12 h. The clinical success rate was 73.6% [142/193 clinically evaluable patients; 95% confidence interval (CI): 67.4%, 79.8%], the bacteriological success rate 70.5% (110/156 bacteriologically evaluable patients; 95% CI:63.4%, 77.7%) and the overall success (both clinical and bacteriological success) rate 65.8% (102/156 bacteriologically evaluable patients; 95% CI: 57.9%, 72.9%). VREF bacteraemia at entry, mechanical ventilation and laparotomy were associated with a worse outcome. Quinupristin/dalfopristin was generally well tolerated. The most common systemic adverse events related to treatment were arthralgias (9.1%) and myalgias (6.6%). Related laboratory abnormalities ere infrequent. In these severely ill patients with VREF infection and no other clinically appropriate therapeutic alternatives, quinupristin/dalfopristin demonstrated substantial efficacy and a good nervous system, cardiovascular, gastrointestinal, renal and hepatic tolerability. [ABSTRACT FROM PUBLISHER]

Background: The transplantation of human organs, and some human tissues, is often the only life-saving therapy available for serious and life-threatening congenital, inherited or acquired diseases. However, it is associated with a risk of transmission of communicable diseases from donor to recipient. It is imperative to understand the characteristics of the donor population (including both potential and actual donors) to inform policies that protect recipient safety. The Tissue and Organ Donor Epidemiology Study (TODES) was a pilot project designed to identify and collect standardized information on deceased persons referred for organ, tissue and/or eye donation, and to estimate (to the extent possible) infectious disease prevalence and incidence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in this population. TODES is summarized here to shed light on addressable limitations on accessing data needed for transplant recipient safety. Limitations, future research needs and potential pathways to solve the remaining data needs are explored., Methods: Retrospective data for all deceased donors during a 5-year period from 2009 to 2013 were obtained from participating organ procurement organizations (OPOs), tissue establishments and eye banks. These decedent data were used to ascertain whether the available real-world data (RWD) could be used to inform donor screening and testing policy., Results: The TODES database contains 291 848 records received from nine OPOs and 42 451 records received from four eye banks. Data were analysed from deceased donors with at least one organ, tissue or ocular tissue recovered with the intent to transplant. Results for potential donors were not analysed. Available RWD at the time of the TODES study were not fit-for-purpose to help characterize the organ, tissue and eye donor populations and/or to inform donor screening policy., Conclusions: Recent advances in electronic data collection systems make it more realistic to now collect fit-for-purpose RWD that address the research needed to improve transplant safety., Competing Interests: Declarations Ethics approval and consent to participate All TODES data were collected on deceased donors, who are not included in the definition of human subjects (45 CFR §46.102(e)). Additionally, OPTN data are collected with the intention of making data available for public and scientific uses [31]. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network focuses on issues related to the transmission of disease through organ transplantation. Providing a review of potential cases of transmission, translating aggregate data into actionable education and guidance for the transplant community, and providing input for policy development, DTAC aims to improve the safety of organ transplantation through a reduction in donor-derived transmission events. Through its nearly 20-year history, DTAC has provided education, guidance, and policy, addressed numerous emerging infections, and continuously focused on the community's understanding of risk assessment related to donor-derived transmission. By updating the DTAC mission to both decrease transmission and safely expand the donor pool with additional guidance to safely use organs previously not considered for transplantation due to transmission concerns, the Committee's role will remain critical., (© 2024 Wiley Periodicals LLC.)

Background: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls., Methods: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection., Results: We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment., Conclusions: In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.)., (Copyright © 2024 Massachusetts Medical Society.)

With the increasing prevalence of marijuana use in the US, many deceased organ donors have a history of marijuana use, raising concerns about infectious risks to transplant recipients. We performed a multicenter retrospective cohort study in which exposed donors were those with recent marijuana use (in the prior 12 months) and unexposed donors were those with no recent marijuana use. Primary outcomes included the following: (1) positive donor cultures for bacteria or fungi, (2) recipient infection due to bacteria or fungi within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Multivariable regression was used to evaluate the relationship between donor marijuana use and each outcome. A total of 658 recipients who received organs from 394 donors were included. Recent marijuana use was not associated with donor culture positivity (aOR: 0.84, 95% CI: 0.39-1.81, P = .65), recipient infection (aHR: 1.02, 95% CI: 0.76-1.38, P = .90), or recipient graft failure or death (aHR: 1.65, 95% CI: 0.90-3.02, P = .11). Our data suggest that organs from donors with a history of recent marijuana use do not pose significant infectious risks in the early posttransplant period., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Emily Blumberg receives research support from Merck, Takeda, Hologic, and Scynexis; was a member of a Data and Safety Monitoring Board (DSMB) for Amplyx; and is a member of Scientific Advisory Committees for Merck and Takeda. Jennifer Han was affiliated with the University of Pennsylvania during the conduct of this research and is now employed by, and holds shares in, the GlaxoSmithKline group of companies. Ebbing Lautenbach is a member of a DSMB for Merck and is a member of a scientific advisory committee for Paratek and Shionogi. None of these conflicts are relevant to this article. All other authors report no disclosures., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: During the COVID-19 pandemic, SARS-CoV-2 monoclonal antibodies for preexposure prophylaxis (SMA-PrEP) offered patients who were immunocompromised another option for protection. However, SMA-PrEP posed administrative, operational, and ethical challenges for health care facilities, resulting in few patients receiving them. Although the first SMA-PrEP medication, tixagevimab and cilgavimab, had its authorization revoked due to compromised in vitro efficacy, new SMA-PrEP medications are currently completing clinical trials. This article provides an operational framework for administrative organization, patient identification and prioritization, equitable medication allocation, medication ordering and administration, and patient tracking., Methods: A retrospective cohort study evaluating our hospital's SMA-PrEP administration strategy was performed. Multivariable logistic regression was used to examine factors associated with receipt of SMA-PrEP., Results: Despite the barriers in administering this medication and the scarcity of resources, our hospital was able to administer at least 1 dose of SMA-PrEP to 1359 of 5902 (23.0%) eligible patients. Even with the steps taken to promote equitable allocation, multivariable logistic regression demonstrated that there were still differences by race, ethnicity, and socioeconomic status. As compared with patients who identified as Black, patients who identified as White (odds ratio [OR], 1.85; 95% CI, 1.46-2.33), Asian (OR, 1.59; 95% CI, 1.03-2.46), and Hispanic (OR, 1.53; 95% CI, 1.02-2.44) were more likely to receive SMA-PrEP. When compared with patients with low socioeconomic status, patients with high socioeconomic status (OR, 1.37; 95% CI, 1.05-1.78) were more likely to be allocated SMA-PrEP., Conclusions: Despite efforts to mitigate health care disparities, differences by race/ethnicity and socioeconomic status still arose in patients receiving SMA-PrEP., Competing Interests: Potential conflicts of interest. D. A. J. has received personal fees for advisory board participation and/or consulting from Biogen, BMS, Cycle Pharma, Horizon, Merck/EMD Serono, Novartis, Roche/Genentech, TG Therapeutics, and Sanofi-Genzyme and grant support to the University of Pennsylvania from Biogen Idec, Roche/Genentech, Merck/EMD Serono, and Novartis. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Chronic kidney disease affects an estimated 37 million people in the United States; of these,>800,000 have end-stage renal disease requiring chronic dialysis or a kidney transplant to survive. Despite efforts to increase the donor kidney supply, approximately 100,000 people are registered on the kidney transplant wait-list with no measurable decrease over the past 2 decades. The outcomes of kidney transplantation are significantly better than for chronic dialysis: kidney transplant recipients have lower rates of mortality and cardiovascular events and better quality of life, but wait-list time matters. Time on dialysis waiting for a deceased-donor kidney is a strong independent risk factor for outcomes after a kidney transplant. Deceased-donor recipients with wait-list times on dialysis of<6 months have graft survival rates equivalent to living-donor recipients with waitlist times on dialysis of>2 years. In 2021,>12,000 people had been on the kidney transplant waitlist for ≥5 years. As the gap between the demand for and availability of donor kidneys for allotransplantation continues to widen, alternative strategies are needed to provide a stable, sufficient, and timely supply. A strategy that is gaining momentum toward clinical application is pig-to-human kidney xenotransplantation. This report summarizes the proceedings of a meeting convened on April 11-12, 2022, by the National Kidney Foundation to review and assess the state of pig-to-human kidney xenotransplantation as a potential cure for end-stage renal disease., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients., Methods: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert., Results: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis)., Conclusion: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients., (© 2024 Wiley Periodicals LLC.)

Background: The COVID-19 pandemic presented a significant challenge for Organ Procurement Organizations (OPOs) with the use of SARS-CoV-2 positive donors varying widely. This study used detailed single OPO data to determine the success of using SARS-CoV-2 positive donors., Methods: We performed a retrospective cohort study including all SARS-CoV-2 positive donors referred to the Gift of Life OPO from January 1, 2021, to June 30, 2023. Descriptive analyses were performed to characterize referral and organ utilization., Results: There were 861 organ referrals with 1 positive SARS-Cov-2 test: 282 were ruled out with telephone evaluation, 431 referrals were ruled out with onsite evaluation ("evaluated nondonors") and 148 became donors. For donors who had both nasopharyngeal and lower respiratory testing completed, there was notable result discordance observed. Median cycle threshold (Ct) values were similar between donors and evaluated nondonors with no change in median donor Ct values over the study period. Transplanted organs from COVID-positive donors included 27 hearts, 88 livers, 5 pancreata, and 107 kidneys; no lung donation occurred. The proportion of COVID-positive donors significantly increased over the study period., Conclusion: This large volume donor referral study demonstrates increasing COVID-19 referrals progressing to donation over time, supporting the increased use of these donors for nonlung transplantation., (© 2024 Wiley Periodicals LLC.)

Background: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population., Methods: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure., Results: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P  < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P  < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P  < 0.001)., Conclusions: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV., Competing Interests: D.L.S. receives honoraria for AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMd, as well as consulting fees from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron, and Springer Publishing. C.M.D. received honoraria from Gilead Sciences for serving on a grant review committee. V.S. received research grant support from Eli Lilly and Company and consulting fees from DiaSorin SpA. M.P. received grant support from Merck, Hologic, Moderna, Shire/Takeda, and Pfizer, as well as provided consultation to/serves on the advisory board for Rebiotix, Takeda, and Union Therapeutics. C.B.S. has received grants paid to her institution from GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics. G.H. is a recipient of research grants from Allovir, Karius, and AstraZeneca. G.H. serves on the scientific advisory boards of Karius and AstraZeneca and has received honoraria from MDOutlook and MAD-ID/ID Connect. J.H. is a recipient of grants paid to his institution from Pfizer, Janssen, and Scynexis. The other authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The public health emergency for coronavirus disease 2019 ended on April 11, 2023, 1 month earlier than its planned termination. The hasty cessation of emergency measures may negatively impact the care of solid organ transplant recipients and other immunosuppressed hosts. Accelerated pathways for drug and vaccine approvals, research funding, and insurance coverage for medical therapies and diagnostic testing are likely to be affected. Health care disparities that characterized the early pandemic may again be intensified. It is imperative that the transplant community promptly anticipate the impact of these changes and prepare accordingly to avoid disruptions in care for the most vulnerable patients., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Bronchial anastomotic dehiscence (AD) is an uncommon complication following lung transplantation that carries significant morbidity and mortality. The objective of this study was to characterize fungal and bacterial infections in ADs, including whether infections following AD were associated with progression to bronchial stenosis., Methods: This was a single-center study of 615 lung transplant recipients between 6/1/2015 and 12/31/2021. Airway complications were defined according to ISHLT consensus guidelines., Results: 22 of the 615 recipients (3.6%) developed an AD. Bronchial ischemia or necrosis was common prior to dehiscence (68.1%). Fourteen (63.6%) recipients had bacterial airway infections, most commonly with Gram-negative rods, prior to dehiscence. Thirteen (59.1%) recipients had an associated pleural infection, most commonly with Candida species (30.8%). Post-dehiscence Aspergillus species were isolated in 4 recipients, 3 of which were de novo infections. Eleven had bacterial infections prior to dehiscence resolution, most commonly with Pseudomonas aeruginosa. Eleven recipients developed airway stenosis requiring dilation and/or stenting. Development of secondary infection prior to AD resolution was not associated with progression to stenosis (OR = .41, 95% CI = .05-3.30, p = .41)., Conclusions: Gram-negative bacterial infections are common before and after AD. Pleural infection should be suspected in most cases. Infections prior to healing were not associated with subsequent development of airway stenosis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA + donors and none have reported quality of life (QOL)., Methods: This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA + lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center., Results: Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA + lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA + lung recipients versus matched comparators., Conclusions: SHELTER adds important evidence regarding the safety of transplanting HCV-RNA + lungs into uninfected recipients and suggests QOL benefits., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

This guidance was developed to summarize current approaches to the potential transmission of swine-derived organisms to xenograft recipients, health care providers, or the public in clinical xenotransplantation. Limited specific data are available on the zoonotic potential of pig pathogens. It is anticipated that the risk of zoonotic infection in xenograft recipients will be determined by organisms present in source animals and relate to the nature and intensity of the immunosuppression used to maintain xenograft function. Based on experience in allotransplantation and with preclinical models, viral infections are of greatest concern, including porcine cytomegalovirus, porcine lymphotropic herpesvirus, and porcine endogenous retroviruses. Sensitive and specific microbiological assays are required for routine microbiological surveillance of source animals and xenograft recipients. Archiving of blood samples from recipients, contacts, and hospital staff may provide a basis for microbiological investigations if infectious syndromes develop. Carefully implemented infection control practices are required to prevent zoonotic pathogen exposures by clinical care providers. Informed consent practices for recipients and their close contacts must convey the lack of specific data for infectious risk assessment. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with carefully developed protocols for pretransplant assessment, syndrome evaluation, and microbiological monitoring., Competing Interests: Conflicts of interest Dr. Fishman serves on the scientific advisory boards of Jura Bio, Well Medical Inc. , Sfunga Inc. , and as a consultant to eGenesis Inc and Makana Inc. He receives royalties from UpToDate. Dr. Fishman holds Patents 6190861; 6699663; 7,465,573. Molecular sequence of swine retrovirus and methods of use (J.A. Fishman, sole inventor, filed November, 1995)., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined., Methods: A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2018. Exposed subjects were those with a CRE BSI. Unexposed subjects were those with a non-CRE BSI. A multivariable survival analysis was performed to determine the association between CRE BSI and risk of all-cause mortality within 60 d. Multivariable logistic regression analysis was performed to determine independent risk factors for CRE BSI., Results: Of 897 cases of Enterobacterales BSI in SOT recipients, 70 (8%) were due to CRE. On multivariable analysis, CRE BSI was associated with a significantly increased hazard of all-cause mortality (adjusted hazard ratio, 2.85; 95% confidence interval [CI], 1.68-4.84; P < 0.001). Independent risk factors for CRE BSI included prior CRE colonization or infection (adjusted odds ratio [aOR] 9.86; 95% CI, 4.88-19.93; P < 0.001)' liver transplantation (aOR, 2.64; 95% CI, 1.23-5.65; P = 0.012)' lung transplantation (aOR, 3.76; 95% CI, 1.40-10.09; P = 0.009)' and exposure to a third-generation cephalosporin (aOR, 2.21; 95% CI, 1.17-4.17; P = 0.015) or carbapenem (aOR, 2.80; 95% CI, 1.54-5.10; P = 0.001) in the prior 6 months., Conclusions: CRE BSI is associated with significantly worse outcomes than more antibiotic-susceptible Enterobacterales BSI in SOT recipients., Competing Interests: E.A.B. receives research support from Merck, Takeda, and Hologic; is a member of a Data and Safety Monitoring Board (DSMB) for Amplyx; and is a member of Scientific Advisory Committees for Merck and Takeda. E.L. is a member of a DSMB for Merck and is a member of a scientific advisory committee for Paratek and Shionogi. K.A. serves on a scientific advisory board for Becton Dickinson. J.H.H. was affiliated with the University of Pennsylvania during the conduct of this research and is now employed by, and holds shares in, the GlaxoSmithKline group of companies. None of these conflicts are relevant to this article. The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Due to the ongoing opioid epidemic in the United States, deceased organ donors increasingly have a history of injection drug use (IDU), raising concerns about infectious risks to solid organ transplant (SOT) recipients. We sought to determine how recent IDU among deceased organ donors impacted donor culture results and recipient outcomes., Methods: A retrospective cohort study was performed at three transplant centers. Exposed donors were those with "recent IDU" (in the prior 12 months). Primary outcomes included (1) positive donor cultures for bacteria or Candida species, (2) recipient bacterial or Candida infection within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Mixed effects multivariable regression models were used to evaluate the relationship between recent donor IDU and each outcome., Results: A total of 658 SOT recipients who received organs from 394 donors were included. Sixty-six (17%) donors had a history of recent IDU. Recent IDU in donors was associated with a significantly increased odds of donor culture positivity (aOR 3.65, 95% CI 1.06-12.60, p = .04) but was not associated with SOT recipient infection (aHR 0.98, 95% CI 0.71-1.36, p = .92) or graft failure or death (aHR 0.67, 95% CI 0.29-1.51, p = .33)., Conclusion: Donors with recent IDU are more likely to have positive cultures, but their recipients' outcomes are unaffected, suggesting organs from donors with recent IDU may be safely utilized., (© 2022 Wiley Periodicals LLC.)

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRβ repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRβ clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.

Background: Antimicrobial prophylaxis is well-accepted in the liver transplant (LT) setting. Nevertheless, optimal regimens to prevent bacterial, viral, and fungal infections are not defined., Objectives: To identify the optimal antimicrobial prophylaxis to prevent post-LT bacterial, fungal, and cytomegalovirus (CMV) infections, to improve short-term outcomes, and to provide international expert panel recommendations., Data Sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central., Methods: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel., Prospero Id: CRD42021244976., Results: Of 1853 studies screened, 34 were included for this review. Bacterial, CMV, and fungal antimicrobial prophylaxis were evaluated separately. Pneumocystis jiroveccii pneumonia (PJP) antimicrobial prophylaxis was analyzed separately from other fungal infections. Overall, eight randomized controlled trials, 21 comparative studies, and five observational noncomparative studies were included., Conclusions: Antimicrobial prophylaxis is recommended to prevent bacterial, CMV, and fungal infection to improve outcomes after LT. Universal antibiotic prophylaxis is recommended to prevent postoperative bacterial infections. The choice of antibiotics should be individualized and length of therapy should not exceed 24 hours (Quality of Evidence; Low | Grade of Recommendation; Strong). Both universal prophylaxis and preemptive therapy are strongly recommended for CMV prevention following LT. The choice of one or the other strategy will depend on individual program resources and experiences, as well as donor and recipient serostatus. (Quality of Evidence; Low | Grade of Recommendation; Strong). Antifungal prophylaxis is strongly recommended for LT recipients at high risk of developing invasive fungal infections. The drug of choice remains controversial. (Quality of Evidence; High | Grade of Recommendation; Strong). PJP prophylaxis is strongly recommended. Length of prophylaxis remains controversial. (Quality of Evidence; Very Low | Grade of Recommendation; Strong)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Maribavir was approved by the U.S. Food and Drug Administration in November 2021 for the treatment of adult and pediatric patients with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet. Maribavir is an oral benzimidazole riboside with potent and selective multimodal anti-CMV activity. It utilizes a novel mechanism of action which confers activity against CMV strains that are resistant to traditional anti-CMV agents, and also offers a more favorable safety profile relative to the dose-limiting side effects of previously available therapies. Maribavir was initially studied as an agent for CMV prophylaxis in solid organ and hematopoietic stem cell recipients, but initial phase III trials failed to meet clinical efficacy endpoints. It has been more recently studied as a therapeutic agent at higher doses for refractory-resistant (R-R) CMV infections with favorable outcomes. After an overview of maribavir's chemistry and clinical pharmacology, this review will summarize clinical efficacy, safety, tolerability, and resistance data associated with maribavir therapy.

Background: Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase., Methods: In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16., Results: 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80-42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs., Conclusions: Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE)., Competing Interests: Potential conflicts of interest. R. K. A.: study grant support: AiCuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, and Takeda/Shire. S. A.: research funding as a scientific expert and site principal investigator: Altona, BioMérieux, Biotest, GlaxoSmithKline, Merck, Merck Sharp & Dohme, Qiagen, Shire, a Takeda company; honoraria for lectures paid to their institution: Biotest, Merck Sharp & Dohme, IQone; support for attending meetings: BioMérieux, Biotest, Quality Control for Molecular Diagnostics; advisory board (unpaid): Quality Control for Molecular Diagnostics. Primary investigator for this study in France. B. D. A.: research funding for work as an investigator: Scynexis, Shire, a Takeda company; research funding to institution for work as an investigator: Astellas, Cidara, F2G, Leadiant; royalties or licenses: UpToDate; consulting fees: Astellas, Scynexis; leadership or fiduciary role: Past President Infectious Diseases Society of America. E. A. B.: research support to their institution: Hologic, Merck, Takeda; scientific medical advisor (unpaid): Merck; Data and Safety Monitoring Board: Amplyx; leadership or fiduciary role: board member (including office holder) American Society of Transplantation. R. F. C.: institutional research grants: AiCuris, Ansun Biopharma, Chimerix, Janssen, Karius, Merck, Novartis, Oxford Immunotec, Pulmotect, Shire, a Takeda company, Viracor; consulting fees: ADMA Biologics, Ansun Biopharma, Janssen, Merck, Molecular Partners, Qiagen, Shire, a Takeda company; honoraria: Genentech, Merck, Oxford Immunotec, Partner Therapeutics, Pulmotect, Shire, a Takeda company; Data Safety Monitoring Board or Advisory Board: Enanta, Duke; stock or stock options: Xenex. C. C.: departmental research funding: Merck, Shire, a Takeda company; consulting fees for advisory board and speaker bureau participation: Merck, Takeda. R. F. D.: departmental research funding: Janssen, Merck, Novartis, Omeros, Roche Diagnostics; consulting fees for advisory boards and speaker bureau participation: Bristol Myers Squibb, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Merck, Omeros, Pfizer, Sanofi Oncology, Sobi, Shire, a Takeda company. D. F. F.: research support for work as an investigator: Astellas, Merck, Nobelpharma, Novavax, Shire, a Takeda company; Data Safety Monitoring Board: Amplyx; advisory boards: Merck, Takeda. N. K.: advisory board and speaker’s fees: Astellas, Biotest, Chiesi, CSL Behring, Merck Sharp & Dohme, Neovii, Novartis Pharma, Sandoz, Sanofi, Shire, a Takeda company. D. K.: consultant: Roche, Sanofi, Takeda; grant/research support: Merck, Qiagen, Roche, Takeda; speaking fee: Astellas. J. M.: consulting fees from Shire/Takeda during the conduct of the study, as well as consulting fees and nonfinancial support from Amgen, Astellas Pharma, Basilea, Cidara, F2G, Schering-Plough, Scynexis; and grants, consulting fees, and nonfinancial support from Bio-Rad, Gilead Sciences, Merck, Pfizer Inc, outside the submitted work; honoraria: Astellas, F2G, Gilead, Pfizer Inc, Merck Sharp & Dohme, Mundipharma. F. M. M.: consultant: AlloVir, Amplyx, Avir, Emcure, F2G, Gilead, Janssen, Kyorin, Merck, Regeneron, ReViral, Symbio, United Medical; investigator and research funding: Ansun, Chimerix, Cidara, Scynexis, Shire, a Takeda company, WHISCON; research funding: AlloVir, Amplyx, F2G, Gilead, Merck, Regeneron. G. A. P.: consulting fees: ADMA Biologics, AlloVir, Amplyx, Astellas, Behring, Cidara, Octapharma, Partner Therapeutics, Shionogi, Shire, a Takeda company, Siemens Healthineers; investigator: Merck, Shire, a Takeda company; honoraria for speaking engagement: Basilea, Merck, Merck Sharp & Dohme Europe. F. P. S.: research support for work as an investigator: Ansun Biopharma, Gilead, Merck, Novartis, Qiagen, Shire, a Takeda company, SlieaGen, WHISCON; travel funding to meetings: Shire, a Takeda company; lecture honoraria: Janssen; consulting fees: Takeda. O. W.: research grants for clinical studies, speaker’s fees, honoraria, and travel expenses: Alexion, Amgen, Astellas, Basilea, Biotest, Bristol Myers Squibb, Chiesi, Correvio, Gilead, Hexal, Janssen, Dr. F. Köhler Chemie, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda, Teva, UCB; unrestricted grant from the Rudolf-Ackermann-Stiftung (Stiftung für Klinische Infektiologie). J. W., A. K. S., and M. F.: employees of and holding stock/stock options in: Takeda Development Center Americas, Inc. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

There are limited data on the characteristics and clinical course of fungal infections in patients on durable left ventricular assist device (LVAD) support. We sought to further characterize the epidemiology and outcomes of LVAD patients with fungemia. We performed a retrospective review of patients receiving LVAD support from January 2012 through June 2020 at a large academic institution. Among 336 patients on LVAD support, five (1.4%) were diagnosed with fungemia during the study period. Three patients had diabetes with mean hemoglobin A1c 7.1% (R 6.6, 7.4). Fever and leukocytosis (mean white blood count 17.0 thousand/µL [R 12.5, 29.9]) were the most common symptoms. Fungemia was diagnosed early after LVAD implantation (mean 14.4 support days [R 2, 19]). All patients were infected with Candida species, and four isolates were susceptible to fluconazole. Central nervous system outcomes included an ischemic stroke, subarachnoid hemorrhage, and malignant hemorrhagic stroke. Two patients were successfully transplanted, and two patients on destination therapy remain on suppressive fluconazole. In conclusion, fungemia is a rare and severe complication in LVAD patients occurring early postimplant., (Copyright © ASAIO 2021.)

Background: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety., Methods: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors., Results: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history., Conclusion: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

BACKGROUNDCOVID-19 remains a global health emergency with limited treatment options, lagging vaccine rates, and inadequate healthcare resources in the face of an ongoing calamity. The disease is characterized by immune dysregulation and cytokine storm. Cyclosporine A (CSA) is a calcineurin inhibitor that modulates cytokine production and may have direct antiviral properties against coronaviruses.METHODSTo test whether a short course of CSA was safe in patients with COVID-19, we treated 10 hospitalized, oxygen-requiring, noncritically ill patients with CSA (starting at a dose of 9 mg/kg/d). We evaluated patients for clinical response and adverse events, measured serum cytokines and chemokines associated with COVID-19 hyperinflammation, and conducted gene-expression analyses.RESULTSFive participants experienced adverse events, none of which were serious; transaminitis was most common. No participant required intensive care unit-level care, and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyperinflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I IFN gene expression signatures and other transcriptional profiles associated with exacerbated hyperinflammation in the peripheral blood cells of these patients.CONCLUSIONShort courses of CSA appear safe and feasible in patients with COVID-19 who require oxygen and may be a useful adjunct in resource-limited health care settings.TRIAL REGISTRATIONThis trial was registered on ClinicalTrials.gov (Investigational New Drug Application no. 149997; ClinicalTrials.gov NCT04412785).FUNDINGThis study was internally funded by the Center for Cellular Immunotherapies.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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 =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]., 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., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality., Methods: A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association., Results: Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01-2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15-1.36, p = .16)., Conclusions: MDROs on donor culture increase the risk of early posttransplant infection but do not appear to affect long-term graft or recipient survival, suggesting organ donors with MDROs on culture may be safely utilized. Future studies aimed at reducing early posttransplant infections associated with donor MDROs are needed., (© 2021 Wiley Periodicals LLC.)

Background: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT., Methods: Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited., Results: A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6-133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01)., Conclusions: Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence., (© 2021 Wiley Periodicals LLC.)

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described., Methods: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients., Results: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality., Conclusions: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients., Methods: A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients was identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed., Results: From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1-9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome were systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change, and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1-11 time points per trial., Conclusions: Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation, and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability, and usefulness of trial evidence., Competing Interests: S.C. is supported by the Australian National Health and Medical Research Council (NHMRC) Postgraduate Scholarship, the Microba recipient grant, the Metro South Research Support Scheme, and the Royal Australasian College of Physicians (RACP) Jacquot NHMRC Research Excellence top-up award. E.A. is supported by a NHMRC Postgraduate Scholarship and RACP Jacquot NHMRC Award for Excellence. C.M.H. is the recipient of research grants paid to her institution from Baxter Healthcare and Fresenius Medical Care and from Otsuka, Janssen, and GlaxoSmithKline for trial steering committee activities, paid to her institution. D.W.J. has received consultancy fees, research grants, speaker’s honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care. He has received consultancy fees from Astra Zeneca and AWAK, speaker’s honoraria from Ono, and travel sponsorships from Amgen. He is a current recipient of an Australian NHMRC Practitioner Fellowship. N.M.I. has received consultancy fees and speakers honoraria from Alexion Pharmaceuticals, Novo Nordisk, and Amgen. A.T. is supported by the NHMRC Research Fellowship. A.K.V. receives grant support from the Royal Australasian College of Physicians (Jacquot Research Establishment Award) and the Princess Alexandra Research Foundation. D.B. receives institutional research grant funding from CareDx, speaking honoraria from CareDx and Veloxis and is a consultant for AlloVir, Amplyx, Argenyx, CareDx, Medeor, Natera, Sanofi, and Veloxis. D.B. is supported by NIDDK U01 DK116042-01 and R01DK102981. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Transplanting kidneys from hepatitis C virus (HCV) viremic donors into HCV-negative patients (HCV D-RNA-positive/R-negative) has evolved from experimental to "standard-of-care" at many centers. Nevertheless, most data derive from single centers and provide only short-term follow-up., Methods: The Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC) study was a multicenter (7 sites) trial of HCV D-RNA-positive/R-negative kidney transplantation (KT) followed by 8 weeks of glecaprevir/pibrentasvir (G/P) initiated 2 to 5 days post-KT. Prespecified outcomes included probability of KT (vs. matched waitlist comparators) and 1-year safety outcomes, allograft function, and survival., Results: Among 63 enrolled patients, 1-year cumulative incidence of KT was approximately 3.5-fold greater for the MYTHIC cohort versus 2055 matched United Network for Organ Sharing (UNOS) comparators who did not opt-in to receive a kidney from an HCV-viremic donor (68% vs. 19%, P  < 0.0001). Of 30 HCV D-RNA-positive/R-negative KT recipients, all achieved HCV cure. None developed clinically significant liver disease or HCV-related kidney injury. Furthermore, 1-year survival was 93% and 1-year graft function was excellent (median creatinine 1.17; interquartile range [IQR]: 1.02-1.38 mg/dl). There were 4 cases of cytomegalovirus (CMV) disease among 10 CMV-negative patients transplanted with a kidney from an HCV-viremic/CMV-positive donor., Conclusion: The 1-year findings from this multicenter trial suggest that opting-in for HCV-viremic KT offers can increase probability of KT with excellent 1-year outcomes. Trial Registration: NCT03781726., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Antibiotic use in deceased organ donors has not been previously described. In a retrospective cohort of 440 donors, we found 427 (97%) received at least one antibiotic course, 312 (71%) received broad-spectrum antibiotics, and 61 (14%) received potentially redundant antibiotics during their terminal hospitalization, suggesting a need for stewardship., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Solid organ transplant recipients (SOTRs) are at increased risk for adverse outcomes with coronavirus disease 19 (COVID-19). Early data show a lower severe acute respiratory syndrome virus 2 (SARS-CoV-2) spike antibody immune response among SOTRs leading to patient concerns about vaccine efficacy. Public health messaging has largely left out immunocompromized individuals leading to a higher risk of vaccine misinformation. The American Society of Transplantation recommends COVID-19 vaccination for all SOTRs; however, patient concerns and beliefs about vaccination are largely unknown., Methods: We conducted a transplant-center-based, pragmatic pilot trial to encourage COVID-19 vaccination among 103 unvaccinated SOTRs. We assessed vaccine concerns, barriers to vaccination, answered questions about efficacy, side effects, and clinical recommendations., Results: A total of 24% (n = 25) of SOTRs reported that they will schedule COVID-19 vaccination after the study call, 46% reported that they will consider vaccination in the future, and 30% said they will not consider vaccination. Older age and White race were associated with lower willingness to schedule the vaccine, whereas Black race and longer time from transplant were associated with higher willingness. Common vaccine concerns included lack of long-term data, inconsistent messaging from providers, scheduling inconvenience, and insufficient resources. Follow-up approximately 1 month after the initial outreach found 52% (n = 13) of liver transplant recipients, and 10% (n = 3) of kidney transplant recipients subsequently received COVID-19 vaccines for a vaccination rate of 29% among respondents., Conclusion: Transplant center-based vaccine outreach efforts can decrease misinformation and increase vaccination uptake; however, vaccine-related mistrust remains high., (© 2021 Wiley Periodicals LLC.)

Background: COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear., Methods: We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant., Results: The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy., Conclusions: We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Multidrug-resistant Gram-negative bacterial infections are increasingly common among solid organ transplant (SOT) recipients, leading to challenges in the selection of empiric antimicrobial therapy. We sought to develop a clinical tool to predict which SOT recipients are at high risk for extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (EB) bloodstream infection (BSI)., Methods: A multicenter case-control study was performed. The source population included SOT recipients with an EB BSI between 2005 and 2018. Cases were those with ESBL-EB BSI; controls were those with non-ESBL EB BSI. The population was subdivided into derivation and validation cohorts based on study site. The predictive tool was developed in the derivation cohort through iterative multivariable logistic regression analyses that maximized the area under the receiver-operating curve (AUC). External validity was assessed using the validation cohort., Results: A total of 897 SOT recipients with an EB BSI were included, of which 539 were assigned to the derivation cohort (135, 25% ESBL-EB) and 358 to the validation cohort (221, 62% ESBL-EB). Using multivariable analyses, the most parsimonious model that was predictive of ESBL-EB BSI consisted of 10 variables, which fell into four clinical categories: prior colonization or infection with EB organisms, recent antimicrobial exposures, severity of preceding illness, and immunosuppressive regimen. This model achieved an AUC of 0.81 in the derivation cohort and 0.68 in the validation cohort., Conclusions: Though further refinements are needed in additional populations, this tool shows promise for guiding empiric therapy for SOT recipients with EB BSI., (© 2021 Wiley Periodicals LLC.)

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development., (© 2021 by the American Association for the Study of Liver Diseases.)

Patients pursuing solid organ transplantation are encouraged to receive many vaccines on an accelerated timeline. Vaccination prior to transplantation offers the best chance of developing immunity and may expand the pool of donor organs that candidates can accept without needing posttransplant therapy. Furthermore, transplant recipients are at greater risk for acquiring vaccine-preventable illnesses or succumbing to severe sequelae of such illnesses. However, a rising rate of vaccine refusal has challenged transplant centers to address the phenomenon of vaccine hesitancy. Transplant centers may need to consider adopting a policy of denial of solid organ transplantation on the basis of vaccine refusal for non-medical reasons (i.e., philosophical or religious objections or personal beliefs that vaccines are unnecessary or unsafe). Arguments supporting such a policy are motivated by utility, stewardship, and beneficence. Arguments opposing such a policy emphasize justice and respect for persons, and seek to avoid worsening inequities or medical coercion. This paper examines these arguments and situates them within the special cases of pediatric transplantation, emergent transplantation, and living donation. Ultimately, a uniform national policy addressing vaccine refusal among transplant candidates is needed to resolve this ethical dilemma and establish a consistent, fair, and standard approach to vaccine refusal in transplantation., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Health care workers have been prioritized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but vaccine hesitancy among workers may limit uptake. Institutions may wish to consider SARS-CoV-2 vaccine mandates for health care workers, but such proposals raise important ethical questions. Arguments supporting mandates emphasize the proposed favorable balance of harms and benefits for both individuals and communities, as well as moral duties of health care workers and organizations. Arguments in opposition seek to challenge some claims about utility and raise additional concerns about infringement on autonomy, damage to organizational relationships, and injustice. While available SARS-CoV-2 vaccines remain under an experimental designation, mandates may be excessively problematic, but following approval by the Food and Drug Administration mandates may be reconsidered. The authors summarize ethical arguments and practical considerations, concluding that mandates may be ethically permissible in select circumstances., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to afflict millions of people worldwide. Patients with end-stage heart failure and left ventricular assist devices (LVADs) may be at risk for severe COVID-19 given a high prevalence of complex comorbidities and functional impaired immunity. The objective of this study is to describe the clinical characteristics and outcomes of COVID-19 in patients with end-stage heart failure and durable LVADs., Methods: The Trans-CoV-VAD registry is a multi-center registry of LVAD and cardiac transplant patients in the United States with confirmed COVID-19. Patient characteristics, exposure history, presentation, laboratory data, course, and clinical outcomes were collected by participating institutions and reviewed by a central data repository. This report represents the participation of the first 9 centers to report LVAD data into the registry., Results: A total of 40 patients were included in this cohort. The median age was 56 years (interquartile range, 46-68), 14 (35%) were women, and 21 (52%) were Black. Among the most common presenting symptoms were cough (41%), fever, and fatigue (both 38%). A total of 18% were asymptomatic at diagnosis. Only 43% of the patients reported either subjective or measured fever during the entire course of illness. Over half (60%) required hospitalization, and 8 patients (20%) died, often after lengthy hospitalizations., Conclusions: We present the largest case series of LVAD patients with COVID-19 to date. Understanding these characteristics is essential in an effort to improve the outcome of this complex patient population.

Background: Approximately 40% of all Enterobacterales (EB) bloodstream infections (BSIs) among solid organ transplant recipients (SOTRs) are due to extended-spectrum β-lactamase (ESBL)-producing organisms, but risk factors for such infections remain ill defined in this population. We sought to determine the risk factors for ESBL-EB BSIs among SOTRs., Methods: A multicenter case-control study was performed. All SOTRs with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 January 2007 and 30 June 2018 and at The Johns Hopkins Hospital between 1 January 2005 and 31 December 2015 were included. Cases were those with an ESBL-EB BSI. Controls were those with a non-ESBL-EB BSI. Multivariable logistic regression was performed to determine risk factors for ESBL-EB BSI., Results: There were 988 episodes of EB BSI, of which 395 (40%) were due to an ESBL-EB. On multivariable analysis, the independent risk factors for ESBL-EB BSI included: ESBL-EB on prior culture (aOR, 12.75; 95% CI, 3.23-50.33; P < .001), a corticosteroid-containing immunosuppression regimen (aOR 1.30; 95% CI 1.03-1.65; P = .030), acute rejection treated with corticosteroids (aOR 1.18; 95% CI 1.16-1.19; P < .001), and exposure to third-generation cephalosporins (aOR 1.95; 95% CI 1.48-2.57; P < .001), echinocandins (aOR 1.61; 95% CI 1.08-2.40; P = .020), and trimethoprim-sulfamethoxazole (aOR 1.35; 95% CI 1.10-1.64; P = .003)., Conclusions: We identified several novel risk factors that are uniquely important to the SOTR population, including exposure to trimethoprim-sulfamethoxazole and corticosteroid-containing immunosuppressive regimens. Further studies exploring these associations and testing interventions aimed at these modifiable risk factors among SOTRs are needed., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exploded onto the world stage in early 2020. The impact on solid organ transplantation (SOT) has been profound affecting potential donors, candidates, and recipients. Importantly, decreased donations and the pressure of limited resources placed on health care by the pandemic also disrupted transplant systems. We address the impact of COVID-19 on organ transplantation globally and review current understanding of the epidemiology, outcomes, diagnosis, and treatment of COVID-19 in SOT recipients., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The medical needs of the transgender population are increasingly recognized within the US health care system. Hormone therapy and gender-affirming surgery present distinct anatomic, hormonal, infectious, and psychosocial issues among transgender kidney transplant donors and recipients. We present the first reported experience with kidney transplantation and donation in transgender patients. A single-center case series (January 2014-December 2018) comprising 4 transgender kidney transplant recipients and 2 transgender living donors was constructed and analyzed. Experts in transplant surgery, transplant psychiatry, transplant infectious disease, pharmacy, and endocrinology were consulted to discuss aspects of care for these patients. Four transgender patients identified as male-to-female and 2 as female-to-male. Three of 6 had gender-affirming surgeries prior to transplant surgery, 1 of whom had further procedures posttransplant. Additionally, 4 patients were on hormone therapy. All 6 had psychiatric comorbidities. The 4 grafts have done well, with an average serum creatinine of 1.45 mg/dL at 2 years (range 1.01-1.85 mg/dL). However, patients encountered various postoperative complications, 1 of which was attributable to modified anatomy. Thus, transgender kidney transplant patients can present novel challenges in regard to surgical considerations as well as pre- and posttransplant care. Dedicated expertise is needed to optimize outcomes for this population., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The extent to which donor multidrug-resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO-positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR-Gram-negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR-GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR-GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39-0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64-15.68, P = .01). Though donor MDR-GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)