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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.)

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.)

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: 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.)

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.

Antibiotic prophylaxis in the perioperative period is the standard of care for nearly all surgical procedures and routinely prescribed during solid organ transplantation (SOT). The primary goal of perioperative antibiotic prophylaxis is to minimize postoperative surgical site infections (SSIs). SSIs are a significant issue in SOT. Depending on the organ transplanted, SSIs occur in 3% to 53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. SOT recipients are also at increased risk of developing SSIs with antimicrobial-resistant organisms. In this article, we describe the epidemiology and risk factors for SSIs in SOT and examine the available literature to guide the use of different regimens for perioperative antibiotic prophylaxis for each organ. We have further addressed specific situations that are unique to each organ transplant type, such as the use of extracorporeal membrane oxygenation in thoracic organ transplantation, as well as an approach to perioperative antibiotic prophylaxis in the setting of recipient and/or donor infection before transplantation. We provide potential approaches to the selection, dosing, and duration of perioperative antibiotic prophylaxis for each of these clinical situations.

Background: Ledipasvir-sofosbuvir is effective at eradicating hepatitis C virus (HCV) infection in the general population and in HCV-monoinfected kidney transplant recipients, but there are no data to guide its use in human immunodeficiency virus/HCV coinfected kidney transplant patients., Methods: We treated 6 human immunodeficiency virus/HCV coinfected kidney transplant recipients with ledipasvir-sofosbuvir at our 2 centers. All were infected with genotype 1 and 66% had received kidneys from HCV+ donors., Results: All patients cleared the virus while on therapy and 100% have achieved a sustained virologic response at 12 weeks after completion of ledipasvir-sofosbuvir. Tacrolimus dosing required adjustment during and after ledipasvir-sofosbuvir therapy but antiretroviral regimens did not., Conclusions: Ledipasvir-sofosbuvir was well tolerated. Although all patients in our series were treated posttransplant, the ideal timing of HCV therapy in this population is unknown, and the impact of HCV clearance on posttransplant outcomes is yet to be determined.

Background: While donor-derived infections (DDI) remain uncommon, multiple reports describe DDI with pathogens that cause central nervous system (CNS) infection resulting in significant recipient disease. The Ad Hoc Disease Transmission Advisory Committee (DTAC) reviewed the records of potential donor-derived disease transmission events (PDDTE) to describe donor characteristics and outcomes associated with DDI from CNS pathogens., Methods: All PDDTE reported from January 2008 to September 2010 were reviewed for characteristics suggesting CNS infection in the donor or the recipient. Identified cases were further examined to determine if donor CNS infection resulted in recipient infection., Results: Ninety-one PDDTE cases in which there was concern for CNS infection in the donor or recipient were identified. Further review confirmed CNS infection in 12 donors, six of whom transmitted infection to 10 of 15 exposed recipients with five recipient deaths. Pathogens included Balamuthia mandrillaris, Cryptococcus neoformans, lymphocytic choriomeningitis virus, and West Nile virus. Listed cause of death at procurement for these donors included stroke, anoxia, acute disseminated encephalomyelitis, and meningoencephalitis. Confounding diagnoses were present in 6 of 12 donors that would have allowed them to be considered at low risk of transmitting a CNS pathogen. Of the six donors with no confounding conditions, three exhibited at least two suspicious "DTAC warning criteria" for CNS infection., Conclusion: Careful clinical assessment of donors combined with a high index of suspicion for ambiguous or misleading findings associated with CNS infection can reduce, but not eliminate, DDI with CNS pathogens.

Purpose of Review: Multidrug-resistant (MDR) bacteria can cause serious infections in solid-organ transplant recipients. This review focuses on the role of MDR bacteria in posttransplant infections., Recent Findings: The incidence of MDR bacterial infections among solid-organ transplant recipients is increasing steadily. There is wide variability in the specific MDR bacteria causing infection based on the organ transplanted, geography, timing with respect to transplantation, and additional risk factors. Rarely these infections can be transmitted via the transplanted organ. Prompt recognition and early appropriate treatment of MDR bacterial infections are especially critical in this immunosuppressed population. In order to promptly initiate appropriate antimicrobial therapy for these organisms, high-risk patients should receive appropriate broad-spectrum antibiotics., Summary: MDR bacterial infections vary widely and require careful antibiotic selection to reduce mortality.

Background: Donor-derived Strongyloides stercoralis infection occurs rarely after transplantation, and the risk factors are not well understood. We present cases of two renal allograft recipients who developed Strongyloides hyperinfection syndrome after receipt of organs from a common deceased donor who received high-dose steroids as part of a preconditioning regimen., Methods: The two renal transplant patients who developed Strongyloides hyperinfection syndrome are reported in case study format with review of the literature., Results: Microscopic examination of stool from one renal transplant patient and of tracheal and gastric aspirates from the other transplant patient revealed evidence of S. stercoralis larvae. Retrospective testing of serum from the deceased donor for Strongyloides antibodies by enzyme-linked immunosorbent assay was positive at 11.7 U/mL (Centers for Disease Control reference >1.7 U/mL positive). One patient was treated successfully with oral ivermectin. The other patient also had complete resolution of strongyloidiasis, but required a course of parenteral ivermectin because of malabsorption from severe gastrointestinal strongyloidiasis., Conclusions: These case studies provide some of the best evidence of transmission of S. stercoralis by renal transplantation. Because of the high risk of hyperinfection syndrome and its associated morbidity and mortality, high-risk donors and recipients should be screened for Strongyloides infection, so that appropriate treatment can be initiated before the development of disease. This study indicates that parenteral ivermectin can be used safely and effectively in patients in whom severe malabsorption would preclude the effective use of oral formulation. These cases also suggest that reconsideration should be given for the safety of steroids in donor-preconditioning regimens.

Background: Cytomegalovirus (CMV) disease in transplant patients is known to have a substantial clinical and economic burden, and its prevention is expected to have long-term benefits. Evidence from the Improved Protection Against CMV in Transplant trial proved that prolonged prophylaxis of 200 days with valganciclovir compared with 100 days significantly reduces the incidence of CMV in high-risk kidney transplant seropositive donors/seronegative recipients. The aim of this study was to develop a cost-effectiveness model to evaluate prolonged prophylaxis of 200 days with valganciclovir and its long-term economic impact., Methods: An economic model was designed to simulate long-term costs and outcomes of prolonged prophylaxis with valganciclovir (200 vs. 100 days) in a cohort of 10,000 high-risk renal transplant patients over 5 and 10 years. The first year of the model was based on the results of the Improved Protection Against CMV in Transplant trial and the extension to the long-term periods (5 and 10 years); and quality of life data were based on evidence retrieved through a systematic literature search. This analysis was conducted from the US healthcare payer perspective., Results: For the 5-year time horizon, the incremental cost-effectiveness ratio of US $14,859/quality-adjusted life year (QALY) suggests that 200-day valganciclovir prophylaxis is cost effective over the 100-day regimen considering a threshold of US $50,000/QALY. The 10-year analysis revealed the 200-day prophylaxis as cost saving with a 2380 QALY gain and simultaneously lower cost., Conclusion: Prolonged prophylaxis with valganciclovir reduces the incidence of events associated with CMV infection in high-risk kidney transplant recipients and is a cost-effective strategy in CMV disease management.

Background: Whether the early reduction in cytomegalovirus (CMV) disease seen at 1 year with prolongation of antiviral prophylaxis (up to 200 days) persists in the long term is unknown., Methods: This international, randomized, prospective, double-blind study, compared 318 CMV D+/R- kidney transplant recipients receiving valganciclovir (900 mg) once daily for up to 200 days vs. 100 days. Long-term outcomes including CMV disease, acute rejection, graft loss, patient survival, and seroconversion were assessed., Results: At 2 years posttransplant, CMV disease occurred in significantly less patients in the 200- vs. the 100-day group: 21.3% vs. 38.7%, respectively (P<0.001). Between year 1 and 2, there were only 10 new cases of CMV disease; 7 in the 200-day group and 3 in the 100-day group. Patient survival was 100% in the 200-day group and 97% in the 100-day group (p=not significant). Biopsy-proven acute rejection and graft loss rates were comparable in both groups (11.6% vs. 17.2%, P=0.16, and 1.9% vs. 4.3%, P=0.22, in the 200-day vs. 100-day groups, respectively). Seroconversion was delayed in the 200-day group but was similar to the 100-day group by 2 years posttransplant (IgM or IgG seroconversion; 55.5% in the 200-day group vs. 62.0% in the 100-day group at 2-years; P=0.26). Assessment of seroconversion at the end of prophylaxis was of limited utility for predicting late-onset CMV disease., Conclusion: Extending valganciclovir prophylaxis from 100 to 200 days is associated with a sustained reduction in CMV disease up to 2 years posttransplant.

Objectives: To identify the proportion of U.S. transplant surgeons who are adequately vaccinated against hepatitis B virus (HBV), identify characteristics associated with inadequate vaccination, and assess the proportion who had been evaluated for immunization following potential HBV exposures., Summary Background Data: It is unknown what proportion of transplant surgeons are appropriately vaccinated against HBV or evaluated for immunization following operative exposures., Methods: We mailed questionnaires and to all active U.S. transplant surgeons. We compared demographic characteristics of responders and nonresponders to evaluate the potential for nonresponse bias., Results: Of 619 eligible respondents, 347 (56.1%) returned completed questionnaires. Of the 311 surgeons for whom HBV vaccination was indicated (all surgeons with neither a prior history of HBV infection nor a prior adverse reaction to the vaccine itself), 70 (22.5%; 95% confidence interval [CI], 18.0-27.6%) received fewer than the recommended 3 injections. Surgeon characteristics associated with inadequate vaccination included length of clinical practice (odds ratio [OR], 1.5 per 10-year increment in duration of practice; 95% CI, 1.1-2.2), increased fear of infection (OR, 1.2 for each unit increase in fear out of 10; 95% CI, 1.1-1.4), and lack of recent testing for HBV infection (OR, 2.0; 95% CI, 1.1-3.8). Of the 94 surgeons (27.3%) reporting at least one needle-stick exposure while operating on an HBV-infected patient, 14 (14.9%) were inadequately vaccinated; of these 14, only 5 (35.7%) sought appropriate serologic testing and counseling for active immunization. Surgeons underestimated both the risks of percutaneous exposure while operating, and of becoming infected with HBV if exposed., Conclusions: Many transplant surgeons are inadequately vaccinated against HBV and fail to seek evaluation following possible exposures. Underestimation of the risks of HBV exposure and transmission may relate to these failures. Requiring documentation of HBV vaccination and immunity to maintain operating room privileges may protect surgeons, their patients, and operating room staff.