Donor-derived infections in the United States: Opportunities to learn from the Disease Transmission Advisory Committee's experience.

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.

Sodium-Glucose Cotransporter 2 Inhibitors and Mycotic Genital or Urinary Tract Infections in Heart Failure.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) improve clinical outcomes in persons with heart failure (HF). This class of agents has been consistently associated with an increased risk of mycotic genital infections (MGIs), and in some, but not all, trials, urinary tract infections (UTIs). Other medications widely used for cardiac conditions do not cause MGIs and UTIs, so cardiologists and their supporting teams will be encountering clinical questions that they previously did not have to address. This review provides clinicians with practical recommendations about SGLT2i use in individuals with HF as related to the associated MGI and possible UTI risks. Overall, given the benefit of SGLT2is in clinical outcomes, the threshold for not initiating or discontinuing SGLT2is due to concerns for MGIs or UTIs should be high for persons with HF. Likewise, when SGLT2is are discontinued for such concerns, the threshold for reinitiation should be low.

Challenging boundaries: Organ transplants from donors with Listeria central nervous system infections.

Pretransplant mortality rates in the US remain high and are connected to effective organ donation and utilization. Thus, there is a need to maximize the utilization of available donors. In some cases, this has been safely achieved using organs from donors with infectious complications. For example, several studies describe the use of organs from donors with bacterial meningitis due to pathogens such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenza, and Escherichia coli, with good outcomes. Listeria is an aerobic and facultatively anaerobic, nonspore-forming, Gram-positive rod that can affect the central nervous system, causing meningitis and meningoencephalitis. Due to its virulence, ability to cause intracellular infection, and lack of clinical data, people dying with listeria may not be evaluated for organ donation, may not have organs recovered, or may have their organs recovered but not transplanted. Herein, we describe the outcomes of 7 solid organ transplant recipients who received organs from 2 donors with Listeria monocytogenes central nervous system infection.

The nuts and bolts of transplant infectious disease training.

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

Consensus position statement on advancing the standardised reporting of infection events in immunocompromised patients.

Patients can be immunocompromised from a diverse range of disease and treatment factors, including malignancies, autoimmune disorders and their treatments, and organ and stem-cell transplantation. Infections are a leading cause of morbidity and mortality in immunocompromised patients, and the disease treatment landscape is continually evolving. Despite being a critical but preventable and curable adverse event, the reporting of infection events in randomised trials lacks sufficient detail while inconsistency of categorisation and definition of infections in observational and registry studies limits comparability and future pooling of data. A core reporting dataset consisting of category, site, severity, organism, and endpoints was developed as a minimum standard for reporting of infection events in immunocompromised patients across study types. Further additional information is recommended depending on study type. The standardised reporting of infectious events and attributable complications in immunocompromised patients will improve diagnostic, treatment, and prevention approaches and facilitate future research in this patient group.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

Minimizing the Risk of Donor-Derived Events and Maximizing Organ Utilization Through Education and Policy Development.

Herein, we review the current knowledge of donor-derived disease and current US Organ Procurement and Transplantation Network policies to minimize the risk. During the process, we also consider actions to further mitigate the risk of donor-derived disease. The overarching goal is to provide an infectious disease perspective on the complex decision of organ acceptance for transplant programs and candidates.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

A Case Report of Breakthrough Infections With 2 SARS-CoV-2 Variants in a Lung Transplant Patient.

A lung transplant (LT) patient developed 2 distinct episodes of COVID-19, confirmed by whole-genome sequencing, which was caused by the Delta, and then followed 6 weeks later, by the Omicron variant. The clinical course with Omicron was more severe, leading us to speculate that Omicron may not be any milder among LT patients. We discuss the potential mechanisms behind the Omicron not being any milder among LT patients and emphasize the need for outcomes data among these patients. Until such data become available, it may be prudent to maintain clinical equipoise as regards the relative virulence of the newer variants among LT patients.

Transplantation for chagas' disease: closing the knowledge gap.

PURPOSE OF THE REVIEW: This review examines the most recent literature on the epidemiology and treatment of Chagas Disease and the risk of Chagas Disease Reactivation and donor-derived disease in solid organ transplant recipients. RECENT FINDINGS: Chagas disease is caused by infection with the parasite Trypansoma cruzi . In nonendemic countries the disease is seen primarily in immigrants from Mexico, Central America and South America where the disease is endemic. Benznidazole or nifurtimox can be used for treatment. Posaconazole and fosravuconazole did not provide any additional benefit compared to benznidazole alone or in combination. A phase 2 randomized controlled trial suggests that shorter or reduced dosed regimes of benznidazole could be used. Based on a large randomized controlled trial, benznidazole is unlikely to have a significant preventive effect for established Chagas cardiomyopathy. Transplantation has become the treatment of choice for individuals with refractory Chagas cardiomyopathy. Cohort studies show similar posttransplant outcomes for these patients compared to other indications. Transplant candidates and donors with chronic T. cruzi infection are at risk for Chagas disease reactivation and transmitting infection. Screening them via serology is the first line of prevention. Recipients with chronic infection and those receiving organs from infected donors should undergo sequential monitoring with polymerase chain reaction for early detection of reactivation and preemptive treatment with antitrypanosomal therapy. SUMMARY: Patients with chronic T. cruzi infection can be safely transplanted and be noncardiac organ donors.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Through Solid Organ Transplantation and Outcomes of Coronavirus Disease 2019 Among Recent Transplant Recipients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmissible through lung transplantation, and outcomes among infected organ recipients may be severe. Transmission risk to extrapulmonary organ recipients and recent (within 30 days of transplantation) SARS-CoV-2-infected recipient outcomes are unclear. Methods: During March 2020-March 2021, potential SARS-CoV-2 transmissions through solid organ transplantation were investigated. Assessments included SARS-CoV-2 testing, medical record review, determination of likely transmission route, and recent recipient outcomes. Results: During March 2020-March 2021, approximately 42 740 organs were transplanted in the United States. Forty donors, who donated 140 organs to 125 recipients, were investigated. Nine (23%) donors and 25 (20%) recipients were SARS-CoV-2 positive by nucleic acid amplification test (NAAT). Most (22/25 [88%]) SARS-CoV-2-infected recipients had healthcare or community exposures. Nine SARS-CoV-2-infected donors donated 21 organs to 19 recipients. Of these, 3 lung recipients acquired SARS-CoV-2 infections from donors with negative SARS-CoV-2 testing of pretransplant upper respiratory tract specimens but from whom posttransplant lower respiratory tract (LRT) specimens were SARS-CoV-2 positive. Sixteen recipients of extrapulmonary organs from SARS-CoV-2-infected donors had no evidence of posttransplant COVID-19. All-cause mortality within 45 days after transplantation was 6-fold higher among SARS-CoV-2-infected recipients (9/25 [36%]) than those without (6/100 [6%]). Conclusions: Transplant-transmission of SARS-CoV-2 is uncommon. Pretransplant NAAT of lung donor LRT specimens may prevent transmission of SARS-CoV-2 through transplantation. Extrapulmonary organs from SARS-CoV-2-infected donors may be safely usable, although further study is needed. Reducing recent recipient exposures to SARS-CoV-2 should remain a focus of prevention.

COVID-19 Vaccination is Associated With Favorable Outcomes Among Lung Transplant Patients With Breakthrough Infections.

BACKGROUND: There are limited data regarding the clinical efficacy of COVID-19 vaccines among lung transplant (LT) patients. METHODS: We included all LT patients diagnosed with COVID-19 between March 1, 2020, and December 10, 2021 (n = 84; median age 55, range, 20-73 years; males 65.5%). The study group was divided into 3 groups based on the vaccination status (patients who did not complete the primary series for any of the vaccines: n = 58; those with 2 doses of messenger RNA (mRNA) or 1 dose of the adenoviral vector vaccine, vaccinated group: n = 16; those with at least 1 additional dose beyond the primary series, boosted group: n = 10). RESULTS: Pulmonary parenchymal involvement on chest computed tomography scan was less common among the boosted group (P = .009). The proportion of patients with new or worsening respiratory failure was significantly lower among the vaccinated and boosted groups and these patients were significantly more likely to achieve the composite endpoint of oxygen-dependence free survival (P = .02). On multivariate logistic regression analysis, higher body mass index, restrictive lung disease as the transplant indication, and preinfection chronic lung allograft dysfunction were independently associated with acute or acute on chronic respiratory failure while being on therapeutic dose anticoagulation and having received the booster dose had a protective effect. CONCLUSION: COVID-19 vaccines appear to have several favorable effects among LT patients with breakthrough infections including lower likelihood of allograft involvement on imaging (among boosted patients), need of hospitalization, and complications such as new or worsening respiratory failure.

Short-term kidney transplant outcomes from severe acute respiratory syndrome coronavirus 2 lower respiratory tract positive donors.

OBJECTIVE: In this study, we aim to assess short-term allograft outcomes following deceased donor kidney transplantation from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lower respiratory tract (LRT) nucleic acid testing (NAT) positive donors. METHODS: From September to December 2021, SARS-CoV-2 NAT positive organ donors, whose solid abdominal organs were transplanted at our academic medical center were identified. Donors were stratified into having tested positive for SARS-CoV-2 in an upper respiratory tract (URT) or LRT sample. For this study, the SARS-CoV-2 LRT NAT positive deceased kidney donors and their respective recipients were examined. Donor and recipient demographic data, coronavirus disease 2019 (COVID-19)-related history, patient outcomes, as well as postoperative graft function were evaluated. RESULTS: Thirteen SARS-CoV-2 positive deceased donors were identified. Of these, eight were LRT NAT positive and yielded nine kidneys. These allografts were successfully transplanted into vaccinated and unvaccinated recipients. All recipients received standard induction immunosuppression and did not receive any prophylactic therapy for SARS-CoV-2. Two recipients had delayed graft function. At 1-month post-transplant, there was no clinical evidence of donor-derived COVID-19 or graft loss, and all recipients were free from dialysis. CONCLUSION: We describe the first case series of SARS-CoV-2 LRT NAT positive deceased kidney donors for vaccinated and unvaccinated recipients with excellent short-term allograft outcomes and no clinical evidence of donor-derived COVID-19 post-transplantation. Given the increasing prevalence of SARS-CoV-2 in the population, utilization of SARS-CoV-2 LRT NAT positive deceased donors could be considered an acceptable source of organs for renal transplantation, especially as multi-center experiences and longer-term follow-up emerge.