A 67-year-old female underwent an en-bloc double lung transplantation for idiopathic pulmonary fibrosis. The post-transplant course was complicated by refractory septic shock. Despite empiric antimicrobial coverage with vancomycin, meropenem, micafungin, and posaconazole, she continued to require high-dose vasopressors and remained unable to wean from veno-venous extracorporeal membrane oxygenation (ECMO). Blood cultures were positive for Candida Kefyr (teleomorph: Kluyveromyces marxianus), the same organism that had been isolated from donor bronchoalveolar lavage cultures 5 days prior to transplant. Micafungin and posaconazole doses were increased, and intravenous (IV) liposomal amphotericin B was added. Within 2 days, her hemodynamics improved, allowing successful weaning from ECMO. However, repeat blood cultures demonstrated persistent candidemia. Chest computed tomography revealed pericardial and bilateral pleural effusions, suspicious for mediastinitis and empyema. Transesophageal echocardiography confirmed pericardial effusion but showed no vegetations. Chorioretinal lesions were noted bilaterally without vitritis. Micafungin and posaconazole were discontinued and IV voriconazole was started for eye penetration. Amphotericin B was continued for 4 weeks and voriconazole for 3 months. Repeat blood cultures showed clearance of fungemia, and ophthalmology eye exam showed no further signs of chorioretinitis. Donor-derived infections are a rare complication of solid organ transplantation, with fungal infections posing a unique challenge due to their high morbidity and mortality. To our knowledge, there are no documented cases in the literature of possible donor-derived C. kefyr leading to blood stream infection in the recipient. This case highlights the need for heightened clinical vigilance and prompt multidisciplinary management to mitigate the impact of post-transplant complications.

Background:Endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed in liver transplant recipients for the management of biliary complications. While frequently medically necessary, ERCP carries a risk of post-procedural infections, particularly in immunosuppressed transplant patients. Prophylactic antibiotics are sometimes recommended, but their role remains uncertain. We aimed to address this knowledge gap. Methods:This single-arm systematic review and meta-analysis included randomised controlled trials (RCTs), prospective and retrospective cohort studies, and case-control studies evaluating the use of prophylactic antibiotics prior to or during ERCP (for any indication) in liver transplant recipients. No restrictions were placed on patient age, sex, or ethnicity. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched for relevant studies published between database inception and June 2025. Primary outcomes of interest were incidence of post-ERCP cholangitis, infection, or pancreatitis, incidence of overall procedural complications, and mortality attributable to procedural complications. The quality of included studies was assessed via ROBINS-I. This work is registered with PROSPERO, CRD42024604381. Findings:This review included 26 studies involving more than 3800 liver transplant recipients undergoing over 7300 ERCP procedures. All studies were non-randomised, comprising nine prospective and 17 retrospective studies. The pooled complication rate was 25.7% per patient and 6.7% per procedure; the pooled cholangitis rate was 8.6% per patient and 3.5% per procedure; and the pooled pancreatitis rate was 6.1% per patient and 1.9% per procedure. In the overall cohort, the pooled mortality rate due to post-ERCP complications was 1.1% with two deaths reported among 594 patients. Both fatalities were attributed to sepsis secondary to cholangitis. Bile cultures were positive in 80.1% of the samples with a sensitivity of 63.7% to prophylactic antibiotics used and 24.3% of isolates resistant to more than one antibiotic. The highest resistance was observed against gentamicin (54.1%) and ceftriaxone (53.7%) while resistance was lower for piperacillin/tazobactam (26.2%) and carbapenems (26.6%). Resistance rates were higher in transplant recipients compared to the general ERCP population. Interpretation:Despite widespread prophylactic antibiotic use, post-ERCP infections and antimicrobial resistance remain prevalent in liver transplant recipients. These findings support more targeted prophylactic strategies using agents with lower resistance rates, particularly in patients undergoing repeat ERCPs. This single-arm analysis did not include a direct comparator group of patients without antibiotic prophylaxis. Future prospective studies and randomised controlled trials are essential to determine the optimal prophylactic regimen, dose, and duration in this high-risk population. Funding:None.

BACKGROUND:Lung transplant recipients (LTRs) are at risk for Mycobacterium avium complex (MAC) infections, in part due to the presence of structural lung disease pre-transplant and relatively higher levels of immunosuppression post-transplant. There is a lack of data regarding outcomes of LTR with MAC infections pre-transplant. METHODS:This is a single-center retrospective analysis of patients who received lung transplants (LTs) from 2013 to 2020 with 1) evidence of MAC on culture or polymerase chain reaction before or at the time of transplant or 2) granulomas on explant pathology and positive acid-fast bacillus stains with no other mycobacteria identified. Patients were deemed to have MAC pulmonary disease (MAC-PD) if they met the American Thoracic Society/Infectious Disease Society of America criteria. RESULTS:Fourteen patients (14/882, 2%) met inclusion criteria. Seven patients (7/14, 50%) had pre-transplant MAC-PD, four of whom had cavitary disease. None of the 14 patients had smear-positive cultures at the time of transplant. Two patients in our cohort received treatment for MAC before transplant. Thirteen patients were bilateral LTR (13/14, 93%). One single LTR was the sole patient to receive MAC treatment post-transplant. No patients developed MAC-PD after transplant. CONCLUSION:The bilateral LTR in our cohort did not develop MAC-PD despite not receiving MAC treatment post-transplant. It is possible source control was achieved with native lung explantation. Our observations suggest patients may not uniformly require pre- or post-transplant MAC treatment if they are smear-negative and undergo bilateral LT.

PURPOSE OF REVIEW:Infections in lung transplant recipients remain a major challenge and can affect lung allograft function and cause significant morbidity and mortality. New strategies for the prevention and treatment of infection in lung transplantation have emerged and are reviewed.RECENT FINDINGS:For important vaccine preventable infections (VPIs), guidance has been updated for at risk solid organ transplant (SOT) recipients. However, data on the efficacy of newer vaccines in lung transplant, including the respiratory syncytial virus (RSV) vaccine, are limited. Studies demonstrate improved vaccination rate with Infectious Diseases consultation during pretransplant evaluation. Two new antiviral agents for the treatment and prevention of cytomegalovirus (CMV) in SOT, letermovir and maribavir, are being incorporated into clinical care. CMV-specific cell-mediated immune function assays are more widely available. Antibiotics for the management of multidrug resistant pathogens and Burkholderia cepacia complex have been described in case series and case reports in lung transplant.SUMMARY:Although new vaccines and novel therapies for preventing and treating infections are available, larger studies evaluating efficacy in lung transplant recipients are needed.

Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in infants, older adults, and patients with weakened immune systems. Disease severity differs by underlying immunologic pathologies, with worse outcomes associated with progression from upper to lower respiratory disease. In this review we address the impact of RSV in immunocompromised populations, and discuss the limited available treatments and the potential impact of newer RSV prevention strategies on immunocompromised adults and children.

BACKGROUND Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure. AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections. METHODS From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review. RESULTS All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance. CONCLUSION Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Introduction: Alcohol-associated liver disease is associated with hepatic inflammation and uniquely predisposes patients to infections and associated acute-on-chronic liver failure (ACLF). Alcohol use is among the leading causes of ACLF and associated mortality in the critical care setting. We aimed to compare baseline characteristics and outcomes of infections in patients with alcohol-associated cirrhosis (ALD) and non-alcohol associated cirrhosis (NALD) in the Medical Intensive Liver Unit (MILU). Methods: From our prospective registry of patients admitted to our MILU between August 2018-September 2022, we identified 80 culture-positive patients with ALD and 82 with NALD. Chi-squared and t-tests were used to compare the 2 groups on comorbidities, acute characteristics of infection, and clinical outcomes. Results: Compared to NALD patients, patients with ALD were younger (56 years vs 61 years, P = 0.003) and had higher rates of pre-infection ascites and hepatic encephalopathy (98% vs 88%, P = 0.018; 95% vs 82%, P = 0.009 respectively) (Table 1). The majority of infections were bacterial (87%) (Enterococcus faecium, Escherichia coli, and Klebsiella spp) followed by fungal (13%) (Candida). Rates of fungal infections and multi-drug resistant (MDR) infections were similar between patient groups. At time of infection, bilirubin (13.88 vs 8.58, P = 0.003), MELD-Na (31.62 vs 27.92, P = 0.006) and Child Pugh scores (11.39 vs 10.70, P = 0.012) were significantly higher in ALD patients; degree of ACLF severity was similar between patient groups. ALD patients more frequently required intubation (81% vs 62%, P = 0.007), but had similar rates of vasopressor requirements, ICU, and hospital LOS. Rates of listing for liver transplant (LT) were lower in ALD patients (43% vs 63%, P = 0.039), while rates of LT among listed patients and in-hospital mortality were similar. The 2 groups did not differ in survival (Figure 1). Conclusion: Critically ill ALD patients are younger with higher markers of liver disease severity at time of acute infection but have similar rates of organ failure or ACLF grade, and comparable outcomes of mortality, LOS, MDR infection, ACLF severity, and rates of LT as NALD patients in the critical setting following infection. Future studies elucidating the impact of ALD severity and active alcohol use on predisposition to infection and ACLF-related outcomes are needed. Table 1. - Comparison of Baseline Characteristics, Acute Infections, and Outcomes Between Patients with Alcohol and Non-Alcohol Associated Cirrhosis Non-Alcohol Associated Cirrhosis Alcohol-Associated Cirrhosis P-value N = 82 N = 80 Age 61 (10) 56 (11) 0.003 Sex 44 (54%) 51 (64%) 0.19 Race 0.54 White 63 (77%) 60 (75%) American Indian/Alaska Native 1 (1%) 0 (0%) Asian 1 (1%) 0 (0%) Black 9 (11%) 15 (19%) Declined 1 (1%) 0 (0%) Multiracial/cultural 2 (2%) 2 (3%) Unavailable 5 (6%) 3 (4%) Charlson Comorbidity Score 5 (4-7) 6 (5-8) 0.15 Hepatocellular carcinoma 12 (15%) 5 (6%) 0.082 Decompensation-Defining Complications Pre-Infection Ascites 72 (88%) 78 (98%) 0.018 Hepatic encephalopathy 67 (82%) 76 (95%) 0.009 Hepatorenal syndrome 32 (39%) 41 (51%) 0.12 EV history/Variceal bleeding 57 (70%) 61 (76%) 0.34 Hepatopulmonary syndrome 2 (2%) 0 (0%) 0.16 Porto-pulmonary hypertension 3 (4%) 3 (4%) 0.98 Hepatic hydrothorax 14 (17%) 16 (20%) 0.63 SBP 27 (33%) 30 (38%) 0.54 Coagulopathy 59 (72%) 62 (78%) 0.42 Thrombocytopenia 62 (76%) 59 (74%) 0.79 Characteristics on Day of Infection Infectious micro-organism 0.22 Bacterial 74 (90%) 67 (84%) Fungal 8 (10%) 13 (16%) Creatinine 2.523 (1.89) 2.26 (1.39) 0.31 INR 1.94 (.81) 2.22 (1.08) 0.068 Bilirubin 8.58 (10.87) 13.88 (11.70) 0.003 Child-Pugh score 10.70 (1.77) 11.39 (1.73) 0.012 MELD-Na 27.93 (7.65) 31.62 (9.11) 0.006 MDRO 33 (40%) 38 (48%) 0.35 ACLF grade 0.79 0 12 (15%) 9 (11%) 1 16 (20%) 15 (19%) 2-3 54 (66%) 56 (70%) Comparison of Outcomes Death during admission or hospice 51 (62%) 53 (66%) 0.59 Vasopressor required 4 (31%) 4 (33%) 0.89 Mechanical ventilation 51 (62%) 65 (81%) 0.007 Reason for intubation 0.082 Airway protection 14 (27%) 28 (43%) Respiratory failure 37 (73%) 37 (57%) ICU Length of stay (days) 5 (2-9) 5 (2-10.5) 0.54 Hospital length of stay (days) 15 (7-25) 17 (9-32.5) 0.072 ICU to Hosp Admit (days) 1 (0-10) 1 (0-11.5) 0.60 Evaluated for transplant 51 (62%) 54 (68%) 0.48 Listed 32 (63%) 23 (43%) 0.039 Organ listed 0.49 Liver 22 (71%) 19 (79%) Liver and kidney 9 (29%) 5 (21%) Hold placed 21 (66%) 11 (48%) 0.19 Transplant occurred 13 (16%) 13 (16%) 0.95 Figure 1.: Comparison of Survival Between Patients With ALD and non-ALD Cirrhosis With Infections.

The authors declare that they have no conflict of interest. These data were derived from the following resources available in the public domain: (SRTR, PubMed)

Coronavirus disease-19 has had a marked impact on the transplant population and processes of care for transplant centers and organ allocation. Several single-center studies have reported successful utilization of deceased donors with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. Our aims were to characterize testing, organ utilization, and transplant outcomes with donor SARS-CoV-2 status in the United States. We used Scientific Registry of Transplant Recipients data from March 12, 2020 to August 31, 2021 including a custom file with SARS-CoV-2 testing data. There were 35 347 donor specimen SARS-CoV-2 tests, 77.5% upper respiratory samples, 94.6% polymerase chain reaction tests, and 1.2% SARS-CoV-2-positive tests. Donor age, gender, history of hypertension, and diabetes were similar by SARS-CoV-2 status, while positive SARS-CoV-2 donors were more likely African-American, Hispanic, and donors after cardiac death (p-values <.01). Recipient demographic characteristics were similar by donor SARS CoV-2 status. Adjusted donor kidney discard (odds ratio = 2.08, 95% confidence interval [CI] 1.66-2.61) was higher for SARS-CoV-2-positive donors while donor liver (odds ratio = 0.44, 95% CI 0.33-0.60) and heart recovery (odds ratio = 0.44, 95% CI 0.31-0.63) were significantly reduced. Overall post-transplant graft survival for kidney, liver, and heart recipients was comparable by donor SARS-CoV-2 status. Cumulatively, there has been significantly lower utilization of SARS-CoV-2 donors with no evidence of reduced recipient graft survival with variations in practice over time.

Emerging data support the safety of transplantation of extra-pulmonary organs from donors with SARS-CoV-2-detection. Our center offered kidney transplantation (KT) from deceased donors (DD) with SARS-CoV-2 with and without COVID-19 as a cause of death (CoV + COD and CoV+) to consenting candidates. No pre-emptive antiviral therapies were given. We retrospectively compared outcomes to contemporaneous DDKTs with negative SARS-CoV-2 testing (CoVneg). From February 1, 2021 to January 31, 2022, there were 220 adult KTs, including 115 (52%) from 35 CoV+ and 33 CoV + COD donors. Compared to CoVneg and CoV+, CoV + COD were more often DCD (100% vs. 40% and 46%, p < .01) with longer cold ischemia times (25.2 h vs. 22.9 h and 22.2 h, p = .02). At median follow-up of 5.7 months, recipients of CoV+, CoV + COD and CoVneg kidneys had similar rates of delayed graft function (10.3%, 21.8% and 21.9%, p = .16), rejection (5.1%, 0% and 8.5%, p = .07), graft failure (1.7%, 0% and 0%, p = .35), mortality (0.9%, 0% and 3.7%; p = .29), and COVID-19 diagnoses (13.6%, 7.1%, and 15.2%, p = .33). Though follow-up was shorter, CoV + COD was associated with lower but acceptable eGFR on multivariable analysis. KT from DDs at various stages of SARS-CoV-2 infection appears safe and successful. Extended follow-up is required to assess the impact of CoV + COD donors on longer term graft function.

Introduction: Kidneys from deceased donors with SARS-CoV-2 infection during donor evaluation have not been accepted by most transplant centers due to concerns for productive COVID-19 infection and organ injury from COVID-related complications or viral transmission leading to de novo recipient infection. Our transplant center developed protocols to accept such kidneys. We aimed to compare clinical outcomes of kidney transplants (KT) from deceased donors with and without SARS-CoV-2 infection (CoVDpos and CoVDneg, respectively). Methods: We retrospectively reviewed donor and recipient data and key clinical outcomes for all CoVDpos KTs performed at our center between 02/01/2021 and 01/31/2022, and compared such data to all consecutive CoVDneg KTs performed during the same period. Donor organ acceptance was pre-established by a protocol developed specifically to select CoV positive deceased donors. No COVID-directed therapies were provided to CoVDpos KT recipients. Standard of care induction therapy (lymphocyte-depleting agents) and a CNI-based maintenance regimen was used for all transplant recipients independent of donor type. Recipient vaccination prior to transplantation was not required in early 2021 but mandated after November 2021. Results: There were 221 KTs, including 112 (51%) KT recipients (from a total of 63 CoVDpos deceased donors) and 109 KTs from CoVD neg deceased donors. Median time from positive SARS-Co-2 PCR test to donation was 16 days with a mean PCR threshold cycle of 30. Mean KDPI was 36+/-21 vs 45%+/-24 for the CovDpos vs CovDneg, respectively. DCD donors were more common in CovDpos when compared to CovDneg KTs (71% vs 47%, p <0.001). Of the 63 CoVDpos donors, 30 (48%) died of COVID complications, mostly hypoxic respiratory failure, with 5 on VV ECMO. Pretransplant vaccination was 96.5% of CoVDpos recipients and 87.2%of CoVDneg KT recipients. Having a CoVDpos kidney transplant was not associated with increased incidence of DGF (15.2% vs 22%, p=NS). KT recipients of CoVDpos organs had similar eGFR at last follow up when compared to recipients of CovDneg kidneys (47+/-20 vs 2+/-23 ml/min/1.73m2, p=NS). In a multivariable analysis, only recipient age, recipient BMI and DCD were independently associated with post-transplant GFR, while donor Covid-19 infection status was not found to be statistically significant. There was 1 patient death (from progressive pre-existent interstitial lung disease in the absence of SARS-CoV-2 detection from lower airway by BAL) 4 months post-KT, compared to 4 patient deaths in the CovDneg group, all from non-COVID-19 related illnesses. No kidney transplant recipients developed COVID-19 immediately post-transplant. Conclusions: Kidney transplant outcomes including graft function was similar in recipients of CoVDpos to those of CoVDnegs out 12 months post-transplant. There was no clinical evidence of SARS-CoV-2 transmission demonstrating the safety of this protocolized approach. Careful utilization of kidneys from CoVDpos donors could minimize unnecessary discard of organs.

Transplantation of solid organs from donors with active SARS-CoV-2 infection has been advised against due to the possibility of disease transmission to the recipient. However, with the exception of lungs, conclusive data for productive infection of transplantable organs do not exist. While such data are awaited, the organ shortage continues to claim thousands of lives each year. In this setting, we put forth a strategy to transplant otherwise healthy extrapulmonary organs from SARS-CoV-2-infected donors. We transplanted 10 kidneys from five deceased donors with new detection of SARS-CoV-2 RNA during donor evaluation in early 2021. Kidney donor profile index ranged from 3% to 56%. All organs had been turned down by multiple other centers. Without clear signs or symptoms, the veracity of timing of SARS-CoV-2 infection could not be confirmed. With 8-16 weeks of follow-up, outcomes for all 10 patients and allografts have been excellent. All have been free of signs or symptoms of donor-derived SARS-CoV-2 infection. Our findings raise important questions about the nature of SARS-CoV-2 RNA detection in potential organ donors and suggest underutilization of exceptionally good extrapulmonary organs with low risk for disease transmission.