Razonable, Raymund R.

Abstract Rationale Fungal infections are a significant cause of morbidity in lung transplant recipients. Infections caused by non-Aspergillus species (spp.) fungi, such as Alternaria, Cladosporium, Fusarium, Lomentospora, Mucorales, and Scedosporium, among others, occur infrequently, but recognized cases are increasing. There is a paucity of data assessing post-transplant outcomes following pre-transplant fungal colonization with these non-Aspergillus spp. fungal organisms. Methods We retrospectively reviewed all adult (>18 years) patients who underwent bilateral lung transplantation at either Mayo Clinic Rochester and Mayo Clinic Jacksonville between 01/01/2016 through 12/31/2024, comparing those with pre-transplant fungal colonization to those without fungal colonization. Fungal colonization was defined as positive respiratory culture in either sputum, tracheal aspirate, bronchial brush, bronchoalveolar lavage (BAL) fluid, or swab of explanted lung in asymptomatic patients without radiological or endobronchial evidence of infection. Patients who underwent single lung transplantation, multi-organ transplantation, and those who had previously undergone organ transplantation were excluded from the study. Our primary outcome was severe post-transplant fungal infection, which we defined as proven or probable invasive fungal infection (based on EORTC/MSG criteria), that required hospitalization or additional procedural intervention. Baseline characteristics were summarized using medians with interquartile ranges or counts with percentages, group balance was assessed using standardized mean differences, and associations with post-transplant fungal infection and mortality were evaluated using unadjusted risk ratios (RR) with 95% confidence intervals. Results Of the 449 lung transplant recipients who were included in analysis, a total of 83 patients (18.5%) had pre-transplant fungal colonization, 45 patients (10.0%) with Aspergillus spp. and 38 patients (8.5%) with non-Aspergillus fungi. Compared to those without pre-transplant fungal colonization (n = 366), those with fungal colonization differed significantly in age, gender, body mass index (BMI), Cytomegalovirus (CMV) mismatch status, and transplant indication. The pre-transplant fungal colonization cohort had 4 patients (4.8%) develop any severe fungal infection post-transplant (2 Aspergillus spp. and 2 non-Aspergillus spp.). Pre-transplant fungal colonization was not associated with severe post-transplant fungal infection [RR 1.36 (0.45-4.06)] or with severe post-transplant Aspergillus spp. infection specifically [RR 0.80 (0.18-3.55)]. Unadjusted mortality was also not statistically significant [RR 0.74 (0.47-1.17)]. Conclusions In our cohort of bilateral lung transplant recipients, pre-transplant fungal colonization was not associated with severe post-transplant invasive fungal infection. Although limited by the retrospective nature of the study, the results provide supportive evidence that pre-transplant fungal colonization should not be a precluding factor for undergoing lung transplantation. This abstract is funded by: None

Cytomegalovirus (CMV) establishes lifelong latency following primary infection and can reactivate to cause severe illness in immunocompromised hosts. CMV DNAemia in non-HIV-infected, non-solid organ/bone marrow transplant (NHNT) hosts is poorly characterized, with limited clinical insights. We aim to describe the clinical presentation, prognostic indicators, and outcomes of CMV DNAemia among NHNT patients. We used the TriNetX international patient database to identify adult patients diagnosed with CMV DNAemia from 2016 until March 2023. We evaluated hospitalization, intensive care unit (ICU) level care, and all-cause mortality at 30 days and 1 year. We also completed a post-propensity score analysis comparing clinical characteristics of survivors versus non-survivors at 90 days. We identified 1123 NHNT patients with CMV DNAemia, most of whom had neoplasms (63%). Venous thromboembolism occurred in 31% of the population. The 30-day hospitalization and all-cause mortality rates were 35% and 14%, respectively. After propensity score matching and Bonferroni correction, weakness, purpura, acute respiratory failure, malnutrition, encephalopathy, and hypotension were associated with increased 90-day all-cause mortality. NHNT patients with CMV DNAemia carry a substantial morbidity and all-cause mortality. Further studies are warranted to clarify whether CMV DNAemia is a causative factor or an incidental finding in this population.

ABSTRACT Background Cytomegalovirus (CMV) infection remains one of the most prevalent and consequential post solid organ transplant (SOT) infections. Treatment is often challenging, especially when dealing with refractory and resistant CMV infections. Methods We performed a retrospective multicenter cohort study of SOT recipients with clinically significant CMV infection (csCMVi) during 2010–2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Analysis was done with Kaplan‐Meier, univariable logistic regression analysis, and multivariable Cox regression. Results We included 145 SOT recipients with csCMVi, majority were liver transplant (49%). Most common induction was an anti‐IL‐2 antibody (43.9%). The majority ( n = 82; 56.5%) were CMV D+/R‐ mismatch and presented asymptomatic infection (50.3%). After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R‐ mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48–0.95, p = 0.029) while lower absolute lymphocyte count (ALC) had a higher risk of early refractory csCMVi (OR 1.54; CI 1.01–2.44, p = 0.048). Drug‐resistant csCMVi occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2.00; CI 1.08–3.93, p = 0.031). 25 patients (17.2%) experienced recurrent csCMVi within 6 months. 30 patients (20.7%) died; refractory, resistant or recurrent CMV infections were not associated with mortality. Conclusion Refractory csCMVi is associated with a low ALC and an earlier onset after transplant. Resistant csCMVi is associated with high initial CMV DNA levels. Recurrence of csCMVi is common and potentially associated with low ALC at the end of antiviral treatment.

ABSTRACT Introduction Cytomegalovirus (CMV) causes substantial morbidity after solid organ transplantation. Valganciclovir (VGCV) remains a first‐line prophylactic agent, but it has significant myelosuppressive effect. Letermovir is approved for CMV prophylaxis in high‐risk kidney transplant recipients, but data on its use outside of that population are limited. We describe characteristics and outcomes of letermovir prophylaxis in non‐kidney transplant recipients. Methods We performed a retrospective, multi‐center study of all adult non‐kidney solid organ transplant recipients (SOTr) who received letermovir (March 2018–June 2024) for CMV prophylaxis. Outcomes included breakthrough and post‐prophylaxis delayed‐onset CMV infections, adverse events, and survival. Results A total of 64 patients were included in the final analysis. Of those, letermovir was used for primary prophylaxis in 56.2% of patients, while the remainder received it for secondary prophylaxis. The main rationale behind selecting letermovir was myelosuppression related to VGCV. During the median follow‐up of 361 days (IQR, 190–536), 40.6% remained on letermovir (median, 387 days); 25.0% completed prophylaxis (median, 116 days); and 34.3% discontinued prematurely (median, 49 days), mainly for cost barriers or adverse effects. Breakthrough infections occurred in 9 patients (14.1%), but only three (4.7%) were clinically significant. After stopping letermovir, 39.5% (15/38 among those who discontinued letermovir) developed post‐prophylaxis delayed‐onset CMV infection. Overall survival was 81.2%; there was one death attributed to CMV. Conclusion In this cohort of non‐kidney solid organ recipients, letermovir was well tolerated with low rates of clinically significant breakthrough infections. Early discontinuation was commonly cost‐driven. Post‐prophylaxis delayed‐onset CMV infections remain common. Large‐scale registry studies are needed to provide evidence for use of letermovir in non‐kidney transplant recipients.

Abstract Background Adenovirus is a ubiquitous dsDNA virus with potential for end-organ disease. End-organ or disseminated adenoviral disease (EOD) occurs more frequently in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. We aim to characterize the clinical manifestations and outcome of adenovirus viremia in adults, including HSCT and SOT recipients. We describe severity of illness, organ-involvement, and graft and patient survival. Methods This retrospective, multi-site, study enrolled adults patients with positive adenovirus PCR in blood and other clinical specimens from January, 2010 through April, 2025. We excluded patients with insufficient medical records, follow up less than 30 days, and isolated conjunctivitis without viremia. EOD was defined by the presence of clinical signs or symptoms consistent with organ involvement, confirmed by a positive adenovirus PCR or by histopathology. Descriptive and comparative statistics were performed using R. Results Fifty patients with adenovirus viremia were included in this study. The most common immunocompromising conditions were corticosteroid use (84%, n = 42), HSCT (40%, n = 20) and SOT (34%, n = 17) (Table 1). Only 3 patients (6%) had no known immunocompromising condition. 20 patients (40%) had EOD while 30 patients (60%) had isolated viremia. Lungs were the most affected organ, followed by the gastrointestinal tract and liver (Figure 1). EOD was more prevalent in older patients (60 vs. 41 years, p =0.03) and in those with higher initial plasma viral load (673364 vs. 6593, p=0.005). The most common treatment was reduction in immunosuppression (Table 2). Cidofovir was more often used in patients with EOD. Adenovirus-related outcomes were worse in patients with EOD [higher rates of mortality (45% vs. 13.3%) and ICU admission (60% vs. 20%)] vs. without EOD (Table 3). Conclusion Adenovirus viremia is associated with high mortality in a cohort of mostly immunocompromised adults, particularly those with EOD. Older age and a higher initial plasma viral load are associated with EOD. Patients with EOD had worse clinical outcomes such as ICU admission and adenovirus-related mortality. Disclosures All Authors: No reported disclosures

Abstract Background Hematopoietic stem cell transplant (HSCT) recipients are susceptible to infections with respiratory viruses resulting in higher morbidity and mortality. Parainfluenza virus (PIV) infection in the setting of leukopenia is associated with higher risk of lower respiratory tract infection and mortality. Intravenous immunoglobulin (IVIG) has been used as adjunctive treatment in viral respiratory infections, although data guiding its use is limited.Table 1:Patient CharacteristicsTable 2:Clinical Outcomes Methods We conducted a retrospective cohort study of adult HSCT recipients diagnosed with PIV infection at our institution from January 2014 to September 2024. Diagnosis of PIV infection was made via BioFire® Respiratory Panel multiplex polymerase chain reaction (PCR) or viral culture from nasopharyngeal or bronchoalveolar lavage. Data on clinical characteristics and outcomes were collected and reviewed.Table 3:Clinical Outcomes for Patients with IgG <767 mg/dL Results A total of 110 HSCT recipients were diagnosed with PIV infection by PCR or viral culture within the study period. Patient characteristics and clinical outcomes are summarized in Tables 1 and 2. PIV type 3 was the most common, followed by PIV type 4 and type 1. Eighteen patients (16.36%) had co-infections with another virus. A total of 16 patients received IVIG at time of PIV infection. The mean cumulative IVIG dose was 28.75 grams. Patients who received IVIG were more likely to have been hospitalized due to symptoms related to the viral infection (p=0.03) and had a lower immunoglobulin G level (p< 0.001). Overall, there was no significant difference in rates of mechanical ventilation (12.5% vs 7.45%, p=0.616), development of secondary fungal or bacterial infection (12.5% vs 12.7%, p=1), or 90-day mortality (18.75% vs 6.38%, p=0.123) among patients treated with or without IVIG, respectively. Similarly, in a subset analysis of patients with IgG level < 767 mg/dL, there were no significant difference in outcomes for patients treated with or without IVIG (Table 3). Conclusion There were no significant differences in clinical outcomes, including rates of mechanical ventilation, secondary infections, or 90-day mortality, between HSCT patients who received IVIG and those who did not for PIV infection. Larger studies are needed to gain insight into efficacy of IVIG as adjunctive treatment in PIV infections in this population. Disclosures All Authors: No reported disclosures

Abstract Background Cytomegalovirus (CMV) infection remains one of the most prevalent and important infections following solid organ transplant (SOT). Treatment is often challenging, especially when dealing with refractory and resistant CMV infections.Table 1:Univariable logistic regression analyses of associations with early refractory CMV infectionTable 2:Univariable logistic regression analyses of associations with resistant CMV infection Methods We performed a retrospective cohort study of SOT recipients with clinically significant CMV infection (csCMVi) at a tertiary transplant center in the US during 2010-2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Kaplan-Meier estimation, univariable logistic regression analysis, and multivariable Cox regression were used for outcome analysis.Table 3:Multivariable Cox regression analysis of associations with recurrent CMV infection after primary treatment endedNote: Refractory CMV was not included in the model for recurrent CMV as no patients with refractory infection had recurrence. Results A total of 145 SOT recipients with csCMVi were included. Most patients were recipients of liver (49%), followed by kidney (22.1%), heart (6.9%), lung (5.5%), and pancreas (4.1%). Multiple organ transplants accounted for 12.4% of the cohort. Most common induction was an anti-IL-2 antibody (43.9%) followed by ATG (29.5%). 82 (56.5%) had CMV D+/R- mismatch. In total, 34 (23.4%) had CMV syndrome, 38 (26.2%) had tissue-invasive CMV disease, while the rest (50.3%) were asymptomatic. After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R- mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48-0.95, p=0.029) while lower absolute lymphocyte count (ALC) was higher risk of early refractory csCMVi (OR 1.54; CI 1.01-2.44, p=0.048) (Table 1). Drug-resistant CMV occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2; CI 1.08-3.93, p=0.031) (Table 2). Of 144 patients with post-treatment follow-up, 25 (17.2%) experienced recurrent csCMVi within 6 months. Table 3 shows the associations with recurrence of csCMVi after initial treatment. 30 patients (20.7%) died during a median follow-up of 4 years, but refractory, resistant or recurrent CMV were not associated with mortality. Conclusion Refractory csCMVi is associated with low ALC and an earlier onset post-transplant. Resistant csCMVi is associated with high levels of initial CMV DNA. Recurrence of csCMVi is common and possibly associated with low ALC at the end of antiviral treatment. Disclosures All Authors: No reported disclosures

ABSTRACT This study investigated the association between induction type and long‐term outcomes in kidney retransplant recipients who experienced graft loss due to BK virus–associated nephropathy (BKVAN). Using Scientific Registry of Transplant Recipients data (2003–2021), we identified 277 adult kidney‐alone retransplant recipients with BKVAN‐related graft loss and categorized them by induction regimen: depletional ( n = 217) and nondepletional ( n = 60). The groups were similar overall, except the nondepletional cohort had lower panel‐reactive antibodies, a shorter time between transplants, and more live donor kidneys. Kaplan–Meier curves assessed 10‐year recipient and graft survival, and Cox proportional hazards models, adjusted for key donor and recipient factors, evaluated associations between induction type and outcomes. Rates of delayed graft function, one‐year rejection, and estimated glomerular filtration rate were comparable between groups. Ten‐year recipient and death‐censored graft survival did not differ by induction type (recipient survival: HR 1.09; 95% CI 0.43–2.77; p = 0.85; graft survival: HR 0.85; 95% CI 0.24–2.97; p = 0.79). Recurrent BKVAN‐related graft failure occurred only in the depletional group (5 of 217; 2.3%), while rejection‐related graft failure was more common in the nondepletional group (5 of 60; 8.3% vs. 6 of 217; 2.8%). Although these differences did not translate into long‐term graft survival disparities, they highlight the competing risks of viral recurrence and rejection. Thus, clinicians should interpret these results with caution and weigh the risks and benefits of induction choice in retransplant recipients with prior BKVAN, recognizing that this observational study cannot establish causality.

Abstract Advocacy has long been at the core of the infectious diseases (ID) field, with clinicians and researchers advocating to ensure patients can access the care they need on an individual and global scale. The Infectious Diseases Society of America Training Program Directors’ (PD) Committee met in 2024 and discussed ways that advocacy is and should be incorporated into fellowship training, as well as highlighted the role PDs play in advocating for their trainees. Policies with a negative impact on ID clinical care, public health, and research underscore the importance of mobilizing the field of ID to advocate for the patients and communities we serve, as well as for ourselves. This paper presents ideas generated at this meeting and is meant to serve as a reference for ID PDs, as well as the wider ID community, as a call to action for teaching and participating in advocacy work.

ABSTRACT Purpose The purpose of this study was to evaluate the incidence and risk factors for developing recurrent clinically significant cytomegalovirus infections (csCMVi) in heart transplant recipients. Methods We conducted a retrospective cohort study involving adult heart transplant recipients at three large transplant centers in the United States between January 2011 and March 2019. All patients with a history of csCMVi, defined as CMV disease or CMV infection requiring preemptive therapy, were followed from the date of treatment completion for the primary csCMVi episode. Outcomes of interest were recurrent csCMVi and all‐cause mortality. Results Among 98 heart transplant recipients with csCMVi, 22 (22.4%) episodes of recurrent csCMVi occurred. Median time‐to‐recurrent csCMVi was 31.5 (IQR 21.3–59.8) days following treatment completion. A preceding episode of CMV disease (versus infection) was associated with a lower risk of recurrent csCMVi (HR 0.29, 95% CI 0.08–0.98; p = 0.047). Patients with lymphopenia had higher rates of recurrent csCMVi without statistical significance (HR 2.13, 95% CI 0.88–5.13; p = 0.093). Seroconversion by the end‐of‐therapy among CMV D+/R− mismatched patients was associated with a reduced risk of csCMVi recurrence (HR 0.07, 95% CI 0.02–0.30; p < 0.001). Overall, 17 (17.3%) patients died during follow‐up, which was not significantly higher among those with recurrent csCMVi (HR 2.13, 95% CI 0.78–5.79; p = 0.141). Conclusions About one in five heart recipients with csCMVi developed post‐treatment recurrence. A preceding episode of CMV disease and seroconversion was protective against recurrence. Lymphopenia may be a practical biomarker to stratify recurrence risk. Overall, recurrent csCMVi was not significantly associated with mortality.