bluuebunny/crossref_metadata_2025_split huggingface dataset:
2704. Real-world safety and effectiveness of letermovir for preventing cytomegalovirus (CMV) disease in patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT): Final results of post-marketing surveillance (PMS) in Japan
Authors: Fukuda Masaki , Hattori Junko , Ohkubo Rika , Watanabe Asuka , Maekawa Shinichiroh 
Published: November 2023

Abstract

Background
CMV is one of the most common opportunistic infections in patients undergoing allo-HSCT. Letermovir is an inhibitor of CMV DNA terminase that is approved for CMV prophylaxis in patients undergoing allo-HSCT. We report the final results of a PMS that collected data on its safety and effectiveness of letermovir in real-world clinical practice after its approval in Japan.

Methods
The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Patients who underwent HSCT and started letermovir between May 2018–May 2022 at one of 136 centers in Japan were registered in the PMS. Safety data collected in the PMS included adverse events (AEs)/adverse drug reactions (ADRs), which were assessed by the physicians. Clinical effectiveness outcomes were the development of CMV disease, CMV antigen status, and use of preemptive therapy within 48 weeks of starting letermovir. The database was locked on October 5, 2022.

Results
Overall, 932 patients who underwent HSCT were registered, of which 821 were included in safety analyses. ADRs occurred in 11.33% of patients and serious ADRs occurred in 3.05%. The five most common ADRs were nausea (1.58%), renal impairment (1.46%) and acute graft versus host disease (0.61%), CMV test positive (0.61%), and hepatic function abnormal (0.61%). AEs related to renal disorders occurred in 6.67% and 4.30% of patients treated with intravenous and oral letermovir, respectively. AEs related to cardiac disorders occurred in 3.05% of patients treated with oral/intravenous letermovir. Of 670 patients eligible for the effectiveness analyses at Week 48, CMV antigens were detected in 38.36% (Figure 1).

Conclusion
This final analysis PMS in Japan provides further evidence supporting the effectiveness and long-term safety of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

Disclosures
Masaki Fukuda, MSD K.K.: Grant/Research Support|MSD K.K.: Salary provided by MSD K.K. Junko Hattori, PhD, MSD, KK: Grant/Research Support|MSD, KK: Salary Rika Ohkubo, PhD, MSD K.K.: Grant/Research Support|MSD K.K.: Salary provided by MSD K.K. Asuka Watanabe, n/a, MSD K.K.: Grant/Research Support|MSD K.K.: Salary provided by MSD K.K. Shinichiroh Maekawa, n/a, MSD K.K.: Grant/Research Support|MSD K.K.: Salary provided by MSD K.K.
2705. Predictors of Severe COVID-19 among Solid Organ Transplant Recipients
Authors: Gillcrist Marion , Waller Stephen , Taylor Ryan M , Bahr Nathan C , Cibrik Diane M , Shah Zubair , Montgomery Robert , Eid Albert 
Published: November 2023

Abstract

Background
While some studies have found worse COVID-19 outcomes among solid organ transplant (SOT) recipients, others found no difference when comorbidities and other risk factors for severe disease were accounted for. It remains unclear whether immunosuppressive medications increase the risk of progression to severe disease in SOT recipients.

Methods
We conducted a retrospective case-control study of SOT recipients diagnosed with COVID-19 at the University of Kansas Medical Center between January 1, 2020 and December 31, 2022. Severe COVID-19 was defined by hypoxia while the patient was on room air during a 21-day period after the COVID-19 diagnosis was established. We fit a logistic regression model with severe COVID-19 as the response variable and adjusted for prescription of mycophenolate, tacrolimus and prednisone and a set of covariates including age, sex, race, body mass index, hypertension, diabetes mellitus, prespecified time period of COVID-19 diagnosis during the pandemic, chronic heart disease, chronic lung disease, malignancy, end stage renal disease, cirrhosis, smoking, receipt of COVID-19 vaccine, and receipt of monoclonal antibodies.

Results
A total of 570 SOT recipients were diagnosed with COVID-19. Our cohort consisted of 458 kidney, 73 liver, 54 heart, 43 pancreas, and 8 lung recipients. The median patient age was 54 years, 59% were male, and 70% were white. Severe COVID-19 developed in 127/570 (22.3%) patients. A total of 58/570 (10.2%) patients died. A multivariable analysis showed that age (OR = 1.04; p &lt; 0.01), race other than white (OR = 1.88; p = 0.02), chronic heart disease (OR = 1.91, p = 0.01), chronic lung disease (OR = 2.21; p = 0.02), lack of prior COVID-19 vaccination (OR = 2.09; p = 0.01), and not receiving treatment with monoclonal antibodies (OR = 3.82; p &lt; 0.01) were associated with severe COVID-19. Being on treatment with mycophenolate, tacrolimus, or prednisone at the time of COVID-19 diagnosis was not associated with severe disease.

Conclusion
Patients receiving mycophenolate, tacrolimus, or prednisone at the time of COVID-19 diagnosis were not more likely to experience severe disease. Overall mortality in our SOT population was 10%.

Disclosures
All Authors: No reported disclosures
2717. Beware the bacteria: risk of bacterial infections persists more than 60 days post CAR-T
Authors: Mathur Poonam , Riedel David J , Bork Jacqueline T , Prakash Katya , Hardy Nancy , Baddley John W 
Published: November 2023

Abstract

Background
Immunosuppressive conditioning regimens for chimeric antigen receptor-modified T cells (CAR-T) and subsequent T cell dysfunction increase risk for infection. Prior studies of infection risk after CAR-T have found bacterial infections are most common in the first month, and viral infections are more frequently seen after 30 days. We evaluated longer-term infection outcomes, up to 180 days post CAR-T infusion.

Methods
We performed a retrospective chart review of 144 patients who received CAR-T infusion at our institution between March 2018 and March 2022. We collected data on demographics, type and timing of infections, onset and treatment of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or Cytokine Release Syndrome (CRS), and mortality up to 180 days after CAR-T infusion. We determined if ICANS, CRS, or treatment for either was associated with infections using Chi-square test.

Results
The mean age of patients in our cohort was 59 years. Most patients were male (65%), White (66%), and had not received a prior stem cell transplant (78%). Fifty-one (35%) patients had at least one infection during the study period (29% bacterial, 13% viral, 2% fungal). Mortality was 23% at 180 days. Most infections occurred within 60 days post CAR-T (Figure 1). Infections occurring between days 61 and 180 were mostly bacterial. In addition, ICANS ≥grade 3 and CRS ≥grade 2 occurred in 22 (15%) and 54 (38%) patients, respectively; both were significantly associated with bacterial infection (p&lt; 0.05).
Figure 1
Infections 180 days after CAR-T. *includes bacteremia, pneumonia, and skin and soft tissue infections.

Conclusion
This cohort analyzed long-term infection outcomes post CAR-T. Most infections occurred early after CAR-T, within 60 days, and ICANS and CRS were associated with bacterial infection. We found that infections still persisted late after CAR-T, between Days 61 and 180, and were predominately bacterial, rather than viral or fungal. The low rates of fungal infection throughout the study period may be due to our institution’s fungal prophylaxis protocol. Future analyses will elucidate risk factors for infections in the late CAR-T period.

Disclosures
David J. Riedel, MD, MPH , Gilead: Advisor/Consultant
2719. Oral Antibiotics for Treatment of Gram-Negative Bacteremia in Solid Organ Transplant Recipients: A Propensity Score Weighted Retrospective Observational Study
Authors: Nussbaum Eliezer Zachary , Koo Sophia , Kotton Camille N 
Published: November 2023

Abstract

Background
Treatment of gram-negative bloodstream infections (GNBI) with oral rather than intravenous (IV) antimicrobial agents can reduce length of stay, catheter associated complications and improve patient satisfaction. There is minimal data regarding this practice in solid organ transplant recipients (SOTR). We assessed the safety and efficacy of oral step-down therapy for treatment of uncomplicated GNBI in SOTR.

Methods
We identified all SOTR within the Massachusetts General and Brigham and Women’s Hospital systems from 2016-2021 with uncomplicated GNBI that were transitioned from IV to oral agents to complete treatment. We identified a second group of patients with uncomplicated GNBI who remained on IV antimicrobials for the entirety of treatment but had an infecting organism susceptible to at least a moderately bioavailable oral agent. We conducted a propensity score weighted retrospective study to compare outcomes of the oral and IV groups. Primary endpoints were mortality, recurrence of bacteremia and re-initiation of IV antibiotics within 30 days of treatment completion. Secondary endpoints included length of stay, C. difficile infection, treatment associated complications, and need for tunneled central venous access.

Results
120 GNBI from 107 patients met inclusion criteria in the oral group and 42 GNBI from 40 patients in the IV group. There was no statistically significant difference in mortality, bacteremia recurrence, or re-initiation of IV antibiotics between oral and IV groups. Compared with the IV group, patients transitioned to oral antibiotics had an average length of stay that was 1.97 days shorter (p=0.005, 95% CI -3.56, -0.39 days). Odds of developing C. difficile were 8.4 times higher in the IV group (p=0.015, 95% CI 1.5, 46.6) and the odds of developing other treatment associated complications were 6.4 times higher in the IV group (p=.002, 95% CI 1.9-20.9). 55% of patients in the IV group required placement of a tunneled central venous catheter. There was no difference in total duration of antibiotic treatment between groups.
Baseline Patient Characteristics
Infecting Species, Source of Infection and Antibiotic Therapy
Clinical Outcomes in Oral and IV Antibiotic Treatment Groups

Conclusion
Conversion from IV to oral therapy with moderate to highly bioavailable antimicrobials was effective and associated with fewer treatment related adverse events in SOTR with uncomplicated GNBI.

Disclosures
Sophia Koo, MD, SM, Aerium Therapeutics: Advisor/Consultant|GSK: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support
2722. Risk of Infectious Adverse Events of Venetoclax Therapy in the Treatment of Hematologic Malignancies: A Systematic Review and Bayesian Meta-Analysis of Randomized Controlled Trials
Authors: Prosty Connor , Katergi Khaled , Nguyen Alex , Luo Owen , Sorin Mark , Cherniak Vladimir , Sebag Michael , Demir Koray , McDonald Emily , Lee Todd C , Cheng Matthew 
Published: November 2023

Abstract

Background
Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia and chronic lymphocytic leukemia. Recent post-marketing studies on venetoclax suggested that it may predispose to opportunistic infections (OIs). We sought to systematically review the randomized controlled trial (RCT) evidence on venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia.

Methods
We systematically reviewed the RCTs comparing venetoclax therapy to active (i.e., a regimen with additional anti-cancer agents) or placebo controls in patients with hematologic malignancies, irrespective of treatment line. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis and we computed the probability of any increased risk in infectious or neutropenic complications (Risk Ratio [RR] &gt;1). Subgroup analyses were conducted based on treatment line, use of an inactive comparator, malignancy type, and prophylaxis strategy. Additionally, we pooled the incidence rates of fatal OIs between venetoclax and comparator arms and compared them by univariate meta-regression.

Results
Seven RCTs were included comprising 2067 patients. In venetoclax versus comparator regimens there was a 81.1% probability of any increase in IAEs (RR=1.14, 95% Confidence Interval [95%CI]=0.76-1.66). The probabilities of venetoclax increasing the risk of grade 3-5 and fatal IAEs were 86.6% (RR=1.16, 95%CI=0.86-1.55) and 81.1% (RR=1.40, 95%CI=0.66-2.94), respectively. There was a 97.2% likelihood that venetoclax increased the risk of grade 3-5 neutropenia (RR=1.44, 95%CI=1.01-2.10). Venetoclax treatment did not increase the incidence of fatal OIs (P=0.55).

Conclusion
Our results suggest that venetoclax likely increases the risk of high-grade neutropenia and IAEs overall, but not fatal OIs. However, our analyses did not identify any specific IAEs that would benefit from routine anti-infective prophylaxis or pre-emptive testing.

Disclosures
Michael Sebag, MD, PhD, Amgen: Advisor/Consultant|BMS: Advisor/Consultant|Focus Therapeutics: Advisor/Consultant|Gilead: Advisor/Consultant|Janssen: Advisor/Consultant|Novartis: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Matthew Cheng, MD, Amplyx Pharmaceuticals: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|GEn1E lifesciences: Advisor/Consultant|GEn1E lifesciences: Stocks/Bonds|Kanvas Biosciences, Inc.: Board Member|Kanvas Biosciences, Inc.: Pending patents|Kanvas Biosciences, Inc.: Ownership Interest|Merck: Honoraria|nomic bio: Advisor/Consultant|nomic bio: Stocks/Bonds|Pfizer: Honoraria|Scynexis Inc.: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria
2725. Bacterial blood stream infections in Pediatric Liver Transplant Patients: Prevalence, Organisms and Risk factors. A Systematic review
Authors: Shieb Mohamad , Hasanain Rand , Arshad Zara , Nawaz Faisal A , Kashyap Rahul , Stern Eric J 
Published: November 2023

Abstract

Background
Bacterial blood stream infection (BSI) is a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient population. This systematic review aims at pooling global data from the leading transplant institutions to identify the overall prevalence and risk factors associated with bacterial BSI and the most common causative organisms.

Methods
A systematic review of PubMed and OVID databases was conducted for the past 20 years. Initial search from both databases had a yield of 252 unique articles which were reviewed independently by two authors. Data related to demographics, prevalence, organisms and risk factors were extracted from the articles and subsequently analysed. The systematic review was registered on PROSPERO (ID: CRD42023403206).
The PRISMA flow diagram visually summarises the screening process

Results
A total of 14 articles were included from the United States of America, France, Italy, Thailand, Japan, Spain and Korea. A total of 4215 liver transplants were included in the final analysis. The overall prevalence of BSI in pediatric liver transplant patients was 23.5% with the highest prevalence reported in Japan (39.5%) and lowest in the USA (18.7%). Mean age of the patients was 25 months and 54% were females. The most common organisms reported were Staphylococcus epidermidis at 22.8% followed by Enterococcus species (16.6%), Klebsiella species (11.9%) and Escherichia coli (11.4%). Among the risk factors studied, postoperative biliary complications, past medical history of biliary atresia and younger age were the risk factors most associated with BSI.
Prevalence of bloodstream infections (BSI) post pediatric liver transplant in included countries.
Bacterial organisms isolated in blood cultures in pediatric post liver transplant patient with a bloodstream infection.

Conclusion
Bacterial BSI post pediatric liver transplantation occurs with high prevalence. Further studies need to be conducted to better define risk factors for BSI and determine the best empirical antibiotic management for BSI in this population as the distribution of organisms varies greatly from otherwise healthy pediatric patients.

Disclosures
All Authors: No reported disclosures
2727. Risk factors and clinical outcomes of tuberculosis among hematopoietic stem cell transplant recipients in endemic country: A single-center, case-control study
Authors: Tanchotikul Kamolchanok , Lohawatcharagul Tuntanut , Jutivorakool Kamonwan , Bunworasate Udomsak , Vanichanan Jakapat 
Published: November 2023

Abstract

Background
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis following reactivation from latent infection. Immunocompromised individuals, including hematopoietic stem cell transplant (HSCT) recipient, are at risk for active TB which can lead to poor outcomes. Currently, the epidemiological data and risk factors related to TB infection among HSCT recipients especially in endemic country are still limited.

Methods
A matched single-center, case-control study was conducted in King Chulalongkorn Memorial Hospital. Cases were defined as HSCT recipients who were diagnosed proven or probable active TB between January 2008 to December 2020. For each case, 5 controls were matched by gender, age (±5 years), and type of transplant. Risk factor associated with TB was determined using multivariate cox regression.

Results
During the study period, a total of 570 patients underwent HSCT. Eleven patients were diagnosed with active TB represented incidence of 1.93%. Pulmonary involvement was the most common presentation (64%) followed by pleura (18 %), pleuropulmonary (9%) and pericardium (9%). Active TB was diagnosed at median duration of 3.76 months (1.33-22.88) after HSCT. Overall median duration for treatment was 6 months (IQR, 1.2-11.5). Autologous HSCT recipients mostly received rifampin-based regimen while allogeneic HSCT recipients received quinolone-containing regimen. Eight patients (73%) were cured, while another 3 (27%) patients died. There was no significant difference in mortality and primary disease relapse between case and control group. In multivariate analysis, previous TB contact or infection (OR 5.852 95%CI 1.268-27.011) and invasive aspergillosis (OR 6.113 95%CI 1.467-25.475) were associated with active TB in HSCT recipient.

Conclusion
Incidence and mortality of TB among HSCT recipients were higher compared to general population. Active TB was diagnosed shortly after HSCT and previous TB exposure was a significant risk factor. These findings may suggest reactivation of latent TB is the main pathogenesis of this patient population in endemic country.

Disclosures
All Authors: No reported disclosures
2728. Bronchial Cultures at Time of Transplant Affect Anastomotic Outcomes in Lung Transplant Recipients
Authors: Veisblatt Jesse , Altneu Eric , Kashem M Abul , Toyoda Yoshiya , Axelrod Peter , Mishkin Aaron D 
Published: November 2023

Abstract

Background
Anastomotic complications after lung transplant cause significant morbidity and mortality. Estimates of complication prevalence in lung transplant recipients range from 5-20%. Many factors are hypothesized to contribute to airway complications, including the presence of bacteria and fungi at time of transplant. Our aim was to examine the contribution of airway cultures at the time of transplant to airway complications.

Methods
We performed a retrospective analysis of lung transplant recipients who developed bronchial complications at a single, tertiary care center between January 1, 2016 and March 31, 2020. We identified 68 cases with anastomotic complications during this time period, then compared this cohort to 131 cases without bronchial complications. Primary outcomes were airway complications at 30 and 90 days. Please refer to the attached tables for variables of interest.

Results
Of 199 total study participants, 68 (34%) were found to have airway complications. Overall, the most common bacterial isolate was Staphylococcus aureus (72 MSSA and 17 MRSA). The most common fungal isolate was Candida albicans (87). When examining the patients with airway complications, MRSA isolates at time of transplant showed a statistically significant increase in airway complications (p=0.03, OR=3). An increase in airway complications was not seen for patients with other positive bacterial or fungal cultures at 30 days or 90 days.
Microbiological Risk Factors for Airway Complications
Patient Demographics and Characteristics

Conclusion
MRSA isolates at time of transplant correlated to increased 30 day and 90 day bronchial complications. This study helps confirm the importance of monitoring airway cultures at the time of transplant. A multi-center study with a larger sample size may be needed to further delineate contributions of specific microorganisms, surgical techniques, as well as perioperative and prophylactic antimicrobials on bronchial complications.

Disclosures
Aaron D. Mishkin, MD, Pfizer: Grant/Research Support|Takeda: Advisor/Consultant
2734. Evaluation of Empiric Antimicrobial Therapy for End-Stage Liver Disease Patients at an Academic Medical Center
Authors: Kim Annie , Kaip Emily A , Quan David , Doernberg Sarah B , Jariwala Ripal 
Published: November 2023

Abstract

Background
Patients with end-stage liver disease (ESLD) are prone to decompensation secondary to infections, with an increasing prevalence of multidrug-resistant organisms (MDROs). These patients often receive broad-spectrum antimicrobials prior to transplant, pre-disposing them to resistant pathogens. Our study assessed institutional guideline adherence, antimicrobial prescribing, and the incidence of MDROs in this population.

Methods
This IRB-approved, retrospective chart review included pre-transplant inpatients with ESLD on the adult liver transplant service who received antimicrobials between 1/1/20 and 10/30/20. Patients were excluded if they started antimicrobials post-transplant or transferred from another institution on parenteral antimicrobials. Per institutional guidelines for empiric antimicrobials in suspected infection in ESLD, patients were categorized into three infectious risk categories: Floor/Non-High-Risk (F-NHR), Floor/High-Risk (F-HR), and ICU or MELD greater than 35 (ICU/M35). Antimicrobial prescribing in each group was evaluated for guideline adherence and microbiology data. Results were analyzed using descriptive statistics.

Results
We included 92 patients: 28 F-NHR, 50 F-HR, and 14 ICU/M35. Table 1 summarizes baseline characteristics. The frequency of guideline adherence for the F-NHR, F-HR, ICU/M35 groups, respectively, was 11 (39%), 4 (8%), and 4 (29%) patients. For the F-NHR group, ceftriaxone (CRO) was most prescribed (n=17, 61%). For the F-HR group, 18 (36%) received CRO; 16 (32%) received vancomycin and piperacillin-tazobactam. In the ICU/M35 group, 13 patients (93%) received meropenem plus linezolid, and 11 (79%) also received caspofungin.
No methicillin-resistant Staphylococcus aureus or carbapenem-resistant Enterobacterales were isolated. Two patients (14%) in the ICU/M35 group experienced C. difficile infection within 30 days of antimicrobial initiation.Table 1.Baseline characteristics among guideline cohorts

Conclusion
Our study showcases opportunities to optimize internal ESLD antimicrobial protocols and curtail unnecessary antimicrobial exposure. Study limitations include a small cohort at a single center. Future directions include data dissemination and protocol updates.

Disclosures
David Quan, PharmD, Mallinckrodt Pharmaceuticals: Advisor/Consultant Sarah B. Doernberg, MD, MAS, Basilea: Clinical events committee/adjudication committee participation|F2G: Grant/Research Support|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Janssen/J+J: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clinical events committee/adjudication committee participation