bluuebunny/crossref_metadata_2025_split huggingface dataset:
933. Incidence and Risk Factors for Cytomegalovirus Infection in Intestinal Transplant Recipients
Authors: Fernandez Anmary A , Simkins Jacques , Martin Eric , Anjan Shweta , Garcia Jennifer , O’Brien Christopher , Vianna Rodrigo , Natori Yoichiro 
Published: December 2021

Abstract

Background
Cytomegalovirus (CMV) infection is the most common infection after solid organ transplantation. Data on CMV infection in intestinal transplant recipients is limited.

Methods
This is a single-center retrospective cohort study which includes all consecutive intestinal transplant recipients who were transplanted between 2009 and 2019. We excluded recipients that showed CMV seronegativity of both donor and recipient. We also excluded those patients who did not have more than 3 months of follow-up. Univariate and multivariate analyses were performed to identify the risk factors for CMV infection. Of note, at our center CMV prophylaxis in intestinal transplant recipients is one year of valganciclovir.

Results
A total of 173 recipients were transplanted; 46 recipients were because of CMV serostatus and 32 due to short follow-up. Ninety-five recipients were included finally. The characteristics of our cohort are summarized in Table 1. Of note, the median age was 32 years [range 0-67] and 44 (46.3%) were male. Eighteen (18.9%) recipients needed to stop valganciclovir prophylaxis due to the side effect, especially cytopenia. Twenty-one recipients developed CMV infection including asymptomatic viremia (12/21, 57.1%), CMV syndrome (5/21, 23.8%) and end-organ disease (2 (9.5%) pneumonitis and 2 (9.5%) colitis) at median time of 155 [Interquartile range, IQR 28-254] days from transplant. The median peak viral load and time to negativity were 16000 [IQR 1500-43892] IU/ml and 56 [IQR 49-109] days, respectively. Younger age (p=0.007, Odds ratio 1.03, 95% confidence interval 1.003-1.055) was the independent factor associated with CMV infection.

Conclusion
Despite prolonged prophylaxis, 21 (22.1%) of intestinal transplant recipients developed CMV infection around 5 months post-transplant. This may be because they cannot tolerate valganciclovir prophylaxis and early termination was required. Further strategy should be developed to prevent CMV infection in this vulnerable population.

Disclosures
All Authors: No reported disclosures
934. Epidemiology and Outcomes of Epstein-Barr Virus DNAemia in Adult Solid Organ Transplant Recipients
Authors: Dong Sara W , Blair Barbra M , Alonso Carolyn D 
Published: December 2021

Abstract

Background
Immunosuppression in solid organ transplantation (SOT) increases the risk of Epstein-Barr virus (EBV) DNAemia, which may herald development of post-transplant lymphoproliferative disease (PTLD). The objective of this study was to characterize the epidemiology and risk factors for EBV DNAemia and to describe the impact of these factors on development of PTLD in a cohort of SOT recipients.

Methods
We retrospectively examined adult (≥18 years) SOT recipients between 1/1/2015 to 12/31/2019. Demographics, immunosuppression, and clinical outcomes were examined. Subjects were stratified as having a positive (EBV viral load &gt; 200 copies/mL) or negative viral load. Sustained EBV DNAemia was defined as EBV DNA detection ( &gt; 200 copies/mL) on at least 3 consecutive samples. Categorical variables were analyzed using chi-square or Fishers exact test. Mann-U Whitney test was used for continuous variables.

Results
442 SOT recipients (258 kidney, 141 liver, 22 kidney-pancreas (KP), 15 kidney-liver, 6 pancreas) were examined. Most subjects (430, 97%) were EBV intermediate risk (recipient (R)+). 8 subjects (2%) were EBV high risk (donor (D)+, R-) and 4 (1%) were EBV low risk (D-/R-). EBV viral loads were obtained in 177/442 (40.0%) recipients. DNAemia was detected in 18/442 subjects (4.1%). It was most common in pancreas recipients(1/6; 16.7%) compared with kidney (10/258; 3.9%), liver (5/141; 3.5%), and KP recipients (1/22; 4.5%). DNAemia was most frequently observed in the D+/R- (3/8; 37.5%) group compared to intermediate risk (R+) (15/430; 3.5%) and D-/R- (0%) groups. Median time to EBV viral load detection was 14 months (range 3-60). In univariate analysis, EBV high-risk serostatus was the factor most strongly associated with development of EBV DNAemia (p&lt; 0.001). Sustained DNAemia (median viral load 1829 copies/mL; peak viral load 1.9 million copies/mL) was observed in 8 subjects (1.8%). PTLD developed in 6 subjects (1.4%); 50% had sustained DNAemia prior to diagnosis.

Conclusion
While uncommon, development of sustained EBV DNAemia was associated with subsequent development of PTLD in our cohort of adult SOT recipients. These data provide guidance for identifying subjects at risk for PTLD above and beyond baseline EBV high-risk serostatus.

Disclosures
All Authors: No reported disclosures
935. A Hospital Cluster of the Emerging Drug-resistant Yeast Saprochaete clavata
Authors: Chan Xin Hui S , Cubillo-Garcia Cristina , Ali Shanom , Gorton Rebecca , Rhodes Johanna , Choy Bennett , Fisher Matthew , Thomson Kirsty , Gant Vanya , Stone Neil , Satta Giovanni 
Published: December 2021

Abstract

Background
Saprochaete clavata, an ascomycetous yeast intrinsically resistant to echinocandins, is a rare yet emerging pathogen associated with invasive infections in immunosuppressed patients, particularly those with haematological malignancies. It is commonly misidentified as the closely-related S. capitata. Outbreaks have been associated with a high mortality rate of &gt;50%, due in part to delayed diagnosis and resistance to commonly-used antifungals. Environmental source identification is challenging, although dishwashers and milk flasks have been implicated in previous hospital clusters.

Methods
We describe a cluster of five haematology-oncology patients with disseminated S. clavata infections between April 2020 and April 2021 following current or recent admissions to the same ward.

Results
All had prolonged (median=24 days, range=9-210) and profound immunosuppression from chemotherapy and/or stem cell transplantation for acute myeloid leukaemia (n=3) or lymphoma (n=2) at the time of culture positivity. Four were severely neutropaenic (median=0.08/mm3, range=0.01-0.26). Median patient age was 62 years (range=58-73). S. clavata was isolated from blood (n=3), urine (n=2), and liver tissue (n=1) samples. Whole genome sequencing of these isolates was performed to confirm the presence of an outbreak. All patients received empirical treatment with intravenous caspofungin before culture-guided therapy with intravenous liposomal amphotericin B +/- oral flucytosine. Two of the five patients died although both had advanced refractory malignancy. Detailed environmental sampling of fridges/freezers, drains, and vents in patient rooms and clean areas for handling or storage of food and medication failed to identify a clear point source despite isolation of multiple environmental organisms. No further cases have emerged after intensification of the cleaning regimen in these areas.

Conclusion
Our experience highlights the emerging threat of drug-resistant yeasts particularly in the immunocompromised. Management of such outbreaks requires a multidisciplinary approach incorporating antifungal stewardship, infection control, and environmental microbiology, alongside close clinical liaison between haemato-oncologists and infection specialists.

Disclosures
All Authors: No reported disclosures
937. A Clinical Prediction Tool to Determine Risk of Infection in the First Year Following Heart Transplant
Authors: Perry Whitney , Chow Jennifer , Nelson Jason , Kent David , Snydman David R 
Published: December 2021

Abstract

Background
Invasive infection is a dangerous complication of heart transplant (HT). No objectively-defined set of risk factors has been established which can reliably predict infection in this population. The aim of this study was to develop a clinical prediction model for use at one month post-HT with the ability to predict serious infection in the first year.

Methods
A retrospective cohort study of all HT recipients at a single center between 2000 and 2018 was performed, excluding dual-organ recipients, those who died within one month of HT, and those with insufficient data. The composite endpoint included cytomegalovirus infection (CMV), herpes simplex (HSV) or varicella zoster virus infection (VZV), blood stream infection (BSI), and invasive fungal infection (IFI). The follow-up period extended from 1 month to 1 year post-HT. A least absolute shrinkage and selection operator (LASSO) regression model was fit using 13 candidate variables. A C-statistic, calibration curve, and Brier score were used to assess model performance.

Results
375 patients were analyzed; 93 outcomes occurred (65 CMV, 3 HSV, 2 VZV, 28 BSI, and 15 IFI). 12 of 13 variables remained in the final model: year of transplant, age at transplant, ischemic cardiomyopathy, diabetes, immune-mediating disease, need for renal replacement therapy in first month, CMV risk status (high, intermediate, low) derived from donor-recipient serology, use of basiliximab induction, use of cytolytic agent in first month, use of ritixumab in first month, rejection treated with high-dose steroids in first month, lymphocyte count under 0.75 x103cells/µL at 1 month, and inpatient status at 1 month. The C-statistic was 0.82 and Brier score 0.142. The calibration curve is shown in Figure 1.
Figure 1. Calibration plot

Actual versus predicted probability of infection by 1 year. Gray line = ideal Dotted line = smoothed non-parametric calibration curve

Conclusion
This model synthesizes multiple highly-relevant clinical and laboratory parameters, available at 1 month post-HT, into a unified, objective, and clinically-useful prediction tool for the occurrence of serious infection in the first post-transplant year. Good discrimination and calibration are demonstrated. External validation is required before generalized use.

Disclosures
Jennifer Chow, M.D., M.S., Merck (Grant/Research Support)Takeda (Grant/Research Support) David R. Snydman, MD, Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Takeda (Shire) (Advisor or Review Panel member)
939. Predicting Attributable Mortality in Pediatric Patients with Cancer Admitted to the Intensive Care Unit for Suspected Infection
Authors: Rubnitz Zach , Agulnik Asya , Merritt Pamela , Ferrolino Jose Amadeo A , Dallas Ronald , Tang Li , Sun Yilun , Allison Kim J , Wolf Joshua , Wolf Joshua 
Published: December 2021

Abstract

Background
Infection and sepsis are important contributors to mortality in children with cancer. Although pediatric risk prediction scores have improved identification of children at high risk of death in the PICU, the value of these tests in immunocompromised children is unknown.

Methods
In this IRB-approved retrospective study performed at St. Jude Children’s Research Hospital, we evaluated the performance of 4 pediatric risk scores, the Pediatric Risk of Mortality (PRISM), Pediatric Sequential Organ Failure Assessment (pSOFA), Quick Sequential Organ Failure Assessment (qSOFA) scores (using data available at 1, 6, 12 and 24 hours) and the Paediatric Index of Mortality 3 (PIM-3) score (at 1 hour), to predict attributable mortality (death ≤ 60 days without organ dysfunction recovery). Inclusion criteria: Age &lt; 24 years, active cancer therapy (other than bone marrow transplantation), and admission to PICU between 2013 and 2019 with suspected infection (collection of a blood culture and initiation of antibiotic therapy). Scores were calculated using the worst value obtained for each variable. Score distributions were compared by the Mann-Whitney U test, and optimal cutoffs selected by maximizing Youden’s index. An unadjusted p-value &lt; 0.05 was considered statistically significant.

Results
Of 202 episodes of PICU admission for suspected infection in 168 participants, there were 12 attributable (6%) and 4 unrelated (2%) deaths. Demographic and cancer-related characteristics were not associated with mortality (Table 1). Of the 4 prediction scores, only the PRISM score at 24 hours was associated with mortality (P = 0.012; Table 2). For PRISM score ≥ 18, sensitivity was 58.3%, specificity was 81.6%, positive predictive value was 16.7%, and negative predictive value was 96.9% for attributable mortality.
Table 1. Risk factors for attributable mortality in pediatric patients with cancer admitted to the intensive care unit with suspected infection.

Table 2. Association between risk prediction scores and attributable mortality in pediatric patients with cancer admitted to the intensive care unit with suspected infection.

Conclusion
In children with cancer admitted to PICU with suspected infection, early pediatric risk prediction scores did not predict mortality. The PRISM score calculated at 24 hours did predict mortality but was relatively insensitive. Further research is needed to develop a risk score for immunocompromised children and to validate the 24 hour PRISM score in this population.

Disclosures
Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose
941. Isavuconazole Prophylaxis Against Invasive Fungal Infection: A Pooled Analysis with a Comparison of Posaconazole Delayed-release Tablet Prophylaxis
Authors: Lee Chaeryoung , Hong Sung Kwan , Kim Jong Hun 
Published: December 2021

Abstract

Background
There are limited data regarding the use of isavuconazole as primary antifungal prophylaxis against invasive fungal infection (IFI) among immunocompromised patients. Therefore, the purpose of this study was to assess efficacy and breakthrough IFIs of isavuconazole prophylaxis by a pooled analysis of the reported cases of isavuconazole prophylaxis with a comparison of cases of posaconazole delayed-release tablet prophylaxis.

Methods
Pubmed was searched for English-written articles published up to April 2021. Studies that reported cases of primary antifungal prophylaxis with isavuconazole or posaconazole delayed-release tablet in adults ≥ 18 years were reviewed. Breakthrough IFI was defined as the occurrence of proven or probable IFI while on prophylaxis.

Results
For overall isavuconazole prophylaxis, a total of 818 courses of prophylaxis was identified from 12 studies. Breakthrough IFIs were noted in 41 patients. The median duration of isavuconazole prophylaxis of these patients before the diagnosis of IFI was 17 days. The most common breakthrough IFI was candidiasis (34.1%), followed by aspergillosis (24.4%) and mucormycosis (12.2%). Sixteen patients died (39.0%). Among patients with hematologic malignancies or hematopoietic stem cell transplantation, isavuconazole prophylaxis (404 courses) was compared with posaconazole delayed-release tablet prophylaxis (1952 courses). The incidence rate of breakthrough IFIs was higher in the cohort of isavuconazole prophylaxis (24 patients of 404 courses) than in the cohort of posaconazole delayed-release tablet prophylaxis (44 patients of 1952 courses). Aspergillosis (40.9%) was the most common breakthrough IFI in the cohort of isavuconazole prophylaxis among patients with hematologic malignancies or hematopoietic stem cell transplantation, followed by candidiasis (27.3%) and mucormycosis (18.2%).

Conclusion
Although isavuconazole is licensed to treat aspergillosis and mucormycosis, breakthrough IFIs including aspergillosis, mucormycosis, and candidiasis may occur while on isavuconazole prophylaxis. Therefore, further studies are needed to define the benefits and risks of isavuconazole prophylaxis.

Disclosures
All Authors: No reported disclosures
942. Pulmonary Infections in Intestinal Transplant Recipients with Preexisting Pulmonary Nodules
Authors: Cardenas Jorge , Natori Yoichiro , Anjan Shweta , Vianna Rodrigo , Garcia Jennifer , Simkins Jacques 
Published: December 2021

Abstract

Background
Pulmonary nodules in asymptomatic patients could represent latent pulmonary infections. Intestinal transplant (ITx) recipients with preexisting pulmonary nodules might be at higher risk for pulmonary infections. However, data is lacking.

Methods
This retrospective study included adult patients that underwent intestinal transplantation (ITx) from 5/2016 to 5/2020. Chest computed tomography (CT) scans performed within 12 months prior of ITx were obtained to evaluate for preexisting pulmonary nodules. Screening for endemic mycoses, Aspergillus, Cryptococcus and latent tuberculosis infection (LTBI) performed within 12 months prior ITx was obtained. We assessed for worsening pulmonary nodules, and fungal and mycobacterial infections during the 1st year post-transplant. Survival at one year post-transplant was also assessed.

Results
Forty-three patients underwent ITx. Twenty-three (53%) were Female. Median age was 46 years (range: 18-67). Chest CT scans were performed in 36(84%) patients prior to ITx. Preexisting pulmonary nodules were found in 30 (83%) of the patients. All were asymptomatic. Nodules were not calcified in 10 (33%) patients, calcified in 4 (13%), some calcified and some not calcified in 4 (13%) and unclear in 12 (40%). All the patients screened negative for fungi [Coccidioides antibody (Ab) was done in 15 (50%) patients, Blastomyces Ab and Histoplasma Ab in 7 (23%) each, Histoplasma urine antigen (Ag) and Aspergillus serum galactomannan in 3 (10%) each, and Cryptococcus serum Ag in 10 (33%) patients]. QuantiFERON-TB (QFT) was negative in 35 (81%) patients, positive in 2 (5%) and indeterminate in 6 patients (14%). QFT-Gold In-Tube was replaced to QFT-Plus in 3/2019. Post-transplant worsening of pulmonary nodules was noted in 12 (40%) patients and bronchoscopy was performed in six of them. Note that only 1 (3%) of the patients that had pre-existing pulmonary nodules developed a pulmonary infection (invasive pulmonary aspergillosis diagnosed 33 days after ITx). Our cohort survival at one year post-transplant was 79%.

Conclusion
Preexisting pulmonary nodules was common in our ITx cohort. However, only one case of pulmonary infection was noted among those who had preexisting pulmonary nodules. Clinical monitoring is essential.

Disclosures
All Authors: No reported disclosures
943. Epidemiology of Actinomycosis in a Tertiary Care Cancer Center
Authors: El-Atoum Mohammad , Almyroudis Nikolaos , Mullin Katherine M , Segal Brahm H 
Published: December 2021

Abstract

Background
Actinomyces are human commensals with significant pathogenic potential. The aim of this study was to determine the epidemiology of Actinomycosis in a tertiary care cancer center and identify species most commonly associated with invasive disease.

Methods
We retrospectively reviewed all patients referred to our institution with suspected or documented solid or hematological malignancies and positive cultures for Actinomyces species from July 2007 to June 2020 (13 years). Species identification was performed by VITEK® automated system (bioMerieux Inc.). Probable invasive actinomycosis was defined as cases with consistent clinical presentation, suggestive radiographic findings, and a positive culture from a nonsterile site, but lack of histopathological confirmation. Proven invasive actinomycosis was defined as the presence of consistent clinical symptoms, suggestive radiographic findings, a positive culture and histopathological confirmation, or cultures from sterile site without histopathological confirmation. Contaminants were considered positive cultures from sterile or non-sterile site without evidence of disease.

Results
Of 233 cases with positive cultures 194 (83.3%) were considered contaminants and 39 (16.7%) diagnostic of invasive actinomycosis. Of 39 cases of invasive actinomycosis, 64% were documented in patients with solid tumors, 13% in hematological malignancy and 23% among individuals without proven malignancy, 25 (64%) were probable and 14 (36%) proven. Of patients with proven/probable actinomycosis 27 (69%) had polymicrobial growth. Abdominopelvic was the most frequent site of invasive actinomycosis. A. odontolyticus was the most common species isolated (41%) followed by A. meyeri (28%) in patients with invasive disease, and A. odontolyticus (42%) among contaminants.

Conclusion
The majority of positive cultures for Actinomyces species were considered contaminants. In our cohort Invasive actinomycosis affected mainly patients with solid tumors. Abdominopelvic was the most common site of invasive disease. Species most commonly associated with invasive actinomycosis were A. odontolyticus followed by A. meyeri with A. israelii isolated less frequently.

Disclosures
All Authors: No reported disclosures
944. CMV Peak Viral Load, Recurrence, Duration, and Outcomes in Kidney Transplant Recipients
Authors: Avery Robin K , Avery Robin K , Ostrander Darin B , Lu Na , Akinwande Felicia , Kim Min Young , Gopinath Shilpa , Permpalung Nitipong , Ezennia Obichukwu , Tang Yuexin , Marr Kieren 
Published: December 2021

Abstract

Background
Cytomegalovirus (CMV) infection continues to cause morbidity in kidney transplant recipients, despite prophylaxis and pre-emptive therapy. Predictors of poor outcomes remain incompletely characterized. We questioned whether markers of CMV replication (CMV peak viral load, recurrent episodes, or duration of CMV DNAemia) are associated with adverse outcomes in the current era.

Methods
We studied 605 people who underwent kidney transplant at Johns Hopkins University (2010 – 2018). Mean follow-up was 45.5 months. The average age was 51.85 years and 39.7% were female. Donor-seropositive, recipient seronegative (D+/R-) patients received valganciclovir 900 mg/day for 6 months, while R+ patients received valganciclovir 450 mg/day for 3 months. CMV recurrence was defined as CMV DNAemia after two undetectable CMV PCR’s. Outcomes of acute rejection, graft failure, and death were evaluated in univariate analysis; p values were calculated by Fisher’s exact test.

Results
Peak CMV viral load was not associated with any outcomes (Table 1). There was a trend of increased graft failure in people who had long duration ( &gt;6 month) DNAemia (Table 2). More than two episodes of CMV reactivation was associated with graft failure and rejection (Table 3).

Conclusion
CMV reactivation is associated with kidney rejection and failure in univariate models. Multivariate analyses and longitudinal modeling will provide increased data upon which to better instruct preventative strategies.

Acknowledgments
Funding for the research study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Disclosures
Robin K. Avery, MD, Aicuris (Grant/Research Support)Astellas (Grant/Research Support)Chimerix (Research Grant or Support)Merck (Grant/Research Support)Oxford Immunotec (Grant/Research Support)Qiagen (Grant/Research Support)Takeda/Shire (Grant/Research Support) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder) Kieren Marr, MD, Merck (Grant/Research Support, Advisor or Review Panel member)