bluuebunny/crossref_metadata_2025 huggingface dataset:
926. COVID-19 Infections After SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients
Authors: Saharia Kapil , Streit Judy , Beekmann Susan E , Polgreen Philip M , Kuehnert Matthew , Segev Dorry , Baddley John W , Miller Rachel
Published: December 2021

Background

Solid organ transplant recipients (SOTR) have lower humoral responses following SARS-CoV-2 vaccination. Whether this equates to reduced vaccine effectiveness in SOTR or impacts disease severity is not yet known. We used the IDSA Emerging Infections Network (EIN) to identify SARS-CoV-2 cases in vaccinated SOTR. We describe their clinical characteristics and outcomes.

Methods

On 4/7/21, we requested case reports via the EIN listserv of COVID-19 infection following SARS-CoV-2 vaccination in immunocompromised individuals. Case reports were collected until June 7th. Online data collection included patient demographics, dates of SARS-CoV-2 vaccine administration and clinical data related to COVID-19 infection. We performed a descriptive analysis of these patient factors and compared differences between early onset (< / = 21 days after completing vaccine series) and late onset infection ( > 21 days after completing vaccine series).

Results

As of 6/7/21, 34 cases of COVID-19 infection after vaccination in SOTR were submitted. Most cases (79%) occurred in individuals who were fully vaccinated. Only 3 cases (8.5%) occurred in SOTR within their first year after transplantation. Clinical characteristics are listed in Table 1. The vaccine administration date was known for 26 SOTR among whom symptoms occurred a median of 26.5 days (IQR 21.75 days, range 5-79 days) after completing the COVID-19 vaccine series. Twenty-three SOTR (68%) required hospitalization of which 12 had critical illness. Outcome data was available for 29 individuals of whom 20 (69%) demonstrated improvement. When comparing SOTR with early versus late onset COVID-19 infection in relation to vaccination timing, there were no differences in disease severity (80% vs 75% with severe or critical disease, p=NS) or outcome (30% vs 31% died or deteriorating, p=NS).

Table 1: Characteristics of Solid Organ Transplant Recipients with COVID-19 Infection Following SARS-CoV-2 Vaccination

Conclusion

SARS-CoV-2 infections after vaccination are occurring in SOTR, including cases of critical illness, suggesting reduced vaccine effectiveness within this vulnerable population. We did not appreciate any correlation between time from vaccination and COVID-19 disease severity or outcome. Further studies evaluating the true incidence of and risk factors for breakthrough infections among vaccinated SOTR are needed.

Disclosures

Matthew Kuehnert, M.D., American Association of Tissue Banks (Board Member)ICCBBA (Board Member)Musculoskeletal Transplant Foundation (Employee) John W. Baddley, M.D., Eli Lilly (Consultant)Pfizer (Consultant)R-Pharm (Consultant)Viela Bio (Consultant)
927. Clinical Characteristics and Outcomes of Norovirus Infection in Patients with Hematologic Malignancies: A Retrospective, Single Center Study
Authors: Brooks Taylor , Crilley Thomas A , Russell Gregory B , Gaglani Bhavita , Jakharia Niyati
Published: December 2021

Background

Norovirus (NV) gastroenteritis has been identified as a cause of significant morbidity among hematopoietic stem cell transplant (HSCT) recipients, often with associated complications. Current guidelines recommend symptomatic relief with antimotility agents, rehydration, and reduction in immune suppression. Nitazoxanide (NTZ) is an anti-parasitic agent but some literature suggests a benefit of nitazoxanide therapy for NV.

Methods

We conducted a single center, retrospective chart review study and evaluated adult patients (age >18 years) who had NV infection and either: 1) underwent stem cell transplantation; or 2) received myeloablative chemotherapy within 4 weeks of NV diagnosis by positive test on gastrointestinal pathogen panel during the time period from January 2015 through March 2020.

Results

26 patients were reviewed. 14 patients (54%) had a history of HCST prior to infection. Three patients (12%) received both myeloablative chemotherapy and HSCT within four weeks of NV infection. Six patients (46%) had autologous, six (46%) had matched unrelated donor, and one (8%) had haploidentical allogeneic transplants. Nine (69%), three (23%), and one (8%) underwent myeloablative, reduced intensity and non-myeloablative conditioning, respectively. Median duration of diarrhea was 4.5 days (IQR = 2.25-7 days). Three (12%) patients received NTZ or intravenous immune globulin. The 6 month mortality was 42% (11/26), however, none of the deaths were directly attributable to NV infection.

Conclusion

NV infection led to severe diarrheal disease in our cohort. Overall mortality was high, and a trend toward increased mortality was seen among patients receiving NV-directed therapy; these patients likely received NV-directed therapy due to the severity of their illness. Clinicians must have a high suspicion for this illness and obtain PCR testing for timely diagnosis and management.

Table 1. Characteristics of patients with hematologic malignancies and norovirus infection

Disclosures

All Authors: No reported disclosures
928. Clinical Characteristics and Microbiology Testing Patterns Among Transplant Recipients Admitted to Acute Care Hospitals for Suspected Infection
Authors: Hill T Matthew , Scott Erick R , Bercovici Sivan
Published: December 2021

Background

Solid organ transplant (SOT) is a growing option for patients with end-stage organ diseases. Immunosuppressive therapy (IT) is utilized in this population to minimize risk of allograft rejection, which increases infection risk particularly of atypical pathogens that can complicate the infection-related diagnostic journey. The purpose of this analysis was to evaluate baseline clinical characteristics and microbiological testing utilization patterns among a cohort of patients with a history of SOT and IT.

Methods

This retrospective cohort study utilized a US hospital-based, service-level database. Patients were selected from a subsample of database facilities utilizing plasma microbial cell-free DNA diagnostic assays. The study period was 1/1/2017-3/21/2020. Eligible patients were identified by 1st observation of SOT status and IT. Subsequent inpatient admissions for suspected infection were analyzed.

Results

We identified 749 patients with SOT history and use of IT, 56.4% were male, and the mean age was 52.8 (18.7) years. Kidney was the most prevalent transplant category (49.1%), followed by liver (14.1%), lung (10.9%), and heart (10.3%), and 9.7% were multi-organ. Patients experiencing multiple transplants had the most chronic conditions with a mean Elixhauser comorbidity score of 26.3 (14.7). The median length of stay was 4 [3-7] days. The median number of tests per encounter was 6 [IQR=3-11]. Culture was the most utilized test category (2 [1-4]). Blood culture was the highest utilized culture and overall test at 13.5% of all tests observed, while CMV PCR (7.8%) and multi-panel EIA (2.7%) were the most frequent molecular and antigen tests, respectively. Lung transplant recipients had the greatest utilization of tests overall (9 [3.5-17]) versus other transplant categories (6 [3-10]), consistent with the observed test rate in the 1st 48 hours of presentation (4 [1-7] vs. 2 [1-5]).

Conclusion

This analysis suggests that the infection-related diagnostic journey among patients with a history of SOT involves high utilization of microbiological testing, with greater utilization among lung transplant recipients versus other SOT recipients. Variation in clinical characteristics and microbiological testing patterns were observed across SOT categories.

Disclosures

T Matthew Hill, PharmD, PhD, Karius, Inc (Employee, Shareholder) Erick R. Scott, MD, MHS, Karius, Inc (Employee, Shareholder) Sivan Bercovici, PhD, Karius (Employee)
929. Recurrent Nocardiosis in Solid Organ Transplant Recipients: An Evaluation of Post-Treatment Prophylaxis
Authors: Yetmar Zachary A , Wilson John , Beam Elena
Published: December 2021

Background

Nocardia more commonly causes infection in immunocompromised individuals, notably with a relapse rate of approximately 5%. Solid organ transplant recipients will often receive post-treatment prophylaxis as the underlying immunosuppression is unable to be completely removed. However, data supporting this practice is sparse. We sought to evaluate recurrence of nocardiosis in solid organ transplant recipients, specifically evaluating the role of post-treatment prophylaxis.

Methods

We conducted a retrospective cohort study of solid organ transplant (SOT) recipients at our medical center diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy. Patients were excluded if they had not yet completed therapy, died prior to completing therapy, or there was no post-therapy follow-up. The primary outcome was Nocardia recurrence. Continuous variables were presented as mean or median with interquartile range (IQR).

Results

108 patients meeting inclusion criteria were analyzed. 72 (66.7%) were male and median age was 60 years (IQR 52-65). Most common SOT types were kidney (47.2%), heart (17.6%), kidney-pancreas (11.1%), and lung (11.1%). Median time from transplantation to diagnosis of nocardiosis was 396 days (IQR 154-1071). Most common sites of infection were lung (88.0%), skin (16.7%), brain (13.9%), and blood (6.5%). Multi-organ infection was present in 22.2% and 24.1% were on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at diagnosis. Post-treatment prophylaxis was utilized in 55 (50.9%) patients (Table 1). TMP-SMX was the most common prophylaxis (87.3%; Figure 1). Four patients experienced Nocardia recurrence, 2 of which were receiving TMP-SMX prophylaxis at time of relapse (Table 2). These were dosed as double strength tablet daily and weekly, respectively. Median time from treatment completion to relapse was 255.5 days (range 107-871).

Figure 1. Post-Treatment Prophylaxis Regimens for Nocardia in 55 Patients

Conclusion

Nocardia recurrence in solid organ transplant recipients is an uncommon occurrence. Double strength daily and weekly TMP-SMX prophylaxis does not appear to be entirely protective and relapse may be dependent upon other factors such as primary treatment length. Further study into the use of post-treatment prophylaxis is warranted.

Disclosures

All Authors: No reported disclosures
931. Epidemiology and Clinical Outcomes of SARS-CoV-2 Infection Among Pediatric Solid Organ Transplant Recipients: A Single-Center Case Experience
Authors: Sotelo Jesus , Akkoyun Esra , Chery Giselle S , Aqul Amal , Desai Dev M , Sue Paul K , Power Alyssa
Published: December 2021

Background

The impact of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection among pediatric solid organ transplant (SOT) recipients remains unclear. We sought to characterize the clinical epidemiology and outcomes following SARS-CoV-2 infection among pediatric SOT recipients in Dallas, TX.

Methods

Retrospective review of all SOT recipients with laboratory confirmed COVID-19 infection from March 1, 2020 –March 31, 2021. Demographic, clinical, and outcome data were stratified by transplant type and disease severity. Fischer’s exact test and Kruskall-Wallis test were used to evaluate risk factors for more severe disease among hospitalized children.

Results

Twenty-six SOT recipients with a median age of 14 years were included in the study. Fifteen (58%) were female, eighteen (69%) were Hispanic and thirteen (50%) were overweight/obese. Median time post-transplant was 3.6 years (1311 days, interquartile range (IQR) 394-2881). Fourteen patients were liver recipients, seven kidney, three heart, and two multiorgan. The majority of patients (65%) had a known community exposure and presented with fever (50%), cough (38%) and GI symptoms (19%). Half of all cases were hospitalized (n=13), with 2 requiring intensive care unit (ICU) admission, but no patients required positive pressure ventilation. Median hospital stay was 3 days. Five of the thirteen hospitalized patients were categorized as having moderate disease. No patients developed severe disease and there were no deaths. Older children, as well as children with multiple co-morbidities were noted on univariate analysis to be at higher risk for moderate, as compared to mild, disease.

Conclusion

SARS-CoV-2 infection among pediatric SOT recipients are at increased risk for hospital admission but demonstrate an overall mild /moderate disease course. Larger studies are required to elucidate the risk of morbidity between pediatric SOT recipients and immunocompetent children with SARS-CoV-2.

Disclosures

Amal Aqul, MD, Albireo pharma Inc. (Consultant)
932. Clinical Characteristics of Persistent and Relapsing Babesiosis at an Academic Medical Center in New York City, 2015-2020
Authors: Rogers Wesley , Kirkman Laura , Simon Matthew , Westblade Lars
Published: December 2021

Background

Current guidelines recommend at least 6 weeks of therapy for immunocompromised babesiosis patients; however, limited data exists to guide management in this population. We describe our institutional experience with immunocompromised babesiosis patients.

Methods

We reviewed all adult patients reported to the New York City Department of Health and Mental Hygiene with a diagnosis of babesiosis at New York-Presbyterian (NYP)/Weill Cornell Medical Center and NYP/Lower Manhattan Hospital between 2015 and 2020. We compared characteristics and outcomes between patients receiving prolonged treatment (≥ 6 weeks; “cases”) and standard treatment (7-10 days; “controls”). Variables were compared using Fishers exact test or Wilcoxon Rank Sum test.

Results

Among 35 patients diagnosed with babesiosis, 10 (29%) received at least 6 weeks of therapy. 5/10 (50%) received extended treatment due to persistent and/or relapsing parasitemia, evidence of hemolysis and/or clinical symptoms at 6 weeks from diagnosis (Table 1). The median age was 67 years and immunocompromising conditions included: anti-CD 20 therapy (40%), history of stem cell transplant (20%), anti-TNF alpha (10%), beta-thalassemia (10%), Waldenstrom’s macroglobulinemia (10%). Among case patients, the median treatment duration was 53 days (IQR 42-153) and 100% of patients received azithromycin/atovaquone based regimens with adjunctive agents including doxycycline (60%), clindamycin (20%) and proguanil (20%). Compared to control patients, case patients had higher frequency of blood transfusions (50% vs 12%; p=0.03), however, there was no difference in median peak parasitemia (1.13% vs 0.6%), rates of hospital admission (80% vs 88%), length of stay (6 vs 4 days), organ dysfunction (10% vs 4%) and mortality (0% vs 0%) (Table 2).

Conclusion

We found a high frequency (29%) of babesiosis patients at our medical center received at least a 6-week treatment course due to immunocompromising conditions. Although immunocompromised patients received longer treatment courses and had more severe anemia, in contrast to prior studies, we found other complications such as hospitalization rates, length of stay, organ dysfunction and mortality were comparable between both patient groups.

Disclosures

Lars Westblade, PhD, Accelerate Diagnostics Inc (Grant/Research Support)BioFire Diagnostics (Grant/Research Support)Hardy Diagnostics (Grant/Research Support)Roche (Consultant, Advisor or Review Panel member)Shionogi Inc (Advisor or Review Panel member)Talis Biomedical (Advisor or Review Panel member)
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

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

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 > 200 copies/mL) or negative viral load. Sustained EBV DNAemia was defined as EBV DNA detection ( > 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< 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

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 >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

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

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 < 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 < 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

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

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

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

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 ( >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)
945. Bacteremia in Patients with Solid Tumors: Epidemiology, Clinical Features and Risk Factors for Mortality. Results from a Multicenter Study in Argentina
Authors: Costantini Patricia E , Torres Diego , Dictar Miguel , Nenna Andrea , Valledor Alejandra , Jordán Rosana , Laborde Ana , Lambert Sandra , Benso José , Carena Alberto , Luck Martín , Racioppi Agustina , Barcan Laura , Eusebio María José , Gonzalez Ibañez María Luz , Tula Lucas , Pasteran Fernando , Corso Alejandra , Rapoport Melina , Bronzi Marcelo , Nicola Federico , Valle Sandra , Chaves María Laura , Greco Graciela , Monge Renata , Damiano María Cristina García , Blanco Miriam , Herrera Fabián
Published: December 2021

Background

Current information regarding bacteriemia in patients with solid tumors is scarce

Methods

To assess the etiology, clinical features and outcome in patients with solid tumors and bacteremia, we carried out a prospective multicenter study. Episodes of bacteriemia in adult cancer patients in 9 centers, from May 2014 to February 2021, were recorded. To identify factors associated with 30-day mortality, variables with p < 0.05 in univariate analysis were included in a logistic regression model for multivariate analysis

Results

Three hundred and thirty-two episodes of bacteremia were included, with 51% being women (mean age 59). The state of underlying disease was: recent diagnosis 27%, remission 27%, relapsed 29% and refractory 17%. Seventy-three percent had received chemotherapy in the last 30 days, 25% were receiving steroids. Neutropenia was present in 23% (mean duration 3 days). The most frequent sources were: abdominal 39%, urinary tract 21%, respiratory 15%, catheter 10% and skin and soft tissue 9%. The microorganisms were: Gram negative bacilli (GNB) 67% (Enterobacterales 84%), Gram positive cocci 36% (Staphylococcus aureus 33%) and polimicorbial 11%; 20% were multidrug resistant organisms (MDR-O), being 88% of them GNB (MDR-GNB). ESBL and KPC carbapenemase producing were the most frequent mechanisms of resistance. Mortality at day 7 and day 30 was 16% and 27%, respectively. In the univariate analysis, the risk factors for 30-day mortality were Charlson index, refractory underlying disease, use of steroids, polimicrobial bacteremia, Staphylococcus aureus, GNB resistant to carbapenems, APACHE and Pitt scores, hypotension, respiratory source and ICU admission. In multivariate analysis, risk factors for 30-day mortality were refractory underlying disease, GNB resistant to carbapenems and ICU admission, while 7-day clinical response was associated with lower mortality

Conclusion

Bacteremia is a serious complication in cancer patients, with high mortality. The state of underlying disease, infection caused by GNB resistant to carbapenems, and the severity of presentation are associated with increased mortality. Our results stress the importance of infection control measures and antibiotic stewardship to prevent colonization with MDR-O

Disclosures

All Authors: No reported disclosures
947. Nocardiosis in Renal Transplant Recipients Linked to Decreased Utilization of Trimethoprim/Sulfamethoxazole During COVID-19
Authors: McSweeney Terrence , Marvin Jennifer , Cohen Elizabeth A , Do Vincent , Belfield Kristen , Virmani Sarthak , Davis Matthew , McManus Dayna , Tirmizi Samad , Topal Jeffrey E
Published: December 2021

Background

The renal transplant population is at increased risk of Nocardiosis due to impaired T-cell mediated immunity with immunosuppression. Pneumocystis jirovecii (PJP) prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX) provides coverage against Nocardia spp. unlike alternative agents such as atovaquone (ATQ), aerosolized pentamidine (AP), and dapsone. During the COVID-19 pandemic, patients receiving AP were transitioned to ATQ to avoid the use of nebulized medication. This, in turn, led to decreased use of TMP/SMX as patients on oral ATQ were not reassessed for the use of TMP/SMX as would have occurred while on AP. Additionally, an increased incidence of Nocardia infections was observed during this time. The objective of this study was to determine the association between the incidence of Nocardia infections and number of TMP/SMX prophylaxis-days in pre- versus COVID-19 cohorts.

Methods

This was a single center retrospective chart review of all renal transplant recipients between September 2018 – August 2019 (pre-COVID-19 cohort) and April 2020 – March 2021 (COVID-19 cohort). Patients were included if they were at least 18 years of age and a recipient of a cadaveric or living donor kidney transplant. Exclusion criteria included multi-organ transplant, pediatric patients, and repeat transplants. The primary outcome was incidence of Nocardiosis within the first 6 months post-transplant in the pre- and COVID-19 cohorts.

Results

A total of 218 patients were included (Table 1). Induction therapy and initial immunosuppression did not differ significantly between groups, nor did rates of rejection within 180 days of transplant (Table 2). Although the pre-COVID-19 cohort had a higher rate of neutropenia, there was no difference in median absolute lymphocyte count between the two groups. The COVID-19 cohort had a decreased percentage of TMP/SMX prophylaxis-days (59.2% vs. 72.5%, p < 0.0001) and an increased incidence of Nocardia infections in the first 6 months post-transplant (4% vs. 0%, p=0.0292). All 4 cases of Nocardia infections occurred in patients receiving ATQ.

Conclusion

The increased incidence of Nocardiosis was associated with a decreased use of TMP/SMX for PJP prophylaxis which may have been an unintended consequence of increased use of ATQ in lieu of AP during COVID-19.

Disclosures

All Authors: No reported disclosures
950. The Challenge of Fellowship Interviews During COVID-19: An Online Post-interview Survey
Authors: Mahatanan Rattanaporn , Vergo Maxwell , Zuckerman Richard A
Published: December 2021

Background

COVID-19 has significantly disrupted social and personal interactions, including fellowship recruitment. In-person interviews were replaced by virtual interviews, which created uncertainties for both programs and candidates. We distributed a survey to interviewees for fellowship programs in an effort to gather data and improve the process.

Methods

An anonymous online survey on the Qualtrics® platform assessed satisfaction with the interview process, evaluated the advantages and disadvantages of virtual interviews, and requested comments to improve the process. Surveys were sent out to candidates within 7 days of interview for Infectious Disease and Palliative care fellowship programs at our institution.

Results

Surveys were sent to 51 candidates, 24 (47%) responded; 8 (33%) from Palliative care and 16 (67%) from ID. All candidates felt that they had a good sense about the programs and enough information to make a decision for ranking. Most candidates felt that they conveyed themselves well (71%) to very well (25%) during interview except one person who did not. 63% of candidates felt that the process was seamless, although 3 (12.5%) mentioned technical difficulties during the interviews. While 79% felt that the time spent on the interview was about right, 16% of candidates felt that interviews were too long and 1 person felt that it was too short. Cost-saving was the top advantage of the virtual interview with time-saving second. Interestingly, ability to interview at more programs was not ranked as highly as an advantage. Despite these advantages, 19 of 24 (79%) of candidates would have preferred an in-person interview if it was available. Lack of personal interaction and inability to see the location were equally chosen to be the greatest disadvantages of the virtual process by most of the candidates.

Conclusion

Despite the challenges of the virtual interview process, our survey showed positive feedback from candidates regarding their experiences. The lack of social interaction and inability to explore the location were important, prompting 79% of candidates to prefer an in-person interview if that was an option. Many factors should be considered to ensure an equitable and comprehensive process where candidates and programs can make decisions to optimize outcomes.

Disclosures

All Authors: No reported disclosures