bluuebunny/crossref_metadata_2025 huggingface dataset:
1059. Evaluating Hepatitis C Screening Rates and Successful Interventions at an Outpatient Medicine/Pediatrics Practice
Authors: Abreu Carina , Wales Danielle P , Eichelman Abigale , Ata Ashar , Ramani Rohini , Waxman Michael
Published: January 2021

Background

Despite the 2013 United States Preventive Services Task Force (USPSTF) recommendations, Hepatitis C (HCV) screening rates among patients born between 1945-1965 has remained below 25% (MacLean, 2018). At our outpatient academic suburban primary care practice in Albany County, NY, our hepatitis C baseline prior to interventions was 31.75%. In collaboration with Project FOCUS through Gilead, our practice attempted to increase screening rates among this birth cohort.

Methods

We performed a retrospective chart review on patients eligible for HCV screening with birth years 1945-1965 at the time of their visit at the Albany Med Internal Medicine/Pediatrics practice. We report monthly HCV screening from January 2018 to April 2020. In addition, we determined whether HCV screening rates differed by race, gender, ethnicity, private vs public insurance, and risk stratification or RAF (standard vs. high-risk patient).

Results

The chance that a test conducted for eligible patients increased from 29.9% (pre-intervention) to 58.76% in 2019 (post-intervention). From June 2019- December 2019, the testing rates were consistently above the 2019 average (Figure 1). There were no significant differences in HCV screening due to gender, race, ethnicity, or type of insurance (Table 1).

Figure 1. Hepatitis C Screening Rates at an Outpatient Medicine/Pediatrics Practice 2018-2020

Table 1. Demographics - Hepatitis C Screening Rates

Conclusion

In this outpatient Med/Peds practice, hepatitis C screening rates increased dramatically after incorporation of an EMR prompt, as well as nursing-generated orders for patients due for screening. There was no statistical difference in screening based on race, ethnicity, gender, or insurance type. Of note, high-risk patients were more likely to be screened, perhaps as they receive more case management services and are more likely to be in the office, increasing the opportunities for screening. The next step would be to adapt these interventions to screening all patients age 18-79, as per the updated 2020 USPSTF guidelines.

Disclosures

Danielle P. Wales, MD, MPH, Gilead (Grant/Research Support) Abigale Eichelman, MA, Gilead FOCUS Foundation (Other Financial or Material Support, Employee of Albany Medical Center with Salary Support on Grant) Ashar Ata, MD, MPH, PHD, GILEAD FOCUS Foundation (Grant/Research Support) Michael Waxman, MD, MPH, Gilead FOCUS Foundation (Grant/Research Support)
1060. Evaluation of ALT at Sustained Virologic Response (SVR) in Patients with Treated Hepatitis C Virus (HCV) Infection
Authors: Theppote Amanda , Nelson Amy , Stafford Kristen A , Wilson Eleanor , Kottilil Shyam , Kaplan Roman
Published: January 2021

Background

With the advent of directly acting antiviral agents, HCV cure rates exceed 90% in real world studies with an excellent safety profile, but viral load tests of cure are expensive and may limit access to treatment, especially in resource-limited settings. Elevated alanine aminotransferase (ALT) has been shown to correlate with hepatocellular damage. Few studies have evaluated the use of ALT in direct acting antiviral (DAA) treated HCV patients post-treatment as a marker of treatment success. In this large retrospective cohort study, we evaluated the ability of serum ALT level at SVR to predict treatment outcome.

Methods

We collected baseline demographics, treatment characteristics, and outcomes of DAA-treated patients treated between January 2015 through January 2019 in the VA Maryland Healthcare System as standard of care, and patients in federally qualified health centers in Washington, DC treated between May and November 2015 in the ASCEND study (NCT02339038). Using the ASCEND study as a training set and VA data as the confirmatory set, receiver operating curves (ROC) were generated to determine the predictive value of ALT at SVR for treatment outcome.

Results

In total, 1415 patients were included, with 1010 patients from the VA and 405 from the ASCEND cohort. We found 96% (n=1360) of patients achieved SVR; < 4% (n =55) relapsed. Baseline demographics are in Table 1. The ALT at SVR were 21.19 IU/L (SD 13.98) and 17.89 IU/L (SD 11.62) in the VA and ASCEND data, respectively compared to 57.84 (SD 41.06) and 42.53 (SD 19.61) who relapsed. With the VA and ASCEND data combined, the mean ALT at SVR was 20.25 (SD 13.43) in comparison to an ALT of 53.11 (SD 36.33) for those patients who relapsed. ROC analysis revealed that ALT > 22 predicted an increased risk of relapse (Figure 1).

Table 1:Characteristics of Subjects Completing Hepatitis C Treatment

Figure 1: ROC Curve

Conclusion

In this real-world cohort, we found that ALT greater than 22 at SVR corresponded with an increased risk of relapse and was independent of variables previously associated with relapse, including HIV coinfection status, sex, treatment history, and fibrosis staging. Limiting HCV viral load testing to patients with ALT > 22 at SVR may reduce the overall burden of HCV treatment costs for the majority of HCV treated patients.

Disclosures

Shyam Kottilil, MD PhD, Arbutus Pharmaceuticals (Grant/Research Support)Gilead Sciences (Grant/Research Support)Merck Inc (Grant/Research Support, Advisor or Review Panel member)
1061. False Positive Human Immunodeficiency Virus Testing Due to Acute Hepatitis A Infection: A Case Series
Authors: Bandres Maria V , Mueller Daniel
Published: January 2021

Background

In our urban, underserved patient population, Human Immunodeficiency Virus (HIV) is hyper-endemic, and HIV screening is frequently performed. Although HIV screening tests have high specificity, false positives can occur. Numerous reasons for false positive testing have been cited, including vaccinations, autoimmune diseases, and viral infections. In 2019, Philadelphia experienced a large Hepatitis A outbreak, during which time false positive HIV screening tests were discovered. Our aim was to further describe these patients who had been diagnosed with acute Hepatitis A infection and in whom false positive HIV testing had occurred.

Methods

We conducted a retrospective chart review of adult patients admitted to our hospital between January 2017 and December 2019 who had a positive Hepatitis A Virus (HAV) IgM. Demographics, HIV tests, viral hepatitis tests, and liver tests were recorded. False positive HIV was defined as a positive HIV screen (p24 antigen and HIV-1 and 2 antibody combo), followed by a negative differentiation assay for HIV-1 and 2 antibodies, combined with a negative HIV PCR.

Results

A total of 156 unique patients were found to have acute HAV, with 138 cases identified in 2019. Of these, 3 patients had confirmed false positive HIV testing, and 1 patient had suspected false positive HIV testing (HIV-2 differentiation assay indeterminate, with very low local prevalence of HIV-2), for a false positive test rate of 2.6% (4/156). Ages ranged from 36-47 years, 3 were male, and 2 were persons who injected drugs (PWID). Three patients had prior negative HIV testing. Two patients had fevers during admission, but none of the four were febrile at the time of HIV test collection. Three patients had elevated transaminases, and two had abnormal coagulation testing. Coinfection with Hepatitis C was found in three patients. One patient had follow-up HIV testing performed, which was negative.

Conclusion

To our knowledge, this is the first report of false positive HIV testing related to acute HAV. Prevalence of false positives was low, but awareness can facilitate patient counseling. With low sample size, conclusions cannot be drawn about risk factors related to false positive testing.

Disclosures

All Authors: No reported disclosures
1062. HCV GET-UP: A Group Evaluation and Treatment Uptake Intervention Improves HCV Linkage to Care for PWID
Authors: Norton Brianna L , Norton Brianna L , Gutierrez Nataly Rios , Cunningham Chinazo O , Litwin Alain H
Published: January 2021

Background

Though PWID represent the overwhelming majority of those living with HCV in the United States, most have not been treated. PWID often have reduced access to specialty care, as well as limited HCV knowledge, low perceived vulnerability to poor HCV-related health outcomes, poor self-efficacy, high levels of perceived stigma, and mistrust of healthcare providers. We therefore evaluated an primary care based HCV Group Evaluation and Treatment UPtake (HCV GET-UP) intervention to improve HCV medical evaluation and treatment uptake for HCV+ PWIDs.

Figure 1

Methods

We enrolled 84 HCV+ PWID and randomize them 1:1 to a 4-week group evaluation intervention followed by individual treatment (intervention) versus onsite treatment alone (control). The group consisted of 4 weekly 1-hour sessions focused on HCV education, peer motivation, and health behavior change skills, along with an HCV medical evaluation. Both arms received HCV treatment according to national guidelines. Baseline questionnaires were performed via Audio Computer-Assisted Self-Interview (ACASI) technology. Clinical Data was extracted from the medical chart. Our primary outcomes were HCV linkage to care (HCV evaluation) and treatment uptake. Bivariate analyses were performed to evaluate HCV treatment outcomes between arms using chi square tests.

Results

Of the 76 participants that have currently completed the study (84 enrolled) 35% identified their race as black, 61% identified their ethnicity as Hispanic, 79% were male, and 25% of the participants were homeless. 87% had genotype 1, 28% were HIV+, and 20% had cirrhosis. Baseline urine tocixicologies were positive for cocaine in 38% of participants and 40% for heroin. Of those randomized to the group treatment arm vs individual arm 87% vs 62% were linked to care (p=0.012), 51% vs. 41% initiated treatment (p=.35), 41% vs. 35% completed treatment (p=0.6), and 33% vs. 27% (p=0.6)

Conclusion

HCV GET-UP, a primary-care based group evaluation and treatment uptake intervention significantly improved linkage to care for HCV+ PWID. Though this is encouraging, we must integrate other interventions to aid PWID as they move through the more proximal steps of the HCV cascade, for HCV cure still remains elusive for the majority of PWID enrolled.

Disclosures

Chinazo O. Cunningham, MD, MPH, General Electric Health (Other Financial or Material Support, My husband is currently employed by General Electric Health and receives stock and stock options.)Quest Diagnostics (Other Financial or Material Support, My husband was previously employed by Quest Diagnostics and received stocks and stock options.) Alain H. Litwin, MD, MPH, MS, Gilead (Advisor or Review Panel member)Merck (Advisor or Review Panel member)
1068. Large-Scale Migration and the Changing Viral Hepatitis Prevalences in North America: A modeling approach
Authors: Valles Kenneth A , Roberts Lewis R
Published: January 2021

Background

Infection by hepatitis B and C viruses causes inflammation of the liver and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. The WHO’s ambition to eliminate viral hepatitis by 2030 requires strategies specific to the dynamic disease profiles each nation faces. Large-scale human movement from high-prevalence nations to the United States and Canada have altered the disease landscape, likely warranting adjustments to present elimination approaches. However, the nature and magnitude of the new disease burden remains unknown. This study aims to generate a modeled estimate of recent HBV and HCV prevalence changes to the United States and Canada due to migration.

Methods

Total migrant populations from 2010-2019 were obtained from United Nations Migrant Stock database. Country-of-origin HBV and HCV prevalences were obtained for the select 40 country-of-origin nations from the Polaris Observatory and systematic reviews. A standard pivot table was used to evaluate the disease contribution from and to each nation. Disease progression estimates were generated using the American Association for the Study of the Liver guidelines and outcome data.

Results

Between 2010 and 2019, 7,676,937 documented migrants arrived in US and Canada from the selected high-volume nations. Primary migrant source regions were East Asia and Latin America. Combined, an estimated 878,995 migrants were HBV positive, and 226,428 HCV positive. The majority of both migrants (6,477,506) and new viral hepatitis cases (HBV=840,315 and HCV=215,359) were found in the United States. The largest source of HBV cases stemmed from the Philippines, and HCV cases from El Salvador.

Conclusion

Massive human movement has significantly changed HBV and HCV disease burdens in both the US and Canada over the past decade and the long-term outcomes of cirrhosis and HCC are also expected to increase. These increases are likely to disproportionally impact individuals of the migrant and refugee communities and screening and treatment programs must be strategically adjusted in order to reduce morbidity, mortality, and healthcare expenses.

Disclosures

All Authors: No reported disclosures
1072. The Impact of Hepatitis C-Related Knowledge on Perceptions of Stigma Among Infected Individuals
Authors: Saine M Elle , Szymczak Julia E , Forde Kimberly A , Moore Tyler M , Bamford Laura P , Barg Frances K , Schnittker Jason , Holmes John H , Mitra Nandita , Re Vincent Lo
Published: January 2021

Background

Stigma is an important and understudied barrier to hepatitis C virus (HCV) infection treatment and elimination. Education to dispel disease-based myths and misinformation has been identified as a key intervention point to reduce disease-related stigma; however, the association between knowledge about HCV infection and perceptions of stigma among HCV-infected patients remains unknown.

Methods

To address this gap and evaluate the association between patient-level HCV knowledge and HCV-related stigma, we conducted a cross-sectional study among 270 HCV-infected patients (147 [56%] HIV-coinfected) from 5 clinics across Philadelphia. HCV-related stigma was measured using the validated 33-item HCV Stigma Scale (range, 33-132). HCV-related knowledge was measured via the National Health and Nutrition Examination Survey (NHANES) Hepatitis C Follow-up Survey (2003-2008), an eleven item True/False survey (range, 0 to 11) comprising statements about HCV-related health effects and transmission. The association between HCV knowledge and HCV-related stigma was evaluated via linear regression by HIV status. Self-reported demographic, behavioral, and clinical covariates were evaluated in adjusted analyses.

Results

The median overall HCV knowledge score was high at 9 out of 11 points (IQR, 9-10). Median knowledge scores did not significantly differ between HIV/HCV-coinfected and HCV-monoinfected participants (10 versus 9; p=0.29). However, higher HCV knowledge scores were associated with higher HCV-related stigma score among HCV-monoinfected participants (p=0.03) but not among HCV/HIV-coinfected participants (p=0.12). Differences by HIV status were also observed when adjusting for demographic, behavioral, and clinical covariates.

Conclusion

Regardless of HIV status, the majority of both HIV/HCV-coinfected and HCV-monoinfected participants in this study answered questions about HCV knowledge correctly. Surprisingly, greater HCV knowledge was associated with increased HCV-related stigma among HCV-monoinfected participants, but this association was not observed among coinfected participants. Additional studies are needed to understand why this association was observed only among monoinfected persons.

Disclosures

M. Elle Saine, PhD, MA, Leonard Davis Institute of Health Economics Research (Grant/Research Support)
81. Physicians’ Knowledge, Attitude, and Practice regarding Prolonged Antimicrobial Use
Authors: Kim Da Young , kim Dahye , Heo Eunjeong , kim Hyung-sook , Park Ji Young , lee Hyunju , Seo Jun-won , Jung Jongtak , Moon Song Mi , Song Kyoung-Ho , Kim Eu Suk , Kim Hong Bin
Published: January 2021

Background

To reduce unnecessary long-term antibiotic therapies, pharmacist-led intervention followed by the involvement of infectious diseases (ID) specialist was implemented. In addition, a survey for the prescribers was conducted to find the gaps for improvement.

Methods

The “less is better” intervention was implemented between August 1, 2018 and February 28, 2019, which was focused on those to whom antibiotics had been administered for over 15 days. However, the following patients were excluded: patients having hematologic diseases, patients in the neonatal intensive care units, and patients who were recommended to maintain antibiotics by ID specialist. Treatment duration according to the indications was compared between pre-intervention period (Aug to Sep 2017) and post-intervention period. A questionnaire based on clinical vignettes was distributed among 140 prescribers.

Results

Among 500 prescriptions assessed as a prolonged treatment, 475 (95%) were stopped after intervention. Over the pre- and post-intervention period, pneumonia was the most common indication of prolonged antibiotic use (43.8 versus 43.0%). The treatment durations decreased from 21.0 (interquartile range [IQR], 27.3-18.0) days pre-intervention to 16.0 (IQR, 20.0-15.0) days post-intervention (p=0.000).

The survey response rate was 76.4% (107/140). Regarding community-acquired pneumonia, there was a significant difference between knowledge and practice, showing that 53% were aware of the standard duration, but 72% actually prescribed for a longer duration. There was a similar trend for the treatment of urinary tract infection (30% versus 83%, p=0.024). The reasons why the physicians prescribed antibiotics of a prolonged duration in spite of adequate knowledge were not only the lack of symptom alleviation in patients but also organizational factors.

Conclusion

The duration of long-term antibiotic treatment was shortened by active participation of pharmacist as well as ID specialists. However, gaps between the knowledge and practice on the duration of antibiotic treatment were also found. Therefore, it is necessary to implement appropriate feedback and education based on clinical scenario in order to improve the physicians’ antibiotic prescription.

Disclosures

All Authors: No reported disclosures
1082. Characterization of Ceftriaxone-Resistant Viridans Streptococci Bacteremia Among Patients at a Comprehensive Cancer Center
Authors: Marsland Paula , Jain Rupali , Tverdek Frank , Hendrie Paul , Liu Catherine , Pergam Steven A , Bourassa Lori
Published: January 2021

Background

Viridans streptococci (VS) are opportunistic oral commensals and a common cause of bacteremia, particularly in neutropenic patients. We sought to investigate the prevalence of ceftriaxone (CTX) resistance in VS blood isolates at our medical center among patients with cancer or treated with hematopoietic cell transplant (HCT), and to describe treatment and clinical course.

Methods

In this retrospective single center cohort study, we identified CTX-resistant (CTX-R) VS isolates among patients between January 2005 – June 2020. VS in blood cultures were identified using a combination of biochemicals and mass spectrometry. Susceptibility testing was performed by Kirby Bauer and E-Test. Demographic data, clinical outcomes, and antimicrobial use, including prophylactic, empiric treatment and definitive therapy choices were assessed through electronic medical record review.

Results

Of unique VS with sensitivities (n=693), 27 (3.9%) patients had confirmed CTX-R VS bacteremia over the 15-year period; the majority were S. mitis (23/27 [85%]). 17 (63%) were cancer center patients, of whom 15/17 (88%) had a known hematologic malignancy, 11 (65%) had undergone HCT, and 15 (88%) were neutropenic (absolute neutrophil count ≤500 cells/microliter). Of CTX-R strains, 15/17 (88%) had concomitant resistance to penicillin, erythromycin (12 [71%]), and levofloxacin (12 [71%]); all were sensitive to vancomycin. Most were on levofloxacin prophylaxis (11/17 [65%]) at the time of diagnosis. Initial empiric antibiotic choices primarily included cefepime, ceftazidime, or meropenem, with 16/17 (94%) receiving concomitant empiric vancomycin; 14/17 (82%) were de-escalated to vancomycin once sensitivities were obtained. 2/17 (12%) patients died within 30 days of CTX-R VS bacteremia. Despite increasing susceptibility testing among VS isolates, there did not appear to be an increase in the percentage of CTX-R over time.

Conclusion

VS is a common pathogen in neutropenic cancer patients treated with chemo and/or BMT, and multi-drug resistant CTX-R strains are of concern. In the modern era of ambulatory cancer care, prescribers must be cautious using ceftriaxone monotherapy in the absence of susceptibility information, particularly among patients with hematologic malignancies.

Disclosures

Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)
1084. Epidemiology and Long-term Outcomes of Cytomegalovirus (CMV) in Pediatric Liver Transplant Recipients (PLTR) at Texas Children’s Hospital (TCH)
Authors: Deray Kristen Valencia , Hosek Kathleen , Munoz Flor M , Moulton Elizabeth A , Demmler-Harrison Gail J , Leung Daniel H , Bocchini Claire
Published: January 2021

Background

Despite widespread use of prevention strategies, CMV DNAemia remains common in PLTR. Contemporary data, however, is limited. We sought to determine the frequency of, risk factors for, and long term outcomes of CMV DNAemia in a large, single center cohort of PLTR.

Methods

A retrospective cohort study of PLTR < 22 yrs of age transplanted from 2011-2018 was completed. Per protocol, CMV prophylaxis with ganciclovir/valganciclovir was universally implemented; high risk (HR)(D+/R-) and intermediate risk (IR)(R+) patients received 6 months while low risk (LR)(D-/R-) patients received 3 months. Primary outcomes included any CMV DNAemia, CMV DNAemia >1000 IU/mL and long term outcomes including rejection, graft failure, hepatic steatosis (HS), and de novo autoimmune hepatitis (AIH). Associations with CMV DNAemia were measured using Fisher exact and multivariate regression. Survival analysis, time to CMV infection, and time to PLTR long term outcomes were assessed using Kaplan-Meier plots.

Results

Among 270 PLTR, 81 (30%) had quantifiable CMV DNAemia; 36 (13%) had CMV DNAemia >1000 IU/mL. Fifty (19%) developed CMV DNAemia while on prophylaxis. Median time (range) to CMV DNAemia was 162 days (5-2213). HR (OR 4.18; 95% CI 1.84-9.49, p< 0.01) status was associated with CMV DNAemia and time to CMV DNAemia. CMV DNAemia was not associated with age at transplantation or cold ischemic time.

Eight PLTR (3%) developed CMV syndrome (4 HR, 3 IR, 1 LR), the median peak (range) DNAemia was 2133 IU/mL (202-58000) for these patients. No PLTR developed CMV tissue invasive disease.

CMV DNAemia was not associated with rejection (15% vs. 33%, p=0.62), graft failure (7% vs. 13%, p=0.17), HS (8% vs. 12%, p=0.32), or AIH (10% vs. 8%, p= 0.68). CMV DNAemia was associated with a longer time to rejection (p=0.02). Time to development of graft failure, HS, and AIH were not associated with CMV DNAemia (Figure 1). Finally, there was no difference in survival during the study follow-up period (1 – 9 yrs) for PLTR with vs. without CMV DNAemia (p=0.58).

Figure 1

Conclusion

This large cohort of PLTR demonstrates high rates of CMV DNAemia but low rates of CMV disease. HR status remains associated with CMV DNAemia. CMV DNAemia did not increase the risk of long term adverse outcomes such as rejection, graft failure, HS, and AIH.

Disclosures

All Authors: No reported disclosures
1085. Epidemiology and Outcomes of Histoplasmosis in Transplant Recipients
Authors: Rutjanawech Sasinuch , Larson Lindsey , Franklin Alexander , Hendrix Michael Joshua , Powderly William , Spec Andrej
Published: January 2021

Background

Histoplasmosis in transplant recipients is understudied. We reviewed a large cohort of histoplasmosis in patients with solid organ and stem cell transplants in an endemic area to describe the epidemiology, clinical findings and outcomes.

Methods

We performed a single-center retrospective cohort study of patients diagnosed with histoplasmosis between 2002 and 2017. Demographic data, clinical findings, diagnostic methods, treatment, and mortality were collected. We compared the characteristics of patients with history of transplant to non-transplant (NT) patients.

Results

We identified 261 patients with histoplasmosis. Of those, 28(11%) were transplant recipients; 8(29%) liver, 8(29%) lung, 6(21%) kidney, 3(11%) heart, and 3(11%) stem cell.

Median time from symptom onset to diagnosis was 6 vs 34 days in transplant vs NT groups (p=0.001). Lung was the most common organ involvement (89% in transplants vs 78% in NT, p=0.168). Spleen involvement was more commonly found in transplant patients (29 vs 14%, p=0.039). In patients with disseminated disease, urine antigen was 100% sensitive in transplant patients compared to 78% in the NT group (p=0.038). Duration of treatment was 13 vs 6 months in transplant vs NT patients (p= 0.003). Mortality was comparable between groups (14 vs 15% in transplant vs NT, p=0.918).

Median time from transplant to diagnosis was 4.21 years. However, five patients (18%) developed histoplasmosis within 6 months. For these early diagnosed patients, ICU admission rate was 80 vs 30% (p=0.04) and rate of mechanical ventilator use was 80 vs 22% (p=0.011) compared to patients diagnosed later.

Table 1: Patient characteristics

Table 2: Organ involvement

Table 3: Diagnostic test positivity

Conclusion

Transplant recipients with histoplasmosis are likely to be diagnosed early and be treated longer. Urine antigen is highly sensitive for diagnosis of disseminated disease. Histoplasmosis that occurs within the first 6 months after transplantation tends to be more severe.

Disclosures

Andrej Spec, MD, MSCI, Astellas (Grant/Research Support)Mayne (Consultant)Scynexis (Consultant)
1093. Infectious Complications after Pancreatic Islet Transplantation
Authors: Raval Milan , Lam Anna , Cervera Carols , Senior Peter , Shapiro James , Kabbani Dima
Published: January 2021

Background

Despite the significant advancement in islet transplantation over the past three decades, our understanding of infectious complications post islet transplant remains limited.

Methods

This is a single center retrospective review of Islet transplant recipients at the University of Alberta between February 2006 and December 2015. All infectious episodes events occurring after transplant were categorized as opportunistic and non-opportunistic.

Results

We analyzed 142 patients receiving a median of 2 islet transplants per patient, with 18 patients receiving 1 transplant (13%), 77 (54%) 2, 33 (23%) 3, 13 (9%) 4 and 1(1%) 5 transplants. Median age at first transplant was 50 years and 85 (47%) were male. Lymphocyte depleting agent with thymoglobulin or alemtuzumab was used for induction in 94% in first and 53% in second transplant. CMV serostatus was CMV D+/R- 61 (43%), CMVD+/R+ 52 (37%), CMVD-/R+ 16 (11%) and CMVD-/R- 13 (9%). CMV infection occurred in 21 patients (15%) [CMVD+/R- 6 (9.8%) and CMVR+ 15 (22.1%), p=0.06]. Other opportunistic infections included VZV 7 (4.9%), Nocardia 3(2.1%), and Pneumocystis jirovecii pneumonia 1. Non-opportunistic infections included skin and soft tissue infection 14 (9.9%), urinary tract infection 11 (7.7%), pneumonia 7 (4.9%) clostridium difficile infection (CDI) 4 (2.8%), and non-CDI gastroenteritis 5 (3.5%) (Table 1).

Table 1: Infectious Complication post islet transplant

Conclusion

Although the rate of infections after islet cell transplant is less frequent than other types of transplants, opportunistic infections, especially CMV, are not uncommon and should be considered in this setting.

Disclosures

Carols Cervera, MD, PHD, Merk (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Lecture fees) James Shapiro, MD, PHD FRCS(Eng) FRCSC MSM FRSC, ViaCyte (Consultant) Dima Kabbani, MD, Merck (Research Grant or Support)
1097. Microbial Cell Free DNA Sequencing for Prediction of Culture-Negative Infection Events in Children with Cancer
Authors: Goggin Kathryn , griffen Amanda , Kohler Christina , Allison Kim J , Inaba Yuki , Ahmed Asim A , Hollemon Desiree D , Brenner Abigail , Maron Gabriela , Maron Gabriela , Sun Yilun , Tang Li , Margolis Ellie , Gawad Charles , Wolf Joshua
Published: January 2021

Background

Culture-independent diagnostics may help diagnose or predict infection; microbial cell free DNA sequencing (mcfDNA-seq), can detect a wide range of pathogens directly from plasma. Immunocompromised children who develop febrile neutropenia (FN) without documented bloodstream infection (BSI) may have undiagnosed bacterial infection, but identification of this is difficult, and the proportion of such episodes is unknown, as is the relative contribution of non-bacterial etiologies. We analyzed mcfDNA-seq results in a convenience sample of FN cases without known etiology.

Methods

Participants were < 25 years of age and undergoing treatment for cancer. Remnant plasma was prospectively obtained and stored. Samples from Days 0 and -1 underwent mcfDNA-seq by Karius Inc., reported in molecules per microliter (MPM) of plasma. Samples from participants without impending or recent fever or infection were also tested.

Results

There were 8 episodes in 7 patients; 4 (50%) had a common bacterial pathogen identified by mcfDNA-seq on Day 0 (Table 1). In 2 (50%) of these cases, the same organism was also identified on Day -1, at a lower concentration. One fungal pathogen was identified prior to and at onset of FN. A common bacterial pathogen was identified in 3/64 (5%) control samples from the population.

Culture-negative sepsis was the final diagnosis in one episode; Streptococcus mitis, an important cause of neutropenic sepsis, was found in Day 0 and Day -1 samples. In an episode where E. coli was identified by mcfDNA-seq, FN recurred after antibiotic discontinuation.

Table 1. Quantitative mcfDNA-seq Results for Prediction & Diagnosis of Febrile Neutropenia Episodes

Conclusion

In this sample of culture-negative FN episodes in pediatric patients leukemia, mcfDNA-seq identified a bacterial pathogen in 50% of cases. The same organism was identifiable on the day prior to FN in 50% of cases, suggesting that predictive testing might be feasible.

Disclosures

Asim A. Ahmed, MD, Karius (Employee) Desiree D. Hollemon, MSN, MPH, Karius inc (Employee) Charles Gawad, MD PhD, Karius inc (Grant/Research Support) Joshua Wolf, MBBS, PhD, FRACP, Karius inc (Grant/Research Support)
1098. Norovirus Infection in Cancer Patients Undergoing Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T)
Authors: Kondapi Divya S , Ramani Sasirekha , Olvera Adilene , Atmar Robert L , Estes Mary K , Okhuysen Pablo C
Published: January 2021

Background

CAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients.

Methods

We reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications.

Results

The median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count< 1000/mm3 at diarrhea onset. Three had diarrhea for >14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting >14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1).

Table 1: Patient characteristics (N=9)

Table 2: CAR-T related factors

Table 3: NoV Genotypes

Conclusion

NoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy.

Disclosures

Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)
1101. Pulmonary Aspergillosis Complicating Non-Influenza Respiratory Virus Infections Among Solid Organ Transplant Recipients
Authors: Apostolopoulou Anna , Clancy Cornelius J , Viehman J Alex , Nguyen Minh Hong T
Published: January 2021

Background

Invasive pulmonary aspergillosis (IPA) complicating influenza (flu) has been increasingly recognized. We have shown that IPA occurred in 22% of solid organ transplant (SOT) patients (pts) with flu. Associations between IPA and non-flu respiratory infections (non-flu-RVI) in SOT are unknown.

Methods

Retrospective review of consecutive pts transplanted from Jan 15, 2010-Dec 19, 2017. Pts who died within 100 days of SOT were excluded. Non-flu-RVI IFI was defined according to revised EORTC/MSG criteria. IFI had to occur within 100 days of non-flu-RVI. Colonization (COL) was defined as recovery of mold from airways in absence of IFI.

Results

3,077 pts were included. 256 cases of non-flu-RVI were identified in lung (28%), multi-organ (16%), heart (6%), liver (1.3%) and kidney (1%) SOT pts. Parainfluenza (PIV) was most common (44%), followed by Respiratory Syncytial Virus (RSV, 60%) and Adenovirus (ADV, 15%). Median time to non-flu-RVI infections was 18.1 mos. 24% of pts with non-flu-RVI had lower tract disease. ADV was associated with longer hospital stay (median 14.5 days) than PIV (6.5 days) or RSV (6 days) (p=0.004). 59% of pts with non-flu-RVI required admission, and 64% received augmented steroids. Aspergillus was recovered from respiratory culture in 17% of non-flu-RVI pts. No other fungi were identified. Median time from non-flu-RVI to + culture was 29 days (Figure). 23% of pts with + culture had proven (7) or probable IPA (3), respectively; 77% had COL. 8% (3/37), 5% (6/114) and 7% (1/15) of pts with ADV, PIV, RSV infections developed IPA, respectively. 36% of pts were treated with a mold-active azole after + culture. Multivariate analysis identified lung transplant (p=0.02), PIV infection (p=0.02) and cumulative steroid dose in preceding 7 days (p=0.015) as independent risk factors for Aspergillus culture positivity. Cumulative steroid dose in preceding 7 days was an independent risk factor for IPA (p=0.03).

Cumulative incidence of Aspergillus infections within 100 days of non-flu RVI

Conclusion

IPA and COL occurred in 4% and 13% of non-flu-RVI in SOT recipients. Routine antifungal prophylaxis is not recommended for SOT pts with non-flu-RVI. The value of prophylaxis at time of PIV infection for lung transplant pts with recent steroid augmentation should be studied.

Disclosures

Cornelius J. Clancy, MD, Astellas (Consultant, Grant/Research Support)Cidara (Consultant, Research Grant or Support)Melinta (Grant/Research Support)Merck (Consultant, Grant/Research Support)Needham Associates (Consultant)Qpex (Consultant)Scynexis (Consultant)Shionogi (Consultant)
1102. Reconstitution of CMV-specific cell-mediated immunity during letermovir prophylaxis in hematopoietic stem cell recipients
Authors: Abidi Maheen , Gutman Jonathan , Weinberg Adriana
Published: January 2021

Background

Patients who are cytomegalovirus (CMV) seropositive (R+) prior to hematopoietic cell transplant (HCT), have 30% incidence of clinically significant CMV reactivation in the absence of prophylaxis. At our institution, letermovir prophylaxis through Day 100 is used in CMV R+ high-risk (HR) (cord blood, haplocord, haploidentical) HCT recipients. We hypothesized that clinically nonsignificant CMV reactivation during letermovir prophylaxis may lead to reconstitution of CMV specific cell mediated immunity (CMV CMI), which may protect the host against CMV disease after letermovir discontinuation.

Methods

Blood samples from CMV R+ HR HCT recipients on letermovir were tested by dual color CMV specific IL2/IFNg FLUOROSpot pre-transplant and on Days 100, 182 and 360 post-transplant. Clinical and virologic information were obtained from medical records.

Results

Among 35 participants enrolled to date, 19 were eligible for this analysis, which included only participants with CMV CMI defined as ≥20 spot-forming cells/106 PBMC pre-transplantation and follow up ≥180 post-transplantation. Median age was 51.5 years (range 22-75), 9 were women, 9 were white non-Hispanic, 8 were Hispanic and the most common underlying malignancy was acute myeloid leukemia (n=10). 14 participants had CMV CMI reconstitution at Day 100; including 5 with and 9 without low level CMV DNAemia, defined as <5000 international units/ml in whole blood quantitative polymerase chain reaction assay, while on letermovir prophylaxis. Among the 14 participants, 11 remained free of clinically significant CMV reactivation for a median (range) of 260 (80; 260) days post-letermovir discontinuation, while 3 developed acute graft vs. host disease (aGvHD) followed by clinically significant CMV reactivation. 5 participants did not reconstitute CMV CMI at Day 100 and none of them had DNAemia while on letermovir. 1 of 5 participants without CMV CMI reconstitution or aGvHD developed CMV disease after letermovir discontinuation.

Conclusion

High-risk patient populations can reconstitute CMV CMI while on letermovir. Ongoing investigation will help establish predictive parameters for CMV CMI that may allow risk stratification for CMV monitoring and letermovir usage.

Disclosures

Maheen Abidi, MD, Merck (Research Grant or Support) Jonathan Gutman, MD, Merck (Research Grant or Support) Adriana Weinberg, MD, GSK (Grant/Research Support)merck (Grant/Research Support)
1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
Authors: Garner Will , Samanta Palash , Dorritie Kathleen , Sehgal Alison , Winfield Denise , Agha Mounzer , Boudreau Robert , Nguyen Minh Hong T , Haidar Ghady
Published: January 2021

Background

CAR T -cell therapy (CTT) is a novel treatment for B-cell cancers. CTT patients (pt) are at risk of infection due to neutropenia, cytokine release syndrome (CRS), and CAR T-cell related encephalopathy syndrome (CRES), which are treated with steroids and tocilizumab (anti-IL-6). This is a single-center study evaluating the risk factors for infection after CTT.

Methods

A retrospective review was conducted of 60 consecutive CTT recipients between 7/17/17 and 9/5/19. Data was collected from 6 months (mo) pre- and at least 6 mo post-CTT. Data was censored for death, additional chemotherapy, or loss to follow up. Cox proportional hazard and Poisson regression were used.

Results

Median age was 66 (23-84) years; 48% (29) were female. The most common cancer was non-Hodgkin lymphoma (89%, 54). 25% (15) had a prior stem cell transplant (SCT). 73% (44) and 45% (27) of pts developed CRS and CRES, respectively. 43% (26) received steroids; 65% (39) received tocilizumab. In the 6 mo pre-CTT, 39 infections occurred in 45% (27) of pts. 103 infections occurred in 66% (40) after CTT; 33 (55%) had an infection within 6 mo. Infections were bacterial (52%; 54/103), viral (30%; 37/103), fungal (10%; 10/103), mycobacterial (1%; 1/103), protozoal (1%; 1/103). Cumulative incidence of infection in the first 6 mo are shown in Fig 1. All-cause and infection-related mortality were 32% (19) and 15% (9), respectively. Mortality among pts with fungal infections was 20% (2/10). Infection density was 1.28 and 0.58 infections per 100 pt-days between days 0-30 and 30-89, respectively. Factors associated with infection post CTT were number (no.) of infections in the 6 mo prior to infusion (HR 1.62, CI [1.1-2.38]; p=0.015), no. of lines of therapy in the 6 mo pre-CTT (HR 1.52, CI [1.01-2.27]; p=0.04), prior allogeneic SCT (HR 5.96, CI [1.34-26.47]; p=0.019), and no. of tocilizumab doses. Grade 1 CRS and grade 2 CRES were risk factors between days 0-30 and 0-180, respectively (HR 4.67, CI [1.02 -21.4], p = 0.047; HR 2.48, CI [1.17-5.23], p = 0.02).

Fig 1: Cumulative Incidence of Infection 6 Months Post CAR T-cell Therapy

Conclusion

Infections after CTT are common. Infection before CTT was associated with risk of infection after CTT. Pt selection may ameliorate this risk. Mortality due to fungal infections was high. Randomized-controlled trials of antifungal prophylaxis in high-risk pts are needed.

Disclosures

All Authors: No reported disclosures
1106. The incidence and risk factors associated with varicella zoster virus infection in kidney transplant recipients after 1-month acyclovir prophylaxis in a CMV preemptive therapy era
Authors: Kim Haein , jung Joo hee , Jung Jiwon , Kim Min Jae , Kim Hyosang , Shin Sung , Chong Yong Pil , Kim Young-Hoon , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Park Su-Kil , Han Duck Jong , Kim Sung-Han
Published: January 2021

Background

Varicella zoster virus (VZV) infection is a well-known opportunistic infection in solid organ transplant recipients. Since the various strategies of the use of anti-herpetic drugs including ganciclovir or acyclovir have evolved, the epidemiology of VZV infection is changing. However, there are limited data on the recent incidence and risk factors of post-transplant VZV infection in popular preemptive ganciclovir era for CMV infection. We evaluated the incidence, risk factors and clinical characteristic of patients with development of post-transplant VZV infection in kidney transplant (KT) recipients after 1-month acyclovir prophylaxis in the hospital that adopted preemptive ganciclovir therapy for CMV infection.

Methods

All adult patients with seropositive CMV antibody admitted to a KT unit from January 2014 to December 2017 were retrospectively reviewed in a tertiary-care hospital in South Korea. Our hospital adopted preemptive ganciclovir therapy for CMV infection in all CMV seropositive KT recipients. We administered acyclovir prophylaxis for 1-month to CMV seropositive KT recipients. The primary endpoint was VZV infection development after KT.

Results

A total of 1295 KT recipients was followed up for 4295.8 person-years. The median follow-up period was 46.6 months (interquartile range (IQR) 34.3-59.5). Of the 1295 recipients, 100 (7.7%, 2.33 per 100 person-years, 95% confidence interval (CI) 1.89-2.83) patients developed VZV infection after KT. The median time for VZV infection development was 9.5 months (IQR 4.7-22.1). All patients had VZV-associated skin lesion, 9 postherpetic neuralgia, 2 visceral involvement and 3 disseminated infection. Of 100 patients, 16 patients need hospitalization due to VZV infection. In multivariate analysis, deceased donor KT (Hazard ratio (HR) 1.6; 95% CI 1.0-2.39, p = 0.05), mycophenolate maintenance immunosuppressive therapy (HR 0.3; 95% CI 0.14-0.75, p = 0.01) and rejection episode (HR 0.31; 95% CI 0.14-0.71, p = 0.01) were independently associated with VZV infection development after KT.

Conclusion

About one tenth of CMV seropositive KT recipients developed zoster after 1-month ACV prophylaxis during CMV preemptive strategy, especially in those who received deceased donor KT, mycophenolate therapy, and rejection episodes.

Disclosures

All Authors: No reported disclosures
1108. Transplantation and Immigration: Comparing Infectious Complications Between Foreign-born vs. U.S.-born Kidney Transplant Recipients in Minnesota
Authors: Espinoza Eloy E Ordaya , Shaughnessy Megan , Walker Patricia F , Husmann Rachel , Hale Gabriel , Stauffer Jacob , Stauffer William
Published: January 2021

Background

Immigrant patients face barriers to kidney transplantation due to language, cultural, and economic issues. Unprepared health systems and providers further contribute to health disparities in transplantation. Foreign-born patients are also at risk for reactivation of latent infections which differ from U.S.-born population. Stratifying transplant recipients according to country of birth could guide clinicians in the prevention, anticipation, diagnostics, and treatment of post-transplant infections.

Methods

A retrospective, observational, multicenter study of patients that underwent kidney transplantation from 1/2014-12/2018 at the University of Minnesota Medical Center and Hennepin Healthcare is being conducted. Sociodemographic, clinical, and laboratory data are collected, including infectious episodes during the first year post-transplant.

Results

One-hundred patients are included in this preliminary analysis (recruitment goal is 800 patients). Sixty-five patients were males (65%), with median age 56 years (range 20 – 77). The majority were Caucasians (64%), followed by Asians (12%) and Africans (9%). Living donation was 59%. Seventy-eight patients developed infectious complications during the first year after transplantation, for a total of 175 infectious episodes: viral etiology (51%), followed by bacterial (42%) and fungal (7%). No tropical diseases were found. Comparing foreign-born (30%) vs. U.S.-born (70%), foreign-born recipients had a higher frequency of latent tuberculosis infection (LTBI) (37% vs 1%, p< 0.001), hepatitis B core antibody positive (20% vs 0, p< 0.001), and deceased donor transplant (67% vs 30%, p= 0.001). CMV mismatch (3% vs 36%, p= 0.002) was more frequent in U.S.-born recipients; CMV reactivation was similar in both groups. While not statistically significant, more foreign-born recipients had an infection in the first year post-transplant (90% vs 73%, p= 0.1), and higher median infectious episodes (2 vs 1, p= 0.6).

Comparison of foreign-born vs U.S.-born kidney transplant recipients (n=100, preliminary data)

Conclusion

Per this preliminary data, foreign-born transplant recipients had a higher frequency of LTBI, hepatitis B core antibody and infectious complications, but lower frequency of CMV mismatch. No cases of tuberculosis, hepatitis B reactivation or tropical diseases were observed.

Disclosures

Patricia F. Walker, MD, DTM&H, FASTMH, UpToDate (Other Financial or Material Support, Royalties from UpToDate for chapter on refugee screening)