bluuebunny/crossref_metadata_2025_split huggingface dataset:
223. Predicting Mortality Among Immunocompromised Patients Who Present With Bloodstream Infection
Authors: Henig Oryan , Rao Krishna , KB Putler Rosemary , Patel Twisha S , Albin Owen , Kaye Keith S 
Published: October 2019

Abstract

Background
The revised definition of sepsis (Sepsis-3) uses Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) to identify patients with sepsis instead of systemic inflammatory response syndrome (SIRS) criteria. Subsequent studies revealed contradictory results pertaining to qSOFA, and limited data are available for immunocompromised patients. The objectives of this study were to (1) evaluate the performance of Sepsis -3 in a cohort of immunocompromised patients with microbiologically-proven sepsis, defined as having received antibiotics and having bloodstream infection (BSI); and (2) to compare its performance in the BSI cohort to its performance in immunocompromised patients who received antibiotics but did not have BSI (Non-BSI cohort).

Methods
Adult patients with hematologic malignancy or solid transplant recipients admitted to Michigan Medicine between 2012–2017 with suspected infection were included based on criteria used in the Sepsis-3 study: having both a body fluid culture and having received intravenous antibiotics. SOFA, qSOFA and SIRS components within 1 day of the index date (culture date or antibiotic date, whichever came first) were extracted from the medical record. For each group, a baseline risk model for mortality was created including age, gender, race, and Charlson comorbidity index. Each score (SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2) was added to the baseline risk model as a dichotomous variable and AUROC values were calculated.

Results
2822 patients with a mean age of 56.8±15.6 were included. 349 (12.4%) had BSI. The most common immune compromising conditions were solid-organ transplantation (47%), lymphoma (21.3%) and acute leukemia (17%). 14% of patients in the BSI cohort died during hospitalization compared with 6.6% in the non-BSI cohort (P < 0.001). For the BSI cohort, when SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2 scores were added to the model, the AUROC values were less than those for the non-BSI cohort (table). The addition of SOFA ≥6 to the baseline risk model produced the highest AUROC values in both the BSI and non-BSI cohorts (figure).

Conclusion
Among immunocompromised patients, an SOFA score ≥6 was the strongest predictor of mortality. Surprisingly, sepsis scores performed better in the non-BSI cohort than in the BSI cohort.

Disclosures
All authors: No reported disclosures.
227. Prevalence, Comorbidities and Expenditures of S. aureus Bacteremia in Liver Transplant Recipients: A 2012–2016 Nationwide Analysis
Authors: Ramakrishna Jahanavi M , Kroner Paul , Helmi Haytham , Libertin Claudia R 
Published: October 2019

Abstract

Background
Bacteremia due to Staphylococcus aureus is a known complication of liver transplantation (LT). Studies have shown that LT recipients are more predisposed to S. aureus infections than other solid-organ transplant patients; however, these studies have been limited in scope and mostly based out of single centers.

Methods
This is a retrospective cohort study using 2012–2016 NIS, the largest public inpatient database in the United States. All patients with ICD9-10CM procedural codes for LT were included. The cohort was stratified into two groups depending on whether they had MSSA or MRSA infection. The odds of inpatient mortality in both groups of patients undergoing LT were determined. The inpatient mortality odds were then compared with those of patients undergoing LT without associated S. aureus infection. Other outcomes included inpatient morbidity, resource utilization, hospital length of stay (LOS), and inflation-adjusted total hospital costs and charges. Multivariate regression analyses were used to adjust for demographic variables and Charlson Comorbidity Index.

Results
A total of 26,415 patients underwent LT in the study period, of which 180 had MSSA and 160 had MRSA infection reported. The mean age was 51.5 years and 35.6% were female. Patients with MSSA and MRSA displayed significantly higher inpatient mortality rates (11.1% and 9.4%, respectively) compared with non-MSSA/MRSA patients (3.4%) who underwent LT (P < 0.01). After adjusting for confounders, patients with MSSA infection displayed higher mortality odds (aOR: 4.45, P < 0.01), while patients with MRSA infection had non-statistically significant higher inpatient mortality odds (aOR: 3.10, P = 0.12) compared with patients without MSSA/MRSA infection. Both MSSA and MRSA cohorts displayed higher mortality odds if the infection resulted in sepsis (aOR: 9.92 and 5.70, respectively; P < 0.01).

Conclusion
There is a direct correlation between S. aureus bacteremia and increased mortality rates and incidence of sepsis and shock in LT recipients. Patients with S. aureus bacteremia spent more days in hospital and had higher cost of healthcare. Preventing and aggressively treating S. aureus infections in the immediate post-LT setting is key to reducing mortality, morbidity and resource utilization in patients undergoing LT.

Disclosures
All authors: No reported disclosures.
231. Microbial cell-free DNA Sequencing to Detect Borrelia burgdorferi DNA in the Plasma of Pediatric Patients with Lyme Disease
Authors: Handel Andrew S , Ho Carine , Hollemon Desiree D , Hong David K , Beneri Christy 
Published: October 2019

Abstract

Background
Diagnosing Lyme disease often involves laboratory evaluation, yet available tests have limitations. Serology remains negative for weeks after infection occurs, and may then remain positive for years. Borrelia burgdorferi blood PCR testing has low sensitivity, rendering it unhelpful. We sought to determine whether an emerging technology, next-generation sequencing (NGS) of microbial cell-free DNA (mcfDNA), can detect B. burgdorferi DNA in the plasma of pediatric patients with erythema migrans (EM).

Methods
Patients aged 1–17 years with a clinically-identified single or multiple EM were enrolled. Two clinical investigators were required to agree on the EM finding, with no evidence of an alternative diagnosis. Subjects were excluded if they previously had Lyme disease, had received antibiotics within 30 days prior to enrollment, or if the rash had resolved before the first blood draw. Three blood samples were taken during the study period: one before antibiotics were administered, then 1–3 weeks and 2–3 months later. At enrollment, plasma was tested for Lyme disease using C6 antibody with reflex to Western Blot and mcfDNA sequencing (Karius, Inc., Redwood City, CA). Briefly, mcfDNA was extracted from plasma and NGS performed. Human reads were removed and remaining sequences were aligned to a curated microbial database. Only mcfDNA testing was performed at follow-up visits.

Results
We enrolled 5 subjects (ages 4–15 years old, median age 4). Four subjects had a single EM and negative Lyme serology. One subject had approximately 20 EMs and positive serology (C6-antibody=7.52 (Positive >1.09), 3/3 IgM, 2/10 IgG). All 14 plasma samples, including five pre- and nine post-antibiotic samples, were negative for B. burgdorferi DNA by mcfDNA sequencing. No other infections, including other tick-borne infections, were detected.

Conclusion
NGS of mcfDNA did not identify B. burgdorferi DNA in the plasma of pediatric patients with active EM rashes. This approach is unlikely to be helpful in diagnosing early localized Lyme disease. This may be because spirochetes are localized to the periphery of the rash in EM and spirochetemia likely occurs at later stages of infection. Follow-up studies are planned to investigate how NGS of mcfDNA performs during early and late disseminated Lyme disease.

Disclosures
All authors: No reported disclosures.
255. Breakthrough Mucormycosis (BT-MCR) on Antifungals Having Mucorales Activity Portrays Worse Prognosis compared with BT-MCR on Mold-Active Antifungals with no Mucorales Activity
Authors: Axell-House Dierdre B , Jiang Ying , Kyvernitakis Andreas , Lewis Russel E , Raad Issam I , Kontoyiannis Dimitrios P 
Published: October 2019

Abstract

Background
BT-MCR is known to develop in the setting of agents having Aspergillus but no Mucorales activity. However, BT-MCR can occur even with the use of antifungals having with Mucorales activity in patients with hematologic malignancies and or stem cell transplant (HM).

Methods
We reviewed the records of HM patients treated for MCR (1994 to 2019) at MD Anderson Cancer Center. We identified patients with BT-MCR on antifungals having Mucorales activity: posaconazole (POSA), isavuconazole (ISA), and amphotericin B (AMB) (group A), and patients with BT-MCR on agents having Aspergillus but no Mucorales activity: voriconazole (VRC), itraconazole (ITZ), echinocandins (group B). BT-MCR was defined as MCR diagnosis (dx) after ≥7days (d) of antifungal use. The primary outcome was 42d mortality after the BT-MCR dx. Chi-square or Fisher’s exact test was used for categorical variables and Wilcoxon rank-sum test used for continuous variables. Cox regression model was used to evaluate the independent variables on outcome.

Results
We identified 11 patients in group A (3 POSA, 5 ISA, 3 AMB) and 81 patients in group B (61 VRC, 13 echinocandins, 7 ITZ). Both groups were not different in terms of age, sex, underlying HM (AML/MDS in 100% vs. 88% in groups A and B, respectively), status of HM (active disease in 82% vs. 67%), prior stem cell transplant (45% vs. 54%) or GvHD (80% vs. 84%), neutropenia at dx (55% vs. 42%), prior receipt of >600 mg of prednisone (45% vs. 41%) or ICU at MCR dx (36% vs. 26%). Similarly, Mucorales species (Rhizopus spp. in 55% vs. 49%) and type of infection (sino-pulmonary in 73% vs. 68%) were no different between the groups. However, both d42 (82% vs. 46%, P = 0.025) and d84 (100% vs. 60%, P = 0.007) mortality was worse in group A. Similarly, median time to death was faster in patients in group A (26d, range 7-80d), vs. group B (42d, range 4–3146d, P = 0.031). Kaplan–Meier analysis showed a similar difference (Figure 1). In multivariate analysis, neutropenia (P = 0.038) and ICU at dx (P = 0.002) were independent factors on day 42d mortality in all 92 patients with prior Mucorales–active antifungals showing a trend associated with poor outcome (P = 0.17).

Conclusion
BT-MCR on agents having Mucorales activity is a marker of poor prognosis in HM patients. Early use of investigational immunotherapy and salvage antifungal chemotherapy studies is needed in that subgroup of patients.

Disclosures
All authors: No reported disclosures.
268. Fungal NGS: Identification of Etiological Agents of Invasive Fungal Infection by High-throughput Sequencing
Authors: Nelsen Donald J , Sinha Rohita , Tyler Aaron J , Westergaard Jordyn , Nutt Jamie , Wissel Mark , Kleiboeker Steve , Altrich Michelle 
Published: October 2019

Abstract

Background
Invasive fungal infections (IFI) cause severe symptoms that affect immunocompromised and transplant patient populations. Antifungal therapies vary depending on the pathogenic species, and delays in diagnosis can lead to graft loss and an increase in morbidity and mortality. Therefore, rapid identification of fungi causing IFI is critical for informing antifungal therapy. Such actionable genus/species information can be obtained quickly via Next-generation Sequencing (NGS). In this study, an NGS assay was developed to identify fungal species responsible for IFI, allowing for selection of effective antifungal therapies.

Methods
Internal transcribed spacer (ITS) regions 1 and 2 were used for fungal identification. Primers were taken from published research and/or designed/modified by assessment in fungal sequence alignments. A DNA sequence database was compiled and a reference-assisted assembly approach utilizing % sequence ID and % coverage was developed for species identification. End-point PCR was conducted on DNA extracted from 19 pathogenic fungal species, and mixed communities (MC) for preliminary sensitivity and inclusivity. Sensitivity was assessed using dilutions of template DNA into the PCR reaction.

Results
NGS data of 14 individual species and 4 MC passed quality control checks. Using only ITS1 and ITS2, species identification was expected for 10 of 14 individuals. We observed species identification in 9 individual samples, and 13 were identified within the top 5 results. All individuals were identified to genus. In MC analyses, combinations of 3, 4, 6, and 10 fungal species resolved 100% of the genera present, but failed to resolve species adequately with only 2 loci evaluated. Unexpectedly, 3 tested Aspergillus spp. were correctly identified with this limited data in both single and MC samples. The lower limit of detection was assessed at 5,000 genomic equivalents/mL of eluate.

Conclusion
The inclusivity and sensitivity demonstrated here of an NGS approach for identification of etiological agents of IFI support this assay’s potential utility as an aid in the treatment of IFI in at-risk patient groups. This assay allows for rapid identification (<4 days) of fungal species to aid clinicians in improving case outcomes.

Disclosures
All authors: No reported disclosures.
274. Impact of Fungal Serologies in the Management of Veteran Patients with Suspected Endemic Mycoses
Authors: Ordaya Eloy E , Drekonja Dimitri M 
Published: October 2019

Abstract

Background
Endemic mycoses are caused by the dimorphic fungi Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidiodes species. Histoplasmosis and blastomycosis are endemic in Minnesota, with travel to coccidioidomycosis endemic areas being common. Diagnosis is challenging, in part due to confusion regarding laboratory testing. In our institution, we have observed that fungal serologies are often ordered when such infections are suspected, but results rarely seem to affect management. We reviewed the impact of serologic testing on the management of a Midwest veteran population.

Methods
Retrospective, observational study of patients with any serologic testing for endemic mycoses performed from January2014 to December 2018 at the Minneapolis VA Health Care System. To focus evaluation on the utility of serologic testing, we excluded patients with fungal antigen testing.

Results
Of 127 patients tested, 62 (49%) had only serologic testing. Patients were predominantly males (95%) with a median age of 66 years (range 27–93). Nineteen (31%) were tested in the hospital and had a median stay of 8 days (range 1–48). Median Charlson score was 4 (range 0–12). Travel to an endemic area for coccidioidomycosis was frequent (27/62: 44%), with Arizona being the most common destination (20/27: 74%). Median illness duration was 30 days (range 1–720). Respiratory symptoms predominated (43/62: 69%), followed by nonspecific (6/62: 10%), neurologic (5/62: 8%), and musculoskeletal (2/62: 3%) symptoms. Five (8%) were asymptomatic. Abnormal imaging was common, with 27/62 (44%) patients having an abnormal chest radiograph (consolidation 15%, nodules 11%, and interstitial pattern 8%), and 44/62 (71%) having abnormal CT findings (nodules 55%, ground glass opacities 18%, and consolidation 15%). Six patients (10%) had positive serology, but antifungals were started only in one case. Fungal serology results impacted management in 19/43 (44%) patients seen in clinic, but in 0/19 tested as inpatients (P < 0.001). The most common action (16/19: 84%) was to cease diagnostic workup (table).

Conclusion
Fungal serologies can be useful in patients evaluated in clinic who present with respiratory symptoms, abnormal imaging, and potential fungal exposure. Testing in hospitalized patients appears to offer little benefit.

Disclosures
All authors: No reported disclosures.
279. Evaluation of β-d-Glucan Utilization in Thailand: Single Academic Center Experience
Authors: Manothummetha Kasama , Reinprayoon Rongpong , Torvorapanit Pattama , Reinprayoon Navaporn , Ratanawongphaibul Kitiya , Chindamporn Ariya , Permpalung Nitipong 
Published: October 2019

Abstract

Background
β-d-glucan (BG) detection was first available in Thailand in 2016 to aid diagnosis of invasive fungal infections (IFIs). Given a paucity of real-world experience of BG use in resource-limited countries, this study was conducted to describe appropriateness of BG testing and sequelae of BG results.

Methods
A retrospective study included all patients with at least 1 BG ordered at King Chulalongkorn Memorial Hospital, Bangkok, Thailand during March 2016 to December 2018. Descriptive statistics were used.

Results
83 patients were tested by BG assay (Fungitell, Associates of Cape Cod, Inc.): 6 with hematopoietic stem cell transplant, 12 with solid-organ transplant, 20 with active cancer receiving chemotherapy, 34 receiving high dose steroids (≥20 mg/day of prednisone for ≥3 weeks) and 11 with other conditions. Seventy-three patients were tested under infectious disease (ID) service’s recommendations. There were 13 and 20 cases of proven and probable IFIs, respectively. Among 13 proven IFIs, there were 11 positive, 1 indeterminate and 1 negative (mucormycosis) BG results. Among 49 cases with positive BG results, 24 were determined to be false-positive results. Median turn-around time for BG results was 16 (IQR: 9–23) days. Due to high turn-around time, only 8 patients were started on antifungal agent(s) and 3 underwent bronchoscopy due to positive BG results. All proven IFI cases were started on antifungal treatment prior to BG availability.

Conclusion
Approximately 87% of BG use in Thailand was ordered in patients with risk factors for IFIs. This could be due to majority of BG test was recommended by ID specialist. Despite being used in right clinical context, 49% had false-positive BG results. Another barrier of BG use in Thailand was high turn-around time due to small numbers of BG ordered and relative high cost to run the assay. Therefore, the utility of BG for aiding diagnosis or management of fungal infection in our setting is limited.

Disclosures
All authors: No reported disclosures.
286. Hepatitis B Vaccine Compliance: Comparing 2-Dose and 3-Dose Vaccines
Authors: Bruxvoort Katia , Slezak Jeff , Huang Runxin , Sy Lina S , Towner William , Ackerson Bradley , Reynolds Kristi , Qian Lei , Carlson Cheryl M , Solano Zendi , Hyer Randall N , Janssen Robert , Jacobsen Steven J 
Published: October 2019

Abstract

Background
Less than 1 in 3 US adults who initiated the 3-dose (0, 1, 6 months) hepatitis B vaccine series have completed it. HepB-CpG (Heplisav-B; Dynavax) is a new licensed adjuvanted vaccine that requires only 2 doses (0, 1 month). As part of a cluster study performed at Kaiser Permanente Southern California, we compared compliance with second dose and series completion for HepB-CpG vs. comparator vaccine (Engerix-B; GlaxoSmithKline) recipients.

Methods
The cohort included adults not on dialysis who received their first dose of hepatitis B vaccine in family or internal medicine departments from 8/7/2018 to 2/1/2019. Second dose compliance was assessed for the full cohort, but series completion was assessed for a subset vaccinated from August 7, 2018 to September 30, 2018 to allow at least 6 months’ follow-up. Compliance rates were estimated using the Kaplan Meier method. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard regression with robust variance to account for within medical center correlation, adjusting for age, race/ethnicity, census block income and education, prior healthcare utilization, and factors that trigger alerts for hepatitis B vaccination (diabetes and testing for sexually transmitted infections).

Results
There were 6500 HepB-CpG and 7733 comparator vaccine recipients (1,442 and 2,604 prior to September 30, 2018). Rates of second dose compliance at 60 days were 32.9% for HepB-CpG and 29.1% for comparator vaccine, and rates of series completion at 210 days were 56.9% and 20.6%. There was no significant difference in second dose compliance (aHR 1.14, 95% CI: 0.91, 1.47), but HepB-CpG recipients were 5 times more likely to complete the series (aHR 5.17; 95% CI: 3.84, 6.98). Second dose compliance and series completion were significantly less likely among Blacks compared with Whites and significantly more likely among Asians, adults ≥60 years compared with those < 30 years, and adults living in census blocks with a median annual income of $40,000–69,000 compared with < $40,000.

Conclusion
Overall, second dose compliance was similar, but series completion was better for HepB-CpG recipients than comparator vaccine recipients, suggesting that the 2-dose vaccine could lead to improvements in coverage and protection against hepatitis B virus.

Disclosures
All authors: No reported disclosures.
303. A Surrogate Rodent Model for Studying Hepatitis C Virus-specific CD8 T-cell Impairment and Vaccine Prevention
Authors: Hartlage Alex S , Kapoor Amit 
Published: October 2019

Abstract

Background
Virus-specific CD8 T cells are essential for control of acute hepatitis C virus (HCV) infections, yet spontaneously fail in most patients leading to lifelong chronicity and increased risk for severe liver diseases. Efforts to study HCV-specific CD8 T-cell impairment have been hampered by a lack of small animal models. Recently, we established a rat model of chronic HCV-like infection using a hepacivirus homolog identified in Rattus norvegicus. The nature of virus-specific CD8 T-cell immunity in this model has yet to be determined.

Methods
Using two MHC class I tetramers against epitopes located in the E1 and NS5B proteins, we tracked the induction and phenotype of virus-specific CD8 T cells during chronic infection. Responses to infection were similarly analyzed in immune rats that had been vaccinated against the NS3-5B proteins, a strategy that is effective in this experimental setting.

Results
Virus-specific CD8 T cells expanded vigorously in liver shortly after infection but did not develop into functional effectors based upon failure to produce cytokines (IFNγ, TNFα, IL-2, IL-4, IL-10, IL-17A) following peptide stimulation. Notably, subversion of responses was not due to viral escape from T-cell recognition, but rather an intrinsic defect in the antiviral response. Indeed, these populations expressed the inhibitory receptor programed cell death-1 and other markers consistent with an arrested effector-like state precluded from long-term memory formation (CD127-CD27+CD28+CD62L-GranzymeB+). In contrast, adenoviral immunization of naïve rats protected virus-specific T cells from functional impairment after infection and supported memory response development, including against the E1 epitope not encoded by vaccine.

Conclusion
Together, our findings reveal a spontaneous failure of virus-specific CD8 T cells following rat hepacivirus challenge that is highly reminiscent of human HCV infections. Furthermore, these results highlight the utility and significance of this model for understanding mechanisms of HCV persistence and protective immunity necessary for the development of effective vaccines and immune interventions.

Disclosures
All authors: No reported disclosures.