bluuebunny/crossref_metadata_2025_split huggingface dataset:
260. Detection of Aspergillus fumigatus Infection in Mice with 2-Deoxy-2-[18F]fluorosorbitol
Authors: Yu Yohan , ji Kang Seung , Kim Dong-Yeon , Pyo Ayoung , Ji Sehyeon , Chuluunkhuu Baigali , Kim Soosung , un Shin Sung , Hoon Oh Tae , Jin Kim Uh , Eun Kim Seong , Jang Hee-Chang , Park Kyung-Hwa , In Jung Sook , Min Jung-Joon 
Published: October 2019

Abstract

Background
Invasive aspergillosis is a major cause of infectious morbidity and mortality in immunocompromised patients.However, definitive diagnosis of invasive Aspergillus infection is still difficult due to the lack of a rapid, sensitive and specific diagnostic methods. In this studies, we investigated 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS) which has been reported to be accumulated in Gram-negative bacteria but not in Gram-positive bacteria or healthy mammalian or cancer cells, for the imaging detection of Aspergullus fumigatus infections with PET in vivo.

Methods
[18F]FDS was synthesized by reduction of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) using NaBH4. When the reaction was complete, the mixture was adjusted to a pH value to 6.5–7.5. Subsequently, the solution was filtered directly into a sterile product vial through a Sep-Pak Alumina N cartridge with a sterile filter. The probe uptake assay was performed by incubating bacterial cell and fungi with [18F]FDS (20 µCi) at 37°C for 2 h. Female BALB/c were immunosuppressed with cyclophosphamide and cortisone acetate prior to A. fumigatus intranasal, intramuscular, brain infection. The mircoPET images were obtained at 2 h after i.v. injection of [18F]FDS in infected mice.

Results
In vitro uptake test revealed significantly higher accumulation of [18F]FDS at 2 hin A. fumigatus, C. albicans and R. oryzae rather than with bacterial strains (Figure 1). PET imaging of BALB/c mice with pulmonary A. fumigatus infections showed obvious accumulation of [18F]FDS in the infected lungs compared with control (Figure 2). [18F]FDS PET imaging also detected A. fumigatus muscle and brain infection in mice. In infected shoulder muscle of mice, [18F]FDS PET imaging showed high legion-to-background ratio at 2 h. (4.05 ± 1.59, Figure 3).

Conclusion
[18F]FDS PET study demonstrated stable uptake in infected tissue with A. fumigatus and rapid clearance from the blood and other organs. [18F]FDS could be a useful imaging probe visualizing the invasive aspergillosis in vivo.

Disclosures
All authors: No reported disclosures.
263. Advances in Diagnosis of Progressive Coccidioidomycos: Experience in 164 Cases and 508 Controls
Authors: Myers Robert , Eric Holbrook , Wheat Lawrence J , Kassis Christelle , Durkin Michelle 
Published: October 2019

Abstract

Background
Antibody detection is the main method for diagnosis of coccidioidomycosis but has limitations including sensitivity and turnaround time. The MVISTA Coccidioides antigen enzyme immunoassay (EIA) is recommended for testing CSF in suspected Coccidioides meningitis. The early reports on urine and serum antigen testing evaluated small numbers of patients who were mostly immunocompromised with advanced disease.

Methods
A retrospective study, including all patients in whom Coccidioides antigen testing was performed between January 2013 and May 2017, was conducted at Maricopa Integrated Health System (MIHS). Sensitivity and specificity of antigen testing at MiraVista Diagnostics and antibody testing at MIHS or commercial laboratories were evaluated in 164 cases and 508 controls.

Results
The sensitivity of antigen testing was 51% and specificity was 99%. The sensitivity of antigen detection was highest if both urine and serum were tested (57%) than if only urine was tested (38%). The sensitivity of antibody testing was 84% and the specificity was 94% by immunodiffusion (ID). The sensitivity and specificity of antigen or ID antibody testing both were 94%. Sensitivity of antigen testing was 57% in proven and 58% in probable cases, ID antibody in 85% of proven and 75% of probable and antigen or ID antibody in 93% of proven and 95% of probable cases. Antigen was detected more often in disseminated (79%) than pulmonary cases (42%) as was ID antibody, 91% and 79%, respectively. Antigen testing was more sensitive in immunocompromised (76%) than non-immunocompromised patients (41%) while ID antibody was less sensitive in immunocompromised (74%) than in non-immunocompromised patients (93%). Combined antigen and ID antibody testing provided the highest sensitivity, 94% in all cases, 94% in immunocompromised and 95% in non-immunocompromised patients.

Conclusion
These findings support testing urine and serum for Coccidioides antigen and serum for ID antibodies for diagnosis of progressive pulmonary or disseminated coccidioidomycosis.

Disclosures
All authors: No reported disclosures.
264. Biofilm cells of Trichosporon asahii Show Higher Resistance Than Planktonic Cells to Various Abiotic Stresses
Authors: Metok Yang , Hosuru Subramanya Supram , Nayak Niranjan 
Published: October 2019

Abstract

Background
Biofilms of Trichosporon asahii are known to resist the effects of antifungal drugs, but the study of their susceptibility to various abiotic stresses remains sparse. This study was thus undertaken to compare the level of in vitro resistance of T. asahii biofilm and planktonic cells to various stress factors.

Methods
In this study, one T. asahii clinical isolate identified by amplifying IGS1 sequencing and one reference strain (NCCPF940033) were used. Biofilm and planktonic cells of T. asahii were exposed to increasing concentrations of NaCl (0.5–6 M) and d-sorbitol (3–13 M) for inducing osmotic stress; H2O2 (5–50 mM), menadione sodium bisulfate (0.048–100 mM) and ox bile (1–12%) for oxidative stress; PH 1 to 13 for PH stress; congo red (600–10,000 µg/mL) for cell wall stress; CuSO4·5H2O/ZnSO4/FeSO4 (1.25–2,560 mM) and MgSO4 (250–3,000 mM) for metal stress. The biomass and metabolic activity of biofilms were quantitatively determined by crystal violet method and XTT reduction assay, respectively. Further, spot assay of serially diluted (10–1 to 10–6) planktonic cells was performed on agar plates containing stress and non-stress control to determine relative percentage growth of strains.

Results
Biofilm cells of both the strains exhibited significantly higher (ANOVA) stress resistance than planktonic cells and on an average showed at least 100 times more resistant to stresses than planktonic cells [Minimum Biofilm Eradication Concentration (MBEC) vs. Minimum Inhibitory Concentration (MIC)]; H202 >50 mM vs. 10 mM, Ox bile >12% vs. 2%, Menadione >100 mM vs. 0.39 mM, Zn/Fe/Cu >2,560 mM vs. 10 mM, Mg >3,000 mM vs. 1,000 mM, NaCl >6 M vs. 1.5 M, d-sorbitol >13 M vs. 5 M and Congo red >10,000 µg/mL vs. 800 µg/mL. Besides optimal PH 5–10, extreme acidic and alkaline PH led to complete inhibition of viable planktonic cells. Highest biomass reduction (77.2%) and highest viability inhibition (69%) of biofilm were observed at PH 3 and 13, respectively. Menadione reduced 86.9% biomass and 89.3% viability which accounted the highest biofilm inhibition.

Conclusion
This is the first report on comparing the susceptibility of planktonic and biofilm T. asahii cells to various stress factors. The increased resistance of T. asahii biofilm may serve as a survival advantage against the host adversity.

Disclosures
All authors: No reported disclosures.
266. Clinical Profile and Treatment Outcomes of Candida auris Isolates from a Tertiary Care Hospital in South India
Authors: Warrier Anup R , Wilson Arun , Babu Rachana , Prakash Shilpa , Bhargava Madhav 
Published: October 2019

Abstract

Background
Candida auris is an emerging multidrug-resistant fungus that is rapidly spreading worldwide. In publications from India, it has already accounted for >5% of candidemia in a national survey of ICUs and as much as 30% of candidemia at individual hospitals,but data on treatment outcomes is scarce. This study reviews the various clinical syndromes in our case series, the treatment regimens we opted and their clinical outcomes.

Methods
The present study was a retrospective observational analysis of candida auris isolates obtained from patients admitted in a Aster Medcity, Kochi. Duration of study was 4 months (September 2018 to December 2018). Laboratory confirmation of the candida auris isolates was done as per CDC recommendations for Vitek2. Vitek2 was also used for obtaining the antifungal sensitivity pattern for these isolates.

Results
We had 18 cases of Candida auris identified. The most common syndrome was surgical site infections, 9 out of 18 (50%), followed by Catheter-Associated Urinary Tract Infection (CAUTI 5/18; 28%). We had 3 patients with Central Line-Associated Blood Stream Infections (CLABSI) and one patient who had secondary peritonitis. The overall mortality was 28% (5/18)—mostly contributed by the CLABSI. Considering breakpoints from CLSI as well as CDC, all isolates had their minimum inhibitory concentration (MIC) in the sensitive range for Caspofungin. Both Amphotericin b and Voriconazole had MICs in susceptible range for less than 50% of the isolates and almost all isolates were having very high MICs for Fluconazole, highlighting the increased levels of antifungal resistance which has made this Candida species notorious.

Conclusion
Candida auris is an emerging nosocomial pathogen in India with serious outbreak potential. The anti-fungal susceptibility is indicative of a multidrug-resistant pattern—with favorable MIC to Echinocandin and Voriconazole. Complicated bloodstream infections had high mortality inspite of early Echinocandin use. Of note, 6 patients out of 18, were managed successfully without any anti-fungal use; as they had either mild UTI (fever spikes resolved with catheter removal) or superfical SSI which could be treated with topical wound management.

Disclosures
All authors: No reported disclosures.
269. Epidemiology and Outcomes of Invasive Aspergillosis (IA) Among Pediatric Immunocompromised Patients: A 12-Year, Single-Center Experience
Authors: Al Dhaheri Fatima , Lee Rose , Nakamura Mari M , Marty Francisco M 
Published: October 2019

Abstract

Background
IA remains a leading cause of morbidity and mortality in immunocompromised children, and our understanding regarding epidemiology and outcomes of IA are limited and based on adult studies.

Methods
We conducted a retrospective evaluation of cases of proven or probable IA according to the 2008 EORTC/MSG criteria cared for at Boston Children’s Hospital from 2007 to 2019. We collected data including demographics, clinical characteristics, diagnosis modality, antifungal treatment, and survival. Survival curves over one year were estimated using the Kaplan–Meier method and univariate and multivariate Cox modeling was used to evaluate for risk factors for mortality.

Results
67 patient cases were identified, 20 (30%) with proven IA and 47 (70%) with probable IA. The mean age at diagnosis was 11.9 years (6 months–28 years). Underlying conditions included hematopoietic-cell transplantation (HCT) in 45%, cancer in 21%, and solid-organ transplantation in 18%. Pulmonary IA was the most common (70.1%) presentation. Diagnostic modalities included positive microbiology alone (18%), fungal PCR alone (1.5%), galactomannan alone (28%), and multiple modalities for the remaining cases (52.5%). 44.8% of patients were neutropenic at diagnosis and 78.5% of patients with malignancies were receiving chemotherapy. Immunosuppressive drugs included glucocorticoids in 34.3%, calcineurin inhibitors in 31.3%, and IMDH inhibitors in 25.3%. Voriconazole was the most common treatment used (72%). Twenty-two (33%) deaths occurred in the cohort attributable to IA (6 of which underwent autopsies and 4 had histopathological confirmation) Most deaths occurred in the BMT patients (15 patients, 45% of deaths). The 6 week mortality was 18% while the 12 week mortality was 25.4%. No antifungal or immunosuppressive regimen had a statistically significant impact on mortality.

Conclusion
We demonstrate in our >10-year retrospective cohort analysis of immunocompromised hosts that IA is associated with 49% all-cause mortality with particular impact on the BMT population. No protective nor harmful association was also noted with a particular antifungal or immunosuppressive regimen.

Disclosures
All authors: No reported disclosures.
290. Hepatitis E Virus Serostatus: A Retrospective Assessment of Demographics and Comorbidities to Assess High-risk Populations
Authors: Stone Eric C , Esquer Garrigos Zerelda , Sohail Muhammad R , Razonable Raymund R , O’Horo John C 
Published: October 2019

Abstract

Background
Demographic and epidemiologic characteristics of Hepatitis E virus (HEV) infected patients in the United States are not well-described. HEV infection may result in severe complications and lead to chronic infection and cirrhosis, especially in immunocompromised patients. There are no widely accepted guidelines for HEV screening and testing in the United States. Identifying traits of known seropositive patients and comorbidities may inform better screening and prevention strategies. In this study, we describe rates of liver disease, transplant status, chronic kidney diseases, and diabetes mellitus among patients serologically tested for HEV at our institution.

Methods
We retrospectively reviewed all patients for whom HEV IgM or IgG serologic testing was performed across the Mayo Clinic enterprise using the Advanced Cohort Explorer tool. For patients with any documented HEV serologic test, we abstracted baseline patient characteristics and underlying comorbidities at the time of testing. We then grouped subjects according to serologic testing results by antibody type. Survival at one year from date of testing was also assessed.

Results
A total of 979 unique subjects were identified. The preponderance of subjects was Caucasian (781, 79.8%). Of subjects tested for HEV with serology, 123 (12.6%) had any positive serology. Breakdown of baseline characteristics and selected comorbidities are summarized in Table 1. The largest proportion of subjects, 458 (46.8%), were both IgG and IgM negative and 432 subjects received only IgM or IgG testing. Liver disease was more prevalent in patients with positive vs. negative testing (5.8% vs. 2.1%) as was higher age (average 55.1 years vs. 52.2). One-year survival was similar in all groups.

Conclusion
HEV serology is not commonly tested. Among those tested, seropositivity is uncommon. Our data show higher HEV seropositivity in older adults, which may represent increase risk of exposure over time. Higher percentage of positive testing was also observed in subjects with liver disease, which may indicate a possible etiologic association. Further population-based studies are needed to estimate prevalence of HEV infection and associated liver disease, outcomes in infected patients, and indications for testing in at-risk populations.

Disclosures
All authors: No reported disclosures.
292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
Authors: Rohde Maximilian , Carter Wendy 
Published: October 2019

Abstract

Background
Direct-acting antivirals (DAAs) have substantially increased the rate of sustained virologic response in patients with hepatitis C compared with interferon therapy (IFN), while causing fewer adverse events. However, five recent case series and retrospective studies (Table 1) have reported a possible link between DAA treatment for hepatitis C and reactivation of varicella-zoster virus (VZV). Reported VZV reactivation rates in these studies were 0.23%, 0.72%, 1.50%, 1.74%, and 8.00%.

Methods
To further investigate these reported observations, we analyzed 37 prospective registrational DAA clinical trials, including 13,816 subjects in our analysis. Treatment arms were classified as DAA (N = 7,901), DAA + ribavirin (RBV) (N = 4,348), placebo (N = 997), DAA + IFN (N = 327), or IFN (N = 243). 1,068 (8%) subjects were HIV-coinfected, and 9,024 (65%) subjects were over age 50, both known risk factors for VZV reactivation. Herpes zoster (HZ) events occurring while on-treatment or during follow-up were identified using MedDRA preferred terms.

Results
We identified 36 (0.26%) subjects with HZ events. Thirty-two cases occurred during treatment, and 4 during follow-up. One event was considered severe, and the remaining were mild or moderate in severity. Of the 36 total cases reported, 11 (0.14%) were in DAA arms, 21 (0.48%) were in DAA+RBV arms, 4 (0.40%) were in placebo arms, and none were in DAA+IFN or IFN arms (Table 2). For a more direct comparison, we examined a subset of eight trials (N = 3835) containing both a DAA or DAA+RBV arm and a placebo arm. Of the 8 (0.21%) cases reported, 4 (0.14%) were in the DAA/DAA +RBV arms (N = 2838), and 4 (0.40%) were in the placebo arms (N = 997). While rates of VZV reactivation were increased for HIV-coinfected subjects (0.47% vs. 0.24%) and those over age 50 (0.31% vs. 0.17%) (Table 3), they remained similar to or lower than rates reported in previous studies (Table 1).

Conclusion
Data from prospective DAA clinical trials including 13,816 subjects do not provide evidence for an association between DAAs and VZV reactivation as reported in recent case series and retrospective studies. Low rates of VZV reactivation were observed, particularly in low-risk groups such as those below the age of 50, as would be expected in naturally occurring reactivation.

Disclosures
All authors: No reported disclosures.
328. Kaposi Sarcoma in High Population ART Utilization Setting: An Observational Study in Botswana
Authors: Hysell Kristen , Musimar Zola , Elmore Shekinah N C , Kayembe Mukendi K A , Suneja Gita , Efstathiou Jason , Kovarik Carrie , Wanat Karolyn , Slaught Christa , Triant Virginia A , Lockman Shahin , Dryden-Peterson Scott 
Published: October 2019

Abstract

Background
Despite population antiretroviral treatment (ART) utilization exceeding UNAIDS 90-90-90 targets, Kaposi sarcoma (KS) remains one of the most prevalent malignancies in Botswana. We sought to examine the characteristics and outcomes of KS in the context of high ART utilization.

Methods
Consenting patients at one of four oncology centers for KS treatment were enrolled prospectively (October 2010 to March 2019) and followed quarterly for 5 years. Survival was estimated using Kaplan–Meier estimator and predictors assessed with Cox proportional hazards modeling.

Results
A total of 408 KS patients were enrolled and of those, 396 (97%) were HIV-positive and included in analyses. Median age at diagnosis was 40 years (IQR: 34.1, 46.7) and 247 patients (62%) were male. The median CD4 cell count at the time of KS diagnosis was 253 cells/mL (IQR: 134, 364) and 279 (73%) were receiving ART at the time of KS diagnosis. Among those on ART, the median duration of ART prior to KS diagnosis was 11.9 months (IQR: 2.7, 46.7). The proportion receiving ART prior to KS increased during the surveillance period from 58% to 80% (P < 0.001). Of the 248 (62.6%) patients with recent measurement, 91% had HIV-1 RNA < 1000 copies/mL. Five-year overall survival was 73% (95% CI 68–78%). In multivariable analysis, Female sex and higher income were associated with improved survival, but not age or CD4 cell count. The duration of ART was significantly associated with survival (P = 0.02), with improved survival for individuals on ART < 6 months compared with longer ART (HR 0.54; 95% CI 0.29–0.98). The incidence of KS cases declined by nearly 50%, but has remained relatively stable since 2015.

Conclusion
Survival rates in this cohort were comparable to other KS cohorts. While KS treatment initially declined with ART expansion, KS remains a significant disease burden in Botswana with 80% of cases occurring among individuals receiving ART.

Disclosures
All authors: No reported disclosures.
338. Patients Living with HIV Infection Are Less Likely to Receive the Correct Intensity of Statin Therapy for Cardiovascular Disease Risk Reduction
Authors: Schafer Jason J , Patel Roshni , Hastain Nicholas V , Miano Todd 
Published: October 2019

Abstract

Background
Patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD) should receive risk reduction interventions recommended in current guidelines. This includes routine ASCVD risk assessments and when eligible, statins selected and dosed to achieve appropriate low-density lipoprotein cholesterol (LDL-C) reduction. Recent studies suggest that statins are underprescribed in PLWH, but none have assessed if eligible patients receive the correct statin intensity compared with uninfected controls.

Methods
This retrospective study evaluated statin eligibility and prescribing among consecutive patients in an HIV clinic and an internal medicine clinic at an urban, academic medical center from June-September 2018. To determine statin eligibility, the 2013 American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk was used. Patients aged 40–75 that had a lipid panel obtained within the last year were included. All patients were assessed to determine eligibility for and actual treatment with appropriate statin therapy. Characteristics of patients correctly and incorrectly treated with statins were compared with chi-square testing and predictors for receiving correct statin therapy were determined with logistic multivariable regression.

Results
A total of 221/300 study subjects were statin eligible (Table 1). While many eligible PLWH were receiving a statin (54/106), considerably fewer were on the correct statin intensity for their benefit group (33/106). In the univariate analysis (Table 2), correctly treated patients were less likely to be PLWH or female, and were more likely to have polypharmacy and hypertension. In the multivariable logistic regression analysis (Table 3), PLWH (OR 0.26, CI95 0.12–0.57)) were significantly less likely to receive correct statin therapy, while those with concomitant polypharmacy were significantly more likely to receive correct statin therapy (OR 5.52, CI95 1.94, 15.69).

Conclusion
This study reveals that PLWH may be at a substantial disadvantage in terms of receiving correct statin therapy for ASCVD risk reduction. This finding may be particularly important given the heightened risk for ASCVD in this patient population.

Disclosures
All authors: No reported disclosures.