bluuebunny/crossref_metadata_2025_split huggingface dataset:
225. Bloodstream Infections in Adult Allogeneic Stem Cell Transplant Recipients with Acute Gastrointestinal Graft-vs. -Host Disease within the First 180 Days Post-Transplantation
Authors: Modi Anita R , Rybicki Lisa A , Majhail Navneet , Mossad Sherif B 
Published: October 2019

Abstract

Background
Infections are the most common cause of non-relapse mortality in adult allogeneic stem cell transplant (allo SCT) recipients. Acute gastrointestinal graft-vs.-host disease (GI GVHD) often leads to friable mucosa and interventions increasing infectious risk. We describe the relationships between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI) at our institution.

Methods
We reviewed 441 adults who underwent allo SCT from 2011 to 2017 and were diagnosed with GI GVHD, non-GI GVHD, or no GVHD based on the Modified Glucksberg Scale within the first 100 days of transplant. The maximum grades of GI GVHD and non-GI GVHD were used in the analysis. A BSI episode constituted a blood culture positive for bacteria or fungi and antibiotic treatment. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method.

Results
Overall BSI incidence by day 180 was 32%; Gram-negative bacilli were the predominant organisms. Adjusting for grade of non-GI GVHD, patients with acute grade 4 GI GVHD had higher risk of BSI as compared with patients with no GI GVHD (HR 3.02, P < 0.001), while those with grade 3 GI GVHD had similar risk (HR 1.01, P = 0.98). Patients with grade 1 or 2 GI GVHD demonstrated lower BSI risk compared with those with no GI GVHD (HR 0.48, P = 0.015; HR 0.44, P = 0.08, respectively). Results were similar after adjusting for patient- and transplant-related risk factors for BSI. Grade of GI GVHD had no association with non-BSI risk. Patients who developed BSI or non-BSI had significantly higher overall mortality risk compared with those without infectious complications (HR 2.52, P < 0.001 for BSI; HR 1.60, P = 0.001 for non-BSI).

Conclusion
Acute grade 4 GI GVHD may reliably indicate higher BSI and overall mortality risk in this population. Understanding the relationships between acute GI GVHD and BSI can guide future treatment strategies for adult allo SCT recipients.

Disclosures
All authors: No reported disclosures.
239. Epidemiologic Analysis of a Worldwide Collection of Escherichia coli ST131 Using the 1928D Core Genome (cg) Multilocus Sequence Type (MLST) Reveals Country Specific and Globally Disseminated Clades
Authors: Deshpande Lalitagauri M , Davis Andrew P , Fredrik Dyrkell F , Amellos Dimitrios , Castanheira Mariana 
Published: October 2019

Abstract

Background
Increasing antimicrobial resistance (R) among Escherichia coli (EC) isolates can be associated with the expansion of the pandemic sequence type (ST) 131 that harbors virulence factors and causes more severe infections when compared with other antimicrobial-R EC. We evaluated the core genome MLST (cgMLST) profiles and R genes using the bioinformatics tool 1928D to evaluate the epidemiology of a global ST131 EC collection and unrelated STs.

Methods
A total of 259 EC clinical isolates belonging to ST131 (n = 206), ST131-single loci variant (SLV; n = 25), and 28 non-ST131 isolates collected from 27 countries during 2016–2018 were selected. Whole-genome sequencing FASTQ files were uploaded to the 1928D pipeline to generate MLST, cgMLST and R gene prediction. cgMLST assignment was based on comparing >2,500 genes.

Results
Among 231 ST131 and SLV EC isolates, 7 clades were identified (3 major [178 isolates]; Table) applying cgMLST allele distance (ad) of ≤50 as a cutoff. A total of 21 isolates were not assigned to clades (>50 ad from ST131 and SLV). Based on >95% concordance, 11 alleles differentiated clades II and III from clade I, while 6 alleles separated clades I and III from clade II. Isolates in clades I to IV were ciprofloxacin R (MIC, ≥4 mg/L); clades I and III predominantly carried blaCTX-M-15 (39/43 and 61/66), blaOXA-1 (35/43 and 43/66), and aac(6’)-Ib-cr (39/43, 45/66) while clade II carried blaCTX-M-14-like and rarely aac(6’)Ib-cr (3/69). The most ad between the 7 ST131 clades was 216, while unrelated STs showed variable ad among isolates within that ST. Isolates bellowing to ST1193 were closely related genetically (ad of 30), but other STs had more variability among isolates (ST167, ad 552; ST38, ad 150; and ST69, ad 179).

Conclusion
1928D is a robust platform for epidemiological analysis of isolates, providing additional granularity when compared with MLST. Clades II and III were closely related, but carried different blaCTX-M genes, while clades I and III were not as closely related, but both carried blaCTX-M-15, blaOXA-1, and aac(6’)Ib-cr. These findings suggest that these clades might have acquired R genes at different points in their genetic evolution. A threshold of ≤50 (cgMLST distance) was useful for classifying isolates into clades.

Disclosures
All authors: No reported disclosures.
242. Comprehensive Pathogen Detection for Pediatric Febrile Neutropenia by Metagenomic Next-Generation Sequencing
Authors: Horiba Kazuhiro , Torii Yuka , Hara Yuichiro , Shimada Mayuko , Suzuki Takako , Takeuchi Suguru , Okumura Toshihiko , Kawada Jun-ichi , Muramatsu Hideki , Takahashi Yoshiyuki , Ogi Tomoo , Ito Yoshinori 
Published: October 2019

Abstract

Background
Febrile neutropenia (FN) is a common complication in patients with solid tumors and hematologic malignancies. Identification of the causative microorganisms would contribute to optimization of antimicrobial treatment and thus improve the outcome of FN. However, causative microorganisms are detected in only 10% to 20% of FN patients. Next-generation sequencing (NGS) allows us to comprehensively analyze all microorganisms present in a clinical sample. In this study, we aimed to utilize NGS for the detection of microbial pathogens in infectious diseases and elucidate the infection source in FN.

Methods
FN is defined by two characteristics: (1) neutrophils count < 500/µL, and (2) fever ≥38.0°C. From 2016 to 2018, 112 plasma/serum samples of pediatric FN patients (11 positive blood cultures) were analyzed. Serum samples from 10 neutropenic patients without fever were also analyzed as controls. Shotgun sequencing method was applied for these samples. The metagenomic analyses were performed through the pipeline PATHDET, which has been newly established in our laboratory. Diagnosis based on NGS results was made based on the following criteria: (1) number of reads from all pathogens per million reads (PR) >650, (2) a specific pathogen’s reads per million reads (RPM) >200, and (3) diversity index >3.0. The NGS results were compared with those from blood culture.

Results
Sequencing reads of bacteria isolated through blood culture were identified by NGS in all 11 plasma/serum samples leading to the diagnosis of FN. The causative pathogens were diagnosed by NGS using the above criteria in 11 patients. However, the results were consistent with those of blood culture in only 4 samples. Of 101 cases with negative blood culture results, the causative pathogens were detected in 17 cases: Acinetobacter soli (2 cases), Burkholderia cepacian (1 case), Klebsiella variicola (1 case), and Roseomonas sp. (1 case) were identified at the species level. In addition, 7 cases (e.g., Acinetobacter) were identified at the genus level, and 5 cases (e.g., Enterobacteriaceae) were identified at the family level.

Conclusion
Metagenomic NGS technique has great potential for detecting causative pathogens with greater efficiency than the conventional methods.

Disclosures
All authors: No reported disclosures.
246. Carbapenem-resistant Klebsiella (CRK) Bloodstream Infections (BSIs) Are Caused by Bacterial Populations That Are Genotypically and Phenotypically Diverse
Authors: Nguyen Minh-Hong , Chen Liang , Cheng Shaoji , Squires Kevin , Hao Binghua , Shields Ryan K , Kreiswirth Barry , Clancy Cornelius J 
Published: October 2019

Abstract

Background
The majority of bacterial BSIs are believed to stem from a single, clonal organism. We hypothesized that most CRK BSIs are caused by genetically diverse, clonal strains that exhibit different phenotypes.

Methods
Blood cultures (BCs) that were positive for CRK from each of 10 patients (patients) were streaked onto agar plates, and 100 individual colonies were chosen for Illumina whole-genome sequencing. Strains from 3 patients were tested for in vitro phenotypes and virulence in mice.

Results
Patients had BSIs due to ST258 K. pneumoniae (Kp; 6), non-ST258 Kp (3), and K. michiganensis (Km; 1). 5 patients were infected with strains that differed by core genome single nucleotide polymorphism phylogeny (2–5 unique genotypes/patient) [figure]. 6 patients were infected with strains that differed by gene or plasmid content, and/or gene deletions [table]. Differences in individual patients encompassed antibiotic resistance and putative virulence genes (including mixtures of blaKPC+ and blaKPC– strains, and various capsular (CPS) and porin mutant strains). In total, BSIs in 8 of 10 patients were caused by a genotypically diverse population. In each of 3 patients, genotypically diverse ST258 Kp strains demonstrated significant differences in antibiotic susceptibility, CPS content, mucoviscosity, adherence, resistance to serum killing, and mortality rates and tissue burdens during BSIs of mice. ST258 strains from a pt with and without a KPC-bearing IncFIA plasmid differed in β-lactam susceptibility, but were equally virulent. Progressive loss of CPS in ST258 strains from another patient enhanced serum killing and adherence, and attenuated virulence. Using PCR markers to test 96 colonies per positive BC bottle, we demonstrated that strains selected by the clinical micro lab accounted for 2% to 98% of a population in different patients.

Conclusion
CRK causing BSIs in most patients demonstrated remarkable genotypic diversity, which impacted antibiotic susceptibility, virulence and other phenotypes. Differences were not recognized during hospitalization since clinical labs select single, morphologically distinct colonies for evaluation. Studies are needed to understand the clinical implications of our findings, diversity during other BSIs, and whether clinical lab practices need revision.

Disclosures
All authors: No reported disclosures.
261. A Retrospective Evaluation of Coccidioidomycosis Skin Testing in Patients with Pulmonary Coccidioidomycosis in an Endemic Region
Authors: Mafi Neema , Girardo Marlene , Blair Janis E 
Published: October 2019

Abstract

Background
Making the decision to stop antifungal therapy in patients with coccidioidomycosis can be challenging in patients with risk factors for relapsed infection. Spherulin-based coccidioidal skin testing was re-introduced to the market in 2014 and approved for the detection of delayed-type hypersensitivity in patients with a history of pulmonary coccidioidomycosis

Methods
We searched electronically for patients who had a spherulin skin test placed in our institution from January 1, 2015 through March 1, 2017, and then included patients age 18 years and older who met the definition for confirmed or probable pulmonary coccidioidomycosis. A retrospective chart review was conducted, and included details of clinical illness, antifungal treatment, serology, and chest imaging

Results
From January 1, 2015 to August 31, 2017, 172 patients with coccidioidomycosis had a spherulin skin test placed. We included for further study the 129 patients who had primary pulmonary coccidioidomycosis, followed for a median of 18 months (range 0–50 months); 56 (43.4/%) were male, 108 (85.7/%) Caucasian, median age was 55 years (range18–89).19/12914.7%)) were smokers, 14/129 (10.9%) were diabetic, 2 patients had HIV (1.6%) and 15/129 (11.6) we immunocompromised without HIV. 116/129(89.9%) % received antifungal treatment. Median time from illness to skin test was 13.5 months (range 0–78). Eighty-nine of 129 patients (69%) had a positive skin test, 40 (31%) had a negative test. Antifungal treatment was subsequently discontinued in 75/89 (84%), and one patient (1.2%) with a positive test, experienced relapsed infection. Among 30/40 with negative CST, antifungals were discontinued and none relapsed.

Conclusion
The presence of delayed-type hypersensitivity to coccidioidomycosis, manifested by a positive spherulin skin test, was associated with discontinuation of antifungal therapy, and a low percentage of relapsed infection.

Disclosures
All authors: No reported disclosures.
270. T2MR: A New Tool for Anti-Fungal Stewardship
Authors: Jariwala Ripal , Zeitler Kristen , Montero Jose 
Published: October 2019

Abstract

Background
Candidemia is associated with mortality rates between 30 and 50%. T2 magnetic resonance assay (T2MR) is a costly, rapid diagnostic technology that can detect the five most common Candida species in blood with a sensitivity of 91% and specificity of 99.4%. The clinical role of this tool remains unclear but this study shares our clinical experience with T2MR.

Methods
We conducted a retrospective chart review of patients with T2MR testing performed from April 25, 2017 through April 25, 2018. T2MR ordering was restricted to Infectious Diseases pharmacists and physicians without specific ordering criteria. Variables cataloged included the time between order and result in the medical chart, T2MR result, anti-fungal therapy and duration. Descriptive statistics were reported on collected variables.

Results
Sixty-eight unique patients had T2MR ordered at least once during the study time period. The median age was 62.5 years (interquartile range (IQR), 22–92) and 42 patients (62%) were male. The median time between order and result appearing in the medical chart was 6.21 hours (IQR, 3.55–40.93). Out of 72 tests performed, 4 were positive (2 for C. parapsilosis and 2 for C. krusei/glabrata). Only 1 of 4 T2MR positive patients had concurrent candidemia while 1 patient had suspected fungal endophthalmitis, 1 patient was managed for a fistula, and 1 patient had cutaneous candidiasis. Of the negative tests, 1 patient had a false negative T2MR result despite blood cultures growing C. glabrata. There was only 1 invalid test in our sample. Thirty-six patients were initiated or maintained on anti-fungal therapy at the time of the T2MR test, with micafungin being the most commonly prescribed anti-fungal agent. Negative T2MR patients had a median anti-fungal therapy duration of 2 days (IQR, 0–16). Sixteen patients (44%) had their anti-fungal therapy discontinued within 1 day of the negative T2MR result. There were no patients with a negative T2MR result who subsequently developed candidemia within 30 days after T2MR testing.

Conclusion
Our study showcases the benefit seen with T2MR in curtailing unnecessary anti-fungal exposure. Study limitations include a small cohort and evaluation at a single center. There is an opportunity for this technology to be utilized in anti-fungal stewardship.

Disclosures
All authors: No reported disclosures.
275. Delayed Diagnosis of Histoplasmosis in Pediatric Patients due to Atypical Clinical Presentations
Authors: Gonzalez Saldaña Napoleon , Xochihua Diaz Luis , Palacios Reyes Deborah , Zuyino Mondragon Salinas Izveidy 
Published: October 2019

Abstract

Background
Histoplasmosis is a systemic mycosis with a wide range of clinical manifestations which represents a diagnostic challenge. It affects immunocompromised patients but also, previously healthy individuals that are exposed to a large inoculum of Histoplasma. The aim of our study was to describe the clinical presentation, epidemiologic features, laboratory/imaging findings and outcome of pediatric patients with histoplasmosis.

Methods
a retrospective study including patients diagnosed as Histoplasmosis according to ICD-10 at a tertiary care center in Mexico City during 2009 to 2019. Clinical, epidemiological and laboratory/imaging data were gathered from each patient’s clinical file.

Results
5 patients with diagnosis of histoplasmosis were included; 2 patients were classified as proven with histopathologic confirmation, 2 patients as probable and 1 patient as possible according to the EORTC/MSG. The mean age of presentation was 7 years, 3/5 patients were male and 3/5 reported exposure to bats. Diagnosis was delayed by an average time of 6 months due to the variability of clinical presentations (progressive disseminated histoplasmosis, spinal histoplasmosis, cerebral histoplasmosis, intestinal histoplasmosis and mild acute pulmonary histoplasmosis). For the diagnosis, 1/5 had positive ELISA, 1/5 positive immunodiffusion (M band), 1/5 positive EIA in cerebrospinal fluid and 2/5 with histopathology findings that matched histoplasmosis. Pulmonary imaging with interstitial infiltrates in 4/5 and evidence of cavitation in one patient. Hemophagocytic syndrome was a complication in 1/5 and medullary syndrome was developed in the patient with spinal histoplasmosis which resolved with treatment. Liposomal amphotericin B was the treatment in 4/5, followed by itraconazole as the maintenance therapy.

Conclusion
This study shows variable clinical presentations of Histoplasmosis which resulted in an important delay in diagnosis. This study highlights the importance of diagnostic suspicion in both healthy children and immunocompromised patients, always taking into account epidemiological risks such as exposure to bats.

Disclosures
All authors: No reported disclosures.
278. CNS Blastomycosis: A Descriptive Analysis and Review of Diagnosis and Treatment
Authors: Majdick Kathryn , Kaye Keaton , Shorman Mahmoud 
Published: October 2019

Abstract

Background
Blastomycosis is a systemic infection, well known to regions of the Southeastern and Ohio River Basin in the United States. Inhalation of the dimorphic fungus most often causes pulmonary manifestations. Hematogenous dissemination can affect various organs in immunocompromised hosts. Central Nervous System (CNS) involvement is a rare manifestation of Blastomycosis infection, accounting for 5%–10% of extrapulmonary involvement. It is important to diagnosis early and treat due to the increased morbidity in high-risk patients.

Methods
Our study retrospectively reviewed cases from a Tertiary Care Facility in East Tennessee from 2011 to 2018 with the diagnosis of CNS Blastomycosis. Data collection included demographics, risk factors, varied clinical presentation, methods of diagnosis, treatment plans and outcomes.

Results
Total of 8 CNS Blastomycosis cases were identified. Detailed demographics are presented in Table 1. The average age was 52 years, 7 (87.5%) were male. 6 (75%) were classified as immunocompromised. 6 of the 8 cases were tested for HIV, all of which were negative. MRI brain imaging was utilized in 7 (87.5%) cases, which demonstrated lesion enhancements, Table 2 and Images 1 and 2. CSF was collected in 6 (75%) patients. 5 patients (62%) presented with neurological complaints. All patients received Liposomal Amphotericin B (LAmpB), followed by a prolonged course of azoles. 5 (62%) developed acute renal insufficiency after starting Amphotericin B. 2 (25%) died.

Conclusion
CNS Blastomycosis is a rare diagnosis with increased morbidity and mortality. Obtaining brain imaging in addition to lumbar puncture can help in timely diagnosis of CNS Blastomycosis. Treatment involves lipid formulation of Amphotericin B followed by oral azole therapy, preferably voriconazole. Renal insufficiency was a common finding after this treatment. A high level of suspicion is crucial for recognition of CNS Blastomycosis in endemic regions of the Southeastern and Ohio River Basin.

Disclosures
All authors: No reported disclosures.
287. Exploring the Natural History and Clinical Outcomes of Hepatitis B Core Antibody Positive Hemodialysis Patients in a Large Metropolitan Tertiary Care Hospital System with a Focus on Occult Hepatitis B
Authors: Vahia Amit T , Chitturi Chandrika , Rizzo Olivia , Lwin Nihn , Soman Sandeep , Yee Jerry , Soi Vivek , Uduman Junior , Alangaden George J 
Published: October 2019

Abstract

Background
Occult Hepatitis B (OHB) is defined as hepatitis B core antibody (HBcAb) positivity in the absence of surface antibody (HBsAb) or surface antigen (HBsAg) positivity. The reported incidence ranges from 0.3% to 58% in the hemodialysis (HD) population. Our study is among the first in the United States to examine the natural history of OHB patients (patients). This work is of interest in HD patients to estimate Hepatitis B transmission risk.

Methods
We performed a retrospective analysis of 352 Hep B cAb positive HD patients between 2010 and 2017 in the Henry Ford Health System and Greenfield Dialysis Centers in SE Michigan. This system contains 5 hospitals including a 900-bed tertiary referral center in Detroit, serving a high-risk, medically complex population. Our primary outcomes were the development of HBsAb positivity, considered protective, or development of HBsAg positivity or new Hepatitis B viremia, considered adverse events. Univariate and multivariate logistic regression analysis was performed to study pertinent risk factors for the clinical outcomes comparing OHB and Non-OHB patients. Statistical analysis was performed using SAS 9.4.

Results
Of the 352 HBcAb patients studied, 98 (27%) were OHB patients. Each group shared similar baseline demographics apart from OHB patients having higher ALT and a greater proportion of drug use and Hepatitis C (Hep C) compared with non-OHB patients (Table 1). There were 15 adverse events in the non-OHB group, including 10 viremias. Only 1 adverse event was seen in the OHB group, a patient who developed viremia of 19 copies/mL (Table 2). Conversely, OHB status was a statistically significant predictor of protective HBsAb development in follow-up (P < 0.01), occurring at a 7-fold increased rate compared with non-OHB patients. Univariate analysis showed that a history of liver disease, Hep C, and drug use predicted HBsAb development (Table 3). When studying adverse outcomes, history of liver disease raises the risk of adverse events in unadjusted models (P < 0.05) (Table 4).

Conclusion
OHB patients in our center tend to develop protective HBsAb titers over time rather than develop viremia or antigenemia in contrast to non-OHB patients. Our study finds that OHB confers minimal risk of potential transmission of Hepatitis B among HD patients.

Disclosures
All authors: No reported disclosures.