bluuebunny/crossref_metadata_2025_split huggingface dataset:
2565. Initial and Recurrent Episodes of Clostridioides difficile: Online Education as a Tool to Improve Management Strategies
Authors: Hurst Simi Thomas , Martorano James , Gerding Dale N 
Published: October 2019

Abstract

Background
The most common cause of infectious diarrhea in hospitalized patients, C. difficile is responsible for nearly half a million infections annually. Among persons over the age of 65 years, 1 in 11 die within a month of diagnosis.

Methods
A CME-certified/ABIM MOC educational program was developed to evaluate and improve ID specialists’ application of the latest guideline recommendations for the diagnosis and management of individuals with C. difficile. Modeled on the interactive grand rounds approach, the activity blended case-based presentation with multiple-choice questions. Using a “test then teach” approach to elicit cognitive dissonance, the activity provided evidence-based feedback following each learner response. Educational effectiveness was assessed with a repeated-pairs pre-/post-assessment study design; each individual served as his/her own control. A chi-square test assessed changes pre- to post-assessment. P values < 0.05 are statistically significant. Effect sizes were evaluated using Cramer’s V (< 0.05 modest; 0.06–0.15 noticeable effect; 0.16–0.26 considerable effect; > 0.26 extensive effect). The activity launched on a website dedicated to continuous professional development on May 29, 2018. Data for this initial analysis were collected through March 27, 2019.

Results
To date, 3274 HCPs, including 2946 physicians have participated in the activity. Data from the subset of ID specialists (n = 82) who answered all pre-/post-assessment questions during the initial study period were analyzed. Following activity participation, significant improvements were observed in the proportion of ID specialists who answered all assessment questions correctly (4% pre vs. 74% post; P < 0.0001; V = .555). Improvements were also observed in several specific areas of assessment (table). Additionally, 50% of ID specialists indicated they planned to modify their treatment approach and 18% planned to modify their diagnostic strategies for C. difficile.

Conclusion
Participation in this online, interactive, case-based, educational intervention significantly improved ID specialists’ management strategies for initial and recurrent episodes of C. difficile. These findings highlight the positive impact of well-designed online education.

Disclosures
All authors: No reported disclosures.
2567. Effect of Broad vs. Narrow-Spectrum Clostridioides difficile Treatment on Human Stool Bile Acid Composition Over Time
Authors: Thorpe Cheleste M , Qian Xi , Yanagi Karin , Kane Anne , Alden Nicholas , Snydman David R , Lee Kyongbum 
Published: October 2019

Abstract

Background
Secondary bile acid production by a diverse commensal flora may be a critical factor in preventing recurrence of Clostridioides difficile infection (CDI). Key enzymes involved are bacterial-encoded bile salt hydrolases (BSHs), felt to be “gatekeepers” to secondary bile acid synthesis. Ridinilazole, a novel narrow-spectrum drug for CDI, demonstrated superior sustained clinical response compared with vancomycin in Phase 2. Longitudinal sampling during this trial allowed for assessment of metabolites differentially present in stools during/after therapy with either broad or narrow-spectrum anti-CDI agent. Previous work characterizing subject’s fecal microbiota in this trial showed that unlike vancomycin, ridinilazole has little effect on commensal flora during and after therapy. We hypothesized that ridinilazole’s microbiota-preserving effect is associated with lack of accumulation of conjugated primary bile acids and/or reaccumulation/persistence of secondary bile acids over the course of CDI treatment, when compared with vancomycin-treated subjects. Furthermore, we hypothesized that we would observe correlations between bile acid profiles and predicted BSH gene abundances.

Methods
Sequential stool samples were obtained from 44 subjects treated with either ridinilazole or vancomycin (22 in each arm), ranging from time of CDI diagnosis, at end-of-therapy, and up to 40 days after diagnosis. Bile acids were quantitated by liquid chromatography-mass spectrometry. Using the PICRUSt algorithm, metagenomic predictions of BSH gene abundances were performed.

Results
Stool bile acid compositions differed between ridinilazole-treated and vancomycin-treated subjects at end-of-therapy. In vancomycin-treated subjects, stool composition became dominated by conjugated primary bile acids and decreased levels of secondary bile acids compared with baseline; the ratio of stool conjugated bile acids to secondary bile acids significantly predicted treatment arm. This ratio was also associated with predicted BSH gene abundance in ridinilazole-treated subjects.

Conclusion
Microbiota-preserving CDI treatment with ridinilazole preserves bile acid composition, which may decrease likelihood of recurrence.

Disclosures
All authors: No reported disclosures.
2569. The Gut Microbiome and Acute Graft vs. Host Disease Risk in Hematopoietic Stem Cell Transplantation Recipients
Authors: Ilett Emma E , Reekie Joanne , Jørgensen Mette , Murray Daniel D , Noguera Marc , Paredes Roger , Nørgaard Jens C , Daugaard Gedske , Helleberg Marie , Lundgren Jens , MacPherson Cameron , Sengeløv Henrik 
Published: October 2019

Abstract

Background
16S rRNA gene-based studies report that allogeneic hematopoietic stem cell transplant (aHSCT) recipients with low bacterial diversity and certain bacteria close to engraftment have increased risk of developing acute graft-vs.-host disease (aGvHD). Using shotgun metagenomic data, we aim to confirm and extend these observations in a larger cohort.

Methods
Adult aHSCT recipients with stool samples collected days −30 to +100 relative to aHSCT, but prior to aGvHD, were included. One sample was selected per patient and time point: pre-aHSCT (T1), post-aHSCT pre-engraftment (T2). Complete ascertainment of aGvHD (grades ≥ 2) until day +100 was performed. Bacterial microbiome factors (α-diversity, gene richness and 16 a priori bacteria) and clinical factors were tested for associations with aGvHD across T1:2 in univariable models. Significant factors (P < 0.1) were included in a multivariable model.

Results
Of 147 aHSCT recipients, 35 developed aGvHD a median of 35 days (IQR 24–51) post-aHSCT. We found that higher gene richness was significantly associated with lower aGvHD risk in T2, but not T1, samples (OR 0.65 (95% CI 0.42–1.00), P = 0.04 vs. OR 1.14 (95% CI 0.67–1.94), P = 0.64 per doubling of unique genes). A decreased abundance of Akkermansia muciniphila, Proteobacteria, Blautia and Gammaproteobacteria was observed in those that developed aGvHD, again in T2 samples only (Figure 1). Among clinical factors, donor sex, donor/recipient (related/unrelated) and conditioning regimen (adjusted OR = 0.34 for non-myeloablative vs myeloablative (95% CI 0.15–0.77)) were significantly associated with aGvHD. Conditioning regimen was also strongly associated with microbiome changes; myeloablative recipients had lower gene richness and differences in bacterial abundance, including decreased abundance of aforementioned bacteria, compared with non-myeloablative recipients at T2 (Figures 2and 3).

Conclusion
Post-aHSCT pre-engraftment was a crucial timepoint where microbial changes, including lower gene richness and abundance of certain bacteria, were associated with development of aGvHD. Myeloablative regimes were also associated with both aGvHD and microbiome changes, suggesting that intense conditioning may affect aGvHD risk through perturbation of the gut microbiome.

Disclosures
All authors: No reported disclosures.
2576. The Microbiome of Recurrent Bacterial Vaginosis Compared with Asymptomatic Controls
Authors: Shay Elizabeth O , Goje Oluwatosin , Padmanabhan Roshan , Eng Charis 
Published: October 2019

Abstract

Background
Bacterial vaginosis (BV) affects nearly 1 in 3 women in the United States and is poorly understood. The study of the vaginal microbiome, using 16S rRNA-gene amplicon sequencing, has increased our knowledge of BV. We aimed to characterize the vaginal microbiome of women with recurrent BV firstly in comparison to controls, and secondly in comparison to a sub-population of our asymptomatic controls, positive for Gardnerella vaginalis via a vaginal pathogens DNA direct probe test (DNA probe).

Methods
Women aged 18–40 years, with recurrent BV, and asymptomatic controls were prospectively enrolled. Vaginal samples were collected from each participant. DNA was extracted, amplified using primers targeting the V3-V4 variable region of the 16S rRNA-gene, and then sequenced and processed through a hybrid Qiime MICCA bioinformatics pipeline. We also tested for G. vaginalis using the DNA probe.

Results
Seventeen recurrent BV patients and 46 controls were enrolled. Β diversity (P = 0.045), but not alpha diversity (P = 0.076) differed between groups. The genera Gardnerella and Prevotella were relatively more abundant, while Lactobacillus was relatively less abundant in recurrent BV vs. control groups. Of the patients for whom results of the DNA probe for Gardnerella vaginalis were available, 11 (69%) recurrent BV patients and 14 (35%) controls were positive. Control patients, negative by the DNA probe test, showed decreased alpha diversity (P = 0.0001) and significantly different β diversity (P = 0.001) compared with recurrent BV patients. Neither alpha (P = 0.31) nor β (P = 0.096) diversity differed between recurrent BV patients and controls that were G. vaginalis positive.

Conclusion
The microbiome of recurrent BV patients is distinct from that of asymptomatic controls; recurrent BV patients exhibit different β diversity, less Lactobacillus and more Gardnerella and Prevotella. Asymptomatic Gardnerella vaginalis-colonized controls demonstrate similar microbiome profiles to those of recurrent BV patients. These findings suggest that individual factors may influence whether or not a patient with a BV microbiomic profile experiences symptoms. Further investigation into these mechanisms could yield insights into the treatment of recurrent BV.

Disclosures
All authors: No reported disclosures.
2584. Effects of Fecal Microbiota Transplantation for Decolonizing Multidrug-Resistant Organism
Authors: Seong Hye , Lee Sang kil , Cheon Jae hee , Yong Dong eun , Koh Hong , Kang Yoon gu , Lee Woon Ji , Kim Jung Ho , Choi Heun , Ahn Jin young , Ku Nam su , Jeong Su Jin , Yeom Joon-Sup , Choi Jun yong 
Published: October 2019

Abstract

Background
Increasing prevalence of multidrug-resistant microorganisms (MDRO) results in poor clinical outcomes, longer hospitalizations and higher healthcare costs. It is likely that MDRO colonization can lead infections to vulnerable patients. Currently, however, MDRO decolonization strategies are lacking. The purpose of this study was to prove the efficacy of FMT on decolonization of carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant enterococci (VRE) carriers.

Methods
This study was a prospective, open-label, uncontrolled, single-center pilot study of FMT for digestive tract colonized CPE, VRE, or CPE/VRE patients between March 2018 and February 2019. Fecal solution obtained from healthy unrelated donors was infused to recipient’s gut. Fecal samples of recipients were collected before and after FMT until 1year.We compared characteristics of subjects succeed in decolonization during study period (responders) with subjects who failed to decolonize MDRO by FMT (non-responders). Furthermore, microbiome analyses were performed to investigate the influence of microbial characteristics of recipients on the outcome of FMT.

Results
Decolonization was achieved in 12/23 (52.2%) during study period. Hemoglobin (11.0 vs. 10.0, P = 0.018), low-density lipoprotein cholesterol (102.0 vs. 89.0, P = 0.049), and albumin (3.4 vs. 3.2, P = 0.006) levels were higher in responders. Antibiotic treatment(ATB) within 1 week after FMT were less common in responders (41.7% vs. 90.9%, P = 0.027). Patients with no ATB approached frequent decolonization at 1(75.0% vs. 26.7%; P = 0.037) and 3 months (87.5% vs. 33.3%; P = 0.027). The rates of decolonization were significantly different between CPE, VRE and CPE/VRE colonizer (75.0% vs. 38.5% vs. 66.7%; P = 0.018). Gut microbiome of responders showed a higher richness and diversity than non-responders before(294 vs. 274 by Ace; 2.6 vs. 1.8 by Shannon) and after (345 vs. 260 by Ace; 2.9 vs. 2.1 by Shannon) FMT. The microbiota composition analysis revealed increasing abundance of Bacteroidetes and decreasing abundance of Proteobacteria at 1 month after FMT in responders. However, those changes of microbial composition did not occur in non-responders.

Conclusion
FMT is an effective way to decolonize CPE and VRE by restoration of the gut microbiome.

Disclosures
All authors: No reported disclosures.
2585. Changing Epidemiological Profile of Infantile Parechovirus-A3 Infection in Japan
Authors: Aizawa Yuta , Izumita Ryohei , Yamanaka Takayuki , Habuka Rie , Ikuse Tatsuki , Watanabe Kanako , Otsuka Taketo , Saitoh Akihiko 
Published: October 2019

Abstract

Background
Parechovirus-A3 (PeV-A3) causes severe disease, including sepsis and meningoencephalitis in young infants. The first case of PeV-A3 was reported in Japan in 1999 and, although epidemics have been reported every 2 to 3 years in more than 20 countries, no major epidemic has occurred in Japan since 2014.

Methods
This prospective study included febrile infants (<4 months of age) admitted at Niigata University and its affiliated hospitals, which serve about 2.5 million people, during the period from 2014 to 2018. Neonates and infants younger than 4 months presenting with fever and suspected of having viral sepsis underwent serum and/or cerebrospinal fluid (CSF) testing by real-time PCR for parechovirus-A (PeV-A) and enteroviruses (EVs), and for herpes simplex viruses, if suspected. Bacterial infection was excluded on the basis of the results of bacterial culture of blood, urine, and/or CSF. PeV-A genotype was identified by examining the viral protein 1 (VP1) sequence, and the phylogenetic tree of the VP1 sequence was constructed.

Results
Of the 277 patients evaluated, 135 (49%) were positive for PeV-A (n = 74, 27%) or EVs (n = 61, 22%). Among PeV-A patients, most had PeV-A3 (n = 69; 93%), followed by PeV-A4 (n = 4; 5%). There was a PeV-A3 epidemic in 2014 (n = 43); however, no cases were reported in 2015. In 2016–2018, small numbers of PeV-A3 cases were reported: 10 in 2016, 7 in 2017, and 9 in 2018. In contrast, EV cases were reported throughout this period: 8 in 2014, 22 in 2015, 10 in 2016, 5 in 2017, and 16 in 2018. When data were analyzed by season, the PeV-A3 detection rate in summer (June-August) was 93% (40/43) in 2014 and 65% (17/26) during 2016–2018, indicating an increase in the number of PeV-A3 cases in seasons other than summer. Phylogenetic analysis showed that PeV-A3 strains during 2016–2018 were part of a cluster of epidemics in 2011 and differed from those in 2014.

Conclusion
After the major PeV-A3 epidemics in 2014, we observed changes in the PeV-A3 epidemic profile, namely, a small, but constant, number of cases every year in Niigata, Japan. A future study should investigate if this trend has continued in Japan and other countries and identify the causes of this change in epidemic profile.

Disclosures
All authors: No reported disclosures.
2588. Acute Toxoplasmosis among Pregnant Arab Women in Northern Israel: to Screen or Not?
Authors: Paz Alona , Potasman Asala , Stam Tamar , Potasman Israel 
Published: October 2019

Abstract

Background
The seroprevalence of toxoplasmosis among Israeli Arabs is high. Yet, the regulation of the Israeli Ministry of Health suggests not screening pregnant women for toxoplasmosis. During 2017/8 we have seen a surge in cases of acute toxoplasmosis in pregnancy in Northern Israel. We aimed to explore this surge and compare the rates of acute toxoplasmosis in pregnancy in Northern Israel among Jews and Arabs.

Methods
The database of the lab of Meuhedet HMO (Northern Israel only) was retrospectively screened for all tests for Toxoplasma serology during 2013–2017. We focused on women of childbearing age and compared rates of seropositivity in Jews and Arabs. IgG and IgM were carried out using Abbott Architect, and IgG avidity by Vidas, BioMerieux. Birth rates were retrieved from the central computer of Meuhedet HMO.

Results
: In 2017, Northern Israel had 1,397,833 citizens of whom 53% were Arabs. Of this population, 13% were insured by Meuhedet HMO, and of these 60% were Arabs (Muslims or Christians). During the 5-year period 16,044 Toxoplasma serology tests have been requested (both sexes), of which 26% returned IgG positive. 88% of the positive ones were of Arab citizens (P < 0.0001). Excluding duplicates, we found 118 women of childbearing age with a positive IgM test (2.8%). Of the latter, 37 had a low/medium avidity test (31.4%). 112 of the women were Arabs, while only 6 were Jews (P < 0.0001). Two-thirds of the women had a positive βHCG test at the same time. During this 5-year period there were 23,074 live births in this HMO (11,512 Arab newborns). Thus, had all these women delivered an infected newborn, the rate of congenital toxoplasmosis in the Arab population (97.2/10,000) was 19-fold higher than among the Jewish (5.2/10,000; P < 0.00001). Interview of 35 acute cases during 2017/8 revealed that most of the women had consumed raw meat called “Kibbe Niyye”—a popular dish unique to Northern Israeli Arabs (Galilee) and served on festive occasions.

Conclusion
We found that Northern Israeli Arab women are at a high risk to contract toxoplasmosis during pregnancy due to consumption of traditional raw meat. This finding calls for awareness among women as well as doctors. We believe that the regulation not to screen pregnant women in the Arab sector should be reevaluated.

Disclosures
All authors: No reported disclosures.
2591. The Role of Neutralizing Antibodies (nAb) Against Cytomegalovirus (CMV) Epithelial Cell-entry in Patients with Self-limited (SL) CMV infection after Hematopoietic Cell Transplantation (HCT)
Authors: Zamora Danniel , Green Margaret , Tono Jo , Blazevic Rachel , Edmison Bradley , Stevens-Ayers Terry , Geballe Adam , Boeckh Michael 
Published: October 2019

Abstract

Background
CMV transmission after HCT occurs in 20–30% of CMV-seronegative recipients with CMV-seropositive donors (i.e., CMV D+/R−) and a distinct subset develop transient CMV DNAemia without progression to culture positivity in the absence of antivirals (BMT 1992; 9:221; J Med Virol 2019; 91:1128). The mechanism of SL CMV infection is unknown but may involve nAb, which have been implicated in primary viral clearance, including nAb that inhibit viral epithelial and endothelial cell-entry via CMV pentameric complex (PC). We aimed to describe viral kinetics and the influence of nAb on CMV infection progression in SL CMV-infected patients and controls within a unique cohort from the pre-antiviral era.

Methods
Weekly serum samples from 456 CMV D+/R− allogeneic HCT patients collected between 1978–95 were screened using quantitative CMV DNA PCR. Patients with CMV DNAemia in the first 100 days after HCT followed by a sustained return to undetectable levels without positive surveillance CMV cultures were defined as having SL CMV infection. SL CMV-infected patients were matched 1:1:1 to CMV-infected controls (patients with CMV infection by culture in the same period after HCT ± 14 days) and non-infected controls (patients without CMV DNA or culture positivity) to compare viral kinetics and nAb. A modified nAb assay was used to evaluate serum nAb activity against CMV PC-mediated cell entry (Vaccine 2008; 26:5760; JID 2019; in press).

Results
We identified 9 patients with SL CMV infection and baseline demographics are shown (Table 1). SL CMV-infected patients had a median of 21 days (range 7–54 days) until first positive CMV DNAemia. The median peak CMV DNAemia was 94.2 IU/mL (range 40.2–225.9 IU/mL) and 46,118 IU/mL (range 1,132–284,362 IU/mL) in SL CMV-infected and CMV-infected controls respectively. There was no difference in nAb titers between groups at infection day 0 or in the preceding 4 weeks (Figure 1, Figure 2).

Conclusion
nAb against CMV PC-mediated cell entry did not appear to play a critical role in viral clearance in SL CMV infection after CMV D+/R- allogeneic HCT. Our study illustrates the potential for clearance of relatively low CMV DNAemia after HCT without the addition of antivirals. CMV-specific T-cell immunity or innate immune mechanisms may be more important in early viral control.

Disclosures
All authors: No reported disclosures.
2597. Dolichos biflorus Agglutinin Binds to Pneumococcal Teichoic Acid and Lipoteichoic Acid
Authors: Zhou Meng-Lan , Frost Michael R , Nahm Moon H 
Published: October 2019

Abstract

Background
Dolichos biflorus agglutinin (DBA) is a lectin with a binding specificity toward α-linked N-acetylgalactosamine (α-GalNAc). While DBA is known to bind some, but not all, pneumococci, its target molecule has not been identified. Pneumococcus teichoic acid (TA) and lipoteichoic acid (LTA) have repeating units with α-GalNAc-(1→3)β-GalNAc decorated with phosphorylcholine (PC) at the O-6 positions. Two PC transferases, LicD1 and LicD2, mediate the attachment of PC to GalNAc residues while phosphorylcholine esterase (Pce) removes PCs attached to the terminal GalNAcs. We examined if DBA binds to the terminal α-GalNAc-(1→3)β-GalNAc created by Pce.

Methods
Fifteen pneumococcus strains expressing 14 different serotypes, including one non-encapsulated strain (R36A), were studied with flow cytometry (FC) and confocal fluorescence microscopy (CFM) for DBA binding. Pce enzyme activity was detected with a colorimetric assay using p-nitrophenyl-phosphorylcholine as the substrate. Mutant strains with pce knocked-out were constructed in R36A and D39 by replacing pce with Janus cassette. Both licD genes were sequenced for some of the strains.

Results
Ten of the 15 strains had Pce activity and all of them bound DBA (Table 1). When the pce gene was inactivated in two normally Pce-positive strains (R36A△pce and D39△pce), the strains did not show DBA binding by CFM (Figure 1). Thus, expression of Pce appears to be sufficient for expressing the DBA antigen. Of the five strains that had no Pce activity, two bound DBA. Sequencing of the licD genes in these two strains with positive DBA binding and negative Pce activity revealed one SNP in licD1 and four SNPs in licD2, resulting in a single amino acid difference each for LicD1 and LicD2, compared with R36A and D39.

Conclusion
DBA can bind to the terminal α-GalNAc-(1→3)β-GalNAc of pneumococcal TA and LTA, which is created by Pce. DBA binding is independent of capsule type. The unexpected binding of DBA to the two Pce-negative strains suggests that there is a Pce-independent mechanism for generating the target for DBA binding. Since LicD1 and LicD2 are involved in attaching PC to α-GalNAc-(1→3)β-GalNAc, we are now investigating their role in creating DBA targets independent of Pce.

Disclosures
All authors: No reported disclosures.