bluuebunny/crossref_metadata_2025_split huggingface dataset:
2586. Human Breast Milk Inhibits the Replication of Parechovirus-A3
Authors: Izumita Ryohei , Kon Kazuki , Aizawa Yuta , Watanabe Kanako , Saitoh Akihiko 
Published: October 2019

Abstract

Background
Parechovirus-A3 (PeV-A3) is an emerging pathogen causing sepsis and meningoencephalitis in neonates and young infants. We previously reported that maternal antibodies against PeV-A3 are important to protect neonates and young infants from the infection. Recent studies showed that (1) breastfeeding had a protective effect against enterovirus, which is closely-related virus to PeV-A, and (2) human breast milk (HBM) neutralized enterovirus in vitro. Currently, no report is available related to the antiviral effect of HBM against PeV-A3.

Methods
HBM (colostrum, 3–5 days after childbirth; mature milk, 1 month after childbirth) and serum (within ± 1 week of child’s birthday) samples were obtained from mothers at obstetrics clinic in Niigata, Japan. Neutralizing antibody titers (NATs) against PeV-A3 were measured using the Vero cells.

Results
The anti-PeV-A3 NATs of colostrum (n = 32) ranged from 1:8 to 1:2048, those ≥1:32 was 59% (19/32). Whereas, the anti-PeV-A3 NATs of mature milk ranged from 1:8 to 1:96. and those ≥1:32 was 20% (2/20) (P < 0.001). The median NATs anti-PeV-A3 was higher in colostrum (1:32) compared with mature milk (1:8) (P < 0.001). There was a strong positive correlation between the NATs of colostrum and serum (r = 0.604, P < 0.001, Figure).

Conclusion
This study showed that HBM had high NATs against PeV-A3, which was correlated with serum NATs. Further studies are necessary to investigate which components of HBM has antiviral effects against PeV-A3.

Disclosures
All authors: No reported disclosures.
155. A Case Series of Patients with Gemella Endocarditis
Authors: Ramanathan Abarna , Gordon Steven M , Shrestha Nabin K 
Published: October 2019

Abstract

Background
Gemella is a genus of gram-positive bacteria that thrives best at a high partial pressure of CO2 and is an unusual cause of infective endocarditis (IE).

Methods
We identified cases of Gemella IE in patients aged >18 years old, hospitalized at Cleveland Clinic between July 1, 2007 and January 1, 2017, by screening the Cleveland Clinic IE Registry. Gemella IE was defined as meeting modified Duke Criteria and having Gemella identified as the pathogen (by culture and/or 16S RNA sequencing from explanted valve tissue). Clinical features were obtained by manual chart review.

Results
A total of 13 cases of Gemella IE (G. haemolysans [6], G. morbillorum [3], G. sanguinis [2], and 2 undifferentiated species) were identified within the study period and accounted for <1% of all cases of IE. 9 were native valve IE and 4 were prosthetic valve endocarditis. Age varied from 20 to 86 years and 77% were male. The most common predisposing factors were pre-existing valvular disease (54%) and congenital heart disease (46%). 3 cases had dental manipulation within the prior 3 months, 3 had bioprosthetic valves, 2 had mechanical heart valves, and 2 were actively using intravenous recreational drugs. All cases were left-sided: 38% involved the aortic valve, 23% the mitral valve and 38% involved both. 69% had positive blood cultures, 38% had positive blood cultures and positive valve PCR, and 31% were identified based on positive valve PCR results only. Not one patient had positive valve cultures. 85% had significant valvular regurgitation and locally invasive disease occurred in 4 patients. Central nervous system emboli occurred in 3 cases and metastatic infection, in the form of lumbar diskitis, in one. All patients were treated surgically and the most commonly used anti-microbials were parenteral ceftriaxone and vancomycin, administered for a median duration of 42 days. All cases survived to hospital discharge and none relapsed over a median follow-up of 2.2 years.

Conclusion
Gemella species account for less than 1% of cases of IE, with G. haemolysans being the most common species. In a third of cases valve PCR provided the only means of diagnosis. It is effectively treated with surgery and antibiotics.

Disclosures
All authors: No reported disclosures.
2622. Multiplex Polymerase Chain Reaction (PCR) Panels in Pediatric Hospital Care: New Insights into Factors Driving Antimicrobial Use
Authors: Gaviria Agudelo Claudia L , Howard Milza , Barr Mary M , West Melissa , Whitfield Philip L , Edwards Jonathan , WIlliams Amanda , Newman Patrick , Lindgren William , Mennemeyer Stephen , Chahine Rouba , Morris Susan , Hassoun Ali 
Published: October 2019

Abstract

Background
Multiplex PCR panels are diagnostic tools that first became available in 2011. They have rapid turnaround time and excellent sensitivity and specificity for a wide spectrum of microbial targets. However, it remains controversial whether its widespread use leads to optimal use of antimicrobials. We aimed to determine whether use of these tests was associated with appropriate antimicrobial therapy (AAT).

Methods
We conducted a single-center, retrospective study of hospitalized pediatric patients from 2015 to 2018 looking at 4 different respiratory panels and 1 meningoencephalitis panel (MEP). We analyzed test results and compared them to antimicrobial treatment. Using logistic regression, we analyzed the clinical and laboratory factors associated with AAT (defined as directed antimicrobial therapy based on clinical assessment and tests results).

Results
There were 1,002 encounters in 951 patients. Mean length of stay was 7 days. 53.2% encounters had intensive care unit (ICU) admission. 77.1% of respiratory panels and 17.3% of MEP were positive. Co-detection in respiratory samples was 44.2%. Enterovirus was the most common virus detected while H. influenza was the most frequent bacteria. Respiratory Syncytial Virus was commonly detected with bacteria when compared with other common viruses. 13.4% patients were intubated, concordance with sputum culture was 63%. Patients admitted to the floor were more likely to have AAT than ICU patients (82.5% vs. 71.7%). ICU admission increased the odds of unnecessary antimicrobials (OR 1.6; 95% CI 1.1–2.5). Positive result from a comprehensive respiratory panel (bacteria + virus) decreased the odds of AAT (odds ratio: 0.4, 95% CI 0.3–0.8). Age, season, comorbidity, and intubation were not significantly associated with AAT. Only 0.5% of blood cultures in patients tested for respiratory infection were positive (3/579).

Conclusion
We present new insights into factors driving antimicrobial use in pediatric hospital care. ICU admission was significantly associated with unnecessary antimicrobial use after adjusting for clinical findings and diagnostics. Frequently PCR results were not acted upon or caused additional use of antimicrobials. Further investigation is warranted to understand factors influencing antimicrobial use in pediatric care.

Disclosures
All authors: No reported disclosures.
2625. Incidence of Bronchiolitis Requiring Hospitalization in the First 2 years of Life Among Healthy Term Infants with Different Races/Ethnicities: A Population-based Longitudinal Study
Authors: Inagaki Kengo , Blackshear Chad , Hobbs Charlotte V 
Published: October 2019

Abstract

Background
Race/ethnicity is currently not considered a risk factor for bronchiolitis, except for indigenous populations in western countries. We sought to determine the incidence of hospitalization with bronchiolitis among different races/ethnicities, because such information can lead to more tailored preventive care.

Methods
We performed a population-based longitudinal observational study using the State Inpatient Database from New York state. Infants born between 2009 and 2013 at term without comorbidities were followed for the first 2 years of life, up to 2015. We calculated incidence among different race/ethnicity groups, and evaluated risks by developing Cox proportional hazards regression models.

Results
Of 877,465 healthy term infants, 10 356 infants were hospitalized with bronchiolitis. Overall, incidence was 11.8 per 1,000 births. Substantial difference in infants born in different seasons was observed (Figure 1). The incidence in non-Hispanic white, non-Hispanic black, Hispanic, and Asian infants was 8.6, 15.4, 19.1, and 6.5 per 1,000 births, respectively (table). On multivariable analysis adjusting for socioeconomic status, the risks remained substantially high among non-Hispanic black (hazard ratio [HR] 1.42, 95% confidence interval [CI]: 1.34–1.51) and Hispanic infants (HR 1.77, 95% CI: 1.67–1.87), particularly beyond 2–3 months of age, whereas Asian race was protective (HR 0.62, 95% CI: 0.56–0.69) (Figure 2, 3).

Conclusion
The risks of bronchiolitis hospitalization in the first 2 years of life was substantially higher among infants with non-Asian minority infants, particularly beyond 2–3 months of age. Further research efforts to identify effective public health interventions in each race/ethnic groups with varied socioeconomic status, such as improvement in access to care and anticipatory guidance, is warranted to overcome health disparity.

Disclosures
All authors: No reported disclosures.
156. Clinical Characteristics and Acute-phase Cytokine Response of Solid-Organ Transplant Recipients with Bloodstream Infections Differs According to Bacterial Type and Transplant Status
Authors: Eichenberger Emily , Ruffin Felicia , Jung Sin-Ho , Lerebours Reginald , Sharma-Kuinkel Batu K , Alexander Barbara D , Thaden Joshua , Fowler Vance G , Maskarinec Stacey 
Published: October 2019

Abstract

Background
Clinical outcomes and host immune response in solid-organ transplant recipients (Tx) with Staphylococcus aureus bacteremia (SAB) and Gram-negative bacteremia (GNB) are poorly understood. The aims of this study were to describe (1) clinical characteristics and outcomes and (2) acute-phase cytokine response in Tx recipients with SAB and GNB as compared with matched non-transplant subjects (Non-Tx).

Methods
Thirty-two Tx recipients who were prospectively enrolled in the Blood Stream Infection Biorepository (BSIB) were matched 1:1 with Non-Tx patients on age, race, gender and bacteria using a perfect matching algorithm (Tx-SAB n = 16, Non-Tx SAB n = 16; Tx GNB n = 16, Non-Tx GNB n = 16). GNB included Escherichia coli (n = 16) and Klebsiella pneumoniae (n = 16). Multiplex cytokine testing was performed (Luminex) to evaluate acute-phase serum cytokines levels. Baseline characteristics were summarized using mean with standard deviation (SD), median with interquartile range (IQR), and ranges (min and max), or frequency with %. Differences between the Tx and Non-Tx SAB and GNB were compared using either the equal or unequal variance version of the Student’s t-test or Wilcoxon rank-sum test for continuous variables. Fisher’s exact test was used for categorical variables.

Results
An endovascular source was more common in Tx SAB vs. Non-Tx SAB (75.0% vs. 0.0%; P = 0.0003) and Tx-GNB (42.9% vs. 18.8%; P = 0.006). Fewer SAB cases were attributed to a skin/soft tissue/osteoarticular in Tx vs. Non-Tx (8.3% vs. 91.7%; P = 0.0001). APACHE II scores were higher in Tx SAB vs. Non-Tx SAB (14.0 [IQR: 11.0, 17.5] vs. 10.0 [IQR: 7.0, 12.5] P = 0.02), but not between Tx GNB vs. Non-Tx GNB (14 [IQR: 12.0, 15.5] vs. 13.5 [12.0, 15.0] P = 0.54). No significant difference length of stay, recurrent bacteremia or mortality were noted among or between groups. Patients with SAB had significantly higher levels of IL-10, CCL5, eotaxin vs. GNB in both Tx and Non-Tx. Conversely, IL-5, IL-13 and IL-17 levels were significantly lower in SAB compared with GNB in both Tx and Non-Tx. Within Tx alone, IL-8 and IL-15 were significantly higher in SAB as compared with GNB.

Conclusion
Significant differences exist in etiology and host immune response in Tx and Non-Tx with SAB and GNB. Further research is needed to understand the host immune response to BSI in these patients.

Disclosures
All authors: No reported disclosures.
2639. Respiratory Virus Detections in Asthma-Related Pediatric Hospitalizations: New Vaccine Surveillance Network, United States
Authors: Midgley Claire , Rha Brian , Lively Joana Y , Campbell Angela P , Boom Julie A , Azimi Parvin H , Weinberg Geoffrey A , Staat Mary A , Halasa Natasha B , Selvarangan Rangaraj , Englund Janet A , Klein Eileen J , Harrison Christopher J , Williams John V , Schlaudecker Elizabeth P , Szilagyi Peter G , Singer Monica Nayakwadi , Sahni Leila C , MPH Aaron Curns, , Payne Daniel C , Langley Gayle , Langley Gayle , Watson John , Gerber Susan I 
Published: October 2019

Abstract

Background
Respiratory viruses are associated with most asthma exacerbations (AEx) in children; however, the role of different viruses in AEx is unclear. We describe respiratory virus detections among pediatric inpatients with AEx (AEx-inpatients).

Methods
Through active, prospective surveillance at 7 US medical centers, we enrolled inpatients (<18 years) with acute respiratory illness (ARI) during November 1, 2015–June 30, 2016. We defined an AEx-inpatient as an inpatient with a principal admission or discharge diagnosis of asthma (ICD-10-CM, J45.xx). Mid-turbinate nasal and/or throat swabs were tested by molecular assays for influenza A or B, respiratory syncytial virus (RSV), parainfluenza virus 1–3, rhinovirus or enterovirus (RV/EV), human metapneumovirus and adenovirus. We assessed virus detections among AEx-inpatients throughout the surveillance period or by season (winter: December–February; spring: March–May), and by patient age and history of asthma/reactive airway disease (asthma/RAD).

Results
We tested 3,897 inpatients with ARI; of whom, 954 were AEx-inpatients. Most AEx-inpatients (741/954 [78%]) reported an asthma/RAD history. Viruses were more frequently detected among AEx-inpatients <5 years (350/458 [76%]) than 5–17 years (305/496 [61%], P < 0.001). Most (615/655 [94%]) detections were of single viruses. The most frequent single virus detections were RV/EV (474/954 [50%]) and RSV (76/954 [8%]) but the frequency of each virus varied by season and age group (figure). Single RV/EVs were the most common virus detections in both seasons and all groups. Single RSV detections were prominent among <5 year olds in winter (40/185 [22%]). Among those with single RV/EV or RSV detections, 285/474 (60%) and 49/76 (64%) required supplemental oxygen, respectively (P = 0.676); median length of stay was 1 day (range: 0–45; IQR: 1–2) and 2 days (range: 0–6; IQR: 1–2.5), respectively (P < 0.001).

Conclusion
AEx-inpatients <5 years were more likely to have respiratory virus detections than those 5–17 years. Single RV/EVs formed the majority of virus detections throughout the surveillance period, regardless of age. RSV played a notable role in winter among patients <5 years. These findings could inform prevention or treatment strategies for virus-associated AEx.

Disclosures
All authors: No reported disclosures.
2642. Development of Human Intestinal Organoids as an Antiviral Evaluation Platform for Enteroviruses
Authors: Fuk-Woo Chan Jasper , Tsang Jessica , Zhou Jie , Zhao Xiaoyu , Yuen Kwok-Yung 
Published: October 2019

Abstract

Background
Enteroviruses are non-enveloped, single-stranded positive-sense RNA viruses belonging to the family Picornaviridae. Enterovirus A71 (EV-A71) has caused recurrent outbreaks of hand, foot, and mouth disease especially among children in Asia. Some patients develop severe complications, such as meningitis, encephalitis, myocarditis, and pulmonary edema. A major hurdle for the development of antivirals for EV-A71 infection is the lack of robust antiviral platforms that closely mimic the in vivo setting. Organoids are laboratory-adapted miniaturized organs with preserved three-dimensional micro-anatomical architecture. In recent years, organoid cultures have been increasingly used for studying the pathogenesis of and evaluating antiviral treatment options for viral infections. In this study, we developed human intestinal organoids as a robust platform for evaluating antiviral options for EV-A71.

Methods
An epidemic strain of EV-A71 isolated from a patient with laboratory-confirmed EV-A71 infection was used. We compared the performance of multiple antiviral evaluation assays (virus yield reduction, plaque reduction, and cell protection assays) between human intestinal organoids and Caco-2 cells, using itraconazole (an antifungal previously shown to exhibit potent anti-enteroviral effects) and DMSO as positive and negative controls, respectively.

Results
The antiviral effect of itraconazole was comparable between human intestinal organoids and Caco-2 cells in the virus yield reduction and plaque reduction assays. In the cell protection assay, Caco-2 cells failed to demonstrate significant differences between the itraconazole-treated and DMSO-treated groups. In contrast, cell protection effects were easily observed and quantified in human intestinal organoids. Moreover, the human intestinal organoids allowed the characterization of the different cell types affected in EV-A71 infection with or without itraconazole treatment.

Conclusion
Human intestinal organoids support the replication of EV-A71 and provides a robust platform for antiviral evaluation for EV-A71 infection.

Disclosures
All authors: No reported disclosures.
2651. Protection Against Human Cytomegalovirus Acquisition Is Associated with IgG Binding to Cell-Associated CMV glycoprotein B in Two Historical gB/MF59 Vaccine Cohorts
Authors: Jenks Jennifer A , Nelson Cody S , Pass Robert F , Bernstein David I , Roark Hunter K , Chan Cliburn , Permar Sallie R 
Published: October 2019

Abstract

Background
Human cytomegalovirus (CMV) is the most common congenital infection worldwide. A CMV glycoprotein B (gB) subunit vaccine with MF59 adjuvant achieved ~50% protection in phase II clinical trials in postpartum and adolescent women. Interestingly, postpartum vaccinees showed poor virus neutralization but robust antibody-dependent cellular phagocytosis (ADCP). In this study, we performed a combined humoral immune correlate of risk analysis in vaccinees to define vaccine-elicited immune responses associated with protection and targets for vaccine candidate immunogenicity.

Methods
gB/MF59 vaccinees who became infected and those who remained uninfected were 2:1 matched on race and number of vaccine doses. This study included 42 women from the adolescent (14 infected, 28 uninfected) and 33 from the postpartum cohorts (11 infected, 22 uninfected). IgG binding to whole gB, gB-neutralizing epitopes, FCRs, and whole virions were assessed by standard or multiplex ELISA. IgG binding to gB mRNA-transfected HEK293Ts was measured by flow cytometry. Neutralization of Towne, TB40/E, and AD169-repaired-GFP strains were measured in MRC-5, BJ5Ta, and/or ARPE-19 cells. Phagocytosis was assessed by THP-1 uptake of fluorescently conjugated TB40/E and AD169-repaired-GFP virions. Multiple linear regression controlling for cohort was performed for the combined log-transformed group data (apriori significance cut-off of P < 0.05, Benjamin–Hochberg FDR < 0.2).

Results
Vaccine-elicited antibodies in adolescent and postpartum cohorts exhibited similar magnitude IgG binding to soluble HCMV gB protein, gB-neutralizing domains, and gB-transfected cells. Autologous Towne strain neutralization was observed in both cohorts, but heterologous strain neutralization was observed only in adolescent vaccinees (P = 0.001). Both cohorts exhibited robust phagocytosis of HCMV virions. Regression analyses revealed that risk of HCMV acquisition in vaccinees was associated with magnitude IgG binding to gB-transfected cells (P = 0.006, FDR = 0.15), not neutralization or phagocytosis responses.

Conclusion
Protection against primary HCMV infection was significantly associated with vaccine-elicited IgG binding to gB-transfected cells, suggesting the importance of a native, cell-associated gB conformation in future vaccine candidates.

Disclosures
All authors: No reported disclosures.
2669. Evaluation of Post-Operative Acute Kidney Injury with Piperacillin–Tazobactam Combined with Vancomycin for Lung Transplant Prophylaxis
Authors: Pettit Natasha N , Nguyen Cynthia T , Potter Lisa , Pisano Jennifer 
Published: October 2019

Abstract

Background
Several studies have identified that the addition of vancomycin (VAN) to piperacillin–tazobactam (PT) is associated with a higher incidence of nephrotoxicity when compared with other antibiotic regimens. Beginning in June 2017, our lung transplant antibiotic prophylaxis regimen was modified from PT monotherapy to VAN and PT.

Methods
All adult lung transplant patients between January 1, 2015 and November 10, 2018 were included. Patients were excluded if acute kidney injury (AKI) was present prior to transplant. Rates of AKI within 7 days of transplant were compared between those who received prophylaxis with PT and VAN vs. those receiving alternative regimens (AR). Patients receiving less than 1 dose of vancomycin or less than 3 doses PT (less than 24hours) were deemed to be in the alternative regimen group. AKI was defined as either an increase in serum creatinine (SCr) by ≥0.3 mg/dL within 48 hours or increase in SCr to ≥1.5 times baseline (within 7 days post-transplant). Secondary outcomes included duration of initial prophylactic antibiotic regimens, hospital length of stay (LOS), and all-cause inpatient mortality.

Results
Eighty-six patients were included, 44 (51%) patients received PT/VAN. Baseline characteristics and results shown in Table 1. Of those receiving PT/VAN for prophylaxis, 24 (54%) developed AKI within 7 days of transplant while 15 (36%) of 42 patients receiving AR developed AKI (P = 0.08).

Conclusion
A larger proportion of patients that received PT/VAN for transplant antibiotic prophylaxis experienced AKI within 7 days. Although the difference did not reach statistical significance, a 19% higher incidence of AKI warrants need for further investigation.

Disclosures
All authors: No reported disclosures.