bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

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

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.
2673. Risk Factors for Clostridium difficile Infection in Lung Transplant Patients
Authors: DeRose Joseph L , Axelrod Peter , Samuel Rafik , Clauss Heather
Published: October 2019

Background

Clostridium difficile infection is a serious and common illness affecting almost 500,000 people in the United States each year. Solid-organ transplant recipients are at increased risk for this infection, with lung transplant patients being at the highest risk. Temple University Hospital (TUH) in Philadelphia has performed the most lung transplants in the United States over the last 2 years.

Methods

A retrospective case–control study was performed to identify patients diagnosed with C. difficile following lung transplantation at our institution between January 1, 2014 and April 30, 2018 (N = 35). We randomly selected control patients (N = 35) who had lung transplantation performed during this time but did not develop C. difficile infection. The study objectives were to characterize risk factors that are associated with C. difficile infection in lung transplant recipients and compare clinical outcomes in recipients with and without C. difficile. Statistical analysis was performed using Epi Info (CDC, Atlanta GA).

Results

The average age was 62.4 years, 64.7% were male, 75% were white and 69.1% of transplants were performed for underlying idiopathic pulmonary fibrosis. 52.9% of patients had “non-severe” C. difficile infection as defined by the 2018 Infectious Disease Society of America guidelines. Patients with C. difficile infection were more likely to have been treated for cytomegalovirus (CMV) viremia (OR 8.2, 95% CI 2.4–28.2, P = 0.0006) and were more likely to have received third- to fifth-generation cephalosporins (OR 4.0, 95% CI 1.4–11.2, P = 0.01) and/or carbapenems (OR 3.7, 95% CI 1.4–9.9, P = 0.02). Patients with C. difficile infection were more likely to experience multiple hospitalizations when compared with C. difficile-negative patients (3.6 vs. 8.4, P = 0.003). 22 of the 68 evaluable patients died during the study period, 9 of whom had C. difficile infection (P = NS).

Conclusion

Patients who received lung transplants and developed C. difficile infection were more likely to be treated for CMV viremia, receive antibiotics including cephalosporins and/or carbapenems and require repeat hospitalizations when compared with control patients who did not develop C. difficile infection following transplant.

Disclosures

All authors: No reported disclosures.
2683. Evaluation of the Negative Predictive Value (NPV) of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Swab Screening in Acute Myeloid Leukemia Patients
Authors: Binks Bailee , McManus Dayna , Perreault Sarah , Topal Jeffrey E
Published: October 2019

Background

Methicillin-Resistant Staphylococcus aureus (MRSA) nasal swabs are utilized to guide discontinuation of empiric MRSA therapy. In multiple studies, MRSA nasal swabs has been shown to have a negative predictive value (NPV) of ~99% in non-oncology patients with pneumonia and other infections. At Yale New Haven Hospital (YNHH), a negative MRSA nasal swab is utilized in acute myeloid leukemia (AML) patients to de-escalate empiric MRSA antibiotic therapy. The primary endpoint was to assess the percentage of patients with a negative MRSA nasal swab who developed a culture documented (CD) MRSA infection during their admission. Secondary endpoints included the number of MRSA nasal swabs that were initially negative but converted to positive, and the types of MRSA infections.

Methods

This was a retrospective chart review of AML patients with a suspected infection and a MRSA nasal swab collected at YNHH between 2013 and 2018. Patients were excluded if < 18 years old, prior confirmed MRSA infection or positive MRSA nasal swab within the past year.

Results

194 patients were identified with 484 discrete encounters analyzed. Hematopoietic stem cell transplantation occurred in 83 (43%) patients. A total of 468 (97%) encounters had a negative MRSA nasal swab upon admission with no CD MRSA infection during their hospitalization. Three encounters (0.6%) had a negative MRSA nasal swab with a subsequent CD MRSA infection during their admission. Identified infections were bacteremia (2) and pneumonia (1). Median duration from the negative MRSA nasal swab to CD infection was 16 days. Thirteen encounters (3%) had a positive MRSA nasal swab, 5 of which had a CD MRSA infection. Infections included bacteremia (3), pneumonia (2), and sputum with negative chest X-ray (1). MRSA nasal swab had a sensitivity of 57% (CI 0.56–0.58), specificity of 98% (CI 0.98–0.98) positive predictive value of 31% (CI 0.3–0.32), and NPV of 99% (CI 0.99–0.99).

Conclusion

The results of this retrospective study demonstrate that a negative MRSA nasal swab has a 99% NPV for subsequent MRSA infections in AML patients with no prior history of MRSA colonization or infection. Based on these findings, a negative MRSA nasal swab can help guide de-escalation of empiric MRSA antibiotic therapy in this immunosuppressed population.

Disclosures

All authors: No reported disclosures.
2700. Evaluation of 10- and 13-Valent Protein Conjugate Pneumococcal Vaccine Effectiveness for Children in Korea
Authors: Sohn Sangho , Hong Kwan , Hwang Hari , Chun Byung Chul
Published: October 2019

Background

Pneumococcal vaccination for infants was introduced to the mandatory National Immunization Program (NIP) of Korea in May 2014. Both 10- and 13-valent protein conjugated vaccines (PCV) have been in use with 3 + 1 dose schedule. We assessed the vaccine effectiveness in protecting children from all-cause pneumonia (ACP), pneumococcal pneumonia (PP), invasive pneumococcal diseases (IPD), and acute otitis media (AOM).

Methods

The birth cohort of children born between 2013 and 2015 was identified from the national population registry for retrospective observation. Vaccination status was confirmed through NIP registry by Korean Centers for Disease Control and Prevention, and disease occurrence was detected through the National Health Insurance System. Children who finished at least 3-doses of PCV were classified vaccinated while who did not receive any type of pneumococcal vaccine until study end were classified unvaccinated. The outcome of interest was hospital admission from any of pneumococcal infections among ACP, PP, IPD or AOM. After adjusting for high risk and underlying conditions, the vaccine effectiveness (VE) was calculated with Cox regression. VE of different valent PCV was also compared within fully vaccinated (4-doses) children.

Results

A total of 1,243,432 children were included. Fifty-one percent of children were boys and median age was 30-months. Ninety-eight percent were vaccinated and 89% of them were fully vaccinated. The incidence (per 100,000 person-years) of ACP was 10,982 in vaccinated and 9,276 in unvaccinated, and that of IPD and AOM were 1.0 vs 1.5 and 45.7 vs 31.3, respectively. The vaccine had protective effect for ACP (VE 20.2% [95% CI 19.5–20.9]), PP (VE 25.5% [95% CI 21.1–29.6]), IPD meningitis (VE 93.6% [95% CI 27.1–99.4]) and AOM (VE 4.6% [95% CI 4.1–5.1]). When fully vaccinated with PCV10, compared with PCV13, it was statistically more protective against ACP (VE 22.7% vs. 19.6%, P = 0.033) and PP (VE 50.8% vs. 21.3%, P < 0.001) but not different against AOM (VE 4.2% vs. 6.0%, P = 0.53).

Conclusion

Four-doses of PCV strategy for children in current mandatory NIP is effective for protecting the vaccinated from ACP, PP, IPD, and AOM.

Disclosures

All authors: No reported disclosures.
2713. Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine in Korean National Population Cohort over 65 Years Old
Authors: Sohn Sangho , Hong Kwan , Hwang Hari , Chun Byung Chul
Published: October 2019

Background

Twenty-three valent pneumococcal polysaccharide vaccine (PPSV) has been introduced to the National Immunization Program (NIP) for adults aged 65 years and older in Korea since 2013. We describe the effectiveness evaluation of PPSV among adults against pneumococcal infections including all-cause pneumonia (ACP), pneumococcal pneumonia (PP), and invasive pneumococcal diseases (IPD) using national population cohort.

Methods

Vaccination records of the national population, aged 65 years and older, from NIP registry by Korea Centers for Disease Control and Prevention (KCDC) were matched to their corresponding medical records by National Health Insurance Service (NHIS) for retrospective cohort analysis. Adults vaccinated with 1-dose PPSV between 2013 and 2016 were compared with those non-vaccinated. Primary outcomes were hospitalization due to ACP, PP, and IPD. Vaccine effectiveness (VE) adjusted for high risk and underlying conditions was calculated as one minus hazard rate ratio (HR) using Cox regression.

Results

Records of 6,743,002 cohort members were included. Forty-three percent were male, and median age was 75-years. Among the cohort, 3,425,949 (51%) were vaccinated during the study period. Incidence (per 100,000 person-years) of each disease in vaccinated and unvaccinated, respectively, was 2,184 and 1,584 for ACP, 8.9 and 5.4 for PP, and 1.6 and 1.9 for IPD. VE against IPD was 41.7% (95% CI 28.8–52.3) and against IPD sepsis was 53.5% (95% CI 39.8–64.0). PPSV was also protective against ACP with VE 7.2% (95% CI 6.6–7.8). When stratified by age-group, adults aged 65–74 years were better protected from ACP (VE 16.5% [95% CI 15.6–17.3]) compared with older adults aged 75 years or older (VE –0.4% [95% CI –1.2 to 0.4]), while VE was higher in older adults against IPD (VE 47.6% [95% CI 32.4–59.4]) and IPD sepsis (VE 54.9 [95% CI 38.4–66.9]) than in 65–74 years group (IPD VE 30.4% [95% CI 3.4–49.9]; sepsis VE 49.0% [95% CI 19.7–67.6]).

Conclusion

Single-dose PPSV strategy for adults in general population is protective against PCV, IPD, and IPD sepsis.

Disclosures

All authors: No reported disclosures.
2742. The Impact of Influenza Vaccination on Antibiotic Use in the United States, 2010–2017
Authors: Klein Eili , Schueller Emily , Tseng Katie K , Nandi Arindam
Published: October 2019

Background

Antibiotic resistance is a cause of morbidity and mortality driven by inappropriate prescribing. In the United States, a third of all outpatient antibiotic prescriptions may be inappropriate. Seasonal influenza rates are significantly associated with antibiotic prescribing rates. The impact of influenza vaccination coverage on antibiotic prescribing is unknown.

Methods

We conducted a retrospective analysis of state-level vaccination coverage and antibiotic prescribing rates from 2010 to 2017. We used fixed effects regression to analyze the relationship between cumulative vaccine coverage rates for a season and the per capita number of prescriptions for systemic antibiotics for the corresponding season (January–March) controlling for temperature, poverty, healthcare infrastructure, population structure, and vaccine effectiveness.

Results

Rates of vaccination coverage ranged from 33% in Nevada to 52% in Rhode Island for the 2016–2017 season, while antibiotic use rates ranged from 25 prescriptions per 1,000 inhabitants in Alaska to 377 prescriptions per 1,000 inhabitants in West Virginia (Figure 1). Vaccination coverage rates were highly correlated with reduced prescribing rates, and controlling for other factors, we found that a one percent increase in the influenza vaccination rate was associated with 1.40 (95% CI: 2.22–0.57, P < 0.01) fewer antibiotic prescriptions per 1,000 inhabitants (Table 1). Increases in the vaccination coverage rate in the pediatric population (aged 0–18) had the strongest effect, followed by the elderly (aged 65+).

Conclusion

Vaccination can reduce morbidity and mortality from seasonal influenza. Though coverage rates are far below levels necessary to generate herd immunity, we found that higher coverage rates in a state were associated with lower antibiotic prescribing rates. While the effectiveness of the vaccine varies from year to year and the factors that drive antibiotic prescribing rates are multi-factorial, these results suggest that increased vaccination coverage for influenza would have significant benefit in terms of reducing antibiotic overuse and correspondingly antibiotic resistance.

Disclosures

All authors: No reported disclosures.
2773. Safety and Immunogenicity Study of Eastern Equine Encephalitis Vaccine
Authors: Maryam Keshtkar-Jahromi , Reisler Ronald B , Purcell Bret K , Rivard Robert G , Cardile Anthony P , Liggett Dani , Norris Sarah , Pitttman Phillip R
Published: October 2019

Background

Eastern equine encephalitis virus (EEEV) is an alphavirus with a high mortality rate and serious neurological sequelae in infected persons making this virus an important human pathogen.

Methods

Following written informed consent, eligible subjects received two priming doses of EEEV vaccine, inactivated, TSI-GSD 104, 0.5 mL subcutaneously on days 0 and 28 days followed by a mandatory booster, 0.1 mL intradermal, at 6 months. Serum samples were collected pre-vaccination, days 21–35 following dose 2, as well as before and 21–35 days after dose 3. Sera with a Plaque Reduction Neutralization Test80 titer (PRNT80) ≥ 1:40 were considered responders with adequate titers for the purpose of biocontainment suite entry.

Results

Sixty-seven (67) subjects were enrolled in this study to receive the primary vaccination series. All 67 subjects received at least 1 primary vaccination; 66 completed the 2 primary doses; 58 completed the 2 primary doses and the 6-month dose. Of these, 38 (56.7%) reported one or more adverse events. Fatigue was reported in 13 (19.4%), headache in 9 (13.4%), upper respiratory tract infection in 6 (9.0%), nausea in 5 (7.5%), pyrexia in 5 (7.5%), oropharyngeal pain in 4 (6.0%), myalgia in 4 (6.0%), injection site pain in 7 (10.4%), injection site hematoma in 4 (6.0%) and injection site erythema in 3 (4.5%) subjects. Adverse events were mostly mild or moderate and transient. PRNT80 titers ≥ 1:40 was observed in 39/65 (60%) subjects who received both primary doses of EEEV vaccine compared with 48/57 (84%) subjects who completed the 2-dose primary series and the 6-month dose and also had blood drawn for titer. Females had a higher response rate (61.5%) at the pre 6-month boost titer than did males (34.3%) (p = 0.0231). Similarly, the pre 6-month boost geometric mean titer (GMT) for females was 35.5 vs. 21.9 for males (p = 0.0231). The post 6-month boost GMT for females was 146.7 and 181.5 for males (P = 0.13).

Conclusion

Inactivated Eastern Equine Encephalitis Virus vaccine, TSI-GSD 104, Lot 2-1-89 appears to be safe and immunogenic. This Phase 2 vaccine study supports a priming dose schedule of Days 0 and 28 and 6-month. The 6 month dose is anamnestic improving the overall response rate and level of antibody for this primary dosing schedule.

Disclosures

All authors: No reported disclosures.
2780. Reactogenicity Profile of Adjuvanted Recombinant Zoster Vaccine after Dose 2 According to the Intensity of the Same Event Experienced after Dose 1
Authors: Colindres Romulo , Wascotte Valentine , Brecx Alain , Clarke Christopher , Hervé Caroline , Hyung Kim Joon , Levin Myron J , Oostvogels Lidia , Zahaf Toufik , Schuind Anne , Cunningham Anthony L
Published: October 2019

Background

In the pivotal clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) showed high efficacy against herpes zoster and postherpetic neuralgia. The incidence of reported solicited events was higher in RZV compared with placebo recipients.

Methods

In these phase III, observer-blind, placebo-controlled trials conducted in 18 countries, adults ≥50 years of age (YOA, ZOE-50) and ≥70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Injection-site and general events were solicited for 7 days after each dose via diary cards in a participant subset. For this post-hoc analysis, ZOE-50 and ZOE-70 data from participants having completed the diary cards for both RZV doses were pooled. The intensity of each solicited event after dose 2 was stratified by the intensity of the same event after dose 1.

Results

Solicited injection-site and general events were recorded for both RZV doses by 4,676 and 4,668 vaccinees, respectively (Figure 1). Of 1,235 vaccinees with no injection-site event at dose 1, 881 (71.3%) reported no injection-site event and 20 (1.6%) reported a grade 3 event after dose 2. A total of 433 (9.3%) vaccinees reported a grade 3 injection-site event, either after dose 1 or dose 2. Of 244 vaccinees with grade 3 injection-site events at dose 1, 79 (32.4%) also reported a grade 3 event after dose 2. Of 2,312 vaccinees with no general event at dose 1, 1,617 (69.9%) reported no general event and 67 (2.9%) reported a grade 3 event after dose 2. A total of 499 (10.7%) vaccinees reported a grade 3 general event, either after dose 1 or dose 2. Of 222 vaccinees with grade 3 general events at dose 1, 81 (36.5%) also reported a grade 3 general event after dose 2. In general, vaccinees who did not experience a certain event after dose 1, did not experience this event after dose 2 either. Most vaccinees reporting a specific event at high intensity after dose 1, reported the same event at a lower intensity (or not at all) after dose 2 (Figures 2 and 3).

Conclusion

While not powered to predict event intensity of the second RZV dose, our data provides an overview of event intensity after RZV dose 2 according to the intensity of the same event experienced after dose 1.

Funding: GlaxoSmithKline Biologicals SA.

Disclosures

All authors: No reported disclosures.
171. Rising Rates of Gram-Negative Bacilli Blood Stream (GNB-BSI) Infection in Adults
Authors: Johnson Leonard B , Khatib Riad , Youssef Dima , Hooshmand Babak , Fakih Mohamad G , Riederer Kathleen M
Published: October 2019

Background

Monitoring bloodstream infections provides updates of the microbiology and antibiotic susceptibility trends. We elected to examine GNB-BSI.

Methods

We retrospectively studied adults (≥18 years old) inpatients with gram-negative bacilli (GNB) bloodstream infection (BSI; January 1, 2010–December 31, 2017), determined the demographics, onset place, microbiology and source. The results were stratified to study year and evaluated by the extended Mantel–Haenszel chi square for linear trends.

Results

GNB were encountered in 4520/14314 (31.6%) positive blood culture (BC) accounting for 2811 BSI episodes (2291 patients) with a steadily increasing rate (table). The 3 most common organisms were Escherichia coli (EC; 44.4%), Klebsiella pneumoniae (KP; 19.2%) and Pseudomonas aeruginosa (PA; 9.6%). GNB-BSI rate increase was mainly in EC-BSI (P = 0.01). The rate of other GNB-BSI did not change. Source distribution of EC-BSI did not change and antibiotic resistance did not change.

Conclusion

GNB-BSI is rising, primarily due to EC, without changes in source distribution or antibiotic susceptibility. Prospective studies to look at EC lineage and virulence factors are needed to determine the reason for EC-BSI rise.

Disclosures

All authors: No reported disclosures.
2789. Respiratory Syncytial Disease in Hospitalized Adults: A Retrospective Cohort Study
Authors: Nam Hannah , Ison Michael G
Published: October 2019

Background

Respiratory syncytial virus (RSV) is associated with significant mortality rates amongst hematopoietic stem cell transplant (HSCT) and lung transplant recipients. Although RSV is responsible for ~177,000 hospitalizations and 14,000 deaths annually, few epidemiologic studies including all adults including those with immunocompromise have been conducted over multiple seasons.

Methods

A retrospective cohort study of adults admitted to a large academic medical center in Chicago, IL from 2009 to 2018 was conducted in patients with positive RSV PCR. Specific data on clinical presentation, management, and outcomes were collected by manual chart review. Descriptive statistics were calculated, and Pearson’s Chi-Squared test was utilized to assess association between severe disease status and comorbidities.

Results

A total of 140 patients* were admitted during part of the study period (2016–2018) with positive PCR for RSV. Most patients had otherwise underlying comorbidities prior to admission (lung 44.2%, heart 40.0%, diabetes 20.7%), history of immunocompromise (36.4%, 51) or history of smoking (39.2%, 55). Cough was the most common symptom among all hospitalized adults (90.7%, 127). However, patients with a history of transplant (both HSCT and SOT) more commonly displayed symptoms of fevers at presentation (50%, 10) when compared with non-immunocompromised patients (36.6%, 36). ICU admission occurred in one-third of the hospitalized patients, with no significant difference amongst transplant patients, immunocompromised patients, and non-immunocompromised patients. Need for mechanical ventilation was highest in patients with co-infections. None of the co-morbidities measured were independent risk factors for severe disease. Most patients (78.5%, 110) were discharged home. Among the 12 fatal cases, all were admitted to the ICU with seven (58.3%) requiring mechanical ventilation. Three (25.0%) were immunocompromised while two (16.7%) were HSCT patients, but none were solid-organ transplant patients.

*Ongoing data collection.

Conclusion

RSV patients were diverse in their demographics, treatment, and outcomes. Large percentages of patients had underlying comorbidities such as immunocompromise due to HSCT, lung and heart disease.

Disclosures

All authors: No reported disclosures.
2795. Clinical and Economic Impact of a Ribavirin Intervention Program in Hematopoietic Cell and Solid-organ Transplant Recipients with Respiratory Syncytial Virus Infection
Authors: Leonard Emily , Wrenn Rebekah , Saullo Jennifer , Drew Richard H , Drew Richard H , Sarubbi Christina
Published: October 2019

Background

While data are limited, oral ribavirin (RBV) has been shown to be a cost-effective alternative to aerosolized RBV for the treatment of respiratory syncytial virus (RSV) in immunocompromised patients with significant reductions in acquisition and administration costs. We evaluated the clinical and economic impact of an RBV intervention program at a large, academic medical center.

Methods

This single-center, retrospective cohort study evaluated hematopoietic cell and solid-organ transplant patients admitted to Duke University Hospital (DUH) with documented or suspected RSV receiving aerosolized and/or oral RBV from July 2013 to April 2018. The ID consult service approval requirement was initiated for aerosolized RBV beginning in October 2015. Education was done at this time to promote oral RBV as the preferred therapy for immunocompromised, RSV-infected adults and children. No restrictions or treatment protocols were in place prior to that time for either formulation. Clinical outcomes, adverse effects, and drug acquisition cost were collected. A cost-avoidance analysis was performed using DUH acquisition cost for actual and alternate RBV therapy.

Results

A total of 118 treatments (115 unique adult and pediatric patients) were included. Demographics were comparable between groups with and median age was 52 years in the Oral RBV and 61 years in the Aerosol RBV group. The predominant transplant type was lung (62.5% in Oral RBV and 55.6% in Aerosol RBV) followed by hematopoietic (16.7% in Oral RBV and 27% in Aerosol RBV). The median (range) duration of therapy was 4 (1–16) days for oral RBV and 5 (1–23) days for aerosolized RBV. The total cost avoidance was $2,522,915 with oral RBV. Clinical outcomes are summarized in Table 1.

Conclusion

In our large tertiary care center, the use of oral RBV led to substantial cost avoidance with clinical outcomes comparable to aerosolized RBV in immunocompromised patients. Larger prospective trials evaluating oral RBV for RSV treatment are warranted.

Disclosures

All authors: No reported disclosures.
2797. Rates of Respiratory Syncytial Virus (RSV) Infection among Hospitalized Adults by Congestive Heart Failure Status—United States, 2015–2017
Authors: Kujawski Stephanie A , Langley Gayle , Langley Gayle , Anderson Evan J , Thomas Ann , Bennett Nancy M , Lynfield Ruth , Monroe Maya , Pradhan Eva , Reingold Art , Talbot Keipp , Gerber Susan I , Kim Lindsay
Published: October 2019

Background

Respiratory syncytial virus (RSV) can cause severe disease in older adults and adults with cardiopulmonary conditions, such as congestive heart failure (CHF). RSV vaccines in development may target adults based on age or medical conditions. We assessed rates of RSV infection in hospitalized adults by CHF status using RSV surveillance conducted through the Centers for Disease Control and Prevention’s Emerging Infections Program, a population-based platform in the United States

Methods

RSV surveillance was performed during two seasons (2015–2017) from October 1–April 30 at seven US sites covering an annual catchment population up to 13.7 million adults. Adults (≥ 18 years) admitted to a hospital from the catchment area and with laboratory-confirmed RSV infections identified by clinician-directed testing were included. Demographic data and any history of CHF were abstracted from medical charts. For adults ≥ 65 years, county-level CHF prevalence was obtained from 2015 Centers for Medicare and Medicaid Services (CMS) data. To estimate county-level CHF prevalence for adults < 65 years, we used 2015–2016 National Health and Nutrition Examination Survey and CMS data. We calculated crude incidence rates (and 95% exact Poisson confidence intervals) of RSV by CHF status and age group (< 65 years vs. ≥ 65 years) using RSV cases (numerator) and catchment area county-level population estimates from the US Census (denominator).

Results

During 2015–2017, a total of 2,211 hospitalized RSV cases were identified; 2,055 (92.9%) had CHF status documented. The majority were ≥ 65 years (n = 1236, 60.1%) and 26.8% (n = 550) had CHF. The crude rate of RSV was 62.7 (95% CI: 57.5–68.2) per 100,000 population in adults with CHF compared with 6.1 (95% CI: 5.7–6.4) per 100,000 population in adults without CHF (rate ratio: 10.3, 95% CI: 9.3–11.3). In both age groups, those with CHF had higher rates of RSV than those without CHF. Rates were highest in adults ≥ 65 years with CHF (73.4 per 100,000 population, 95% CI: 66.4–80.9).

Conclusion

Using population-based surveillance, we found that adults with CHF had RSV hospitalization rates 10 times higher than those without CHF. Identifying high-risk populations for RSV infection are critical to inform clinical practice and future RSV vaccine policy.

Disclosures

All authors: No reported disclosures.