bluuebunny/crossref_metadata_2025_split huggingface dataset:
2624. Viral Pneumonia in Children: Facing the Challenge Using the Host Response
Authors: Mastboim Niv Samuel , Gottlieb Tanya , Srugo Isaac , Gervaix Alain , Paz Meital , Navon Roy , Boico Olga , Bamberger Ellen , Klein Adi , Stein Michal , Chistyakov Irina , Oved Kfir , Eden Eran , Shani Liran 
Published: October 2019

Abstract

Background
Diagnosing viral pneumonia in children is challenging. Chest radiographic imaging and clinical findings cannot reliably distinguish viral from bacterial pneumonia. Furthermore, pathogen-based diagnosis is limited by inaccessible site of infection and high asymptomatic detection rates. The objectives of this analysis were twofold: first, to establish pneumonia etiology by applying a rigorous expert panel process, and second, to evaluate whether a novel host-immune signature that integrates viral induced proteins TRAIL and IP-10 together with bacterial CRP, can accurately differentiate viral from bacterial pneumonia.

Methods
This analysis included 1025 febrile children enrolled in two multi-center clinical studies that evaluated the host-immune signature performance: ‘Curiosity’ study (Oved et al., PLoS One 2015) and ‘Pathfinder’ study (Srugo et al., Pediatrics 2017). Pneumonia etiology – viral or bacterial – was determined by a panel of 3 independent experts, after reviewing patients’ clinical, laboratory, microbiological, and radiological data. Only cases with majority panel assignment were included. The host-signature generated one of the three results: viral, equivocal or bacterial, based on predetermined cut-offs.

Results
A total of 709 children were eligible for analysis and had an expert panel etiology determination. Of them, 114 were diagnosed with pneumonia: 51 assigned viral and 63 assigned bacterial (Figure 1). The signature separated viral from bacterial pneumonia with a sensitivity of 94% (95% CI: 85%–99%) and specificity of 95% (85%–99%) with 14% equivocal test results. Out of the 51 children diagnosed with viral pneumonia by the expert panel, 40 (78%) were given antibiotics, and 43 (83%) underwent chest x-ray evaluation. The signature correctly classified 42 of these 51 viral children, indicating its potential to reduce antibiotic overuse rates by 4.4-fold (from 78% to 18%; P < 0.001) and chest x-ray examination by 4.8-fold (from 83% to 18%; P < 0.001).

Conclusion
The TRAIL/IP-10/CRP signature exhibits high accuracy for diagnosing viral pneumonia in children. The signature’s potential to safely decrease unnecessary antibiotics and chest radiographic imaging should be examined in future utility studies.

Disclosures
All authors: No reported disclosures.
2626. Rhinovirus in Children Presenting to the Emergency Department: Role of Viral Load in Disease Severity and Co-Infections
Authors: Waghmare Alpana , Strelitz Bonnie , Lacombe Kirsten , Perchetti Garrett , Nalla Arun , Rha Brian , Midgley Claire , Lively Joana Y , Klein Eileen J , Kuypers Jane , Englund Janet A 
Published: October 2019

Abstract

Background
Rhinovirus (RV) quantitation by reverse transcription-quantitative PCR is limited by variable amplification efficiency across genotypes. We used a precise viral quantitation method, reverse transcription-digital PCR (RT-dPCR), to characterize the role of viral load in clinical outcomes and in viral co-infections in children presenting to a tertiary hospital emergency department (ED).

Methods
Children < 18 years with respiratory symptoms for ≤ 14 days were enrolled from December 1, 2016 to December 31, 2018. Participants had nasal and throat specimens obtained and multiplex PCR testing with a commercial assay (FilmArray; bioMerieux). RV positive samples were quantified using RT-dPCR. Samples with sufficient viral load were sequenced at a 543 bp fragment of the RV VP4/VP2 region. RV species were assigned by comparison to RV sequences in GenBank using BLAST. Clinical data were collected into REDCap. T-tests were used to compare mean viral loads between groups.

Results
Of 1703 children enrolled in the ED, 697 were RV/enterovirus positive by FilmArray [median age 18 months (interquartile range 9–39 months)]. Of 590 subjects with viral load available, 276 (47%) were admitted to the hospital. Among RV mono-infections (N = 434), mean viral load did not differ between subjects admitted vs. discharged from the ED (7.03 log copies/mL for both, P = 0.97). Among admitted subjects with RV mono-infection, viral load also did not differ between subjects requiring supplemental oxygen vs. not (7.01 vs. 7.10 log copies/mL, P = 0.6). Subjects with viral co-infections had lower mean RV viral loads (6.31 log copies/mL) compared with those with RV only (7.03 log copies/mL; P < 0.001) (figure). Significantly different RV viral loads were seen with co-infections with respiratory syncytial virus (RSV), metapneumovirus (MPV) and parainfluenza (PIV), but not with influenza, adenovirus or coronavirus. In 525 sequenced samples (46% RV-A, 4% RV-B, 50% RV-C), viral load did not vary between RV viral species (P = 0.09).

Conclusion
Precise viral quantitation demonstrates children co-infected with RV and RSV, MPV or PIV have lower nasal viral loads than those with RV alone. Among RV mono-infections, RV viral load was not associated with admission or need for supplemental oxygen.

Disclosures
All authors: No reported disclosures.
2644. Evaluation of Clinical Course and Heath-Related Quality-of-Life Following Treatment with Oseltamivir, Laninamivir, and Baloxavir Marboxil in Adult Patients with Seasonal Influenza: Prospective Observational Study
Authors: Yoshino Yusuke , Misu Keita , Wakabayashi Yoshitaka , Ota Yasuo , Kitazawa Takatoshi 
Published: October 2019

Abstract

Background
Influenza is currently being treated in Japan with 4 types of neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir marboxil. Among these, baloxavir marboxil is the newest agent and currently available in limited countries, while the clinical efficacy of this drug in the real world remains to be determined.

Methods
Adult patients with seasonal influenza during the 2018–2019 winter season, who received either oseltamivir (75 mg twice daily for 5 days), laninamivir (40 mg once), or baloxavir marboxil (40 or 80 mg once) at their physician’s discretion in one hospital, were enrolled. The course of the symptoms including fever were surveyed by questionnaire. Health-related quality-of-life (HRQOL) was also examined by using Short Form-8 before and 7 days after admission. The main study endpoints were the time to defervescence and the extent of improvement of HRQOL after treatment initiation. Welch’s t-test and Fisher exact test were used for statistical analysis.

Results
Forty-two patients (oseltamivir group; n = 12, laninamivir group; n = 16, baloxavir group; n = 14) could be followed up. There were no significant differences in clinical backgrounds of all groups. Although there were no significant differences between the oseltamivir and each other groups with the time of defervescence, the average time to defervescence in the baloxavir group was shorter than that in the oseltamivir group (average ± standard deviation; 1.57 ± 0.76 vs. 2.33 ± 1.23 days, P = 0.0853). There were significant differences between the baloxavir and laninamivir groups (2.50 ± 1.26 days, P = 0.0231). There were no significant differences between each group with respect to the change of HRQOL and the time of clearing of other symptoms.

Conclusion
Regarding the antipyretic effect, baloxavir marboxil is clinically superior to laninamivir. Although there was no significant difference between the baloxavir group and the oseltamivir group with respect to the time to defervescence, baloxiavir marboxil also might be clinically superior to oseltamivir because baloxavir marboxil has an advantage over oseltamivir with respect to medication adherence.

Disclosures
All authors: No reported disclosures.
2656. Eliciting Preferences for Zoster Vaccination in US Adults Aged 50 Years and Older
Authors: Patterson Brandon J , Meyers Kelley , Stewart Alexandra , Mange Brennan , Hillson Eric M , Cyr Sonya , Poulos Christine 
Published: October 2019

Abstract

Background
In October 2017, the Centers for Disease Control and Prevention (CDC) recommended the adjuvanted Recombinant Zoster Vaccine (RZV) for all adults aged ≥ 50 years, regardless of previous vaccination. Understanding patient preferences for herpes zoster (HZ) vaccination can inform providers, payers, and policymakers about barriers, hesitancies, and utilization of available vaccines.

Methods
A discrete choice experiment survey was completed by 1,454 US adults aged ≥50 years in January 2019, with targeted sampling quotas of African Americans (25%), recent influenza vaccine recipients (50%), and individuals with autoimmune disease or chronic comorbidities (37%), to enable subgroup analyses. HZ vaccine profiles were characterized using seven attributes: vaccine efficacy (VE), duration of protection, location of service, number of doses, injection-site reaction severity, systemic reactions duration, and out-of-pocket (OOP) costs. In a series of choice questions, respondents chose between a pair of hypothetical HZ vaccine profiles, determined by an efficient experimental design, and a no vaccination option. In a second series, respondents stated intentions to complete a 2-dose vaccination series, conditioned on varying levels of side effects experienced with a first dose and expected OOP costs. Differences across subgroups were explored.

Results
Respondents placed the greatest weight on OOP costs and VE when choosing among HZ vaccination options (Figure 1). African American respondents were more sensitive to increases in OOP costs than non-African American respondents (Figure 2). ~75% of respondents indicated they would complete the series of a two-dose HZ vaccine if the cost of completing the series was $8-$13. Second-dose compliance drops about 25% when OOP costs increase to $140–150.

Conclusion
OOP cost had the greatest influence on respondents’ intention to select and complete HZ vaccination. Efforts to remove financial barriers to improve implementation of the CDC recommendations for HZ vaccination should be considered.
GlaxoSmithKline Biologicals SA, GSK study identifiers: 208677/HO-17-18066.

Disclosures
All authors: No reported disclosures.
2660. Infection Complications Following Mismatched Allogeneic Hematopoietic Cell Transplantation
Authors: Ebisu Yosuke , Natori Yoichiro , Jimenez Antonio , Alencar Maritza C , Morris Michele , Komanduri Krishna V , Camargo Jose F 
Published: October 2019

Abstract

Background
The use of haploidentitical or HLA mismatched unrelated donors permits allogeneic hematopoietic cell transplantation (HCT) in individuals with otherwise no donors available. Post-transplantcyclophosphamide(PTCy) is used for prevention graft-vs.-host disease (GVHD) in recipients of mismatched donors. We hypothesized that type and incidence of infectious complications following allogeneic HCT would vary according to the type of transplant.

Methods
We systematically assessed viral kinetics and reactivation rates for cytomegalovirus (CMV) in a prospective cohort of mismatched unrelated donor (MMUD) HCT recipients who had PTCy at our center (April 2017–March 2019). In addition, we evaluated the incidence of invasive aspergillosis (IA), invasive candidiasis (IC), bloodstream infection (BSI), pneumonia, Clostridium difficile (CDI), and community-acquired respiratory virus. Haploidentical donor and anti-thymocyte globulin (ATG) treated MMUD recipients were served as historical control groups.

Results
A total of 81 patients were analyzed in 3 groups (Table 1): PTCy MMUD (group 1; n = 22), ATG MMUD (group 2; n = 40) and haploidentical (group 3; n = 19). Whereas the 1 year incidence of CMV viremia was similar across groups, the rate of clinically significant (requiring preemptive therapy) CMV viremia was lower in group 1, compared with groups 2 and 3 (18 vs 53%; P = 0.02). The 1 year incidence of CDI was 47% in group 3 vs. 18% in groups 1 and 2 (P = 0.01). There was no significant difference in the incidence of IA (5–18%), pneumonia (30–42%), BSI (32–55%) and CARVs (28–53%) between groups. There were no cases of IC in this cohort. 1 year infection attributable mortality was lower in group 1 (figure), compared with groups 2 and 3, (9%, 62% and 39%, respectively; P = 0.005).

Conclusion
Compared with ATG MMUD and haploidentical donor, PTCy MMUD HCT was associated with lower incidence of clinically significant CMV and lower infection attributable mortality. These findings might be related to the contemporary prophylactic strategies used in this patient population. Larger studies are needed.

Disclosures
All authors: No reported disclosures.
2687. Extended Infusions of Piperacillin/Tazobactam vs. Cefepime for Empiric Treatment of Neutropenic Fever
Authors: Norman Sarah , Henshaw Laura , Reeves David , Moore Sarah , Cheatham S Christian 
Published: October 2019

Abstract

Background
In neutropenic patients, a fever may be the only indication of a severe underlying infection. According to the National Comprehensive Cancer Network (NCCN) guidelines, for high-risk patients, monotherapy with an anti-pseudomonal β-lactam agent should be initiated. NCCN states emerging data may support extended or continuous infusions of β-lactam therapies; however, preference is not given for cefepime or piperacillin/tazobactam. The objective of this study was to compare the outcomes of extended infusions of piperacillin/tazobactam vs. cefepime for the empiric treatment of neutropenic fever.

Methods
This retrospective, single-center cohort study included patients ≥18 years with an absolute neutrophil count (ANC) less than 500 cells/mm3, single oral temperature measurement ≥38.3°C or ≥38°C sustained over 1 hour period and admitted to a bone marrow transplant unit. Patients received extended infusion piperacillin/tazobactam or cefepime as initial antibiotic therapy for at least 48 hours between January 1, 2015 and September 1, 2018. The primary outcome was time to defervescence in hours. Secondary outcomes included time to defervescence and no acetaminophen use within 8 hours, defervescence by 72 hours, hospital length of stay, clinical failure, in-hospital mortality, and acute kidney injury.

Results
73 patients were included in this study (36 received piperacillin/tazobactam and 37 received cefepime). The primary outcome of median time to defervescence was 31.8 hours in the piperacillin/tazobactam group and 25 hours in the cefepime group (P = 0.26). Secondary outcomes in the piperacillin/tazobactam group compared with cefepime, respectively included median time to defervescence and no acetaminophen use: 43 vs. 35 hours (P = 0.16), defervescence by 72 hours: 66.7% vs. 91.9% (P = 0.01), median hospital length of stay 28 vs. 22 days (P = 0.04), clinical failure 22.2% vs. 24.3% (P = 0.83), in-hospital mortality 8.3% vs. 2.8% (P = 0.36), rate of acute kidney injury: 50% vs. 24.3% (P = 0.02).

Conclusion
These findings suggest there is no difference in time to defervescence between extended infusions of piperacillin/tazobactam compared with extended infusions of cefepime for the empiric treatment of neutropenic fever.

Disclosures
All authors: No reported disclosures.
162. Identifying Determinants of Therapeutic Switch to Linezolid among Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Infections
Authors: Nair Rajeshwari , Schweizer Marin L , Perencevich Eli N , Livorsi Daniel J , Goto Michihiko , Alexander Bruce , Beck Brice , Richardson Kelly , Puig-Asensio Mireia 
Published: October 2019

Abstract

Background
In order to target future randomized controlled trials (RCT) of treatment of methicillin-resistant S aureus bloodstream infections (MRSA BSI), it will be important to understand the drivers of antibiotic selection. We aimed to determine factors associated with switching from vancomycin to inpatient linezolid administration during the management of MRSA BSI.

Methods
This retrospective cohort included all patients admitted to Veteran Affairs hospitals from 2007 to 2014 and had received vancomycin for MRSA BSI. Patients were considered to have switched to linezolid from vancomycin if they received at least 2 consecutive days of inpatient treatment and were not on concurrent vancomycin treatment. Cox proportional hazards models were used to identify factors that were associated with switch within 14 days and 30 days. Median with interquartile range (IQR), hazard ratio (HR) and 95% confidence intervals were reported.

Results
Among 7289 patients diagnosed with MRSA BSI during their index admission, 474 (6.5%) switched to linezolid during the admission. The median inpatient duration of vancomycin treatment among all patients was 13 days (IQR: 5–34) and among patients who switched was 16 days (IQR: 6–52). The median inpatient duration of linezolid treatment was 5 days (IQR: 1–13 days). Patients who switched to linezolid were more likely to have a MRSA isolate with MIC >=2 µg/mL (6.8% vs. 4.9%), diagnosis of respiratory tract infection (36.7% vs. 32.9%), or be obese (16.5% vs. 13.6%) than those who continued on vancomycin (P < 0.10). In risk-adjustment models, presence of a respiratory tract infection diagnosis was associated with greater likelihood of being switched to linezolid within 14- and 30-days (HR=1.29, 95% CI 1.01–1.64; HR=1.32, 95% CI 1.06–1.65).

Conclusion
Less than 10% of patients initially treated with vancomycin for MRSA BSI were switched to linezolid in this real-world study. A diagnosis of respiratory tract infection was a major determinant of switching to linezolid. It is important to identify potential subsets of MRSA BSI patients so that future comparative effectiveness RCTs can be targeted to indications with clinical equipoise in real-world practice settings.

Disclosures
All authors: No reported disclosures.
2698. Timing of Standalone Vaccine Administration in Infants Receiving DTaP-Based Combination Vaccines
Authors: Alemayehu Berhanu , Wolfson Lara J , Chen Ya-Ting , Liu Zhiwen , Goveia Michelle , Johnson David , Marshall Gary S 
Published: October 2019

Abstract

Background
The recommended US infant immunization schedule includes doses of DTaP, IPV, Hib and HepB during the first 6 months of life. The majority of infants receive DTaP as one of the two pentavalent combination vaccines (DTaP-IPV/Hib or DTaP-HepB-IPV); standalone HepB or Hib are used to complement these combinations in compliance with the recommendations. Little is known about the timing of standalone vaccine administration in relation to DTaP-based combination vaccines.

Methods
This was a retrospective observational cohort study using the US MarketScan commercial claims and encounters database. Infants included in the study were continuously enrolled in the same insurance plan for ≥13 months after birth, born from 1 July 2010 through 30 June 2016, and had received ≥3 doses of a pentavalent vaccine. Outcomes included the proportion of infants receiving concomitant pentavalent and standalone vaccines, and the deviation in days when these vaccines were not administered on the same date. Birth doses of HepB were not registered in the database but were presumed to have been received; therefore, the first registered HepB claim was considered to be HepB Dose-2, and the second claim was presumed to be HepB Dose-3.

Results
Among infants who received DTaP-IPV/Hib (n = 175,574), 94.8% had claims for ≥3 doses of HepB. Although coverage was high, only 60.7% received HepB Dose-2 on the same day as DTaP-IPV/Hib Dose-1 (around 2 months of age), and only 45.1% received HepB Dose-3 on the same day as DTaP-IPV/Hib Dose-3 (around 6 months of age) (Figure 1). Many infants (46.2%) received HepB Dose-3 after the third dose of DTaP-IPV/Hib. Among infants who received DTaP-HepB-IPV (n = 97,206), 89.9% had claims for the recommended number of Hib doses; most (91% to 98%) of these doses were administered on the same day as doses of DTaP-HepB-IPV (Figure 2).

Conclusion
There was variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. A newly licensed hexavalent vaccine, DTaP-IPV-Hib-HepB, could synchronize and simplify the HepB administration schedule ensuring that more infants have completed the series by 6 months of age.

Disclosures
All authors: No reported disclosures.
2707. Non 13-Valent Pneumococcal Conjugate Vaccine Serotypes Predominate as Causes of Pneumococcal Otitis Media in Children
Authors: Hulten Kristina G , Barson William J , Lin P Ling , Bradley John S , Peters Timothy R , Tan Tina Q , Romero Jose R , Pannaraj Pia S , Kaplan Sheldon L 
Published: October 2019

Abstract

Background
Pneumococcal acute otitis media (AOM) in children due to vaccine-related serotypes (ST) has declined after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), although some serotypes, such has 3, 19A and 19F have persisted. Among non-vaccine serotypes, 35B has been shown to contribute substantially to both OM and invasive infections. This study describes the current epidemiology of pneumococcal OM isolates obtained from the U S Pediatric Multicenter Pneumococcal Surveillance Group (USPMPSG).

Methods
From the USPMPSG database, we collected data from patients <18 years of age with pneumococcal OM isolates from 2014 to 2018. Analysis included demographics, immunization status, antimicrobial susceptibility data and serotype. Statistical comparisons included Fisher’s exact and Wilcoxon rank-sum tests.

Results
A total of 494 patients with isolates were identified within the time period from 5 children’s hospitals. Median age was 1.7 years (range 0–17.6) and 299 (60.5%) were male; 176 (35.7%) had an underlying condition. Thirty-two patients had received no dose of either PCV7 or PCV13. Thirty-five serotypes were identified (3 isolates were non-typeable), of which 6 serotypes [35B (16.8%), 3 (9.5%), 15A (7.9%), 15B (7.9%), 23B (7.9%) and 21 (6.1%)] caused more than half of the total OM infections (figure). Ninety (18.2%) isolates were of PCV13 serotypes. Twenty-five of 476 (5.3%) isolates had a penicillin MIC>2 µg/mL. These were of serotypes 11A, 15A/C, 19A/F, 35B and NT; 10/455 (2.2%) isolates had ceftriaxone MIC>1 µg/mL and were of ST 3, 15A, 19A/F and 35B.

Conclusion
Most pneumococcal OM were caused by non-PCV13 serotypes. Serotype 35B remained the most common serotype among pneumococcal isolates recovered from ear drainage or middle ear cultures. The low proportion of penicillin-resistant isolates along with the increasing proportion of AOM cases being due to non-pneumococcal isolates supports the consideration to switch routine antibiotic treatment for AOM to standard dose amoxicillin-clavulanate from high dose amoxicillin in PCV13 immunized children (Pediatr Infect Dis J 2018;37:1255–1257).

Disclosures
All authors: No reported disclosures.