bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multidisciplinary Study of the Use and Outcomes Associated with Expanded Respiratory Viral Studies at a Mid-Sized Children’s Hospital
Authors: Zhu Chelsea , Sidiki Sabeen , Grider Brittany , Fink Brian , Hubbard Nicole , Mukundan Deepa 
Published: October 2017

Abstract

Background
Acute respiratory infection (ARI) is a leading cause of pediatric hospitalizations in the US and are generally caused by viruses, thus antibiotics are prescribed more often than needed. Identifying viral agents using the respiratory pathogen panel (RPP) can help with judicious use of antibiotics in hospitalized patients. ProMedica Toledo Children’s Hospital, a mid-sized pediatric hospital, began offering the RPP to patients in Dec 2014. This study was conducted to assess if the use of RPP would decrease the antibiotic days of therapy (DOT) and length of hospital stay for patients admitted for uncomplicated ARI and for those seen in the ED.

Methods
This was a retrospective analysis of pediatric hospital inpatient and ED data collected between December 16, 2013 and December 15, 2015. Patients before and after implementation of the RPP were compared. 299 and 263 pediatric patients between 1 month to 18 years of age with uncomplicated ARIs in the pre-RPP and post-RPP periods, respectively, were included for analysis. Similarly, 472 and 461 patients were included from the ED. Clinical data were collected by chart review. Analysis was performed using descriptive and inferential statistics.

Results
Out of 299 admitted patients in the post-RPP period, 63 (21.1%) patients did not receive the RPP (RPP-NT). 201 (67.2%) received it and tested positive (RPP-P), and 35 (11.7%) patients tested negative (RPP-N). RPP-N had an increased length of hospital stay (P = 0.055, borderline significance) and increased number of antibiotic DOT (P = 0.032) than RPP-P. Furthermore, we discovered that older patients (mean = 6.21 years) tested negative with RPP, while younger patients either did not receive the test (mean = 2.43 years) or tested positive (mean = 2.40 years). In the ED, RPP-P received fewer discharge prescriptions for antibiotics than RPP-N and RPP-NT (P &lt; 0.01). The use of RPP was more prevalent in admitted patients than in ED patients (P = 0.01).

Conclusion
Our results suggest that the use of RPP effectively curbs unnecessary antibiotic use for pediatric patients with viral ARIs. Furthermore, age discrepancies among RPP-P, RPP-N, and RPP-NT warrant further study. Lastly, the results suggest that use of RPP in ED should be encouraged.

Disclosures
C. Zhu, IDSA Foundations Medical Scholars Program 2015–2016: Member, Educational scholarship.
A Mid-Turbinate Swab Appears Comparable to Nasopharyngeal Swabs for Quantitative Detection of RSV in Infants
Authors: Blaschke Anne J , Mckevitt Matthew , Ampofo Krow , Lewis Tammi , Chai Hao , Guo Ying , Dorsch Julianna , Vanderhoof Erin , Rosen Pricilla , Freimann Volker , Korgenski E Kent , Toback Seth , Chien Jason 
Published: October 2017

Abstract

Background
Respiratory Syncytial Virus (RSV) is the most common cause of bronchiolitis and pneumonia in infants and children. Diagnosis of RSV can be made by molecular detection of the virus in a swab of respiratory secretions. Nasopharyngeal (NP) swabs are the most frequent swab type validated for the detection of RSV, and are often considered the “gold standard” for quantification studies. However, NP sampling is invasive and uncomfortable. We sought to determine whether a less invasive method, a mid-turbinate (MT) swab, was comparable to NP sampling for quantification of RSV in infants.

Methods
We prospectively enrolled children &lt; 24 months with a confirmed diagnosis of RSV and hospitalized at Primary Children’s Hospital (Salt Lake City, UT) during the 2015 – 2017 RSV seasons. Both an NP and MT swab were collected from each infant from different nostrils; subjects were randomized (1:1:1:1) as to the order of collection. After collection, parents were asked which collection method (NP vs. MT) they preferred. Viral loads were measured by real-time RT-qPCR. Correlation between the viral loads from the MT and NP swabs was examined. A mixed effect model was used to evaluate the mean (SD) viral loads.

Results
83 infants were enrolled and had swabs collected. Median age was 4 months [range 0–23]. 20 infants had swabs collected on multiple consecutive days. Median (Q1,Q3) duration of symptoms prior to enrollment was 5 days (4,7) Median (Q1,Q3) hospital stay length was 2 days (2,4). 1 infant was RSV negative according to the RT-qPCR assay. The mean (SD) viral loads were similar: 7.34 (1.26) and 7.09 (1.25) log10 copies/mL for 77 paired NP and MT swabs, respectively; see Figure 1 for median, range and quartiles. The correlation coefficient between the paired viral loads was high (0.82); see Figure 2 for Bland-Altman plot. Most parents (49/67 [73%]) who watched the swabbing preferred the MT to the NP swab.

Conclusion
MT swabs perform as well as NP swabs for the quantification of RSV in infants. The difference in mean viral load is small compared with the standard deviation. The less invasive MT swabs are preferred by parents for sampling. MT swabs have the potential to replace the NP swab as the “gold standard” for quantitative respiratory viral sampling.

Disclosures
A. J. Blaschke, Gilead Sciences, Inc: Investigator, Research support BioFire Diagnostics, LLC: Collaborator, I have intellectual property in BioFire Diagnostics through the University of Utah and Investigator, Licensing agreement or royalty and Research support
Quality Assessment of Cytomegalovirus PCR Testing at an Academic Tertiary Referral Hospital
Authors: Bluen Benjamin , Gancher Elizabeth , Epstein Shara , Krevolin Kyle , Lee Dong Heun 
Published: October 2017

Abstract

Background
Cytomegalovirus (CMV) Polymerase chain reaction (PCR) test is a valuable tool for diagnosis and therapeutic monitoring of CMV infection. Academic medical centers with a high volume of organ transplant and immunosuppressed patients often utilize CMV quantitative and qualitative PCR testing. CMV qualitative PCR typically does not alter clinical management, and positive CMV qualitative test often needs follow up quantitative test. Despite its lack of usefulness, CMV qualitative PCR is often over-ordered and may unnecessarily raise the cost of hospitalization. We evaluated utility of CMV PCR testing at a tertiary care medical center.

Methods
We reviewed CMV PCR testing done from June 2015-November 2016 at Hahnemann University Hospital in Philadelphia, PA. CMV qualitative test was performed at LabCorp and CMV quantitative test was done at Focus Labs. Data collected included demographics, length of stay, and immunosuppression. Selected patients had either CMV qualitative PCR positive without follow up quantitative PCR, or negative CMV qualitative PCR with unnecessary CMV quantitative PCR ordered.

Results
We evaluated 226 CMV PCR test results including 162 qualitative and 64 quantitative CMV PCR in 139 patients. 39 (28%) patients had superfluous CMV testing. Mean age was 52.6 years, 61% were male, 46% were African American. Mean length of stay was 24 days. A half (N = 19,49%) were immunocompromised. 28 (17.2%) results were positive for CMV qualitative PCR, 7 (25%) of whom follow up CMV quantitative PCR were not sent. Thirty-two patients had negative CMV qualitative testing yet had CMV quantitative PCR sent. Six had redundant CMV quantitative PCR tests within 7 days likely resulting from delayed result report from send out. After performing cost analysis, these unnecessary tests would have saved $3930.

Conclusion
In our cohort, significant unnecessary CMV testing resulted in increased health care cost and patient discomfort. Positive Qualitative CMV PCR without Quantitative testing impairs diagnosis and treatment follow up. Given complicated testing algorithm and limited value of CMV qualitative PCR testing in the adult population, we plan to simplify CMV testing to quantitative only and perform in house testing to shorten result time.

Disclosures
All authors: No reported disclosures.
Molecular Epidemiological Investigation of Human Parainfluenza 3 Virus Outbreak in a Pediatric Bone Marrow Transplantation Unit
Authors: Stapleton Patrick , Perusini Stephen , Thomas Angela , Science Michelle , Schechter-Finkelstein Tal , Gubbay Jonathan B , Patel Samir , Yau Yvonne 
Published: October 2017

Abstract

Background
Human parainfluenza virus 3 (hPIV3), a common cause of respiratory infections in children, can cause nosocomial outbreaks in patients undergoing hematopoietic stem cell transplantation, resulting in significant morbidity and mortality. Between July and August 2016, an increased number of hPIV3 infections were noted in a pediatric bone marrow transplant unit (BMT). Two patients were identified in late July and 4 patients in August. We undertook molecular typing of hPIV3 to determine whether cases represented multiple introductions of community virus strains or patient to patient transmission of a single strain. Previous reports of molecular typing have targeted either the F (fusion protein) gene or HN (hemagglutinin-neuraminidase) gene. We compared results using both methods direct from clinical specimens.

Methods
Nasopharyngeal (NP) swabs from 6 patients in BMT ward and 6 patients hospitalized on other wards had hPIV3 detected by the Luminex NxTAG Respiratory Pathogen Panel over 2 months. For the F gene a single pair of primers were used to first amplify then sequence a 278 basepair (bp) region by reverse-transcriptase PCR (RT-PCR). For HN gene a 1719 bp region was amplified using nested RT-PCR, then sequenced with 6 sets of overlapping primers. The resulting contigs were assembled manually with ContigExpress. Phylogenetic analysis of assembled sequences was performed in MEGA7 using the maximum likelihood method.

Results
For the HN gene sequence of 1715 bp was obtained for 10 of 12 patients (5 in each group). Phylogenetic analysis of HN sequences indicated 2 distinct hPIV3 lineages (Figure 1). The 5 BMT patients differed by a maximum of 1bp, while 5 samples from other wards differed by 14 to 57 bp. For the F gene only 98 bp of common sequence was obtained for 7 patients, all of whom had HN gene sequences available. Phylogenetic analysis of F gene sequence also supported the presence of 2 distinct lineages.

Conclusion
Molecular typing of hPIV3 suggests there was transmission of a single hPIV3 strain within the BMT unit despite protective isolation of all BMT patients in positive pressure single rooms and the use of contact and droplet precautions for infected cases. We found sequencing the HN gene more informative than sequencing the F gene.

Disclosures
All authors: No reported disclosures.
Meterology-driven Prediction of RSV/RHV Incidence in Rural Nepal
Authors: Scott Anna , Englund Janet , Chu Helen , Tielsch James , Tielsch James , Khatry Subarna , Leclerq Steven C , Shrestha Laxman , Kuypers Jane , Steinhoff Mark C , Katz Joanne 
Published: October 2017

Abstract

Background
Incidence of respiratory syncytial virus (RSV) and rhinovirus (RHV) varies throughout the year. We aim to quantify the relationship between weather variables (temperature, humidity, precipitation, and aerosol concentration) and disease incidence in order to quantify how outbreaks of RSV and RHV are related to seasonal or sub-seasonal meteorology, and if these relationships can predict viral outbreaks of RSV and RHV.

Methods
Health data were collected in a community-based, prospective randomized trial of maternal influenza immunization of pregnant women and their infants conducted in rural Nepal from 2011–2014. Adult illness episodes were defined as fever plus cough, sore throat, runny nose, and/or myalgia, with infant illness defined similarly but without fever requirement. Cases were identified through longitudinal household-based weekly surveillance. Temperature, humidity, precipitation, and fine particulate matter (PM 2.5) data come from reanalysis data products NCEP, Era-Interim, and Merra-2, which are produced by assimilating historical in-situ and satellite-based observations into a weather model.

Results
RSV exhibits a relationship with temperature after removing the seasonal cycle (r = -0.16, N = 208, P = 0.02), and RHV exhibits a strong relationship to daily temperature (r =-0.14, N =208, P = 0.05). When lagging meteorology by up to 15 weeks, correlations with disease count and weather improve (RSV: r_max = 0.45, P &lt; 0.05; RHV: r_max = 0.15, P = 0.05). We use an SIR model forced by lagged meteorological variables to predict RSV and RHV, suggesting that disease burden can be predicted at lead times of weeks to months.

Conclusion
Meteorological variables are associated with RSV and RHV incidence in rural Nepal and can be used to drive predictive models with a lead time of several months.

Disclosures
J. Englund, Gilead: Consultant and Investigator, Research support Chimerix: Investigator, Research support Alios: Investigator, Research support Novavax: Investigator, Research support MedImmune: Investigator, Research support GlaxoSmithKline: Investigator, Research support
The Global Burden of Rotavirus Diarrheal Diseases: Results from the Global Burden of Diseases Study 2016
Authors: Khalil Ibrahim Abdel-Messih 
Published: October 2017

Abstract

Background
More than 1,300,000 deaths were attributable to diarrhea in 2015, with more than 400,000 of these deaths from children under 5 years of age. The Global Burden of Disease Study 2016 (GBD2016), an ongoing effort to measure global epidemiological trends, estimates diarrhea disease burden and the burden attributable to rotavirus and other enteric pathogens.

Methods
Diarrhea deaths are estimated using a suite of prediction models for all ages, both sexes, and for all countries and some subnational geographic areas from 1980 to 2016 using an ensemble modeling tool called CODEm. To estimate the burden of rotavirus, we calculated a population attributable fraction using a counter-factual approach by modeling the proportion of diarrheal cases that are positive for rotavirus and applying odds ratios describing the odds of diarrhea given rotavirus detection.

Results
In 2016, rotavirus was the leading cause of diarrhea mortality in children under 5 years old, responsible for 29.5% of diarrhea deaths in this age group (149,200 deaths, 95% Uncertainty Interval (UI): 119,200–189,400), and responsible for 15.3% of diarrhea deaths among all ages (202,300 deaths, 95% UI: 165,800–246,400). The population attributable fraction of diarrhea mortality due to rotavirus is generally stable across geographic regions. The global attributable fraction of rotavirus decreased by 24.2% (95% UI: 16.7–31.6%) between 2005 and 2016

Conclusion
The global deaths attributable to rotavirus in children under 5 is substantial and the burden in older children and adults may be unrecognized. GBD 2016 estimates describe epidemiological trends for rotavirus diarrhea and will inform evidence-based Public Health policy, to reduce the global burden of rotavirus. Our findings call for acceleration of delivery existing rotavirus vaccines and development of more affordable options for Low and Middle Income countries.

Disclosures
All authors: No reported disclosures.
Activity of the Novel Extended-spectrum β-Lactamase Inhibitor AAI101 in Combination with Cefepime Towards a Challenge Panel of Acinetobacter baumannii
Authors: Morrissey Ian , Magnet Sophie , Hawser Stephen , Shapiro Stuart , Seifert Harald , Higgins Paul 
Published: October 2017

Abstract

Background
AAI101 is a novel extended-spectrum β-lactamase inhibitor (BLI), active against ESBLs and a broad array of other BLs. AAI101 in combination with cefepime (FEP) is in Phase 2 development. Infections caused by A. baumannii, a pathogen endemic to the southern US and other global regions, are very challenging to treat, and often require combination therapy. This study examined the activity of FEP/AAI101 against a challenge set of A. baumannii clinical isolates enriched with OXA carbapenemase producers.

Methods
BLs in A. baumannii were identified by genotyping. Broth microdilution MICs and susceptibilities were obtained following CLSI methods and breakpoints (BPs), except for ceftazidime-avibactam (CAZ/AVI) where FDA P. aeruginosa BPs were used. CLSI FEP BPs were used for FEP/AAI101.

Results
All OXA-51 producers had the ISAba1 promoter. MIC90 data and % susceptibilities (%S) for FEP/AAI101 and comparators are shown in the Table: FEP/AAI101 was highly active against meropenem-susceptible (MPMs) isolates. FEP/AAI101 (AAI101 fixed at 8 µg/ml) covered 67% of OXA-51 and 53% of OXA-58 strains. Lower susceptibilities were obtained for OXA-23 and OXA-24/40 producers. FEP/AAI101 was the most active β-lactam product. Colistin (COL) was the only agent with consistently high activity against all A. baumannii isolates.

Conclusion
FEP/AAI101 was the most potent β-lactam product tested against clinical isolates of A. baumannii producing OXA-51 and OXA-58 β-lactamases. Infections by this difficult pathogen often require combination therapy, of which FEP-AAI101 may be a component.

Disclosures
S. Shapiro, Allecra: Employee, Salary
Ceftobiprole Activity When Tested Against Contemporary Bacteria Causing Bloodstream Infections in the US (2016)
Authors: Flamm Robert K , Duncan Leonard R , Shortridge Dee , Smart Jennifer I , Hamed Kamal , Mendes Rodrigo E , Sader Helio S 
Published: October 2017

Abstract

Background
Ceftobiprole medocaril (prodrug of ceftobiprole) is an advanced cephalosporin, approved for adults in multiple European countries for the treatment of hospital-acquired pneumonia (excluding ventilator-associated pneumonia) or community-acquired pneumonia. It is not approved in the US; however, it has achieved qualified infectious disease product status and two phase 3 studies supported by BARDA are planned to begin in the US in 2017.

Methods
A total of 2,787 Gram-positive (GP) and -negative (GN) isolates from bloodstream infections (BSI) from 30 medical centers in the SENTRY Antimicrobial Surveillance Program were evaluated. Isolates were collected in the US during 2016. Susceptibility (S) testing was performed by reference broth microdilution method against ceftobiprole and comparators. Isolates included 693 Staphylococcus aureus (SA), 216 coagulase-negative staphylococci (CoNS), 244 enterococci, 63 Streptococcus pneumoniae (SPN), 74 viridans group streptococci (VGS), 138 β-haemolytic streptococci (BHS), 1,105 Enterobacteriaceae (ENT), 129 Pseudomonas aeruginosa (PSA), 41 Acinetobacter spp. (ASP), 30 Stenotrophomonas maltophila, 19 Haemophilus spp. and 35 miscellaneous bacteria.

Results
Methicillin-resistant S. aureus (MRSA) S rates were lower than for methicillin-susceptible S. aureus (MSSA) for most agents. For levofloxacin (LEV) and erythromycin (ERY), the S rates were LEV: MRSA, 23.2%; MSSA, 86.1%; ERY: MRSA, 9.0%; MSSA, 69.3%. All MSSA and 99.0% of MRSA were S to ceftobiprole, while all MSSA and 96.5% of MRSA were S to ceftaroline (CPT). For CoNS, 98.1% of ceftobiprole MIC values were ≤2mg/L. Ceftobiprole was active against Enterococcus faecalis (96.1% ≤2mg/L) and not against E. faecium (18.9% ≤2mg/L). Against ENT, ceftobiprole (85.0%S) was similar in activity to ceftazidime (CAZ, 87.2%S) and cefepime (FEP, 88.9%S). The MIC50/90 values for ceftobiprole, FEP, and CAZ against PSA were identical at 2/16 mg/L.

Conclusion
Ceftobiprole exhibited potent in vitro activity against GP and GN isolates from contemporary BSI in the US. These results support further clinical evaluation of ceftobiprole for the treatment of BSI.

Disclosures
R. K. Flamm, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; L. R. Duncan, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; D. Shortridge, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; J. I. Smart, Basilea Pharmaceutica International Ltd.: Employee, Salary; K. Hamed, Basilea Pharmaceutica International Ltd.: Employee, Salary; R. E. Mendes, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; H. S. Sader, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant
Activity of Antistaphylococcal Lysin CF-301 against Contemporary Staphylococcus aureus Clinical Isolates from the USA and Europe
Authors: Oh Jun , Traczewski Maria , Schuch Raymond 
Published: October 2017

Abstract

Background
CF-301 is a novel, recombinantly-produced bacteriophage-derived lysin (cell wall hydrolase) and is the first agent of this class in the US to enter into clinical development for the treatment of bacteremia including endocarditis due to S. aureus. Hallmark features of CF-301 include rapid and pathogen-specific bacteriolytic activity, synergy with antibiotics, biofilm-disrupting activity, a low propensity for resistance, and the capacity to suppress antibiotic resistance. This is the first report of an international surveillance study for CF-301.

Methods
349 methicillin-sensitive and –resistant S. aureus (MSSA and MRSA, respectively) isolates were collected from various infection sources at multiple hospitals from 2015–2017 throughout the US, Greece, Hungary and Italy. In addition to the contemporary isolates, a set of 149 MSSA and MRSA clinical isolates from 2011 were also obtained from US hospital sources. MICs for CF-301 were determined using a new antimicrobial susceptibility testing (AST) medium for broth microdilution recently endorsed by Clinical and Laboratory Standards Institute (CLSI) for use with CF-301. The testing medium consists of cation-adjusted Muller Hinton Broth supplemented with 25% horse serum and 0.5 mM DTT (CAMHB-HSD). Susceptibility to conventional antibiotics was also examined in this study using standard methodology (CLSI document M07-A10) and included: vancomycin, trimethoprim-sulfamethoxazole, daptomycin, oxacillin, linezolid, clindamycin, and cefazolin.

Results
CF-301 had MIC50, MIC90, and MIC100 values of 0.5, 1, and 2 μg/mL, respectively, against each set of contemporary MSSA (n = 176) and MRSA (n = 173) clinical isolates. There were no differences noted with respect to the geographic source (in the US and Europe) of isolates. Furthermore, the CF-301 MICs reported here for 2015–2017 isolates were identical to that observed for MSSA and MRSA isolates from 2011.

Conclusion
CF-301 demonstrated potent in vitro activity against a total of 498 clinical S. aureus isolates from a range of human infections (including bacteremia) and different geographies. Contemporary clinical isolates did not demonstrate reduced susceptibility to CF-301 compared with the 2011 isolates.

Disclosures
J. Oh, ContraFect Corp: Employee, Salary; R. Schuch, ContraFect Corp: Employee, Salary