bluuebunny/crossref_metadata_2025_split huggingface dataset:
687. Modeling the Impact of Introduction of Influenza Vaccination on ILI Cumulative Case Count in Cameroon
Authors: Tamoufe Ubald , Ortiz Nancy , Saylors Karen , LeBreton Matt , Meguia Viviane , Djoko Cyrille , Njouom Richard 
Published: November 2018

Abstract

Background
Influenza illness can range from mild to severe, with serious outcomes occurring in children and the elderly. Flu has been studied extensively in geographies where vaccine is often plentiful. The burden of influenza is not well known in tropical regions where vaccine coverage is scant. Our study examines the impact of introducing flu vaccination on cumulative incidence in a Cameroonian population with &lt;0.2% influenza vaccine utilization

Methods
The data consists of 1 year of flu surveillance from patients presenting with influenza-like-illness at clinics in Cameroon. Samples underwent RT-PCR influenza screening. Analysis was performed in Berkeley Madonna. We developed ordinary differential equations (ODE)s under the SEIR compartmental model and calculated R0. We estimated the proportion of cases the clinics observed to make inferences to the catchment population of these health facilities. We developed another set of ODEs to introduce vaccination using a pulse function with a 50% efficacy and 45% vaccination coverage.

Results
We observed 82.9% reduction in flu cases by introducing vaccination at 45% coverage (US average). Cameroon would likely achieve reduced coverage. Therefore, we examined introducing vaccination with 10% coverage, and observed that flu cases were cut by over one third.

Conclusion
This analysis demonstrates that introducing vaccination in Cameroon clinics would reduce influenza cases substantially even with only a small proportion of the population vaccinated. Flu vaccination campaigns should be strongly considered as they can reduce case count which may reduce the likelihood of transmitting flu to those who are at risk the most severe outcomes.

Disclosures
All authors: No reported disclosures.
690. Bacterial Coinfections Among Adults Hospitalized with Community-Associated Influenza, 2016–2017
Authors: Kraushaar Vit , Kirley Pam Daily , Coates Ashley , Reingold Arthur 
Published: November 2018

Abstract

Background
Influenza and bacterial coinfection are associated with increased symptom severity and worse health outcomes. We used data from the population based Influenza Hospitalization Surveillance Network (FluSurv-Net) California site to describe adult influenza hospitalizations with and without bacterial coinfections and evaluate the risk of severe disease.

Methods
We included data from adults hospitalized with laboratory confirmed influenza during the 2016/2017 influenza season who resided in San Francisco, Alameda or Contra Costa counties and had a bacterial culture performed ≤ 3 days after admission. We excluded records for healthcare facility-associated influenza. Univariate analyses were used to describe demographics, clinical characteristics and outcomes. Multivariate logistic regression was used to evaluate the effect of bacterial coinfection as a risk factor for severe outcome, defined as admission to an intensive care unit (ICU) or death during hospitalization.

Results
Among 2,029 adult influenza hospitalizations, 102 had ≥1 positive bacterial cultures. There were 119 bacterial isolates from blood (58), respiratory sites (60), and joint fluid (1). The most frequent blood isolates were Streptococcus pneumoniae (11), and Staphylococcus aureus (10). The most frequent respiratory isolates were S. aureus (30) and S. pneumoniae (7). Coinfected persons were younger (median age 71 vs. 78), and more likely to have past or current alcohol abuse or immunosuppression. Coinfected patients were more likely to be admitted to an ICU (45% vs. 15%) or die (16.0% vs. 3.6%). The median length of hospital stay was twice as long for coinfected patients (6 days vs. 3). In multivariate analyses, bacterial coinfection (aOR, 4.49; 95% CI, 2.99–6.72), chronic lung disease (aOR, 1.52; 95% CI, 1.18–1.95) and cardiovascular disease (aOR, 1.48; 95% CI, 1.15–1.90) were associated with a severe outcome.

Conclusion
Bacterial coinfection was associated with a four-fold higher risk of ICU admission and death during hospitalization. This study highlights the need for clinicians to maintain a high index of suspicion for the presence of bacterial coinfection among patients with influenza requiring hospitalization.

Disclosures
All authors: No reported disclosures.
691. Real-Time Local Influenza Forecasting Using Smartphone-Connected Thermometer Readings
Authors: Miller Aaron , Singh Inder , Pilewski Sarah , Petrovic Vladimir , Polgreen Philip M 
Published: November 2018

Abstract

Background
Information regarding influenza activity can inform clinical and public health activities. However, current surveillance approaches induce a delay in influenza activity reports (typically 1–2 weeks). Recently, we used data from smartphone connected thermometers to accurately forecast real-time influenza activity at a national level. Because thermometer readings can be geo-located, we used state-level thermometer data to determine whether these data can improve state-level surveillance estimates.

Methods
We used temperature readings collected by the Kinsa smart-thermometer and mobile device app to develop state-level forecasting models to predict real-time influenza activity (1–2 weeks in advance of surveillance reports). We used state-reported influenza-like illness (ILI) to represent state influenza activity for 48 US states with sufficient surveillance data. Counts of temperature readings, fever episodes and reported symptoms were computed by week. We developed autoregressive time-series models and evaluated model performance in an adaptive out-of-sample manner. We compared baseline time-series models containing lagged state-reported ILI activity to models incorporating exogenous thermometer readings.

Results
A total of 10,262,212 temperature readings were recorded from October 30, 2015 to March 29, 2018. In nearly all of the 48 states considered, weekly forecasts of ILI activity improved considerably when thermometer readings were incorporated. On average, state-level forecasting accuracy improved by 23.9% compared with baseline time-series models. In many states, such as PA, New Mexico, MA, Virginia, New York and SC, out-of-sample forecast error was reduced by more than 50% when thermometer data were incorporated. In general, forecasts were most accurate in states with the greatest number of device readings. During the 2017–2018 influenza season, the average improvement in forecast accuracy was 24.4%, and thermometer readings improved forecasting accuracy in 41, out of 48, states.

Conclusion
Data from smart thermometers accurately track real-time influenza activity at a state level. Local surveillance efforts may be improved by incorporating such information. Such data may also be useful for longer-term local forecasts.

Disclosures
I. Singh, Kinsa Inc.: Board Member, Employee and Shareholder, equity received and Salary. S. Pilewski, Kinsa Inc.: Employee and Shareholder, equity received and Salary. V. Petrovic, Kinsa Inc.: Employee and Shareholder, equity received and Salary.
694. The CAGE Study: Prevalence of Acute Gastroenteritis and Enteric Virus Infection in the Community
Authors: Schmidt Mark A , Salas S Bianca , Yamshchikov Vladimir , Groom Holly , Rosales Gabriela , Donald Judy , Marsh Zach , Burke Rachel , Mattison Claire , Naleway Allison , Hall Aron J 
Published: November 2018

Abstract

Background
There are currently limited data about the occurrence and characteristics of sporadic acute gastroenteritis (AGE). In this study, we sought to (1) estimate the average point prevalence of AGE over a 1-year period; (2) describe health-seeking behaviors among those with AGE; and (3) calculate the proportion of stool samples testing positive for enteric viral pathogens.

Methods
Starting in October 2016, we recruited 52 weekly, age-stratified, random samples of Kaiser Permanente Northwest members to complete an online survey and, for a subset of participants, to submit a stool specimen. The survey included questions about the occurrence of vomiting and/or diarrhea within the previous 30 days and, for those reporting AGE symptoms, related health-seeking behaviors. Collected stool samples were tested for norovirus, astrovirus, sapovirus, and rotavirus by RT-qPCR.

Results
We received a total of 3,483 surveys from eligible participants, 417 (12%) of whom reported having had AGE symptoms (Figure 1). Of these, 70 (17%) sought related medical care across a spectrum of clinical encounter types (Figure 2). We also received a total of 531 stool samples, 74 from symptomatic and 457 from asymptomatic individuals. Among them, we detected norovirus in 12% and 3% of samples (P = 0.0005), respectively; astrovirus and sapovirus in 1% of samples in each group; and rotavirus in 8% and 7% of samples, respectively.

Conclusion
Our findings of AGE within the community are consistent with previous estimates using models of medically attended AGE occurrence and reported rates of health-seeking behavior. The prevalence of enteric viral infection among people in the community without AGE was generally low. These data can be used to generate age-stratified incidence estimates of community AGE and specifically that associated with enteric viral pathogens. Such disease burden data are needed to guide the development, targeting, and anticipated impacts of interventions, such as vaccines.

Disclosures
M. A. Schmidt, Takeda Vaccines, Inc.: Investigator, Research grant. S. B. Salas, Takeda Vaccines, Inc.: Investigator, Research grant. H. Groom, Takeda Vaccines, Inc.: Investigator, Research grant. G. Rosales, Takeda Vaccines, Inc.: Investigator, Research grant. J. Donald, Takeda Vaccines, Inc.: Investigator, Research grant. A. Naleway, Takeda Vaccines, Inc.: Investigator, Research grant.
695. Regional and Longitudinal Mapping of Escherichia coli Antibiotic Susceptibility
Authors: Legenza Laurel , Barnett Susanne , Lacy Jim , Desotell Natalee , Eibergen Andrea , Rose Warren 
Published: November 2018

Abstract

Background
Antimicrobial resistance (AMR) is a serious threat to global health with local implications. AMR varies regionally; however, limited tools are available to aid practitioners in appropriate antibiotic selection based on statewide antimicrobial susceptibilities. The objective of this study was to map E. coli antibiotic susceptibility regionally and longitudinally in Wisconsin. Methods. Antibiograms from 2009, 2013, and 2015 were collected from health systems, hospitals, and clinics in Wisconsin, resulting in 218 antibiograms representing 201,091 Gram-negative isolates. E. coli antibiotic susceptibility percentages were weighted by number of isolates and aggregated by county per year. Results. Spatial interpolation methods (inverse distance weighted, Kriging) were tested by both county center points and facility geocode where available. Susceptibility data for clinically relevant urinary tract infection antibiotics were interpolated to create geographic visualizations of AMR in Wisconsin. Antibiotics included amoxicillin, trimethoprim/sulfamethoxazole, ciprofloxacin, nitrofurantoin, ampicillin, ampicillin/sulbactam, levofloxacin. The interpolation extends to the furthest health system point in each direction and is presented within state boundaries. Facility geocodes were masked from public display for confidentiality. City names were added for orientation. The mapping depicts regional differences, such as 2015 ampicillin susceptibilities ranging 55–64% (Figure 1). The maps provide a preliminary susceptibility prediction in areas where no AMR data were available. Average susceptibilities were compared across 2009, 2013, and 2015 to map areas with the highest rates of AMR change. Conclusion. The described mapping provides a novel visualization of AMR across Wisconsin. The maps created will be utilized in continued efforts to improve the functionality of AMR data in clinical practice to optimize antimicrobial choice.

Disclosures
All authors: No reported disclosures.
698. Nacubactam Inhibits Class A β-lactamases
Authors: Barnes Melissa D , Good Caryn E , Bajaksouzian Saralee , Taracila Magdalena A , Van Duin David , Kreiswirth Barry N , Jacobs Michael R , Papp-Wallace Krisztina M , Bonomo Robert A 
Published: November 2018

Abstract

Background
Nacubactam, formerly RG6080 and OP0595 (Figure 1A), is a bridged diazabicyclooctane (DBO) that inactivates class A and class C β-lactamases. Unlike avibactam, the DBO that is approved for use in combination with ceftazidime, nacubactam also inhibits penicillin binding proteins (i.e., PBP2) in Enterobacteriaceae. We set out to determine the effectiveness of meropenem-nacubactam against Klebsiella pneumoniae clinical strains and to elucidate the structure–function relationships.

Methods
Minimal inhibitory concentration (MIC) measurements using broth microdilution according to Clinical and Laboratory Standards Institute for meropenem (MERO) ± nacubactam (fixed concentration of 4 mg/L or fixed 1:1 ratio) was performed on 50 clinical K. pneumoniae strains (6 having OXA-48-like β-lactamases and 44 harboring KPC-2 or KPC-3) and 47 isogenic Escherichia coli strains harboring bla genes encoding K. pneumoniae carbapenemase (KPC) variants with single amino acid substitutions in residues that are involved in catalysis. IC50s for selected KPC-2 variants were determined on periplasmic extracts with varying concentrations of nacubactam using nitrocefin as a reporter substrate.

Results
The MERO combinations with either 4 mg/L or a 1:1 ratio of nacubactam effectively lowered the MERO MICs of K. pneumoniae strains (Figure 1B). Similarly, all E. coli strains expressing blaKPC-2 variants were susceptible to the MERO-nacubactam combinations based on the breakpoint of MERO. The strains harboring K73R, S130G, and K234R had slightly elevated MERO-nacubactam MICs relative to wild type but did not have corresponding increases in MERO MICs. Strains with pBC SK-KPC2, K73R or S130G had 0.015 mg/L MERO MICs. The pBR322-K234R strain had a twofold lower MERO MIC than pBR322-KPC-2 (Figure 1C). The IC50 of cell extracts containing the K234R variant is 781 µM, which is 12-fold higher than that for KPC-2 (66 µM) (Figure 1C). Extracts containing the S130G variant were not inhibited by nacubactam (IC50 &gt; 2.6 mM).

Conclusion
Meropenem-nacubactam is an effective β-lactam β-lactamase inhibitor combination for Enterobacteriaceae with KPC or OXA-48 β-lactamases. The single amino acid substitutions K73R, S130G, and K234R in KPC-2 affect the inactivation mechanism.

Disclosures
M. R. Jacobs, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant. K. M. Papp-Wallace, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant. R. A. Bonomo, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant.
711. Molecular Epidemiology of Daptomycin Nonsusceptibility in Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia
Authors: Sundaram Ayesha , Perri Mary Beth , Gurdziel Katherine , Hadid Hind , Herc Erica , Zervos Marcus J 
Published: November 2018

Abstract

Background
While methicillin resistance in S. aureus strains is prevalent, non-susceptibility to vancomycin and daptomycin, first-line treatments for bacteremia, has emerged as well. Little is known about the molecular epidemiology of daptomycin resistance in S. aureus strains.

Methods
A retrospective study was conducted at an 800-bed hospital in Detroit, Michigan. Blood isolates of S. aureus were obtained over time in patients with persistent bacteremia. Isolates were initially classified as MRSA/MSSA and MIC testing was done by the clinical microbiology laboratory; MICs were reconfirmed by a separate laboratory using Etest strips and microdilution broth testing. Non-susceptibility to daptomycin was defined as an MIC &gt; 1 mg/mL. Isolates from each patient were also assessed for genomic similarity using pulse field gel electrophoresis (PFGE) and placed in the same PFGE group if they were 3 80% similar by Dice coefficient. Whole genome sequencing (WGS) on isolates and template strain ATCC29213 was done by the Applied Genomics Technology Center.

Results
There were 27 isolates from seven patients in the following distribution: six isolates each from Patients 1 and 2; three isolates each from Patients 3, 4, and 5; five isolates from Patient 6; and one isolate from Patient 7. All isolates from Patients 1 and 3 (n = 9) were classified as MSSA strains and the remainder were MRSA strains. Daptomycin nonsusceptible strains were found in the initial isolate on therapy in two patients and the MIC increased from first to last isolates in the other five patients. A PFGE dendrogram comparing isolates within each patient and with established CDC lineages determined that (1) each patient’s first and last isolate remained within the same strain type and (2) the PFGE groups were USA100 (n = 8), USA300 (n = 7), USA900 (n = 6), and USA1000 (n = 3). WGS revealed the presence of vraSR, mprF, dltA, cls2, and gdpD, genes implicated in resistance to both vancomycin and daptomycin. However, gdpD was not detected in isolates classified as MSSA.

Conclusion
No genetic modification of strains from each patient was seen between the first isolate obtained and the last. The presence of cell wall regulation genes in both daptomycin susceptible and nonsusceptible strains suggests gene upregulation.

Disclosures
M. J. Zervos, Merck: Consultant and Grant Investigator, Grant recipient.
712. Identification of a Novel Tedizolid Resistance Mutation in rpoB of Methicillin-Resistant Staphylococcus aureus
Authors: Werth Brian , Penewit Kelsi , Salipante Stephen , Shen Tianwei , Xu Libin , Nath Abhinav 
Published: November 2018

Abstract

Background
Tedizolid (TDZ) is an oxazolidinone antimicrobial with broad-spectrum activity against Gram-positive bacteria including methicillin-resistant S. aureus (MRSA). Resistance to TDZ is uncommon but mutations in the 23S rRNA target as well as in the transferable rRNA methyltransferase gene cfr, which also mediate resistance to linezolid and chloramphenicol have been implicated. The objective of this study was to determine whether other TDZ resistance pathways exist in MRSA.

Methods
Using a well-characterized MRSA strain, N315, we selected for TDZ resistance by serial passage in escalating concentrations of TDZ in Mueller Hinton broth (MHB) starting with 0.5× the MIC. Once visible growth was achieved a sample of the broth was diluted 1:1,000 into fresh MHB with twice the previous concentration of TDZ until an isolate with an MIC of ≥4 mg/mL was recovered. This MIC was selected since it is 1 dilution above the breakpoint for resistance ≥2 mg/L). This isolate was subjected to whole genome sequencing (WGS) and MICs to other antimicrobials were assessed. Homology modeling was performed to evaluate the potential impact of the mutation on target protein function.

Results
After 10 days of serial passage we recovered a stable mutant with a TDZ MIC of 4 mg/L. WGS revealed a single nucleotide variant (A1345G) in the rpoB gene corresponding to an amino acid substitution at D449N. The following table and figure summarize the changes in drug susceptibility between the parent and evolved strain and reveals the location of the amino acid substitution relative to the TDZ binding site.

Conclusion
We have identified a novel mutation in the RNA polymerase gene, rpoB, that mediates oxazolidinone and chloramphenicol resistance. This variant lies outside of the rifampin resistance determinant clusters of rpoB that span from 1,384 to 1,464 and 1,543 to 1,590, and as expected did not affect rifampin susceptibility. The underlying molecular mechanism by which this single nucleotide variant confers TDZ resistance remains unclear but may involve transcriptional modulation by altered sigma factor binding.

Disclosures
All authors: No reported disclosures.
713. Vancomycin Heteroresistance in Coagulase Negative Staphylococci (CoNS) Causing Central Line-Associated Bloodstream Infection (CLABSI) in Pediatric Patients with Leukemia
Authors: Dao Tina , Parsons Joshua , Hayden Randall , Rubnitz Jeffrey , Wolf Joshua , Rosch Jason 
Published: November 2018

Abstract

Background
Heteroresistance to vancomycin in Staphylococcus aureus may be associated with poor response to therapy. Although CoNS are the most important CLABSI pathogens in children with leukemia, and treatment failure is common, little is known about the frequency or clinical significance of heteroresistance. This is a retrospective study to evaluate frequency, risk factors and clinical impact of heteroresistance in CoNS CLABSI in immunocompromised children.

Methods
The study was approved by the Institutional Review Board. All patients undergoing treatment for leukemia at St. Jude Children’s Research Hospital with CoNS isolated from blood between 2010 and 2016 were eligible. The first available isolate from each blood culture episode was obtained from the clinical laboratory and tested for vancomycin heteroresistance by population analysis profiling in comparison to the hVISA strain Mu3. Clinical data were collected from the medical record for up to 9 months after the episode. Episodes with ≥2 positive cultures or a single positive culture from a single lumen CVC were classified as CLABSI. Outcomes of interest included treatment failure (death or relapse of infection) or poor response to vancomycin therapy (persistence of bacteremia ≥1 day after initiation of vancomycin or treatment failure). Logistic regression was used to test associations between heteroresistance and exposures, and cumulative incidence analyses were used to test the effect on outcomes.

Results
A total of 74 CoNS isolates were obtained from 65 participants, 39 with ALL and 26 with AML; 25/74 (33.8%) of isolates showed showed heteroresistance. The strongest identified risk factor for infection with a heteroresistant organism was number of days of vancomycin in the preceding 60 days (OR = 1.05/day; P = 0.035). In the 40 CLABSI episodes, heteroresistant isolates had a higher cumulative incidence of poor response and of treatment failure (P = 0.006 and P = 0.003, respectively).

Conclusion
Vancomycin heteroresistance is common in CoNS causing CLABSI in children undergoing treatment for leukemia, and is associated with an increased risk of Treatment Failure. Further research should aim to validate this finding in an independent cohort and identify strategies to improve the diagnosis and treatment of these infections.

Disclosures
R. Hayden, Roche Molecular: Scientific Advisor, Consulting fee. Abbott Molecular: Scientific Advisor, Consulting fee. Quidel: Scientific Advisor, Consulting fee. J. Wolf, Karius Inc.: Investigator, Research support.