bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reductions in MRSA, Clostridium difficile and Intensive Care Unit (ICU) Acquired Bloodstream Infections and over 9 years from 276 United Kingdom ICUs
Authors: Batra Rahul , Wulff Jerome , Harrison David , Edgeworth Jonathan 
Published: October 2017

Abstract

Background
A major focus on preventing resistant organisms and hospital-acquired infections over the past 10 years has seen well-documented reductions in MRSA and C. difficileat hospital and national level. Less is known about national changes in epidemiology of bloodstream infections, and such data is important to frame future national priorities and targets.

Methods
Data from the Intensive Care National Audit and Research Centre Program on MRSA, C. difficile and VRE colonization and ICU-acquired bloodstream infections (UABSIs) from 1,195,103 consecutive patients admitted to 276 UK ICUs (excluding Scotland) from 2007 to 2015 was analyzed.

Results
MRSA and C. difficile colonizations per 1000 patients decreased significantly (MRSA admissions 38.8 to 12.03 (P = 0.00003); MRSA acquisitions 25.4 to 3.1(P = 0.0008); C. difficile admissions 10.6 to 4.1(P = 0.0001); C. difficile acquisitions 11.1 to 3.3 (p = 0.0005). Reductions predominantly occurred between 2007 and 2011 with MRSA but not C. difficile. In contrast VRE admissions and ICU-acquisitions increased from 1.9 to 5.8 (P = 0.002) and 1.5 to 5.6 (P = 0.005), respectively. There were 13,147 UABSI episodes in 11,075 (1.8%) of 621,859 patients staying &gt;48 hours. The UABSI rate fell from 6.6 (95% CI 6.33–6.97) to 1.7 (95% CI 1.5–1.7)/1000 bed days (P &lt; 0.0001), with the reduction taking place between 2007 and 2011 and no significant reduction since. A fixed effect model identified lower age, male sex, severity of illness, larger ICU-size, immunosuppressive therapy (but not immunosuppressive illness) as significant risk factors for UABSI. MSSA, E. coli, Enterococci, Yeast, Klebsiella sp and P. aeruginosa accounted for 73% of all recorded first UABSIs. Greatest reduction was seen for MRSA (97%), Pseudomonas aeruginosa(80%), S. aureus (77%) and Yeast (71%), with lower reductions for E. coli (54%) and Klebsiella(42%).

Conclusion
Large decreases in ICU-acquired bloodstream infections occurred across UK ICUs at the same time as reductions in MRSA and C. difficile, but rates have been static since 2011. Reductions were seen for all organisms. The observation that no material reductions in UABSIs were observed during the last 5 years of the study, despite continued focus on improving infection control practice throughout, implies that benefits from the current intervention framework have been achieved.

Disclosures
All authors: No reported disclosures.
Catheter-free Period Over 2 Days Is Associated with Better Outcome in Catheter-related Bloodstream Infection due to Candida
Authors: Matsuo Takahiro , Mori Nobuyoshi , Hoshino Eri , Sakurai Aki , Furukawa Keiichi 
Published: October 2017

Abstract

Background
Regardless of active antifungal drugs, mortality of candidemia remains high. Although it is well-known that central venous catheter (CVC) is one of the most important risk factors of candidemia and should be removed immediately, little is known about optimal timing of CVC replacement after removal. Here, we analyzed contributing risk factors associated with 30-day mortality for catheter-related bloodstream infection (CRBSI) due to candida and optimal timing of CVC replacement.

Methods
We conducted a retrospective cohort study at St. Luke#129; fs International Hospital between 2004 and 2015. We compared each clinical component in patients who died within 30 days and were alive at 30 days. Also, catheter-free period (from removal to replacement) was compared between group A and B. Fisher#129; fs exact test and Mann–Whitney U test were used in univariate analysis and multivariate linear regression was used for controlling confoundings.

Results
Among 228 patients (pts) with candidemia, 166 patients (73%) were on CVC at diagnosis. Of them, 144 patients (65%) removed CVC after the result of candidemia. Seventy-one patients (31%) replaced CVC. Fifteen patients (6%) died within 30 days (group A) and 56 patients (25%) were alive at 30 days (group B). Median age was 74 in group A and 72 in group B (P = 0.331) (Table 1). In univariate analysis, hematological malignancy (OR 6.75, 95% CI 1.01–44.9) and CVC replacement &lt; 2-days after removal (OR 5.63, 95% CI 1.16–27.3) showed statistically significant increase in group A vs group B (Table 2). In multivariate analysis, CVC replacement &lt; 2-days was independently associated with 30-day mortality (Table 3).

Conclusion
This is the first study to demonstrate the optimal timing of CVC replacement in CRBSI due to candida. CVC replacement &lt; 2 days was an independent risk factor for 30-day mortality.

Disclosures
All authors: No reported disclosures.
Routine Cryptococcal Antigen Screening in Solid Organ Transplant Recipients: Is it Time to Save Lives and Money?
Authors: George Ige , Rajasingham Radha , Powderly William , Boulware David 
Published: October 2017

Abstract

Background
Cryptococcosis affects 1 in 270 solid organ transplant (SOT) recipients with high mortality. In HIV-infected patients, cryptococcal antigen (CRAG) is detectable in blood weeks to months before symptomatic infection and screening is recommended. No screening guidelines exist for SOT recipients.

Methods
We performed a cost-effectiveness analysis of CRAG screening amongst SOT recipients. We estimated costs of screening from Medicare reimbursement of $16.49 for CPT 87899 (Infectious agent antigen detection by immunoassay). We determined the number at risk from a large cohort of 42,634 adult SOT recipients from ICD-9 CM billing data from HCUP State Inpatient Databases of Florida (2006–2012), New York (2006–2011), and California (2004–2010). Cost of screening was compared with the cost of inpatient hospitalization.

Results
Among 42,634 adult SOT recipients, 158 (0.37%) developed cryptococcosis at a median time of 15.5 months (range 0.1 -80) after transplant. During the 43 month follow-up, there was approximately 2.5% annual mortality. The estimated cost of hospital care for cryptococcal meningitis per person is approximately $70,000 in 2016 with current explosive cost of flucytosine at ~$29,000 per 2 weeks. Thus, the total estimated cost of hospital care in the cohort would be $11.0 million in 2016. In comparison, the cost to screen all 42,634 SOT recipients every three months would be $8.8 million. If CRAG screening could detect 75% of asymptomatic cryptococcal antigenemia prior to symptomatic disease requiring prolonged hospitalization, it would be approximately cost neutral ($11.5 million), and even cost saving if above 80% of hospitalizations are averted. Alternatively stated, for every one hospitalization avoided, 4245 persons could be CRAG screened for similar cost and likely better outcome.

Conclusion
Assuming the ability of routine screening to identify 75% of patients who would develop invasive cryptococcosis; CRAG screening every 3 months among SOT recipients likely would be at least cost neutral to the healthcare system. Antecedent duration of cryptococcal antigenemia prior to symptomatic disease in Non-HIV/SOT cohorts to inform optimal screening intervals should be further studied. Prospective SOT cohorts should validate this approach to save lives in a cost-effective manner.

Disclosures
All authors: No reported disclosures.
Galidesivir, a Direct-Acting Antiviral Drug, Abrogates Viremia in Rhesus Macaques Challenged with Zika Virus
Authors: Lim So-Yon , Osuna Christa , Lakritz Jessica , Chen Elsa , Yoon Gyeol , Taylor Ray , MacLennan Steve , Leonard Michael , Giuliano Enzo , Mathis Amanda , Berger Elliot , Babu Ys , Sheridan William , Whitney James 
Published: October 2017

Abstract

Background
Zika virus (ZIKV) was first isolated from a sentinel rhesus monkey in 1947. ZIKV infection in humans is associated with serious neurological and reproductive complications. No antiviral or protective vaccine is yet available. Galidesivir an adenosine analog is a potent viral RNA-dependent RNA polymerase inhibitor with demonstrated broad-spectrum antiviral activity.

Methods
We have conducted four pre-clinical studies in rhesus macaques to assess the safety, antiviral efficacy and dosing strategies of galidesivir against ZIKV infection. Collectively, we have challenged 70 rhesus macaques by various routes using 1x105 TCID50of a Puerto Rican ZIKV isolate. We have evaluated galidesivir therapy administered via IM injection as early as 90 minutes and up to 72 hours after subcutaneous (SC) ZIKV challenge, and as late as 5 days after intravaginal (IVAG) challenge. In these studies, we evaluated the efficacy of a range of loading and maintence doses of galidesivir. The highest dose evaluated has been a loading dose of 100mg/kg BID followed by a maintenance dose of 25mg/kg BID for nine days. We followed multiple endpoints, including ZIKV RNA levels in plasma, urine, saliva, and cerebrospinal fluid. Immune activation, complete blood counts, chemistries and galidesivir pharmacokinetics were also monitored.

Results
Galidesivir was well-tolerated in all studies. All untreated controls developed high-level plasma viremia, and had readily detectable ZIKV RNA in CSF, saliva and urine post-infection. Animals treated in the first 24 hours after SC ZIKV challenge did not develop plasma viremia and were either negative or had significantly reduced ZIKV RNA in bodily fluids. Animals treated with galidesivir later (up to 72 hours) were partially protected; they had detectable plasma ZIKV RNA, but the onset was delayed and/or magnitude significantly reduced compared with controls. Animals infected IVAG were protected by galidesivir treatment up until day 5 after infection, with no blood viremia and significant reductions in ZIKV RNA in the CSF as compared with controls.

Conclusion
Galidesivir dosing in rhesus macaques was well-tolerated and offered significant protection against ZIKV infection. These results warrant continued study and clinical evaluation.

Disclosures
R. Taylor, BioCryst Pharmaceuticals: Employee, Salary; S. MacLennan, BioCryst: Employee, Salary; M. Leonard, BioCryst: Employee, Salary; E. Giuliano, BioCryst: Employee, Salary; A. Mathis, BioCryst Pharmaceuticals: Employee, Salary; E. Berger, BioCryst: Employee, Salary; Y. Babu, BioCryst: Employee, Salary; W. Sheridan, BioCryst Pharmaceuticals: Employee, Salary
Environmental and Climatic Risk Factors for Zika and Chikungunya Virus Infections in Rio de Janeiro, Brazil, 2015–2016
Authors: Fuller Trevon , Calvet Guilherme A , Estevam Camila Genaro , Brasil Patricia , Angelo Jussara Rafael , Smith Thomas B , Bispo Di Filippis Ana M 
Published: October 2017

Abstract

Background
The objective of the present study was to identify drivers of the ZIV epidemic in the state of Rio de Janeiro to predict where the next hotspots will occur and prioritize areas for vector control and eventual vaccination once available.

Methods
To assess climatic and socio-economic drivers of arbovirus epidemics, we mapped rainfall, temperature, and sanitation infrastructure in the municipalities where individuals with laboratory confirmed cases of arboviral infection resided using our spatial pattern risk model.

Results
From March 2015 to May 2016, 3,916 participants from 58 municipalities in the state of Rio de Janeiro were tested for dengue, Chikungunya (CHKV), and ZIKV by RT-PCR and enzyme immunoassays. During the same period, 69,256 suspected cases of dengue, CHKV, and ZIKV were reported to the Rio Health Department, including 23,983 of dengue, 44,572 of ZIKV, and 701 of CHKV. Laboratory confirmed cases included 29 cases (0.7%) of dengue, 1,717 of ZIKV (43.8%), and 2,170 of CHKV (55.4%). Rains in Rio began in October 2015 and were followed one month later by the largest wave of the ZIKV epidemic (Figure 1). ZIKV cases markedly declined in February 2016, which coincided with the start of a CHKV outbreak. Rainfall predicted ZIKV and CHKV in Rio with a lead-time of 3 weeks each time. Social and environmental variables predicted the number of cases. The temporal dynamics of ZIKV and CHKV in Rio de Janeiro are explained by the shorter incubation period of the viruses in the mosquito vector; 2 days for CHKV vs 10 days for ZIKV.

Conclusion
The association between rainfall and ZIKV reflects vector ecology, as the larval stages of Aedes aegypti require pools of water to develop. Rainfall in October 2015 would have produced such pools resulting in increased mosquito abundance likely contributing to the ZIKV epidemic in humans the following month. The decrease in ZIKV in February 2016 and the increase in CHKV likely arose due to within-vector competition. The Pan American Health Organization’s ZIKV Strategic Plan states that controlling arboviruses requires mapping their social and environmental drivers. Our findings contribute to such control efforts.

Disclosures
All authors: No reported disclosures.
Fatty Liver Disease in HIV: Predictors and Response to Statin Therapy
Authors: El Kamari Vanessa , Hileman Corrilynn O , Mccomsey Grace 
Published: October 2017

Abstract

Background
Liver disease has emerged as a leading cause of mortality and morbidity in HIV. Much of the current challenge in liver disease is related to nonalcoholic fatty liver disease (NAFLD). In HIV-uninfected populations, statin therapy has been suggested as potential intervention, but no such data is available in HIV. The aims of this study are to investigate the effect of rosuvastatin on hepatic steatosis in HIV infection, measured by Liver Fat Score (LFS) and to assess the natural history and predictors of changes in hepatic steatosis over 96 weeks.

Methods
This is a secondary analysis of the SATURN-HIV trial, in which HIV+ adults on stable ART with HIV-1 RNA &lt; 1,000 copies/mL and LDL-cholesterol &lt; 130mg/dL were randomized to 10mg daily rosuvastatin or placebo. Changes in LFS and in markers of systemic inflammation and monocyte activation were assessed from entry through week 96. Spearman correlations, multivariable linear regression and logistic regression were used to study relationships among variables.

Results
Overall, 147 patients were randomized (n = 72 to rosuvastatin n = 75 to placebo); 78% were male, 68% African Americans, 8% had chronic hepatitis C and mean age and BMI were 46 years and 29kg/mm2. A significant increase in LFS over 96 weeks was seen in both the placebo and statin arms (p = 0.01 and p &lt; 0.01 respectively, p = 0.49 between groups). Furthermore, the progression from no-steatosis (LFS ≤ -0.64) at baseline to steatosis (LFS &gt; -0.64) at week 96 was higher in rosuvastatin arm (OR = 4.3, p = 0.03), and remained statistically significant after adjusting for demographics, HOMA (baseline and change over 96 weeks), hepatitis C, heavy alcohol use and HIV parameters. Baseline LFS was independently associated with IP-10 (β = 0.82, p = 0.03) and sCD163 (β = 0.43, p = 0.005), and the increase in LFS over 96 weeks was independently associated with IP-10 (β = 2.85, p = 0.02).

Conclusion
In HIV+ subjects on ART, hepatic steatosis increased over time, regardless of statin treatment, and was independently associated with markers of immune activation. The progression from non-steatosis to hepatic steatosis was greater on statin. Despite its effective role in reducing cardiovascular disease risk and inflammation, statin therapy does not appear effective in hepatic steatosis.

Disclosures
C. O. Hileman, Gilead: Medical Advisory Board, Research support; G. Mccomsey, Gilead: Consultant, Consulting fee and Research support; BMS: Consultant, Consulting fee and Research support; GSK/ViiV: Consultant, Consulting fee and Research support; ICON: Consultant, Consulting fee; Merck: Investigator, Research support
Vaccine effectiveness against influenza-associated hospitalization among children aged &lt; 13 years using a hospital-based surveillance system in Minnesota, 2013 – 2016
Authors: Fowlkes Ashley , Friedlander Hannah , Steffens Andrea , Como-Sabetti Kathryn , Boxrud Dave , Bistodeau Sarah , Strain Anna , Ferdinands Jill M , Chaves Sandra S , Reed Carrie , Lynfield Ruth 
Published: October 2017

Abstract

Background
Due to marked variability in circulating influenza viruses each year, annual evaluation of the vaccine’s effectiveness against severe outcomes is essential. We used the Minnesota Department of Health’s (MDH) Severe Acute Respiratory Illness (SARI) surveillance to evaluate vaccine effectiveness (VE) against influenza-associated hospitalization over three influenza seasons.

Methods
Residual respiratory specimens from patients admitted with SARI were sent to the MDH laboratory for influenza RT-PCR testing. Medical records were reviewed to collect patient data. Vaccination history was verified using the state immunization registry. We included patients aged ≥6 months to &lt; 13 years, after which immunization reporting is not required, hospitalized from the earliest influenza detection after July through April each year. We defined vaccinated patients as those ≥1 dose of influenza vaccine in the current season. Children aged &lt; 9 years with no history of vaccination were considered vaccinated if 2 were doses given a month apart. Partially vaccinated children were excluded. We estimated VE as 1 minus the adjusted odds ratio (x100%) of influenza vaccination among influenza cases vs. negative controls, controlling for age, race, days from onset to admission, comorbidities, and admission month.

Results
Among 2198 SARI patients, 763 (35%) were vaccinated for influenza, 180 (8.2%) were partially vaccinated, and 1255 (57%) were unvaccinated. Influenza was detected among 202 (9.2%) children, and significantly more frequently among children aged ≥5 years (17%) compared with younger children (7.4%). The adjusted VE in 2013–14 was 68% (95% Confidence Interval: 34, 85), but was non-significant during the 2014–15 and 2015–16 seasons (Figure). Estimates of VE by influenza A subtypes varied substantially by year; VE against influenza B viruses was significant, but could not be stratified by year. VE was impacted when live attenuated influenza vaccine recipients were excluded.

Conclusion
We report moderately high influenza VE in 2013–14 and a point estimate higher than other published estimates from outpatient data in 2014–15. These results, underscore the importance of influenza vaccination to prevent severe outcomes such as hospitalization.

Disclosures
All authors: No reported disclosures.
Improving Antimicrobial Use by Implementing the CDC Antimicrobial Stewardship Core Elements Across a Diverse Healthcare System
Authors: Lane Michael A , Hays Amanda , Newland Helen , Zack Jeanne , Newland Jason 
Published: October 2017

Abstract

Background
With increasing national focus on reducing inappropriate antimicrobial use, state and national regulatory mandates require hospitals to develop robust antimicrobial stewardship programs (ASP).

Methods
BJC HealthCare is a 13 hospital healthcare system serving the St. Louis, mid-Missouri, and Southern Illinois region and includes adult and pediatric academic medical centers, as well as community and critical access hospitals. In 2015, BJC system leaders engaged relevant clinical and executive stakeholders at each hospital to champion formation of a multidisciplinary system ASP Council. A comprehensive gap analysis was performed to assess current stewardship resources and activities. BJC system clinical leads facilitated the development of hospital specific leadership support statements, identification of hospital pharmacy and medical leaders, and all mandated educational components. To facilitate tracking, reporting and improvement activities, a robust antimicrobial use data dashboard was created. Each hospital has a dedicated ASP team that is supported by the system clinical leads. Hospital learnings are shared at monthly system ASP meetings allowing for broad dissemination.

Results
By leveraging system resources, all 13 BJC HealthCare hospitals met all Joint Commission requirements by January 2017. BJC’s model of ASP allows for the development of broad-based stewardship activities including development of education modules for patients and providers, and clinical decision support tools while allowing individual hospitals to implement activities based on local needs and resource availability. Local hospital teams have developed treatment guidelines, targeted antibiotic pharmacy review, “handshake” stewardship models, and allergy testing protocols. Central support of local hospital ASP has resulted in a 7.6% system decrease in tracked antimicrobial use, including a 16.5% reduction in quinolone usage. Additionally, the C. difficilestandardized infection ratio decreased from 1.08 to 0.622 since program initiation.

Conclusion
Despite significant differences in hospital resources, a system-supported ASP model focused on implementing the CDC core elements can result in significant reductions in antimicrobial use.

Disclosures
J. Newland, Merck: Grant Investigator, Research grant; Allergan: Grant Investigator, Research grant
Phylogenetic Analysis of an Unusual Increase in Salmonella enterica serovar Paratyphi A Infection among Travelers Returning from Myanmar
Authors: Matono Takashi , Morita Masatomo , Izumiya Hidemasa , Kaku Mitsuo , Ohnishi Makoto 
Published: October 2017

Abstract

Background
The proportion of enteric fever cases caused by Salmonella enterica subspecies enterica serovar Paratyphi A (S. Paratyphi A) has recently been increasing in Asian counties, which is a public health concern. In 2015, an unusual increase in S. Paratyphi A infection among Japanese travelers returning from Myanmar was noted, while there is little information on this uptrend in Myanmar.

Methods
Isolates from travelers who returned with enteric fever from 2005 to 2015 were analyzed in order to determine country-specific notification rates (epidemiological investigation). The notification rate was defined as cases returning from each country per 100,000 Japanese travelers who visited to the country. S. Paratyphi A isolates collected from 2001 to 2015 were analyzed by whole-genome sequencing (microbiological investigation).

Results
Yearly notification trends indicated that enteric fever was potentially endemic to Myanmar (5–16 cases/100,000 travelers); the trends were similar to those observed in India (4–21 cases/100,000 travelers). A rapid increase in S. Paratyphi A infection occurred from 2012–2014 (2–4 cases/100,000 travelers) to 2015 (13 cases/100,000 travelers). A phylogenetic tree, constructed based on analysis of 105 S. Paratyphi A isolates (33 and 30 related to Myanmar and Cambodia, and 42 controls), revealed that most Myanmar- and Cambodia-related isolates formed clusters in the same lineage (Figure 1). Additionally, Myanmar-related isolates from 2015 harbored identical phage type 1 and were genetically closely related [each isolates had 0–10 single-nucleotide polymorphisms (SNPs), mostly within 0–7 SNPs] (Figure 2), yielding a wider SNP range than outbreak-associated isolates from Cambodia in 2013 (within a SNP distance of 0–6).

Conclusion
Epidemiological trends and molecular subtyping suggested a possible outbreak of S. Paratyphi A infection occurred in Myanmar in 2015. The recent uptrend of S. Paratyphi Ainfection in Myanmar is important for travelers and clinicians since infection cannot be prevented by typhoid vaccination.
Figure 1. Polygenetic tree of 105 S. Paratyphi A isolates
Figure 2. SNP analyses of S. Paratyphi A isolates from Myanmar in 2015 (A) and Cambodia in 2013 (B).

Disclosures
All authors: No reported disclosures.