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Background Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine that not only acts on the central nervous system, but is also implicated in metabolic regulation, development of lung diseases, and support of hematopoiesis. Recently, a study report that the plasma levels of BDNF were independently associated with mortality in critically ill patients. We aimed to evaluate the role of BDNF in sepsis patients and animal sepsis model. Methods Prospectively enrolled adult sepsis patients (n=168) who visited the emergency room (ER) of Korea University Ansan Hospital from January 2017 to December 2018., and healthy volunteers (n=48) were included in the present study. Serum BDNF level was determined and analyzed in septic patients and healthy volunteers. The effects of BDNF on pro-inflammatory cytokines, AMP-activated protein kinase (AMPK) and NF-κB signaling in septic condition of RAW264.7 cells and mouse peritoneal macrophage, and mouse sepsis model by cecal ligation and puncture (CLP). Results Serum BDNF levels (mean) were significantly decreased in sepsis patients compared to healthy controls (11.78ng/ml vs 18.91ng/ml, p< 0.001) and significantly decreased in non-survivors compared to survivors at discharge (3.16ng/ml vs 13.86ng/ml, p< 0.05). BDNF treatment suppressed LPS-induced pro-inflammatory cytokine (TNF-α, iL-6, and iL-1β) in RAW264.7 cells. Although LPS stimulation diminished AMPK phosphorylation, BDNF was able to decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on down stream signaling events, particularly LPS-induced IκBα degradation in RAW cells and peritoneal macrophage. In CLP model, intra-muscular injection of BDNF after CLP significantly decreased serum levels of TNF-α which was increased compared to sham, and significantly improved survival of mouse (p< 0.01). Conclusion Sepsis results in a decreased production of BDNF, which might be a potential prognostic biomarker and therapeutic target through AMPK signal pathway for sepsis. Disclosures All Authors: No reported disclosures.

Background Scrub typhus causes systemic vasculitis and can lead to complications ranging from pneumonia and acute renal injury to meningitis or encephalitis. In South Korea, it occurs not only in rural areas but also in urban areas, and especially high in older people. We hypothesized that patients with scrub typhus are predisposed to increased risks for developing dementia. Methods We performed a population-based cohort study, in which persons aged between 60∼89 years, used the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. The case definition of scrub typhus was based on the ICD-10 diagnostic code and prescription of doxycycline more than three days. Dementia was defined as patients with the code in expending benefit coverage or patients with the ICD-10 codes, examination codes and drug codes. The control group was selected as stratifying by age and gender at a ratio of 1:5 to the number of the case group in study population. Results During the observational periods, Of 76,073 patients had diagnosed with scrub typhus, 5,026 excluded due to diagnosed with scrub typhus during window period, with dementia or died before index date, 71,047 patients were included as case group. 355,235 patients were included as controls. During a mean follow-up of 5.6±2.9 years, 14,089 (19.8%) patients with previous scrub typhus and 61,807 (15.2%) controls had been developed dementia. Scrub typhus was significantly associated with dementia (adjusted hazard ratio [aHR], 1.12; 95% confidential interval [CI], 1.10-1.15, P< 0.001). Of dementia classification, the risk of Alzheimer dementia was significantly higher in the case group (17.8% vs 15.2%; aHR, 1.15; 95%CI, 1.13-1.18, p< 0.001), however, there was no significant difference in the risk of vascular dementia (2.1% vs 2.2%; aHR, 0.98; 95%CI, 0.83-1.16, p=0.82). Cumulative incidence of dementia during the follow-up period by the history of scrub typhus It shows in both groups dementia incidence increased over time and the case group had higher incident dementia compared with control group. Conclusion History of scrub typhus infection in elderly was associated with increased risk for dementia, especially Alzheimer’s dementia. Our results suggest that prevent measures of dementia could be improved by preventing and treating scrub typhus. Disclosures All Authors: No reported disclosures.

Background Even after the introduction of the Sepsis-3 definition, there is still debate on the ideal antibiotic administration time in patients with sepsis. This study was performed to evaluate the association between the timing of antibiotic administration and mortality in sepsis patients who visited the emergency room. Methods A prospective cohort study was conducted on patients who were diagnosed as sepsis with Sepsis-3 definition among patients who visited the emergency department (ED) of Korea University Ansan Hospital from September 2017 to January 2019. The timing of antibiotic administration was defined as the time in hours from ED arrival until the first antibiotic administration. Cox logistic regression analysis was used to estimate the association between time to antibiotics and 7-, 14-, and 28-day mortality. Results During the study period, a total of 251 patients were enrolled with a 7-, 14-, and 28-day mortality of 16.7%, 36.3%, and 57.4%, respectively. The median time to antibiotic administration was 247 minutes (interquartile range 72 – 202 minutes). The mean age was 72 ± 15 years old and 122 patients (48.6%) were female. The most common site of infection was respiratory infection. The timing of antibiotic administration were not associated with 7-, 14-, and 28-day mortality. Female (adjusted hazard ratio [HR] 2.06 [95% confidence interval (CI) 1.21 – 3.53]; P value = 0.008), SOFA score (aHR 1.17 [95% CI 1.05 - 1.31]; P = 0.005), and initial lactate level (aHR 1.13 [95% CI 1.05 - 1.22]; P = 0.001) increased the risk of 7-day mortality. Female (aHR 2.07 [95% CI 1.48 – 2.89]; P ≤ 0.001), Charlson comorbidity index (aHR 1.12 [95% CI 1.02 - 1.24]; P = 0.025), and initial lactate level (aHR 1.19 [95% CI 1.02 - 1.16]; P = 0.011) increased the risk of 14-day mortality. Female (aHR 1.95 [95% CI 1.50 – 2.54]; P = 0.001) increased the risk of 28-day mortality in patients with sepsis. Conclusion The timing of antibiotic administration did not increase the risk of mortality in the treatment of sepsis patients who visited ED. Rather, the SOFA score, lactate, female, and comorbidity increased the mortality associated with sepsis. Disclosures All authors: No reported disclosures.

Background Fosfomycin is one of the antibiotics that may be a candidate for the next-generation antimicrobial agents againt multidrug-resistant bacteria. To date, it is known that the resistance rate is not high for Escherichia coli. However, it is necessary to update the fosfomycin resistance rates in E. coli according to the studies that extended spectrum β-lactamase (ESBL) producing E. coli strains are highly resistance to fosfomycin. We evaluated the resistance rate of fosfomycin, the resistant mechanism of fosfomycin in E. coli, and the activity of fosfomycin against susceptible and resistant strains of E. coli. Methods A total of 283 clinical isolates was collected from patients with Escherichia coli species during the period of January 2018 to June 2018, in three tertiary hospitals of Republic of Korea. In vitro antimicrobial susceptibility tests were performed in all E. coli isolates using the broth microdilution method according to the Clinical and Laboratory Standard Institute (CLSI). Multilocus sequence typing (MLST) of the Oxford scheme was conducted to determine the genotypes of E. coli isolated. Fosfomycin genes were investigated for all fosfomycin-resistant E. coli strains. Results The overall resistance rate to fosfomycin was 10.2%, compared with 53.4%, 46.3%, 41.3%, 31.1%, 10.6%, 2.5%, and 2.1% for ciprofloxacin, cefixime, cefepime, piperacillin/tazobactam, colistin, ertapenem, and amikacin, respectively. The 29 fosfomycin-resistant isolates did not show a clonal pattern on the phylogenetic tree. MurA and glp genes were identified in all strains. FosA3 were identified in two strains and uhp gene were identified in 4 strains. In time-kill curve studies, fosfomycin was more bactericidal than cefixime against all sensitive E. coli strain. Morever, fosfomycin was more bactericidal than piperacillin/tazobactam against ESBL-producing E. coli strain. Conclusion The resistant rate of fosfomycin to E. coli is still low. Fosfomycin was active against E. coli including ESBL producing strains. Disclosures All authors: No reported disclosures.