bluuebunny/crossref_metadata_2025_split huggingface dataset:
2101. Impact of “Code Sepsis” on Antimicrobial Utilization at an Academic Medical Center
Authors: Kang Minji , Torriani Francesca J , Sell Rebecca , Abeles Shira 
Published: October 2019

Abstract

Background
Balancing antimicrobial stewardship with sepsis management is a challenge. At our academic medical center, a “Code Sepsis” was implemented as a nursing driven initiative to improve early recognition and management of sepsis. Per protocol, Code Sepsis is activated in patients who meet two or more systemic inflammatory response syndrome (SIRS) criteria due to a suspected infection to allow for early implementation of the sepsis bundle, which includes laboratory testing, fluid resuscitation, and antibiotic administration (Figure 1). We analyzed the impact that Code Sepsis had on antimicrobial use among hospitalized patients over a six month period.

Methods
We reviewed the electronic medical records of hospitalized patients with Code Sepsis activation between January 1, 2018 and June 30, 2018 to determine whether antibiotics were “escalated” or “not escalated.” Among patients who had antibiotic escalation, escalation was classified as “indicated” or “not indicated” (Figure 2). A logistic regression model was used to identify characteristics, SIRS or organ dysfunction criteria predictive of indicated antimicrobial escalation.

Results
Code Sepsis was activated in 529 patients with antibiotics escalated in 247 (47%) and not escalated in 282 (53%) (Table 1). Among patients whose antibiotics were escalated, 64% (152) had an indication. In 36% (89), escalation was not indicated as Code Sepsis was due to a suspected noninfectious source, known infectious source already on appropriate antimicrobials, or a suspected infectious source in which diagnostic results had already shown the absence of the infection (Figure 2). Odds of indicated antibiotic escalation increased with the number of SIRS and organ dysfunction criteria (Table 2).

Conclusion
In our efforts to improve sepsis outcomes, we focused on early recognition (Code Sepsis) and intervention (sepsis bundle). However, our Code Sepsis inadvertently led to antibiotic overutilization. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock, we hope to optimize resource utilization and improve patient outcomes.

Disclosures
All authors: No reported disclosures.
2111. Anidulafungin vs. Micafungin Treatment in Adult Patients with Candidemia: A Retrospective Study of Single-Center Experience
Authors: Suh Jinwoong , Yeon Kim Jeong , Seung Chung You , Lee Hojin , Bean Kim Sun , Kyung Yoon Young , Wook Sohn Jang , Ja Kim Min , Hun Kim Jong 
Published: October 2019

Abstract

Background
Candidemia is one of the fatal causes of nosocomial infection, requiring prompt recognition and treatment. Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. Although similar clinical efficacy and safety are well known between caspofungin and micafungin, there are few studies comparing micafungin and anidulafungin. The objective of this study was to evaluate the clinical efficacy and safety between micafungin and anidulafungin treatment for adult patients with candidemia.

Methods
This retrospective cohort study was performed on adult candidemia patients diagnosed from January 2006 through December 2018 at a tertiary medical center, Seoul, South Korea. The study subjects included adult patients ≥19 years with candidemia who were only treated with micafungin or anidulafungin for more than 3 days. Baseline and clinical characteristics were reviewed through electrical medical records. Liver function was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Hepatotoxicity was deﬁned as the elevation of more than CTCAE grade 1 and severe hepatotoxicity was deﬁned as the CTCAE grade 3 or higher elevations.

Results
A total of 98 patients with candidemia was treated with micafungin (n = 46, 46.9%) or anidulafungin (n = 52, 53.1%). In the univariate analysis, there were no significant differences in age, sex, source of candidemia, and comorbidities between the micafungin and anidulafungin groups. Although the clearance time of candidemia after echinocandin treatment was shorter in the anidulafungin than in the micafungin (5.64 ± 2.79 vs. 8.06 ± 5.30 days, P = 0.009) group, there was no significant difference in terms of clinical response (51.9% vs. 46.7%), mycological response (76.9% vs. 67.4%), and mortality (54.3% vs. 55.8%) between these two groups. The overall incidence of hepatotoxicity was similar. Also, there was no difference in the development of hepatotoxicity or severe hepatotoxicity between micafungin and anidulafungin groups for patients with normal baseline liver function test(LFT) and abnormal baseline LFT.

Conclusion
Our results suggest that clinical efficacy and hepatotoxicity may be similar between micafungin and anidulafungin treatment for adult patients with candidemia.

Disclosures
All authors: No reported disclosures.
2114. Correlation Between Antifungal Consumption and the Distribution of Candida Species in a Hospital in Colombia
Authors: Arboleda Harold T , Moreno German A , Ordonez Diaz Karen M 
Published: October 2019

Abstract

Background
In recent years, a shift toward non albicans Candida infections has been described. An increase in the prescription of antifungals has been attributed as the cause of this change, but this issue has not been evaluated in Colombia.

Methods
The distribution of Candida spp. over an 11-year period 2007–2018 were extracted of the software WHONET 5.6. Antifungal drug consumption was measured as the number of defined daily doses (DDD)/100 patient-days over a 6-year period 2012–2018. Spearman’s coefficient was performed to find a correlation between antifungal consumption and distribution of Candida species.

Results
A total of 811 non-duplicate isolates of Candida spp. were included. An increase in the frequency of isolates was observed in the period 2013–2016 (Figure 1). The highest number of isolates were collected from the intensive care unit (ICU) (35.6%) followed of medical ward (22%). Non albicans Candida predominated (58%) in the period evaluated. The shift toward non albicans Candida was presented in 2015 (Figure 2). A non-homologous distribution of albicans vs. non-albicans was noted between ICU and general ward (P = 0.026). 152 (18.7%) isolates were recovered from blood. C. parapsilosis was the most commonly species identified in the blood cultures of ICU in contrast to C. albicans in general ward (Figures 3 and 4).
Intravenous fluconazole was the main antifungal prescribed in ICU (mean 0.094 DDD/100 PD). Oral fluconazole was the principal antifungal prescribed in a medical-surgery ward (mean 0.021 DDD/100 PD) and oncology unit (mean 0.429DDD/100 PD). None of the correlations between antifungal consumption and recovery of non albicans species reached a statistical significance.

Conclusion
The shift toward non albicans Candida is possible even in the presence of a low consumption of antifungals. This finding suggests the possibility of other contributing factors such as cross transmission and microbiome alteration.

Disclosures
All authors: No reported disclosures.
2120. Minimum Inhibitory Concentration Distribution of Fluconazole against Cryptococcus Species and the Fluconazole Exposure Prediction Model
Authors: Chesdachai Supavit , Rajasingham Radha , Nicol Melanie R , Meya David , Bongomin Felix , Abassi Mahsa , Skipper Caleb , Kwizera Richard , Rhein Joshua , Boulware David 
Published: October 2019

Abstract

Background
Fluconazole is lifesaving for the treatment and prevention of cryptococcosis; however, optimal dosing is unknown. Initial fluconazole doses of 100 mg to 2000 mg/day have been used. Prevalence of fluconazole non-susceptible Cryptococcus is increasing over time, risking the efficacy of long-established standard dosing. Based on current minimum inhibitory concentration (MIC) distribution, we modeled fluconazole concentration and area under the curve (AUC) relative to MIC to propose a rational fluconazole dosing strategy.

Methods
First, we conducted a systematic review using the MEDLINE database for reports of fluconazole MIC distribution against clinical Cryptococcus isolates. Second, we utilized fluconazole concentrations from 92 Ugandans who received fluconazole 800 mg/day coupled with fluconazole’s known pharmacokinetics to predict plasma fluconazole concentrations for doses ranging from 100 mg to 2000 mg via linear regression. Third, the fluconazole AUC above MIC ratio were calculated using Monte Carlo simulation and using the MIC distribution elucidated during the systemic review.

Results
We summarized 21 studies with 11,094 clinical Cryptococcus isolates. MICs were normally distributed with geometric mean of 3.4 mg/mL, median (MIC50) of 4 mg/mL, and 90th percentile (MIC90) of 16 mg/mL. The median MIC50 trended upwards from 4 mg/mL in 2000–2012 to 8 mg/mL in 2014–2018. Predicted sub-therapeutic fluconazole concentrations (below MIC) would occur in 38% with 100 mg, 20% with 200 mg, and 8% with 400 mg. AUC/MIC ratio > 100 would occur in 53% for 400 mg, 74% for 800 mg, 84% for 1200 mg, and 88% for 1,600 mg.

Conclusion
Currently recommended fluconazole doses may be inadequate for cryptococcosis. Further clinical studies are needed for rational fluconazole dose selection.

Disclosures
All authors: No reported disclosures.
2150. Detection and Characterization of Viral and Bacterial Pathogens in Tonsillar Tissues of Children Undergoing Tonsillectomy
Authors: Wang Huanyu , Xu Li , Everhart Kathy , Leber Amy 
Published: October 2019

Abstract

Background
The diagnosis of upper respiratory infections is commonly made using nucleic acid amplification technologies for viruses and bacteria. The impact of latency and colonization are not often appreciated. We aimed to detect viruses and bacteria present in tonsil and adenoid tissues from children during the absence of acute infection symptoms.

Methods
Remnant tonsil and adenoid tissues were obtained from children undergoing tonsillectomy procedures. Nucleic acids of viruses and bacteria were detected using laboratory developed PCRs targeting Epstein–Barr virus (EBV), Adenoviruses (AdV), human herpes virus 6 (HHV6), human enteroviruses (HEV), Group A streptococcus (GAS), Kingella kingae (KKN), Staphylococcus aureus (SA), Streptococcus pneumoniae (SPN), Arcanobacterium haemolyticus (AHE), Fusobacterium necrophorum (FNE), Mycobacterium pneumoniae (MPN) and Neisseria meningitidis (NM). The genogroup of AdV and the type of HHV6 were determined as well. Demographics, clinical presentation and detection rates of these viruses and bacteria were analyzed.

Results
During the study period (April 2018 and March 2019), 239 samples were collected from patients <18 years with an average age of 5.1 years. More male subjects than female subjects were included (57.7% vs. 42.3%). Most of the patients underwent tonsillectomy due to adenotonsillar hypertrophy (93.3%). Thirty (12.5%) also had a history of tonsillitis, 224 (93.7%) sleep apnea, 36 (15.1%) otitis media, 35 (14.6%) Eustachian tube dysfunction and 46 (19.2%) had other conditions. The detection of the pathogens among each age group is presented in Table 1. The seasonal distributions of virus positivity are shown in Figure 1.

Conclusion
The detection rates of each virus and bacterium in the tonsillar tissues from children absent of acute infection symptoms vary in each age group and fluctuate among seasons. In the molecular era when syndromic real-time multiplex PCR kits can provide sensitive and rapid results for a wide range of pathogens, it is important to understand the meaning of detection and differentiate between an infection and colonization or latency.

Disclosures
All authors: No reported disclosures.
2159. Accurate Carbapenem Susceptibility Testing Within 5–6 Hours
Authors: Stern Eric , Flentie Kelly , Spears Benjamin , Chen Felicia , DaPonte Kayla , Baker Kristin , Esmurria Ariela , Floyd Fred , Liu Jamie , Pasangulapati Vamsee , Plunkett Niall , Puff Derek , Purmort Nate , Reilly Patrick , Reynolds Andy , Shah Hemal , Somers Mark , Vacic Aleksandar , Briscoe Matthew , Varner Kenny , Chao Alan , Miller Noah , Quon Meghan , Jie Chen Jun , Clancy Mark , Persing Alana , Jane Ferraro Mary , Rosenberg David C 
Published: October 2019

Abstract

Background
Patients infected with multi-drug-resistant (MDR) pathogens may experience long delays to targeted therapies due to the incomplete antimicrobial menus and/or breakpoints tested on current commercial antimicrobial susceptibility testing (AST) systems. Detection of carbapenem resistance poses a challenge to rapid, accurate, minimum inhibitory concentrations (MIC) determinations because some resistant organisms may be inhibited by a carbapenem antibiotic until sufficient carbapenemase production has been achieved and traditional AST platforms must wait to make MIC calls. More accurate carbapenem MICs can be determined by implementing a carbapenemase test alongside rapid AST.

Methods
We demonstrate a novel, proprietary test to detect carbapenemase production that enables rapid MIC testing for carbapenem antibiotics. The test is processed in parallel with the Selux next-generation phenotyping (NGP) AST method, enabling rapid, <6-hour, accurate MIC determinations. The carbapenemase assay utilizes high concentrations of intact bacteria. After 3 hours of incubation, a fluorescent pH indicator is read spectroscopically. The solution pH is lowered by carbapenemase-mediated imipenem degradation and is indicative of enzyme activity.

Results
This assay accurately identifies carabapenemases across multiple enzyme classes and bacterial species. Figure 1 shows the accuracy and speed of NGP AST at determining MICs for representative isolates from the FDA-CDC antimicrobial resistance bank compared with results from overnight broth microdilution (BMD). To date, over 100 challenge strains of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii have been tested with no very major errors and an average time-to-result of 5.3 hours.

Conclusion
By incorporating a rapid, on-board carbapenemase activity assay, the NGP AST platform rapidly delivers accurate carbapenem results. Combined with NGP’s comprehensive antibiotic menus, this platform will therefore ensure prompt delivery of personalized antibiotic therapies for all patients, including those infected with MDROs, and enable streamlined antibiotic stewardship coordination.

Disclosures
All authors: No reported disclosures.
109. Clinical Characteristics and Outcomes of Staphylococcus aureus Bacteremia From a Biliary Source
Authors: Yang Eunmi , Bae Seongman , Seo Hyeonji , Cho Eunbeen , Park Su-Jin , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Jae Kim Min , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Hee Woo Jun , Soo Kim Yang , Pil Chong Yong 
Published: October 2019

Abstract

Background
Staphylococcus aureus can cause various types of infection, but involvement of biliary tract is rare. There were only few case reports and no clinical studies. We assessed the clinical characteristics and outcomes of S. aureus bacteremia from a biliary source (biliary SAB) in a large cohort of SAB patients and compared the cases with those of catheter-related SAB.

Methods
We performed a matched case–control study within a prospective observational cohort of patients with SAB at a 2,700-bed tertiary hospital. All adult patients with SAB were observed for 12 weeks from July 2008 to July 2018. Biliary SAB was defined as the case of S.aureus isolated from blood culture with appropriate clinical biliary infection symptoms (fever, abdominal pain, or jaundice) and signs (abdominal tenderness or liver enzyme elevation with obstructive pattern). Biliary SAB cases were matched 1:3 to control patients with catheter-related SAB based on age, gender, ward, and case year.

Results
A total of 1,818 patients with SAB were enrolled in the entire cohort, and 42 (2%) were biliary SAB. Among patients with biliary SAB, 32 (76%) had solid tumor involving pancreaticobiliary tract or liver, 30 (71%) had biliary drainage stent, 14 (33%) were biliary procedure-related infection, and 24 (57%) had recent broad-spectrum antibiotics exposure (Table 1). When biliary SAB patients were compared with 126 patients with catheter-related SAB, they were significantly more likely to have community-onset SAB, solid tumor, and lower APACHE II score; and less likely to have metastatic infection (P = 0.03) (Table 2). Biliary SAB, solid tumor, and a high Charlson comorbidity index were associated with 12-week mortality. In multivariate analysis, biliary SAB (aOR, 5.5; 95% CI, 2.47–12.25) and a high Charlson comorbidity index (aOR, 1.32; 95% CI, 1.12–1.54) were independent risk factors for 12-week mortality.

Conclusion
Biliary SAB was relatively rare and developed mainly in pancreaticobiliary cancer patients and in recent broad-spectrum antibiotic users. High mortality was probably attributable to underlying cancers. When biliary tract infection caused by S. aureus is clinically suspected, early aggressive treatment for SAB should be considered.

Disclosures
All authors: No reported disclosures.
2164. Activity of Fosfomycin (FOF) and Frequency of Nonsusceptible Inner Colonies During Susceptibility Testing of an International Collection of Clinical Pseudomonas aeruginosa (PA) Isolates
Authors: Smith Elizabeth C , Brigman Hunter V , Anderson Jadyn C , Emery Christopher L , Bias Tiffany E , Landersdorfer Cornelia B , Bergen Phillip J , Hirsch Elizabeth B , Hirsch Elizabeth B 
Published: October 2019

Abstract

Background
FOF has been used clinically for the treatment of PA infections in the absence of established interpretive criteria. A recent study identified a low frequency of nonsusceptible inner colony mutants during disk diffusion (DD) testing of Escherichia coli; however, the frequency of this phenomenon in PA isolates is not well characterized. We sought to determine FOF activity against an international collection of PA isolates and the frequency of inner colony mutants observed during Etest and DD testing.

Methods
Minimal inhibitory concentration (MIC) values were determined for a convenience collection of 109 PA ([70/94] 64.2% MDR) isolates from 4 institutions in the United States and Australia. MIC testing was conducted in duplicate on separate days utilizing agar dilution (AD), broth microdilution (BMD), DD, and Etest as recommended per Clinical and Laboratory Standards Institute (CLSI). CLSI E.coli interpretive criteria (≤ 64 mg/L susceptible) were used for MIC interpretations. The proportion of isolates containing inner colonies was determined using DD and Etest. Inner colony mutants were subcultured and retested using BMD with comparison to the parent isolate MICs.

Results
FOF MICs varied widely and ranged from 1024 mg/L with MIC50/MIC90 values of 64/256 (AD), 64/512 (Etest), and 64/256 (BMD) mg/L. Using E. coli criteria, susceptible/resistant rates were: 60.5/17.4% for AD; 60.5/22.0% for Etest; 86.2/7.3% for DD; and 53.2/17.4% for BMD. Inner colonies were frequently observed in 38.5% and 35.8% of DD and Etest inhibition zones, respectively. After repeat testing, mutant MIC values ranged from 64 to > 1024 mg/L and a majority (85.9%) had MIC values ≥ 512 mg/L.

Conclusion
Observed MIC values of this (64% MDR) collection varied widely with MIC50/90 values commonly at or above the E. coli susceptibility breakpoint. Inner colony mutants were frequently observed and highly resistant. Whole-genome sequencing is currently underway for a subset of parent/mutant pairs to determine whether specific genetic alterations are attributed to the increased MICs. Based on these results, caution should be warranted in extrapolating E. coli breakpoints to other organisms, and treatment of PA with FOF should be further evaluated.

Disclosures
Elizabeth B. Hirsch, PharmD, Merck: Grant/Research Support, Research Grant; Nabriva Therapeutics: Advisory Board; Paratek Pharmaceuticals: Advisory Board.
2179. Detection of Group A Streptococcus in the Saliva of Children Presenting With Pharyngitis Using the cobas®LIAT® PCR System
Authors: DeMuri Gregory P , Wald Ellen R 
Published: October 2019

Abstract

Background
CLIA waived polymerase chain reaction (PCR) has recently become available as a point of care test for Group A Streptococci (GAS) in individuals presenting with pharyngitis, enabling rapid and accurate diagnosis. However, swabbing the pharynx results in discomfort and is often dreaded by young children which may result in poor quality sampling.

Objective
In order to assess the viability of saliva as a sample specimen for GAS, this study compared saliva samples with pharynx swabs of children with sore throat, using swabs inoculated by children sucking on them as they would a lollipop in the context of newly available very sensitive techniques.

Methods
We enrolled children ages 5–15 years presenting with sore throat and known to have a positive rapid streptococcal antigen detection test (RADT) performed on a posterior pharyngeal swab, at the discretion of the primary care provider. The RADT used was the SureVue® (Fisher Scientific) system. A second swab was obtained by having the child suck on the swab in the anterior mouth for 30 seconds and a third swab was obtained from the posterior pharynx. PCR was performed on these two additional swabs using the cobas®LIAT® (Roche) system according to the manufacturer’s instructions.

Results
Seventeen children were enrolled in the study between January and April 2019. The mean age of enrollment was 9.6 years (range 6–15). By design all children were known to have a positive RADT for GAS. The LIAT posterior pharynx swab was positive in all 17 subjects. In addition, the LIAT saliva swab was positive in all 17 subjects.

Conclusion
In this small pilot study, there was 100% concordance between the RADT for GAS and both the posterior pharyngeal and saliva swab using the cobas®LIAT® PCR system. Performing saliva swabs will result in less discomfort and distress to children who are tested for GAS. Further study is needed to determine the sensitivity and specificity of saliva swabs for the detection of GAS in children presenting with acute pharyngitis.

Disclosures
All authors: No reported disclosures.