bluuebunny/crossref_metadata_2025_split huggingface dataset:
1087. Aortic Graft Infections Caused by Propionibacterium acnes at the Minneapolis Veterans Affairs Health Care System (MVAHCS) 2007–2017
Authors: El Rafei Abdelghani , Drekonja Dimitri M 
Published: November 2018

Abstract

Background
Propionibacterium acnes is a Gram-positive microaerophilic bacterium and part of the human skin flora. The ability of P. acnes to cause infections has been recognized, particularly in the presence of hardware. We aimed to define the frequency of P. acnes infections, with a focus on aortic graft infection.

Methods
We used microbiology laboratory records at the Minneapolis Veterans Affairs Health Care System to identify all P. acnes cultures from January 2007 to January 2017. We retrospectively reviewed all adult (≥18 years) patient’s medical records to identify associated infectious syndromes. Case definitions by the management of Aortic Graft Infection Collaboration were used to classify aortic graft infection cases.

Results
We identified 328 positive P. acnes cultures during the study period. P. acnes was classified as a pathogen in 48 (15%), a pathogen of undetermined significance in 70 (21%), and a contaminant in 210 (64%) cases. We identified three cases aortic graft infection which accounted for (2.5%) of infections caused by P. acnes. Median age (range) at presentation was 74 years (67–83). Symptoms included pain (n = 3), fever (n = 2), and altered mental status (n = 1). None were hypotensive. All patients had at least one revision for endoleak prior to presentation. Median time from symptom onset to diagnosis was 120 days (78–140). Microbiological diagnosis was obtained by blood cultures, percutaneous peri-graft tissue aspiration, and operative culture in each patient, respectively. Infection was complicated by metastatic abscess in one patient. All cultures grew on Day 7. All patients were treated with IV ceftriaxone, and two were transitioned to life-long oral suppressive antibiotic therapy. Two patients had complete removal of infected material. No relapse was documented and survival was 100% at 1 year follow-up.

Conclusion
Aortic graft infection is an uncommon subset of infections caused P. acnes. Clinical course is indolent and diagnosis is delayed due to nonspecific clinical presentation. In contrast to endovascular graft infection caused by other organisms, mortality is low when treated with appropriate antibiotic therapy and removal of infected material. The current laboratory practice of holding blood cultures for 5 days may need to be altered when P. acnes is a potential cause of infection.

Disclosures
All authors: No reported disclosures.
1089. Analytical Performance of an Ultrasensitive Immunoassay for Detection of Clostridium difficile Toxins in Stool
Authors: Bartolome Amelita , Almazan Anna , Abusali Salina , Tam Stanley , Lee Eric , Changavi Amogh , Trinh Wendy , Chau Kent , Estis Joel , Noland Brian , Bishop Jeffrey 
Published: November 2018

Abstract

Background
Clostridium difficile infection (CDI) is the main cause for nosocomial diarrhea. Currently available assays for the diagnosis of CDI show deficits in sensitivity, specificity, and/or turnaround time. The Singulex Clarity® C. diff toxins A/B assay, in development for the Singulex Clarity® system, was designed to provide an accurate and automated detection of C. difficile toxins A (TcdA) and B (TcdB) in stool. Here, the analytical performance of the assay is reported.

Methods
Limits of detection (LoD) for TcdA and TcdB in stool and buffer was determined, and a preliminary cutoff, as compared with cell cytotoxicity neutralization assay (CCNA), was established. Analytical reactivity against 38 toxigenic and nontoxigenic C. difficile strains of eight different toxinotypes was determined. Cross-reactivity against 53 other gastrointestinal pathogens and potential interference by 11 endogenous and exogenous substances were determined. Reproducibility was tested with triplicate samples (n = 85), and stability was evaluated in samples stored at room temperature, refrigerated, and frozen conditions, and subjected to three freeze-thaw cycles.

Results
The LoDs for TcdA and TcdB were 0.8 and 0.3 pg/mL in buffer, and 2.0 and 0.7 pg/mL in stool, respectively. Using a preliminary cutoff, the assay demonstrated 96.3% sensitivity and 96.1% specificity compared with CCNA. The Singulex Clarity® C. diff toxins A/B assay detected toxins from all tested strains and toxinotypes. No cross-reactivity or interference were detected. The repeatability was 99%, and samples for C. difficile toxin testing were stable up to 8 hours in room temperature, 1 week in 2–8°C, 6 months in −70°C, and up to three freeze–thaw cycles.

Conclusion
The Singulex Clarity C. diff toxins A/B assay (in development) can detect TcdA and TcdB at very low concentrations and it has high sensitivity and specificity compared with CCNA. The assay demonstrates reactivity to common C. difficile strains, does not show cross-reactivity to common gastrointestinal pathogens, is robust against common interferents, allows for toxin detection in both fresh and frozen stool samples and up to three freeze–thaw cycles, and provides results with high reproducibility.

Disclosures
A. Bartolome, Singulex, Inc.: Employee, Salary. A. Almazan, Singulex, Inc.: Employee, Salary. S. Abusali, Singulex, Inc.: Employee, Salary. S. Tam, Singulex, Inc.: Employee, Salary. E. Lee, Singulex, Inc.: Employee, Salary. A. Changavi, Singulex, Inc.: Employee, Salary. W. Trinh, Singulex, Inc.: Employee, Salary. K. Chau, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary. B. Noland, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary.
1093. Single Molecule Counting Technology for Ultrasensitive Quantification of Clostridium difficile Toxins A and B
Authors: Katzenbach Phoebe , Dave Gipshu , Mukherjee Ali , Todd John , Bishop Jeffrey , Sandlund Johanna , Estis Joel 
Published: November 2018

Abstract

Background
Clostridium difficile, a spore-forming, anaerobic, Gram-positive bacterium, is the leading cause of nosocomial diarrhea. C. difficile infection (CDI) is mediated by two toxins, A (TcdA) and B (TcdB), and the role of each toxin in CDI pathogenesis remains unclear. Many assays used in CDI diagnostics, such as most NAATs and cell cytotoxicity neutralization assay (CCNA), detect presence of only tcdB or TcdB. In this study, an ultrasensitive immunoassay (UIA) powered by Single Molecule Counting technology was used for quantification of TcdA and TcdB, to assess toxin dynamics in CDI.

Methods
Banked samples from 46 patients with suspected CDI were tested with PCR (BD MAX™ Cdiff Assay) and CCNA, and TcdA and TcdB were quantified using the UIA (tested in triplicate). The limits of detection (LoDs) for the TcdA and TcdB assays are 0.04 and 0.12 pg/mL, respectively.

Results
There were 21 PCR+/CCNA+ and 25 PCR−/CCNA− samples. Both toxins were measured above LoD in all PCR+/CCNA+ samples, ranging up to 100,000 pg/mL. The average CV for the PCR+/CCNA+ samples was 9%. The median TcdA concentrations in PCR−/CCNA− and PCR+/CCNA+ samples were 0.19 pg/mL (IQR 0.12–0.67) and 3,301 pg/mL (125–8,737), respectively. The median TcdB concentrations in PCR−/CCNA− and PCR+/CCNA+ samples were 0.12 pg/mL (0.12–0.21) and 2,690 pg/mL (145–30,307), respectively. In the PCR+/CCNA+ samples, TcdA was one or more logs higher than TcdB in two samples, one or more logs lower than TcdB in six samples, and within one log of TcdB in 13 samples. In one sample (4.8% of PCR+/CCNA+ samples), TcdA was at moderately high concentration while TcdB was below a provisional cutoff, indicating that only TcdA was expressed. There was a significant correlation between TcdA and TcdB (Spearman r = 0.753).

Conclusion
The UIA allows for toxin quantification over a concentration range of ≥5 logs, suggesting that the quantitative TcdA and TcdB assays could be of value in CDI characterization and clinical decision making. The TcdA/TcdB ratio varied, and toxin quantification could be a useful tool in further understanding their individual roles in CDI. The TcdA concentration was not lower than TcdB (trended higher), indicating that detection of tcdB or TcdB alone may not be sufficient for accurate CDI diagnostics.

Disclosures
P. Katzenbach, Singulex, Inc.: Employee, Salary. G. Dave, Singulex, Inc.: Employee, Salary. A. Mukherjee, Singulex, Inc.: Employee, Salary. J. Todd, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary. J. Sandlund, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary.
1099. Antibiotic Prescriptions for Acute Gastroenteritis during Office and Emergency Department Visits–United States, 2006–2015
Authors: Collins Jennifer P , Watkins Louise Francois , King Laura M , Bartoces Monina , Fleming-Dutra Katherine , Friedman Cindy 
Published: November 2018

Abstract

Background
Acute gastroenteritis (AGE) is a major cause of office and emergency department (ED) visits in the United States. Most patients can be managed with supportive care alone, although some require antibiotics. Limiting unnecessary antibiotic use can minimize side effects and the development of resistance. We used national data to assess antibiotic prescribing for AGE to target areas for stewardship efforts.

Methods
We used the 2006–2015 National Hospital Ambulatory Medical Care Survey of EDs and National Ambulatory Medical Care Survey to describe antibiotic prescribing for AGE. An AGE visit was defined as one with a new problem (&lt;3 months) as the main visit indication and an ICD-9 code for bacterial or viral gastrointestinal infection or AGE symptoms (nausea, vomiting, and/or diarrhea). We excluded visits with ICD-9 codes for Clostridium difficile or an infection usually requiring antibiotics (e.g., pneumonia). We calculated national annual percentage estimates based on weights of sampled visits and used an α level of 0.01, recommended for these data.

Results
Of the 12,191 sampled AGE visits, 13% (99% CI: 11–15%) resulted in antibiotic prescriptions, equating to an estimated 1.3 million AGE visits with antibiotic prescriptions annually. Antibiotics were more likely to be prescribed in office AGE visits (16%, 99% CI: 12–20%) compared with ED AGE visits (11%, 99% CI: 9–12%; P &lt; 0.01). Among AGE visits with antibiotic prescriptions, the most frequently prescribed were fluoroquinolones (29%, 99% CI: 21–36%), metronidazole (18%, 99% CI: 13–24%), and penicillins (18%, 99% CI: 11–24%). Antibiotics were prescribed for 25% (99% CI: 8–42%) of visits for bacterial AGE, 16% (99% CI: 12–21%) for diarrhea without nausea or vomiting, and 11% (99% CI: 8–15%) for nausea, vomiting, or both without diarrhea. Among AGE visits with fever (T ≥ 100.9oF) at the visit, 21% (99% CI: 11–31%) resulted in antibiotic prescriptions.

Conclusion
Patients treated for AGE in office settings were significantly more likely to receive prescriptions for antibiotics compared with those seen in an ED, despite likely lower acuity. Antibiotic prescribing was also high for visits for nausea or vomiting, conditions that usually do not require antibiotics. Antimicrobial stewardship for AGE is needed, especially in office settings.

Disclosures
All authors: No reported disclosures.
1107. The MAAGE Study: Health Care Utilization for the Treatment of Medically Attended Acute Gastroenteritis
Authors: Mattison Claire P , Groom Holly , Donald Judy , Salas S Bianca , Marsh Zachary , Burke Rachel M , Schmidt Mark A , Hall Aron J , Naleway Allison L 
Published: November 2018

Abstract

Background
Acute gastroenteritis (AGE) exacts a substantial disease burden across the age spectrum, although healthcare utilization for AGE is not well characterized. Through active surveillance of medically attended acute gastroenteritis (MAAGE) encounters within a large, integrated healthcare delivery system, we analyzed demographic patterns of healthcare utilization among AGE patients.

Methods
From April 1, 2014 to September 30, 2016, we collected information on all MAAGE encounters in Kaiser Permanente Northwest (KPNW) patients through daily abstraction from electronic health records using ICD-9/-10 codes. For each patient, a MAAGE episode was defined as all MAAGE encounters &lt;30 days apart.

Results
There were 109,493 MAAGE encounters among 39,451 patients. Patients were 60.4% female and 39.6% male; 10.3% were &lt;5 years old, 9.7% were 5–17, 31.1% were 18–44, 25.4% were 45–64, and 23.5% were ≥65. Among those with known race, 87.2% were white; 4.1% were Asian, 3.6% were black, and 5.1% were other or multiple races. Prevalence of any chronic comorbid condition was 52.9%.
Of 52,107 MAAGE episodes, 81.0% first presented as outpatients; this was most common in those aged &lt;5 (92.1%) and decreased with age to 75.0% in those ≥65. First presenting remotely (email or telephone) ranged from 4.0% in those aged &lt;5 to 19.3% in those ≥65; 52.7% of episodes first presenting remotely had no subsequent visits. Few episodes first presented to an emergency department (3.8% in &lt;5 year olds to 6.6% in 18–44 year olds) or inpatient setting (0.1% in &lt;5 year olds to 1.7% in ≥65 year olds).
Most MAAGE episodes comprised of one encounter (median: 1.0, mean: 2.1). The number of encounters per episode was lowest in those &lt;5 years old (median: 1.0, mean: 1.5) and highest in those ≥65 (median: 2.0, mean: 2.5). Most deaths within 30 days from the start of an episode (131/161) were in those ≥65; there were none in those &lt;5, 1 in those 5–17, 5 in those 18–44, and 24 in those 45–64.

Conclusion
We found that the number of encounters per MAAGE episode increased with age and that outpatient and remote encounters are important settings for the initial clinical management of MAAGE in all ages. These data can help to better quantify the economic burden of AGE and guide appropriate delivery of healthcare services.

Disclosures
All authors: No reported disclosures.
1112. Detection of Enteric Viruses in Children With Acute Gastroenteritis
Authors: Hamdan Lubna , Batarseh Einas , Piya Bhinnata , Stewart Laura , Fonnesbeck Chris , Chappell James D , Payne Daniel C , Hall Aron J , Dunn John , Wikswo Mary E , Halasa Natasha 
Published: November 2018

Abstract

Background
Acute gastroenteritis (AGE) is a major cause of morbidity in children. Viral pathogens are the most common infectious agents. Differences in illness characteristics of AGE with and without virus detection are poorly defined. We compared AGE illness characteristics between children with and without any-virus detected, and with single vs. multiple viruses detected.

Methods
Children between 15 days and 17 years with AGE defined as diarrhea (&gt;3 loose stools/24 hours) or any vomiting within 10 days duration were enrolled in Vanderbilt Children’s Hospital inpatient, ED, and outpatient settings from December 2012 to November 2015. Stool specimens were tested by RT-qPCR for norovirus, sapovirus, and astrovirus and by ELISA (VP6 antigen [Rotaclone®]) for rotavirus.

Results
Of 3,705 children enrolled, 2,892 (78%) specimens were collected. A single virus was detected in 1,109 (38%) stools [51% norovirus, 20% rotavirus, 21% sapovirus, and 8% astrovirus], viral co-detections were found in 115 (4%) stools, and 1,665 (58%) had no detected viruses. Table 1 compares children with and without any-virus detected. Children with a single-virus detected were older than those with &gt;1 virus detected (1.8 vs. 1.5 years [P &lt; 0.05]) with no other significant differences.

Conclusion
Children with any-virus detected had more severe symptoms, higher MVS, and more frequently reported sick contacts compared with no-virus detected. Children with no-virus detected were more likely to present with fever and higher temperatures, which may be due to bacterial organisms. These data highlight the importance of infection-prevention precautions in the community and the need for additional testing to define the etiologic spectrum of AGE in children.

Disclosures
N. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.
1113. Real-Time Evolution of Extensively Drug-Resistant Vibrio cholerae
Authors: Das Bhabatosh 
Published: November 2018

Abstract

Background
Bay of Bengal is known as the epicenter of a number of distinct waves of global transmission of cholera. Vibrio cholerae, the etiological agent of acute diarrhoeal disease cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and acclimatize them into their genome for structuring metabolic process, developing drug resistance and disease. Antimicrobial resistance (AMR) in V. cholerae is a global concern. However, little is known about the identity, source, acquisition process, and stability of the resistance traits in the genome of cholera pathogen.

Methods
Antibiotic susceptibility testing of V. cholerae isolated from different parts of India during 2001–2017 was performed using Discs and E-strips. Whole-genome sequencing of resistant (R), multidrug resistant (MDR), extensively drug resistant (XDR), and pandrug (PDR) resistant V. cholerae was done by next-generation DNA sequencing. Mobile genetic elements (MGEs) linked with AMR genes were tagged by allelic exchange methods. Whole-cell proteome analysis was done by iTRAQ analysis.

Results
Almost 99% of V. cholerae isolates (n = 438) are resistant against ≥2 antibiotics, 17.2% isolates (n = 76) are resistant against ≥10 antibiotics, and 7.5% isolates (n = 33) are resistant against ≥14 antibiotics. Highest resistance was detected against sulfamethaxozole (99.8%, n = 442). In addition, resistance to nalidixic acid (n = 429), trimethoprim (n = 421), and streptomycin (n = 409) are also very high. All the sequenced resistant isolates carrying multiple resistance genes and are linked with MGEs like integrating conjugative elements, transposons etc. Most of the resistance traits are functional and expressed even in the absence of antibiotics.

Conclusion
Our comprehensive analysis of 443 clinical V. cholerae isolates show that the cholera pathogen is continuously evolving to counterbalance the antimicrobial effects of antibiotics. Several MGEs linked with AMR genes and other fitness factors potentially propagate to other bacterial species through HGTs. Knowledge of the present study would be useful to understand the evolution of cholera pathogens and management of cholera by helping selection of specific drug regimen against the pathogens.

Disclosures
All authors: No reported disclosures.
1114. Utility of a Bedside Diagnostic Testing Algorithm to Screen for Hospital-Onset Clostridium difficile Infection
Authors: Nathan Ramesh V , Lenz Amy , Davis Genevieve 
Published: November 2018

Abstract

Background
Molecular assays have improved C. difficile detection in hospitalized patients. However, asymptomatic carriers have been misclassified as hospital onset C. difficile infection (HO-CDI), which has implications for management and infection prevention programs. At our facility, we implemented robust antibiotic stewardship policies in 2016 and had an SIR for HO-CDI of 0.73 for the year. In Q1 2017, this increased to 1.88. These cases revealed that nearly all tests, found positive for C. difficile, did not meet the standard definition of clinically significant diarrhea (CSD). Moreover, many patients did not have a clinical change in condition that supported a diagnosis of C. difficile. We reasoned that an algorithm for appropriate testing for C. difficile would significantly reduce our perceived rates of HO-CDI. We also reasoned that this tool could efficiently be used at the bedside during a clinical assessment.

Methods
To determine which patients had CSD, we designed, educated on and implemented an algorithm to screen for appropriate testing. It required three major elements: three or more loose stools in 24 hours, no gastric motility agents 48 hours prior, and a clinical change in condition (e.g., leukocytosis, fever, abdominal cramping). The completed algorithm accompanied the stool specimen and was required for testing. We evaluated each submitted algorithm for method validation. From this, we determined testing appropriateness and algorithm tool selectivity.

Results
One year pre- and post-algorithm periods (PR-A and PO-A, respectively) were defined. Following its introduction, we noted a 57% decline in rates of HO-CDI (23 cases PR-A vs. 10 cases PO-A), and a 44% reduction in tests sent for C. difficile (average of 41 tests/month PR-A vs. 23 tests/month PO-A). We only used NAAT testing. We also noted a marked rise in adherence to the algorithm as time elapsed. The PDSA tool was used to refine the algorithm, with improved utilization by providers.

Conclusion
A simple bedside algorithm leads to more appropriate testing of patients for HO-CDI. A significant decline in reported rates of HO-CDI was noted. There is an additional benefit of diagnostic stewardship, as fewer tests are sent. This tool can be used immediately and independent of an electronic health record, is very cost effective, and is applicable to hospitals with low rates of HO-CDI.

Disclosures
R. V. Nathan, Merck, Allergan, The Medicines Co.: Speaker’s Bureau, Speaker honorarium.
1116. Comparison of Short-Course vs. Prolonged-Course Antimicrobial Therapy in the Management of Intra-Abdominal Infections
Authors: Phlamon Mina , Petite Sarah , Cole Kelli 
Published: November 2018

Abstract

Background
When managing complicated intra-abdominal infections (IAIs), the current Infectious Diseases Society of America (IDSA) guidelines recommend an antimicrobial treatment duration of 4–7 days. Although recent evidence supports this shorter course of therapy, antimicrobials are still often administered for 10–14 days due to concern for subsequent complications. The purpose of this study was to compare clinical outcomes of short-course (SC) vs. prolonged-course (PC) antimicrobial therapy in the management of IAI at our institution.

Methods
IRB-approved, single-center, retrospective cohort including all patients at the University of Toledo Medical Center who were admitted between January 1, 2012–June 30, 2017 with an IAI, received antimicrobials for ≥48 hours, and had at least one sign of IAI. Patients with concomitant infections at sites other than the abdomen, primary peritonitis or pancreatitis, immunocompromising conditions, or bacteremia were excluded. Primary outcome of clinical cure was compared between SC (≤7 days of antimicrobial treatment) and PC (&gt;7 days) groups. Secondary outcomes included hospital length of stay (LOS), ICU LOS, 28-day all-cause mortality, and 30-day readmission. Multivariable logistic regression was performed to assess for factors associated with clinical cure.

Results
One hundred seventy-five patients were included, 73 SC and 102 PC. Baseline characteristics were similar between groups. Rate of clinical cure for SC vs. PC was 74.0% vs. 67.6% (P = 0.367). Secondary outcomes including hospital LOS (5.5 days vs. 5.8 days, P = 0.372), ICU LOS (3.0 days vs. 5.0 days, P = 0.117), 28-day all-cause mortality (4.1% vs. 2.0%, P = 0.651), and 30-day readmission (19.2% vs. 20.6%, P = 0.818) were also not significantly different. After multivariable logistic regression, the only variable independently associated with clinical cure was diverticulitis (adjusted odds ratio 0.337, 95% CI 0.133 – 0.853).

Conclusion
In patients with IAI, there was no significant difference observed in rates of clinical cure between SC and PC antimicrobial therapy. These results further support the IDSA recommendations for a shorter duration of therapy for patients with IAI.

Disclosures
All authors: No reported disclosures.