bluuebunny/crossref_metadata_2025_split huggingface dataset:
1055. Epidemiology and Mechanisms of Carbapenem Resistance in Recurrent Extended-Spectrum β-Lactamase- Producing Enterobacteriaceae Bacteremia
Authors: Aitken Samuel L , Bhatti Micah , Sahasrabhojane Pranoti , Galloway-Pena Jessica , Li Xiqi , Tverdek Frank P , Reeves Cagney , McDaneld Patrick , Greenberg David , Shelburne Samuel 
Published: November 2018

Abstract

Background
Carbapenems are the treatment of choice for bacteremia caused by extended spectrum β-lactamase producing Enterobacteriaceae (ESBL-E). The emergence carbapenem resistance (CR) in ESBL-E isolates has been described; however, the rate of such resistance in clinical settings is unknown. We describe the frequency and mechanisms of CR in recurrent ESBL-E bacteremia at an NCI-designated cancer center.

Methods
We performed a prospective whole genome sequencing (WGS) study and retrospective cohort review of adult (age ≥18 years) patients with ESBL-E bacteremia between January 2015 and July 2016. Recurrent bacteremia was defined as identification of the same organism in blood culture at any time following initial successful treatment. CR was defined as resistance to meropenem. Carbapenemase production was assessed in the microbiology laboratory using Carba-NP. Available paired isolates underwent WGS via Illumina HiSeq for assessment of clonality and identification of CR mechanisms.

Results
One hundred and sixteen patients with ESBL-E bacteremia were identified. E. coli was the most common organism (86%), followed by K. pneumoniae (12%), and K. oxytoca (2%). Recurrent bacteremia was identified in 17 (15%) patients (E. coli [n = 15], K. pneumoniae [n = 2]). Of these, 6 (35%) were CR and 5/6 (83%) were Carba-NP negative. All six recurrent CR isolates occurred in patients with leukemia. Five isolate pairs were available for WGS. In four of five pairs (three E. coli, one K. pneumoniae), CR emerged from the same strain causing the original infection; one recurrence was caused by a distinct E. coli with a OXA-48-like gene. Compared with parental strains, CR E. coli contained deletions in porin-encoding genes and had increased mapping depth for genes encoding CTX-M ESBLs. The K. pneumoniae was Carba-NP negative with no identifiable CR mechanism.

Conclusion
Emergence of CR following treatment for ESBL-E bacteremia was seen only in leukemia patients and was primarily due to porin loss and amplification of ESBL genes, rather than acquisition of exogenous carbapenemases. These are the first clinical data describing the molecular mechanism of ESBL-E transformation to CR. These data serve as the basis for future studies of antimicrobial stewardship interventions to limit the emergence of CR in ESBL-E.

Disclosures
S. L. Aitken, Shionogi: Scientific Advisor, Consulting fee. Medicines Company: Scientific Advisor, Consulting fee. Merck & Co.: Scientific Advisor, Consulting fee.
1059. Staphylococcus aureus Bacteremia Treatment: Results From Pilot Surveillance in Four US States
Authors: Kabbani Sarah , Jackson Kelly , Epstein Lauren , Gellert Anita , Bernu Carmen , Overton Rahsaan , Nadle Joelle , Dumyati Ghinwa , Lynfield Ruth , Ray Susan M , Epson Erin , See Isaac 
Published: November 2018

Abstract

Background
Staphylococcus aureus treatment guidelines are being revised to include proposed quality measures for evaluation of patients with S. aureus bacteremia (SAB) (e.g., infectious disease [ID] consultation, echocardiogram, and documenting clearance of bacteremia). We describe current management practices of SAB to identify opportunities for quality improvement.

Methods
We conducted a pilot assessment of SAB cases reported to CDC’s Emerging Infections Program active, laboratory- and population-based surveillance from 24 hospitals in four states during 1–2 months in 2017 or 2018. An SAB case was the isolation of S. aureus from a blood culture among adults (≥18 years) in the catchment area. We collected clinical and demographic information and performed a descriptive analysis of management of SAB cases.

Results
Among 109 SAB cases identified, 50 (46%) were methicillin-resistant S. aureus (MRSA). While hospitalized, 87 (80%) patients were evaluated by ID consultation, 90 (83%) underwent an echocardiogram (26 were transesophageal), and 92 (84%) had documented clearance of bacteremia. During the hospitalization, 15 (14%) died and 12 (11%) left against medical advice (AMA). Of those who survived and did not leave AMA, median duration of hospitalization after initial culture was 10.5 days (interquartile range 7–18). In total, 10 survivors (9% of cases) completed at least 2 weeks of antibiotics while hospitalized, and 65 (60% of cases) were discharged on antibiotic therapy. Among the 25 MRSA patients discharged on antibiotics, common treatments were vancomycin (64%), daptomycin (8%), ceftaroline (8%), and linezolid (4%). Among the 40 methicillin-susceptible SAB patients discharged on antibiotics, cefazolin (56%), ceftriaxone (13%), cefepime (5%), linezolid (5%), nafcillin (3%), and vancomycin (3%) were most common. The remainder of outpatient treatments included oral β-lactams, clindamycin, doxycycline, levofloxacin, and erythromycin.

Conclusion
Overall, the majority of patients with SAB underwent evaluation according to the proposed quality measures and received therapy with targeted anti-staphylococcal agents, although opportunities to optimize treatment remain. Hospitalized patients who leave AMA represent a particular challenge for effective SAB therapy.

Disclosures
All authors: No reported disclosures.
1064. Clinical Outcomes of Daptomycin in Combination With Ceftaroline or Anti-Staphylococcal Penicillins for Patients With Persistent MRSA Bacteremia
Authors: Bouchard Jeannette , Oleksiuk Louise-Marie , Shields Ryan K 
Published: November 2018

Abstract

Background
Daptomycin-β-lactam (DAP-BL) combinations demonstrate in vitro synergy against MRSA; however, the clinical efficacy of combo is limited. Our objective was to compare the outcomes of patients with persistent MRSA bacteremia treated with DAP-BL combinations.

Methods
Retrospective, cohort study of hospitalized patients receiving DAP with ceftaroline (CPT) or oxacillin (OXA) between March 2012 and February 2018. Patients with persistent MRSA bacteremia despite ≥4 days of vancomycin therapy were included. Clinical success was defined as resolution of signs and symptoms of infection, microbiological eradication and in hospital survival.

Results
Thirty-two patients included. Forty-four percent were male, median age was 61 (range: 26–78), and the median Charlson score was 2 (range: 0–11). Sixteen percent were IVDU. Sources of bacteremia included endocarditis (31%), bone/joint (31%), skin soft tissue (28%), and catheter (25%); 53% had more than one source. At the onset of combo therapy, median Pitt Bacteremia score was 1 (0–7). ID was consulted in all patients. Twenty-three and nine patients received DAP in combo with CPT or OXA, respectively. Baseline demographics, underlying disease, and clinical characteristics were comparable between groups. Patients receiving DAP-CPT had higher median Pitt Bacteremia scores (2 vs. 1; P = 0.04) and shorter median durations of prior vancomycin (8 vs. 10 days; P = 0.02) than did patients receiving DAP-OXA. Source control was pursued equally between groups. Median time to clearance of bacteremia following combo therapy was 3 (0–24) vs. 2 (−1–16) days in the DAP-CPT and DAP-OXA groups, respectively (P = 0.45). Corresponding rates of clinical success (43% vs. 56%) and microbiologic eradication (78% for both) did not vary between groups (figure). In hospital mortality occurred in 39% of patients receiving DAP-CPT and 0% of patients receiving DAP-OXA (P = 0.03). Adverse events occurred in 35% and 44% of patients, respectively.

Conclusion
We have demonstrated high rates of microbiologic eradication and reasonable clinical success rates with DAP-BL combination therapy. Patients receiving DAP-CPT had higher severity of illness at baseline, which paralleled with higher mortality. These data provide compelling evidence for future studies designed to determine the optimal BL in combination with DAP for persistent MRSA bacteremia.

Disclosures
R. K. Shields, Allergan: Grant Investigator, Research grant. Pfizer: Consultant and Scientific Advisor, Speaker honorarium. Shionogi: Scientific Advisor, Consulting fee. Roche: Grant Investigator, Research grant. Venatorx: Grant Investigator, Research grant. Medicines Company: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Accelerate Diagnostics: Scientific Advisor, Consulting fee.
1065. Evaluation of a Staphylococcus aureus Bacteremia Treatment Checklist
Authors: Soukup Hailey , Holt Jessica 
Published: November 2018

Abstract

Background
Staphylococcus aureus bacteremia (SAB) is associated with high morbidity and mortality. Appropriate management involves repeat blood cultures, echocardiography, drug selection/route, and duration of therapy. Multiple studies have demonstrated improved outcomes in patients who are managed by infectious disease (ID) physicians compared with non-ID physicians; however, not all sites have access to an ID provider. To improve management of SAB, a checklist was developed and approved for use in a large healthcare system in August 2015.

Methods
A retrospective review was conducted on 400 randomly selected patients with SAB, 200 pre- and 200 post-implementation of a four-part management checklist. The primary outcome was overall adherence to the checklist, which included: repeat blood cultures, echocardiography, correct antibiotic/route selection, and appropriate antibiotic duration. Secondary outcomes included adherence when an ID physician was not consulted, adherence to the four components individually, and appropriate imaging.

Results
Adherence to the four part bundle remained stable from 2015 to 2017, with overall adherence rates of 80% and 79%, respectively. From 2015 to 2017, patients without repeat blood cultures (7% vs. 2%, respectively) and inappropriate inpatient antibiotic selection (6% vs. 3%, respectively) improved. Outpatient prescribing (11% vs. 11%), lack of imaging (11% vs. 9%), and antibiotic duration (15% vs. 15%) were consistent from 2015 to 2017, respectively. In 2017, 13 patients were discharged on oral antibiotics and were deemed inappropriate per the study criteria, although 12 of these patients were on appropriate antibiotics while inpatient. Infectious diseases providers were consulted on 96% of cases in 2017, an increase from 90% in 2015.

Conclusion
Adherence to an evidence based treatment bundle remains consistent with a previous analysis, despite an increase in cases with an ID provider consulted. Repeating blood cultures and inpatient prescribing improved over the interval. Focus areas for improvement include imaging, outpatient prescribing, and duration of therapy.

Disclosures
All authors: No reported disclosures.
1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance
Authors: Young Stephen , Mills Ray , Griego-Fullbright Christen , Wagner Aaron , Herding Emily , Nordberg Vickie , Friedland Emily , Bartolome Amelita , Almazan Anna , Tam Stanley , Biscocho Sheryl , Abusali Salina , Sandlund Johanna , Estis Joel , Bishop Jeffrey , Hansen Glen 
Published: November 2018

Abstract

Background
Commercially available tests for Clostridium difficile infection (CDI) make test selection by the laboratory difficult due to the following unsatisfactory characteristics: long turnaround time, poor sensitivity, and/or poor specificity. The Singulex Clarity® C. diff toxins A/B assay (in development) is a rapid and automated immunoassay for the detection of C. difficile toxins A and B in stool, with analytical limits of detection for toxins A and B at 2.0 and 0.7 pg/mL, respectively. In this multicenter study, the clinical performance of the Singulex Clarity C. diff toxins A/B assay was compared with standalone PCR, a multistep algorithm with enzyme immunoassay (EIA) and PCR, and cell cytotoxicity neutralization assay (CCNA).

Methods
Fresh samples from 267 subjects with suspected CDI were tested at two sites (Minneapolis Medical Research Foundation and TriCore Reference Laboratories) with the Singulex Clarity assay, PCR (Xpert®C. difficile), and EIA (C. Diff Quik Chek Complete®) for GDH and toxin testing. The performance of the assays and multistep algorithms were evaluated against CCNA (Microbiology Specialists, Inc.).

Results
The overall CDI prevalence was 15.7%. The Singulex Clarity C. diff toxins A/B assay had 90.5% sensitivity and 96.0% specificity, with a 98.2% negative predictive value when compared with CCNA, and the Clarity assay’s AuROC was 0.9534. PCR had 90.5% sensitivity and 91.1% specificity. Compared with CCNA, the toxin EIA had 47.6% sensitivity and 100% specificity. Testing with a multistep algorithm using EIA with discordant results reflexed to PCR resulted in 85.7% sensitivity and 94.7% specificity.

Conclusion
The ultrasensitive Singulex Clarity C. diff toxins A/B assay is equivalent to the sensitivity of PCR while providing higher specificity. Compared with a multistep algorithm, the Clarity assay provides higher sensitivity and specificity while providing faster time-to-result in a simpler-to-understand, one-step reporting structure, allowing for a standalone, single-step solution for detection of C. difficile toxins in patients with suspected CDI.

Disclosures
E. Friedland, Singulex, Inc.: Employee, Salary. A. Bartolome, Singulex, Inc.: Employee, Salary. A. Almazan, Singulex, Inc.: Employee, Salary. S. Tam, Singulex, Inc.: Employee, Salary. S. Biscocho, Singulex, Inc.: Employee, Salary. S. Abusali, Singulex, Inc.: Employee, Salary. J. Sandlund, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary.
1090. Patient Outcomes With Prevented vs. Negative Clostridium difficile Tests Using Computerized Clinical Decision Support (CCDS)
Authors: Madden Gregory , Enfield Kyle , Sifri Costi 
Published: November 2018

Abstract

Background
Overtesting and overdiagnosis of Clostridium difficile infection (CDI) are increasingly recognized as potentially avoidable causes for unnecessary treatment and cost. Reducing inappropriate testing through diagnostic stewardship may improve C. difficile test utilization. However, the safety of these interventions is not well understood, despite the potential risk for missed or delayed diagnosis. A computerized clinical decision support (CCDS) tool was implemented at a 619-bed tertiary care hospital as part of a multifaceted effort to reduce inappropriate C. difficile testing. The intervention was associated with reductions in tests (41%) and hospital-onset CDI events (31%). We sought to examine patient outcomes associated with the intervention.

Methods
The CCDS was designed to identify patients with a prevented test if a provider initiated the CCDS and aborted the order. Outcomes of patients with either a prevented or negative nucleic acid amplification test (NAAT) were compared retrospectively. A logistic regression model was created to evaluate the association between a prevented test attempt and serious adverse events. Patients with a subsequent positive result within 7 days of the initial trigger and those treated with CDI-effective antibiotics underwent chart review.

Results
Multivariate analysis of 637 cases (490 negative, 147 prevented) showed that a prevented test was not associated with the primary composite outcome (inpatient mortality or ICU-transfer) compared with a negative test (adjusted odds ratio, 0.912; 95% CI 0.513–1.571). Prevented tests were associated with shorter length of stay and similar rates of CDI-related complications. Eleven (7.5%) had a subsequent positive CDI, four within 30 minutes of the prevented test, suggesting nonsignificant delay in testing. Of the remaining seven patients, case review confirmed that five did not meet testing criteria while two met testing criteria at the time of the prevented test. No serious adverse events attributable to delayed CDI diagnoses or unjustified CDI treatment were identified by individual case review.

Conclusion
CCDS-based diagnostic stewardship for CDI may be both a safe and effective means to reduce inappropriate testing.

Disclosures
All authors: No reported disclosures.
1096. Effect of Diarrheal Illness During Pregnancy on Adverse Birth Outcomes in Nepal
Authors: Newman Kira , Gustafson Katie , Englund Janet , Katz Joanne , Magaret Amalia , Khatry Subarna , Shreshtha Laxman , Leclerq Steven C , Tielsch James , Steinhoff Mark C , Chu Helen 
Published: November 2018

Abstract

Background
Adverse birth outcomes, including low birthweight (LBW), small-for-gestational-age (SGA) and preterm birth, contribute to 60–80% of infant mortality worldwide. Little published data exist on the association between diarrhea during pregnancy and adverse birth outcomes. We sought to identify whether diarrhea during pregnancy was associated with adverse birth outcomes.

Methods
We used data from a community-based, prospective randomized trial of maternal influenza immunization of pregnant women and their infants conducted in rural Nepal from 2011 to 2014. Illness episodes were defined as at least three watery bowel movements per day for one or more days with 7 diarrhea-free days between episodes. Diarrheal illnesses were identified through longitudinal household-based weekly symptom surveillance. The c2 test, two-sample t-test, and log-binomial regression were performed to evaluate baseline characteristics and the association between diarrhea during pregnancy and adverse birth outcomes.

Results
Of 3,682 women in the study, 527 (14.3%) experienced one or more episodes of diarrhea during pregnancy. Diarrhea incidence was not seasonal. Women with diarrhea had a median of one episode of diarrhea (interquartile range (IQR) 1–2 episodes) and two cumulative days of diarrhea (IQR 1–3 days). Of women with diarrhea, 16.1% (85) sought medical care. Mean maternal age, parity, biomass cook stove use, home latrine, water source, caste, and smoking did not differ in pregnant women with and without diarrhea. In crude and adjusted analyses, women with diarrhea during pregnancy were significantly more likely to have SGA infants (42.6% vs. 36.8%; adjusted risk ratio=1.20, 95% CI 1.06–1.36, P = 0.005). LBW and preterm birth incidence did not significantly differ between women with diarrhea during pregnancy and those without. There was no significant association between seeking medical care for diarrhea and birth outcomes.

Conclusion
Diarrheal illness during pregnancy was associated with a significantly higher risk of SGA infants in this rural South Asian population. Interventions to reduce the burden of diarrheal illness during pregnancy may have an impact on SGA births in resource-limited settings.

Disclosures
All authors: No reported disclosures.
1102. Food Insecurity and Reported History of Cholera in Haitian Households: An Analysis of the 2012 Demographic and Health Survey (DHS)
Authors: Richterman Aaron , Franke Molly F , Ivers Louise C 
Published: November 2018

Abstract

Background
Food insecurity is defined as a lack of consistent access to food in adequate quantity or quality. Both cholera and food insecurity tend to occur in impoverished communities where poor access to food, inadequate sanitation, and an unsafe water supply often coexist. The relationship between the two, however, has not been previously studied.

Methods
We performed a secondary analysis of household-level data from the 2012 Demographic and Health Survey in Haiti, a nationally and subnationally representative cross-sectional household survey conducted every 5 years. We used multivariable logistic regression to evaluate the relationship between household food insecurity (as measured by the Household Hunger Scale) and (1) reported history of cholera since 2010 by any person in the household and (2) reported death by any person in the household from cholera. We used survey commands to apply sampling probability weights and account for clustering and stratification in sample design. We performed a complete case analysis because there were no missing data on household food insecurity or cholera and &lt;1% for the other covariates of interest.

Results
There were 13,181 households in the survey, 2,104 of which reported at least one household member with history of cholera. Both moderate hunger in the household [adjusted odds ratio (AOR) 1.47, 95% confidence interval (CI) 1.27–1.71; P &lt; 0.0001] and severe hunger in the household (AOR 1.71, 95% CI 1.42–2.05; P &lt; 0.0001) were significantly associated with reported history of cholera in the household after controlling for urban setting, household size, wealth index, water source, time to water source, latrine, and housing materials. Severe hunger in the household (AOR 2.81, 95% CI 1.58–5.00; P = 0.0005), but not moderate hunger in the household, was independently associated with reported death from cholera in the household.

Conclusion
This is the first study to identify an independent relationship between household food insecurity and reported history of cholera and death from cholera. The directionality of this relationship is uncertain and should be further explored in future prospective research.

Disclosures
All authors: No reported disclosures.
1104. Deployment-Associated Infectious Gastroenteritis and Associations With Irritable Bowel Syndrome, Post-Traumatic Stress Disorder, and Combat Stress: A Retrospective Cohort Study Among Deployed United States Military Personnel
Authors: Dunbar Christopher R , Riddle Mark S , Clarkson Kristen , Gutierrez Ramiro L , Alcala Ashley , Byrd Angelique , Porter Chad K 
Published: November 2018

Abstract

Background
Previous studies have shown an association between post-traumatic stress disorder (PTSD) and the development of irritable bowel syndrome (IBS) in deployed service members. Deployment places soldiers at risk for chemical, physical, psychological, and infectious stressors. Acute stress can alter the gastrointestinal barrier leading to gut barrier dysfunction, which is an independent risk factor for infectious gastroenteritis (IGE). We sought to assess if there was an association between IBS and PTSD in military deployed in support of recent and ongoing military operations.

Methods
We conducted a retrospective cohort study of United States service members who participated in a combat deployment to the Middle East from 2001 to 2013 with no prior Axis I disorders or PTSD diagnoses based on data from the Defense Medical Surveillance System. Univariate and multivariate logistic regression models were used to assess the differential risk of PTSD following a combat deployment among those with and without a predeployment diagnosis of IBS. These models were controlled for confounders/covariates of interest (IGE, age, duration of deployment, sex, race, marital status, education level, military rank, branch of service, number of deployments).

Results
Among the 3825 subjects, those who developed IGE had a 34% (P = 0.02) increased risk of PTSD compared with those with no IGE during deployment. Additionally, those with IBS predeployment had a 40% (P = 0.001) increased risk of PTSD upon return from deployment compared with those without IBS predeployment. Duration of deployment was significantly (P &lt; 0.0001) associated with PTSD with an increasing risk with increasing duration of deployment.

Conclusion
IGE and IBS were significantly associated with PTSD further supporting previous studies describing their association. Baseline chronic dysbiosis and acute stress-related microbiota perturbations may lead to short- and long-term resilience and performance deficits in our soldiers that may compromise mission capabilities and decrease the quality of life in returning soldiers. Further understanding the potential interactions between the gut–brain–microbiome may have immediate and long-term impacts on improving warfighter health and performance.

Disclosures
All authors: No reported disclosures.