bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Clostridium difficile and Multidrug Resistant Gram-negative Rods in the Soil from Southeastern Wisconsin
Authors: Lor Angela , Tran Cathy , Jencson Annette , Cadnum Jennifer , Donskey Curtis , Munoz-Price L Silvia 
Published: October 2017

Abstract

Background
Preliminary data suggests that community-onset Clostridium difficile might be more common in rural areas. Thus, farms—specifically livestock farms—might be a major reservoir of C. difficile. Similarly, antibiotic exposures might predispose farm animals for colonization with multidrug resistant Gram-negative organisms. The aim of this study was to determine the prevalence of C. difficile and multidrug resistant gram-negative rods in the soil of Southeastern Wisconsin farms.

Methods
From July to September of 2016, soil samples were collected from farms with livestock animals. Soil samples were collected using gloves and sample containers. Soil samples were collected from farms specifically in or near Washington, Waukesha, and Milwaukee counties which are within the proximity of Milwaukee Metro area. Soil samples were cultured for C. difficile and Gram-negative rods on selective plates and by broth enrichment.

Results
A total of 20 farms participated in this study with a total of 40 soil samples. Out of the 40 soil samples, 20 were from an area where animals roam or where manure was used and the remaining 20 were from an area where animals are prohibited or where there was no manure. Out of the 20 soil samples where animals roam, 10 (50%), tested positive for C. difficile. Out of 20 soil samples where animals are prohibited, 13 samples (65%) tested positive for C. difficile. 2 of the 23 C. difficile isolates recovered were toxigenic. Eight (40%) of the 20 soil samples where animals roam tested positive for fluoroquinolone-resistant bacteria (FQR). While 5 (25%) of the 20 soil samples where animals are prohibited, tested positive for FQR bacteria. An Acinetobacter calcoaceticus was found to exhibit carbapenem-resistance.

Conclusion
We found soil colonization with C. difficile and FQR in 65% and 25%, respectively, where animals are prohibited. Where animals roam we found C. difficile and FQR 50% and 40%, respectively. Our study suggests that farms may be a significant community source for C. difficile and fluoroquinolone resistant organisms. Additional testing should be done to examine factors that might be increasing antibiotic resistance in farms (e.g., antibiotic exposure).

Disclosures
All authors: No reported disclosures.
Induced Human Intestinal Organoids (iHIOs) as Model Systems for Chemotherapy-associated Clostridium difficile (CD) Infections
Authors: Apewokin Senu , Pradhan Suman , Frerick Michael , Weiss Alison 
Published: October 2017

Abstract

Background
Patients undergoing cytotoxic chemotherapy are ten times more likely to develop Clostridium difficile infections (CDI) than the general patient population. Efforts to outline pathophysiologic mechanisms underlying this disproportionate incidence have been limited by the lack of disease-representative experimental models. We hypothesized that iHIOs could serve as toxicity models to evaluate chemotherapy-associated CDI

Methods
Intact iHIOs were exposed to cytotoxic chemotherapy (melphalan) in gut media at therapeutic doses (9 μg/mL; which is the equivalent of 140 mg/m2 human dose).
Cellular death was assessed by accumulation of the membrane permeant dye, Sytox-orange added at 5-days post treatment. iHIOs were also exposed to CD toxin A and B (TcdA and TcdB respectively) and epithelial barrier damage assessed by actin mislocalization and loss of E-cadherin. For controls iHIOs were exposed / microinjected with saline/PBS. Morphological and histological changes were then captured using light and confocal microscopy

Results
Morphologic and histologic assessments demonstrated cell death and epithelial barrier damage

Conclusion
iHIOs demonstrate cell death on exposure to CD toxins and melphalan chemotherapy. These properties could be harnessed in establishing toxicity models for evaluation of chemotherapy-associated CDI

Disclosures
S. Apewokin, T2 biosystems: Investigator, Research support Astellas: Scientific Advisor, Consulting fee
Weight Changes in Fecal Microbiota Transplant for Clostridium difficile
Authors: Hussam Dina , Drees Marci , Myerson Scott , Duffalo Chad , Mosby Danielle , Herdman Christine , Depalma Fedele , Mcgraw Patty , Bacon Alfred E 
Published: October 2017

Abstract

Background
Fecal microbiota transplant (FMT) for relapsing Clostridium difficile infections (CDI) allows for rapid repopulation of the colonic microbiome and may prevent future relapses. FMT is considered safe, however subsequent impact on weight and metabolism are incompletely understood. Animal studies have shown that alterations in microbiota lead to changes in weight; this is also suggested in humans, based on limited anecdotal evidence. This study explores changes in weight associated with FMT.

Methods
We conducted a retrospective observational study of patients who underwent FMT at our 1100-bed community-based academic healthcare system. FMT protocol requires 2 documented CDI relapses and failed vancomycin taper. FMT methods include colonoscopy, EGD and oral capsules. Of note, donor stool (OpenBiome, Boston, Massachusetts) criteria include BMI &lt;30. We conducted chart review for documented provider-measured weights pre- and post- FMT (≤ 1 year), and compared pre-FMT weights to last recorded weight within 1-year period. We also evaluated weights in a subset of patients in the acute (2–6 week post FMT) timeframe.

Results
Between Apr 2014- Oct 2016, 41 patients underwent FMT. Of these, 31 (75%) patients had adequate weight data available for review (Table). Overall patients gained an average 2.4%. During the acute phase, 20 patients (65%) had documented weights; of these 50% lost and 50% gained weight, with overall weight loss of 0.7%.

Conclusion
In this limited population, it appears FMT may predispose to weight gain, which may reflect improved health with CDI cure. However, effects of FMT on patient’s microbiomes must also be considered. As this intervention becomes more widely used we must be increasingly aware of possible metabolic side effects and ensure documentation of weight changes as part of FMT protocols.

Disclosures
All authors: No reported disclosures.
Endogenous Serum IgG Antibodies to Clostridium difficile Toxin B Are Associated with Protection against C. difficile Infection Recurrence
Authors: Kelly Ciaran P , Poxton Ian R , Shen Judong , Railkar Radha , Guris Dalya , Dorr Mary Beth 
Published: October 2017

Abstract

Background
MODIFY I/II were global trials of the efficacy and safety of bezlotoxumab (BEZ), a monoclonal antibody (mAb) against C. difficile toxin B, alone and with actoxumab (ACT), a mAb against C. difficile toxin A. BEZ was superior to placebo (PBO) at preventing recurrent CDI (rCDI) in patients (patients) receiving antibacterials for CDI. The addition of ACT did not improve efficacy. The aims were to explore potential biomarkers for rCDI risk in the patients receiving PBO by measuring endogenous IgG Abs against Cd toxins A and B (eAb-A and eAb-B); it was expected that patients with low eAb levels might be at increased risk of rCDI.

Methods
Serum samples were collected pre-dose (PRE), at Week 4, and Week 12 postdose. eAb titers were measured using an electrochemiluminescence immunoassay. Results were reported as &lt;1:1000, 1:1000, 1:5000, 1:25000, and ≥1:125000. As there is no clearly defined immunological surrogate of efficacy for rCDI tied to a specific eAb-A or eAb-B level, eAb levels were arbitrarily categorized as low (≤1:1,000), medium (1:5000), or high (≥1:25000). The rCDI rate was summarized by eAb category at each time point.

Results
The proportion of patients with higher eAb-A and eAb-B titers increased following the initial CDI episode (Tables 1 and 2). There was no evident correlation between eAb-A titers and the rCDI rate at any time point. The proportion of patients who experienced rCDI within 12 weeks after randomization was highest in patients with low eAb-B titers PRE and at Week 4. rCDI rate in those with low eAb-B titer at all timepoints and in patients who had low titer only at PRE was similar.

Conclusion
The rise in eAb-A and eAb-B titers over time is consistent with a convalescent humoral immune response to toxins A and B following CDI. The lack of correlation between eAb-A titers and rCDI is consistent with the lack of efficacy of ACT in prevention of rCDI. Conversely, higher eAb-B titers are associated with lower risk for rCDI, consistent with the efficacy of BEZ. 22.1% of patients with high eAb-B titers at PRE experienced rCDI. Therefore, eAb-B titers may have marginal utility as a biomarker for rCDI risk and are not likely to improve predictive value over clinical and demographic characteristics such as advanced age, compromised immunity, and CDI history.

Disclosures
C. P. Kelly, TBD: Investigator, Speaker honorarium; J. Shen, Merck & Co., Inc.: Employee, may hold stock/hold stock options in the Company; R. Railkar, Merck & Co., Inc.: Employee, may own stock/hold stock options in the Company; D. Guris, Merck & Co., Inc.: Employee, may own stock/hold stock options in the Company; M. B. Dorr, Merck & Co., Inc.: Employee and Shareholder, may own stock/hold stock options in the Company
Epidemiology and Outcomes of Clostridium difficile Infection in Hospitalized Patients within the US Military Health Care System
Authors: Eberly Matthew , Susi Apryl , Rajnik Michael , Adams Daniel , Nylund Cade 
Published: October 2017

Abstract

Background
Clostridium difficile infection (CDI) has become an emerging epidemic in the healthcare community. Our study aims to characterize the epidemiology and measure the attributable cost, length of stay, and in-hospital mortality of CDI among hospitalized patients in the US military health system (MHS).

Methods
We performed a retrospective cohort study of patients with CDI using MHS database billing records. Cases included all active duty patients, their dependents, or retirees admitted to a US military treatment facility for ≥2 days from October 2008 to September 2015 with a stool sample positive for Clostridium difficile via enzyme immunoassay, tissue cytotoxin assay, toxigenic culture, or polymerase chain reaction (PCR). Patient case-mix adjusted outcomes including in-hospital mortality, length of stay, and hospitalization cost were evaluated by high-dimensional propensity score adjusted logistic regression.

Results
Among 1,156,672 admissions within the MHS from 2008–2015, we identified 1,640 (0.14%) patients with CDI and found a significant increase in the trend of CDI over the 7-year study period (P &lt; 0.001). Median age (IQR) was 63 (41–76) in the CDI hospitalized group and 26 (6–46) in the non-CDI hospitalized group. Male gender was a risk factor for CDI (unadjusted odds ratio, 1.94; 95% confidence interval 1.76–2.14) and the majority of patients (84.5%) were associated with large-size medical centers. Patients hospitalized with CDI had significantly higher hospitalization cost (attributable difference [AD] $51,959, P &lt; 0.001), prolonged hospital stay (AD 11.8 days, P &lt; 0.001), and in-hospital mortality (case-mix adjusted odds ratio 3.28; 95% confidence interval 2.69–4.00).

Conclusion
CDI in hospitalized patients within the MHS is associated with advanced age, large medical centers, and an increased length of stay, hospital cost, and in-hospital mortality. We identified a significantly increased burden of hospitalization among patients admitted with CDI, highlighting the importance of infection control and antimicrobial stewardship initiatives aimed at decreasing the spread of this pathogen.

Disclosures
All authors: No reported disclosures.
Longitudinal Trends of Clostridium difficile Infection (CDI) within Department of Veterans Affairs (VA) Medical Centers—Acute Care and Long-term Care
Authors: Kralovic Stephen , Evans Martin , Simbartl Loretta , Roselle Gary 
Published: October 2017

Abstract

Background
CDI remains a significant and serious healthcare-associated infection within hospital and long-term care (LTC) settings. In 2012 VA began a CDI Prevention Initiative in its acute care (AC) facilities, which expanded to include LTC. Data were collected with regard to CDI cases and healthcare-facility associated (HCFA) status.

Methods
VA used CDC National Healthcare Safety Network (NHSN) Lab-ID Event definitions from CDI/MDRO Module with the exception that HCFA-status was called with a more stringent timeframe at 48 hours after admission. Monthly, VA Medical Centers and LTC Facilities report data to a central repository which includes number of cases meeting NHSN definitions for recurrence, hospital onset HCFA (HO-HCFA), community-onset HCFA (CO-HCFA) and community-onset non HCFA (CO-notHCFA) cases (equivalent of NSHN community-acquired [CA] cases). Data collection began from 2011 forward in AC, and from part of 2012 forward in LTC.

Results
In AC, the number of all cases reported ranged from 6313 to 6595 with no trend for increase/decrease noted from 2011 to 2016. However, when evaluating proportions of each type of CDI contributing to the overall occurrence, there is significant change over the years (P &lt; 0.0001, Chi-Square analysis of proportions) with HO-HCFA and CO-HCFA contributing to less (24.4% and 25.2%, decreases, respectively) and CO cases (particularly CO-notHCFA) contributing to more (38.1% increase) of the cases, (Fig 1). In LTC, there were overall lesser cases ranging from 980 to 789 from 2013 through 2016 (P = 0.05, linear regression), with no significant changes over the years (P = 0.06, Chi-Square of proportions) (Fig 2).

Conclusion
Over time, HO-HCFA and CO-HCFA cases have declined within VA AC facilities. However, an increase of CO-notHCFA cases (similar to NHSN CA cases) has occurred, increasing admission prevalence of CDI at VA facilities. As CDI prevalence on admission is a contributor to risk for HCFA disease, this increased pressure indicates the success of the VA CDI Prevention Initiative in decreases of HO-HCFA is even more substantive than raw rates would indicate. However, it also highlights a group of CDI cases which need a different, focused targeting of prevention strategies.

Disclosures
All authors: No reported disclosures.
A 10-year Review of Clostridium difficile Infection in Acute Care Hospitals in the United States
Authors: Luo Ruihong , Barlam Tamar , Weinberg Janice 
Published: October 2017

Abstract

Background
Many strategies reported to decrease CDI occurrence have been implemented in acute care hospitals in recent years. We assessed the change in incidence, mortality and hospital charges of CDI patients in acute care hospitals during 2005–2014. We also investigated risk factors for hospital-onset CDI (HOCDI) and predictive factors for mortality of CDI patients.

Methods
Using the Nationwide Inpatient Sample database, we identified adult patients (¡Ý 18 years) with CDI by ICD-9-CM codes. The trends of CDI incidence, mortality and hospital charges were evaluated by Poisson regression. The risk for HOCDI and factors to predict in-hospital death of CDI patients were analyzed by logistic regression.

Results
3,337,910 cases of CDI were identified out of a total of 318,703,355 hospitalizations (1.05%). Incidences of non-HOCDI and HOCDI were 0.42% and 0.63% respectively. In the 10-year study period, CDI incidence increased with an annual rate of 3.3% (P &lt; 0.001). The annual incidences of HOCDI and non-HOCDI increased with a rate of 1.4% and 2.0% respectively (P &lt; 0.001). After adjusting for demographics, length of hospital stay and Charlson index, transfer from long-term health facilities (OR=2.02, 95% CI 1.83–2.23) and admission to a teaching hospital (OR=1.10, 95% CI 1.05–1.15) were independent risk factors for HOCDI. The in-hospital mortality of CDI associated hospitalization decreased from 9.7% in 2005 to 6.8% in 2014 (P &lt; 0.001). Transfer from long-term health facilities significantly predicted the risk for in-hospital death in CDI patients (OR= 1.34, 95% CI 1.32–1.36). The sum charge of all CDI hospitalizations increased with an annual rate of 2.0% (P &lt; 0.001). The median charge per CDI hospitalization increased during 2005–2009 (P &lt; 0.001), and then decreased during 2010–2014 (P &lt; 0.001).

Conclusion
During 2005–2014, the mortality in CDI hospitalized patients decreased, but CDI incidence in acute care hospitals increased, resulting in increased total CDI associated hospital charges. Patients transferred from long-term healthcare facilities increased the risk for HOCDI and CDI associated in-hospital mortality. They should be considered as high-risk patients for CDI surveillance when developing mitigation strategies.

Disclosures
All authors: No reported disclosures.
Differences in Clinical Characteristics and Outcomes of Patients with Community-Onset Clostridium difficile Infection who Tested Positive by EIA Compared with NAAT through a Two-Step Algorithm
Authors: Phipps Erin C , Kenslow Nicole , Belovarski Ioan , Hancock Emily B 
Published: October 2017

Abstract

Background
The low sensitivity of toxin enzyme immunoassay (EIA) for the diagnosis of Clostridium difficile infection (CDI) motivated many laboratories to add nucleic acid amplification tests (NAAT) to their testing protocol. However, NAAT do not distinguish between colonization and infection, and indiscriminant testing could lead to over treatment of CDI.

Methods
Active, population-based CDI surveillance has been conducted through the Emerging Infections Program in Bernalillo County, NM since 2011, with test type collected at the individual level since 2014. Community-onset (CO) CDI cases with a first positive test diagnosed by a two-step algorithm (concurrent EIA/GDH, with discordant results reflexed to NAAT) in 2014–2015 were included. We analyzed clinical characteristics and outcomes of patients EIA positive compared with NAAT positive. Demographics, risk factors, treatment, and outcomes were assessed through medical record review.

Results
Among 1,063 cases, 559 (52.6%) were EIA positive only and 504 (47.4%) were NAAT positive only. Of those with stool collected as a hospital inpatient, 57% were NAAT positive (P &lt; 0.001); this increased from 43.4% if tested the day of admission to 61.4% when tested on day three. Conversely, 38.6% of patients with stool collected in an emergency department were NAAT positive (P = 0.004). Fewer cases with complicated outcomes were NAAT positive (40.7%, P = 0.023). Among those with no documentation of recent antibiotic use, 64.3% were NAAT positive (P &lt; 0.001), and 67.8% of cases with no CDI treatment were NAAT positive (P = 0.005). Only 28.3% percent of cases with recurrent CDI were initially NAAT positive (P &lt; 0.001).

Conclusion
EIA negative and NAAT positive CO-CDI cases tended to have a milder clinical presentation than those that were EIA positive. This suggests that some patients positive only by NAAT may have mild CDI or be colonized, rather than infected, with C. difficile. These individuals were less likely to have complicated outcomes, have recent documented antibiotic use, be treated for CDI, or have a recurrent CDI episode than those positive by EIA. Longer hospital stay correlated with increased proportion of testing NAAT positive. Providers may benefit from considering testing protocol and clinical correlation when assessing patients with positive C. difficile test results.

Disclosures
All authors: No reported disclosures.
Clinical Characteristics and Outcomes of Hematologic Malignancy Patients with Clostridium difficile Toxin EIA vs. PCR Positive Test Results
Authors: Ziegler Matthew , Landsburg Daniel , Pegues David , Alby Kevin , Gilmar Cheryl , Bink Kristen , Gorman Theresa , Moore Amy , Han Jennifer 
Published: October 2017

Abstract

Background
C. difficile infection is common in patients with hematologic malignancy. There is increasing recognition that molecular (polymerase chain reaction, PCR) based testing lacks specificity for infection, while detecting patients with colonization. The objective of our study was to evaluate characteristics of patients with toxin enzyme immunoassay (EIA) vs. PCR positive C. difficile test results.

Methods
A retrospective review of inpatients at a tertiary care academic center with hematologic malignancy and a positive C. difficile test from 1/2015 to 1/2016 was performed. Data on demographics, comorbidities, clinical features, and outcomes were collected using medical record review. Characteristics were compared between patients with EIA vs. PCR positive test results using chi-squared or Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables.

Results
A total of 130 patients were included: 51% and 49% had a PCR positive and EIA positive result, respectively. Diagnoses included AML (42%), multiple myeloma (22%), and Non-Hodgkin’s lymphoma (13%). Antibiotic exposure was similar, with a median of 4 days of anti-pseudomonal antibiotics received in the prior 30 days. There was no difference in history of a positive C. difficile test in the prior year (12% in the EIA group, 10% in the PCR group, P = 0.71).
Patients with EIA positive results were more likely to have a WBC ≥15/mm3 (18% vs. 6%, P = 0.02). However, there were no differences in presence of fever, stool frequency, or imaging evidence of colitis at the time of testing. Medications in the prior 72 hours were similar, including the use of proton pump inhibitors of ~40% and of laxatives of 28%. Clinical outcomes were also similar between patients with EIA vs. PCR positive tests: all-cause death (22% vs. 20%), recurrent CDI (9% vs. 13%), colectomy (1% vs. 4%), and megacolon (0% vs. 3%). Most patients received treatment with oral vancomycin for a median duration of 14 days.

Conclusion
In patients with hematologic malignancy, those with EIA vs. PCR positive C. difficile test results were clinically similar. These findings suggest that algorithms for testing and treatment of C. difficile in hematologic malignancy patients will need to be specifically targeted towards this immunocompromised population.

Disclosures
All authors: No reported disclosures.