bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fecal Microbiota Transplantation (FMT) for Recurrent/Refractory Clostridium difficile Infection (CDI) in Pediatric Immunocompromised Patients: A Single-center Experience
Authors: Kwendakwema Natasha , Jensen M Kyle , Pavia Andrew , Knackstedt Elizabeth Doby 
Published: October 2017

Abstract

Background
CDI is a common cause of bacterial diarrhea, especially in immunocompromised patients. Fecal Microbiota Transplanation (FMT) has been shown to be an effective treatment for recurrent and refractory CDI. The outcomes of FMT treatment for recurrent CDI have been well described in adult populations; however, the data for immunocompromised (IC) patients especially among children are limited. We describe the experience of FMT for treatment of CDI in immuncompromised pediatric patients.

Methods
We collected clinical data for IC patients &lt;21 years in our pediatric institution who had received FMT for recurrent, refractory, and/or severe CDI. IC patients included those with: solid organ transplantation (SOT) receiving immunosuppressive medications; neoplasm; hematopoietic stem cell transplantation (HSCT); inflammatory bowel disease (IBD) requiring immunosuppressive medication(s). We collected demographic and clinical data, as well as outcomes, including: resolution of diarrhea, CDI relapse, and adverse events within 3 months post-FMT.

Results
We performed 37 pediatric FMT for recurrent, refractory, and/or severe CDI between September 2012 and February 2017. Of these, 12 were immunocompromised children: 2 with SOT; 3 with neoplasm and/or HSCT; and 7 with IBD on immunosuppressive medication(s). Median age was 11.9 years old (range 3–16 years). 6 (50%) experienced resolution of diarrhea within 1 week post-FMT, and 9 (67%) were C. difficile negative within 3 months of FMT (3 patients did not have follow-up testing). None had CDI relapse within 3 months post-FMT. 3 (25%) had adverse event(s) within 3 months post-FMT, 2 of whom had SAEs: 1 had graft rejection at 2 months post-FMT which ultimately required re-transplantion and 1 had aspiration pneumonitis immediately following FMT. 4 (50%) of the IBD patients had disease remission (clinical, biologic, and/or histologic) in the 3 months post-FMT.

Conclusion
FMT appears to be effective and reasonably safe for recurrent CDI in immunocompromised pediatric patients. However, the small numbers limit conclusions, especially about safety. Larger multicenter studies are needed to precisely determine safety and efficacy in this specialized population.

Disclosures
All authors: No reported disclosures.
Comparative Effectiveness of Vancomycin vs. Metronidazole in Mild Clostridium difficile Infections, and Potential Impact on Subsequent Vancomycin-Resistant Enterococcus (VRE) Isolation
Authors: Youngster Ilan , Lazarovitch Zipora , Bondorenco Marina , Mengesha Betlehem , Toledano Limor , Kachlon Yael , Marchaim Dror 
Published: October 2017

Abstract

Background
The epidemiology and clinical characteristics of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI, with superior cure rates observed in comparative trials. However, controlled comparative efficacy data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent Vancomycin-Resistant Enterococcus (VRE) isolation rates remains unknown at the individual patient level.

Methods
A Retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, Israel, from 2010 to 2015. Adult patients (&gt;18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs..metronidazole was evaluated in the subset of patients with mild CDI. The outcomes of patients, who received vancomycin or metronidazole (but not both), were compared by Cox regression. A prediction score was used to control for possible confounders associated with being treated with vancomycin. The independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation was analyzed using Cox regression.

Results
A total of 413 patients with CDI were included in the study. The majority were elderly (median age 75 years, range 19–120), and had extensive comorbidities (mean Charlson’s combined condition score 6.7 ± 3.4) and significant acute illness indices (35% with severe to fulminant Horn index). Among 126 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a “vancomycin case”. Ten patients had new post-CDI VRE isolation. In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=6.7, P = 0.04).

Conclusion
Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis.

Disclosures
All authors: No reported disclosures.
Epidemiology of Clostridium difficile infection Among Patients with Newly Diagnosed or Relapsed Acute Leukemia: A Single-center Experience
Authors: Garcia Alexandra Franco , McMillen Tracy , Chow Hoi Yan , Eagan Janet , Sun Janine , Kamboj Mini 
Published: October 2017

Abstract

Background
Patients undergoing treatment for hematologic malignancy are at a higher risk for developing Clostridium difficile infection (CDI). We sought to determine the epidemiology of toxigenic C. difficile (TCD) carriage and CDI incidence among patients undergoing with newly diagnosed or relapsed acute leukemia.

Methods
Serial stool samples were collected from 92 patients with new or relapsed acute leukemia admitted at Memorial Sloan Kettering Cancer Center between August 26, 2011 to January 22, 2013. Only the first hospitalization during this time period was included. Screening was performed by toxigenic culture and polymerase chain reaction for tcdB gene regardless of symptoms of diarrhea. Genotyping was done by Multi Locus Sequence Typing (MLST). Acquisition of TCD, development of CDI, and associated clinical variables were recorded.

Results
A total of 92 patients were enrolled in the study. The mean age was 54.3 (median 57.5, range 21–86), 51 were male (55%). The majority (86, 93%) had newly diagnosed acute leukemia and 7% had relapsed disease. 60 patients (65%) had recent healthcare-related exposure, among these were 35 (38%) patients newly referred another facility. The most common chemotherapy regimen was Daunorubicin + Cytarabine in 71 subjects (77%). Systemic antibiotics of any duration during the same hospitalization were used in 89 patients (97%). Median length of stay (LOS) was 30.5 days (range 6–140 days).
Among the 92 subjects, 17 developed CDI within 90 days (18%), 12 (71%) had CDI during the index admission. Five among these 12 had known TCD colonization, genotyping of colonizing and CDI strains from the same patients were identical for all patients. CDI in subsequent hospitalizations occurred in 5 patients, 4/5 were new acquisitions. One patient with TCD colonization never developed CDI.
53 subjects (58%) underwent stem cell transplant at a median time of 4 months (range 2–19 months), 8 (15%) developed CDI within 30 days of the transplant admission.

Conclusion
CDI is exceedingly common among patients with acute leukemia. Acquisition of TCD and CDI occurs early in the treatment course. Approximately half of infections occur in patients with known TCD colonization. Extended LOS and high antibiotic usage are contributors to the high burden of CDI among this population.

Disclosures
All authors: No reported disclosures.
Increasing Economic Burden of Inpatient Clostridium difficile Infection in the United States: National Trends in Epidemiology, Outcomes, and Cost of Care from 2000 to 2014
Authors: Lee Ru Min , Fishman Neil O 
Published: October 2017

Abstract

Background
There is limited data addressing the epidemiology, costs, and outcomes of Clostridium difficile infection (CD) in hospitalized patients in the United States (U.S.). This study aims to estimate the characteristics, outcomes, and economic burden of patients hospitalized for CD in the US.

Methods
The Nationwide Inpatient Sample (NIS) database was used to obtain data from 2000–2014. The NIS contains data from over 7 million hospitalizations in the US per year, generalizable to the American population. The NIS was queried for ICD-9 codes for either a primary or secondary diagnosis of CD (008.45). Information for demographic data, length of stay (LOS), mortality, and hospital charges was evaluated.

Results
There were 1,256,783 total discharges from 2000–2014 with CD as the primary diagnosis and 4,204,338 total discharges during the same period with CD listed as any diagnosis. The number of hospitalizations with CD as primary diagnosis increased from 31,782 in 2000 to 107,760 in 2014. The number of hospitalizations with CD listed as any diagnosis increased from 134,518 to 361,945. Mean LOS decreased from 6.8 to 5.8 days and mean charges per hospitalization increased from $15,810 to $35,898 during the same time period. Aggregate charges increased from $0.51 billion to $3.87 billion annually. Inpatient mortality of CD hospitalizations decreased from a 4.03% in 2005 to 1.67% in 2014. Approximately 42% of those admitted for CD were male and 58% were female.

Conclusion
This study demonstrates that the number of hospitalizations for CD has increased by 339% from 2000 to 2014. Inpatient mortality of CD has decreased, likely from earlier recognition and treatment of CD. The direct cost of admissions with CD as primary diagnosis is nearly $4 billion per year. Our findings affirm that CD infection is an epidemic that remains a significant source of morbidity and mortality with substantial hospitalization and cost burden. This data can be used to support a return on investment for intervention strategies to prevent CD transmission and for new therapies.

Disclosures
All authors: No reported disclosures.
Declining Rates of Clostridium difficile infections (CDI) in Veterans Affairs (VA) Long-term Care Facilities (LTCF)
Authors: Evans Martin , Simbartl Loretta , Singh Maninder , Kralovic Stephen , Roselle Gary 
Published: October 2017

Abstract

Background
Clinically-confirmed hospital-onset CDI rates declined 15% in VA acute care facilities after implementation of a CDI Prevention Initiative in July 2012. A similar initiative was launched in VA LTCFs in February 2014. The Initiative featured a four-part bundle emphasizing 1) environmental management, 2) hand hygiene, 3) contact precautions for suspected or documented CDI cases, and 4) and institutional culture change where infection control becomes everyone’s business. This is a report of subsequent CDI rates in VA LTCFs.

Methods
Multidrug Resistant Organism prevention coordinators at each of the 132 VA reporting sites entered monthly CDI case data from February 2014 to December 2016 into a central database. A clinically-confirmed (CC) LTCF-onset CDI case was defined as a resident with clinical evidence of illness (i.e. diarrhea or histopathologic or colonoscopic evidence of pseudomembranous colitis) and a non-duplicate, non-recurrent positive diagnostic laboratory test collected ≥48h after admission. Quarterly CDI case rate trends were evaluated using negative binomial regression accounting for admission prevalence and diagnostic test type and compared with rates during a 24-month baseline period before implementation of the LTCF Initiative.

Results
During the 35-month analysis period, there were 145,421 admissions, 9,844,927 resident-days, and 1,480 CC-LTCF-onset CDI cases nationwide for a pooled CDI LTCF-onset rate of 1.50/10,000 resident-days. The use of nucleic acid amplification testing (NAAT) increased from 77.8% to 83.5% of facilities during the analysis period. CC-LTCF-onset CDI rates decreased 36% (P &lt; .0001 for trend) (Figure 1).

Conclusion
As with acute care, LTCF-onset CDI case rates declined coincident with implementation of an initiative featuring a four-part bundle of interventions.

Disclosures
All authors: No reported disclosures.
The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds
Authors: Talbot George H , Kleinman Leah , Davies Evan W , Hunsche Elke , Roberts Laurie , Nord Carl Erik 
Published: October 2017

Abstract

Background
Patient perspectives on their disease are undoubtedly important in clinical trials and in practice. To date, no patient-reported outcome (PRO) questionnaire assessing symptoms of Clostridium difficile infection (CDI) has been developed following FDA guidance. The CDI-DaySyms™ is a new comprehensive measure of a broad range of local and systemic CDI symptoms (not only diarrhea) that patients report as meaningful. Objectives were to: finalize the CDI-DaySyms™ items (questions); assign them to domains (concepts); evaluate the questionnaire’s measurement properties; and define responder thresholds.

Methods
Blinded data from a sub-study of two Phase III trials (NCT01987895 and NCT01983683) in CDI patients were analyzed following FDA guidance for validating PRO questionnaires. Patients completed the CDI-DaySyms™ daily from Day 1 until end of treatment. Items were selected for inclusion in the final questionnaire based on a range of validation analyses, input from expert clinicians, and findings from prior qualitative patient research. Responder-threshold analyses used Day-3 data to align with the rapid symptom improvement generally seen in response to CDI therapy.

Results
Data were analyzed for 168 CDI patients (median age 60 years; 67.9% female; 81.5% mild/moderate, 11.3% severe, 7.1% unknown disease severity; 80.4% first CDI occurrence, 19.6% first recurrence). Three of the 13 items in the draft CDI-DaySyms™ were deleted; the remaining 10 were statistically assigned to three domains measuring different symptom concepts (Figure). Individual items in each domain correlated strongly with one another and their domain. Domain scores demonstrated acceptable consistency over time in stable patients, were sensitive to change, and correlated in expected directions with scores of other relevant symptom and disease-severity measures. Responder thresholds were defined as score changes of -1.00, -0.80, and -0.70 for Diarrhea, Abdominal, and Systemic/Other Symptoms domain scores, respectively.

Conclusion
The CDI-DaySyms™ is a valid measure of diarrhea and other CDI symptoms useful in assessing response to therapy. It has good measurement properties, and with only 10 items can be easily administered in clinical trials and in practice.

Disclosures
G. H. Talbot, Actelion: Board Member, Consultant and Scientific Advisor, Consulting fee; L. Kleinman, Actelion: Consultant, Research support; &#x2028; E. W. Davies, Actelion: Employee, Salary; E. Hunsche, Actelion: Employee and Shareholder, Salary; L. Roberts, Actelion: Consultant, Research support; C. E. Nord, Actelion: Scientific Advisor, Consulting fee
Line of Service-Specific Performance and Antibiotic Prescribing Habits Following Introduction of a Two-Step Diagnostic Approach Using NAAT Followed by Enzyme Immunoassay in Cancer Patients with Suspected Clostridium difficile Infection
Authors: Chao Andrew , Yalamanchili Harika , Guevara Eduardo Yepez , Bhatti Micah , Aitken Samuel L , Okhuysen Pablo 
Published: October 2017

Abstract

Background
Patients with cancer are at an increased risk for C. difficile infection (CDI). A two-step approach with a Nucleic Acid Amplification Test (NAAT) followed by enzyme immunoassay (EIA) increases diagnostic sensitivity and specificity and can be used to guide antibiotic therapy. We retrospectively investigated the relative performance of the two-step approach in cancer patients with solid tumors (ST), hematologic malignancies (HS), and hematopoietic stem cell transplant recipients (HSCT).

Methods
We identified 204 patients with a positive NAAT test for CDI as determined by GI multiplex (Biofire) or by Illumigene (Meridian, Bioscience) in whom a reflex EIA was performed for C. difficile A/B toxins between November 2015 and February 2017. Patients were stratified into ST, HM, HSCT groups. We compared the proportion of discordant NAAT+, EIA- results among the three groups. We then compared the clinical presentation and antibiotic use for patients in the NAAT+/EIA- to those with NAAT+/EIA+ results.

Results
Overall an EIA+ result was found in 53 (26%) patients. The proportion of patients with NAAT+/EIA+ results was significantly different between the three lines of service; ST 31/86 (36%), HM 16/62 (26%), and HSCT 6/56 (11%) P &lt; 0.01. A trend towards a higher proportion of positive results was observed for ST compared with the HM group (P = 0.06). Results were similar between the HM and HSCT group. However, patients in the ST were more likely to have a positive EIA when compared with HSCT patients (36% vs. 11% P &lt; 0.01). Clinical presentation and healthcare-association were similar in all three groups regardless of the EIA result. Despite the low proportion of EIA+ confirmatory results, the majority of patients (196/204 96%) received antibiotic therapy targeting CDI. Discontinuation of CDI antibiotics prior to 10 days of therapy was similar in the EIA+ (12%) vs. EIA- (10%).

Conclusion
The relevance of discordant results needs to be interpreted in the context of the line of service/patient care unit. The presence of CDI as determined by NAAT/EIA is low in patients with other potential causes of diarrhea such as in HSCT recipients. A substantial proportion of cancer patients are treated unnecessarily for CDI.

Disclosures
All authors: No reported disclosures.
Using Clinical Decision Support to Improve Evidence Based Testing and Diagnosis of Clostridium difficile Infection
Authors: Miller Bahnsen , O’Neal Catherine , Hamer Diana 
Published: October 2017

Abstract

Background
Diagnosing Clostridium difficile infection (CDI) requires clinical understanding of the disease and knowledge of diagnostic testing limitations. It is important for providers to utilize CDI testing only in patients with suspected disease. Real-time polymerase chain reaction (PCR) assays are sensitive but cannot differentiate between symptomatic and asymptomatic patients. Individual hospitals have reported a 50% to 100% increase in the rate of CDI after substituting toxin tests with molecular tests such as PCR. We conducted a quality improvement project, implementing clinical decision support in ordering diagnostic testing of CDI, while measuring the number of diagnostic tests ordered and positive results.

Methods
We implemented evidence based clinical decision support into Cerner order entry system on March 1, 2016. The Cepheid Xpert C. difficile molecular test is used for diagnosis of CDI at our facility. The decision support included a message stating Òuse the test with caution in patients who are receiving tube feeds or recent laxative useÓ and prompted ordering providers to select one of three indications for using the test: 3 or more diarrheal stools per 24 hour period, leukocytosis with abdominal pain, or ileus. A control chart was used to monitor the number of tests ordered and positive tests per month (inpatient adults) for a total of 24 months; 14 months pre-intervention and 10 months post-intervention.

Results
A decrease in the number of tests ordered per month was seen post intervention. Average number of monthly tests ordered was 207 pre-intervention and 163 post-intervention. After controlling for patient-days per month, there was a 13.5% decrease in the number of tests ordered from a mean of 14.29 vs.. 12.37 tests per thousand patient-days per month. This resulted in special cause variation (Figure 1). There was no special cause variation detected with the number of positive PCRs per month, pre and post intervention.

Conclusion
Implementing decision support into the electronic medical record may assist providers with evidence-based utilization of the C. difficile PCR by decreasing unnecessary testing. This decrease may also have an impact on overall hospital costs, antibiotic utilization, and public reporting related to CDI.

Disclosures
All authors: No reported disclosures.
An Assessment of 2016 National Healthcare Safety Network (NHSN) and National Electronic Disease Surveillance System (NEDSS) Clostridium difficile Infections (CDI) in Nebraska
Authors: Pedati Caitlin , Sullivan Madison , Drake Margaret , Keyser Alison , Safranek Tom , Tierney Maureen 
Published: October 2017

Abstract

Background
In 2016 all acute care hospitals, inpatient rehab facilities, and PPS-exempt cancer facilities in Nebraska were required to report laboratory identified (LabID) Clostridium difficile infections (CDIs) to the National Healthcare Safety Network (NHSN). Test results indicating CDIs must be reported to the Nebraska Department of Health and Human Services (NDHHS) via the National Electronic Disease Surveillance System (NEDSS). NHSN and NEDSS represent unique sources of CDI reports in Nebraska.

Methods
The NHSN Nebraska database was queried for CDIs reported in 2016. All lab tests indicating a CDI in 2016 were extracted from NEDSS. These extracts were analyzed to assess descriptive epidemiologic variables and compared for differences.

Results
In 2016 there were 1,546 CDI LabID events reported to NHSN Nebraska from 28 facilities. There were 249 outpatient CDIs and 1,297 inpatient CDIs. Infections were further characterized as community-onset (N = 773), community-onset, healthcare facility associated (N = 206), and hospital onset (N = 567). An average of 128 CDIs were reported per month (range: 111–155).
In 2016 there were 2,177 lab results indicating a CDI reported to NEDSS among Nebraska residents from 42 facilities. Patient ages ranged from 4 months to 104 years (mean = 58 years). An average of 181 CDIs were reported per month (range: 151–218).
Comparison of the two data sources found 781 reports among 591 unique patients at 11 facilities that were made to NHSN and were not in NEDSS. Additionally, there were 1,092 reports from 931 unique patients at 12 facilities that were made to NEDSS and should have been made to NHSN but were not. There were 9 shared facilities that accounted for the majority of these discrepancies.

Conclusion
NHSN and NEDSS represent two unique data sources that allow for a more comprehensive assessment of CDIs. The number and type of facility that report to each system is slightly different but there is some overlap. Therefore, this comparison allows for detection of a greater number of reports overall and also provides an opportunity for data validation. This assessment identified discrepancies in reporting among 9 facilities that can be targeted for further collaborative efforts to improve CDI reporting and management in Nebraska.

Disclosures
All authors: No reported disclosures.