bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clostridium difficile Testing Algorithm: Is There a Difference in Patients Who Test Positive by Enzyme Immunoassay vs. Those Who Only Test Positive by Nucleic Acid Amplification Methodology?
Authors: Polak Jonathan , Odili Ogheneruona , Craver Mary Ashleigh , Mayen Anthony , Purrman Kyle , Rahman Asem , Sang Charlie Joseph , Cook Paul P 
Published: October 2017

Abstract

Background
Testing for Clostridium difficile infection (CDI) commonly involves checking for the presence of toxins A and B by enzyme immunoassay (EIA) or nucleic acid amplification (NAA). The former is very specific, but not very sensitive. The latter is very sensitive. Beginning in 2011, our hospital incorporated an algorithm that involved testing liquid stool specimens for glutamate dehydrogenase (GDH) and toxin by EIA. For discrepant results, the stool specimen was tested for the presence of toxin by NAA. We sought to determine whether there was a difference in the baseline characteristics or outcomes between the two groups.

Methods
We performed a chart review of all subjects who tested positive for CDI by either method between 2011 and 2016 at Vidant Medical Center, a 909 bed, tertiary care teaching hospital. Testing was only performed on liquid stool specimens. Subjects less than 18 years of age were excluded. Repeat positive specimens were excluded. We collected demographic data including age, gender, baseline temperature, white blood cell count, and serum lactate and albumin. Length of stay and in-hospital mortality were also determined for both groups. Comparison of the two groups was done using t-test for continuous and chi-square analysis for categorical variables.

Results
Over the 6 year period, there were 535 positive test results. 243 specimens tested positive by EIA/GDH (EIA +); 292 specimens tested positive by GDH/NAA (NAA +). Compared with the EIA + group, the NAA + group was younger (61.8 years vs. 65.1 years, P = 0.01). There were no statistical differences in the presence of abdominal tenderness, temperature &gt;38oC, serum albumin, serum lactate, length of stay, or mortality between the two groups. The EIA + group was statistically more likely to have leukocytosis (WBC &gt;20,000 cells/mm3) at the time of the CDI testing compared with the NAA + group (P = 0.0002).

Conclusion
There do appear to be some clinical differences in the presentation of subjects who test positive for CDI by EIA/GDH compared with those who test positive only by GDH/NAA. These differences do not appear to affect length of stay or mortality.

Disclosures
P. P. Cook, Gilead: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient; Pfizer: Grant Investigator and Shareholder, Grant recipient
Toxin Detection by Cell Culture Neutralization Assay [CYT] and Toxin based EIA [Tox EIA] among Recurrent Episodes of CDI Diagnosed by PCR
Authors: Kamboj Mini , Mcmillen Tracy , Chow Hoi Yan , Brite Jennifer , Babady N Esther 
Published: October 2017

Abstract

Background
The Ad Hoc C. difficile surveillance working group defines recurrent C. difficile infection as a second episode occurring &gt;8 weeks after the index case. Due to its high sensitivity, diagnosis of recurrent CDI by PCR is extremely challenging in patients who may have persistent, PCR detectable shedding of toxigenic C. difficile (TCD) for an extended period of time after treatment of the initial CDI episode. CYT, which detects C. difficile toxin antigen, is a cumbersome test to perform but is considered as the current clinical diagnostic gold standard for CDI diagnosis. Aim: To determine the CYT and Toxin A/B EIA positivity among patients with recurrent CDI episodes detected by PCR. We further characterized the performance of diagnostic tests based on whether the recurrent episode was a relapse or reinfection.

Methods
During a three month study period, CYT and Tox A/B EIA was performed on consecutive stool samples submitted from PCR positive recurrent episodes of CDI. For the purpose of this study, recurrence was defined as a second episode of CDI that occurred within 120 days from the most recent episode. MLST analysis was performed as previously described to characterize relapse and reinfection among the recurrent episodes (2).

Results
Thirty-five recurrent episodes occurred over the study period. 21/35 [60%] were positive by CYT and 12/35 [34%] by Tox A/B EIA. Among the recurrent CDI episodes, 16 (46%) were genotypical confirmed as relapse with the original infecting strain. Majority of these relapses were positive by CYT (81%) when compared with Tox EIA (43%). Among patients with geno typically confirmed reinfection (n = 8), CYT and EIA positivity was 63 % and 50 % respectively. For the remaining 11 episodes, TCD was not retrievable in culture, CYT and EIA positivity among this group was 27 % and 9 % respectively.

Conclusion
Forty percent of recurrent CDI episodes detected by PCR could not be confirmed by CYT. EIA missed 66 % of CYT positive recurrent CDI. The performance of CYT and EIA varied among recurrences due to relapse and reinfection. These results have significant implication for reporting of CDI HAI rates.

Disclosures
All authors: No reported disclosures.
Clinical Correlation of a Clostridium difficile Testing Algorithm Reflexing PCR Positive Specimens to Toxin Enzyme Immunoassay (EIA)
Authors: Rios Maria Bueno , Karichu James , Deshpande Abhishek , Fraser Thomas , Isada Carlos , Richter Sandra S 
Published: October 2017

Abstract

Background
An algorithm promoted in the United Kingdom reflexes specimens positive for C. difficile by a nucleic acid amplification test (NAAT) to toxin EIA. Samples positive by NAAT and negative by toxin EIA are reported as “C. difficile could be present (ie, potential C. difficile excretor).” We explored the potential utility of this algorithm to distinguish C. difficile infection (CDI) from colonization compared with retrospective clinical assessment.

Methods
Liquid stool specimens (n = 300) from inpatients (or the Emergency Department) submitted to the Cleveland Clinic Microbiology laboratory for C. difficile PCR testing (Cepheid Xpert C. difficile/Epi) with positive results were included in the study. The CDIFF QUICK CHEK COMPLETE GDH/toxin EIA assay (Alere) was performed according to manufacturer’s instructions. The charts of all patients were reviewed by Infectious Diseases physicians blinded to the EIA results. Using the American College of Gastroenterology (ACG) classification system, CDI status was determined to be mild, moderate, severe, or complicated. Patients without significant diarrhea (&lt;3 unformed stools / 24 hours) were considered colonized. Those without documentation of stools were classified as indeterminate. Correlation of clinical assessment with EIA results was assessed.

Results
Most of the PCR positive specimens (75%) were toxin EIA negative. Correlation of clinical assessment with toxin EIA is summarized in the table below. Among patients colonized vs. those with CDI, the percentages with negative toxin EIA results were 80% and 73%, respectively. GDH antigen results were negative for 25 specimens—17 were from patients considered to have CDI.

Conclusion
Toxin EIA performed on samples positive for C. difficile by PCR does not reliably identify patients considered to have CDI with ACG criteria applied. GDH as an initial screen would not have detected 6.8% of patients with CDI.

Disclosures
S. S. Richter, bioMerieux: Investigator, Research support; BD Diagnostics: Investigator, Research support; Roche: Investigator, Research support; BioFire: Investigator, Research support; OpGen: Investigator, Research support
Impact of a Multi-disciplinary C. difficile Action Team
Authors: Heil Emily , Sivasailam Bharathi , Park SoEun , Diaz Jose , Von Rosenvinge Erik , Claeys Kimberly , Hopkins Teri , Leekha Surbhi 
Published: October 2017

Abstract

Background
Clostridium difficile infection (CDI) is associated with increased length of hospital stay, morbidity, mortality, and cost of hospitalization. Early intervention by experts from multiple areas of practice such as gastroenterology (GI), infectious diseases (ID) and surgery can be essential to optimize care and increase utilization of novel treatment modalities such as fecal microbiota transplant (FMT) and minimally invasive, colon-preserving surgical management.

Methods
A multi-disciplinary C. difficile action team (MD-CAT) was implemented at University of Maryland Medical Center (UMMC) in March 2016 to engage appropriate specialty consultants in the care of CDI patients. The MD-CAT reviews positive C. difficile tests at UMMC and provides guidance and suggestions to the primary team including optimal antibiotic treatment (for CDI and any concomitant infection), and consultant involvement including ID, surgery, and GI, when appropriate. Using retrospective chart review, CDI patient management and outcomes were compared before and after implementation of the MD-CAT. Differences in the time to consults and frequency of interventional treatment was compared using Chi-square or Wilcoxon Rank-sum test.

Results
We compared 48 patients with CDI in the pre-intervention with 89 patients in the post-intervention period. Demographic and clinical characteristics of the groups were similar. MD-CAT intervention was associated with frequent (73%) modification or discontinuation of concomitant antibiotics. Median time to GI and ID consults was significantly shorter in the post group (P = 0.007 and P = 0.004, respectively). Five of 89 (5.6%) of patients received FMT or colon-preserving surgical intervention in the post-intervention group compared with no patients in the pre-intervention group. There was no difference in 30-day all-cause mortality or CDI recurrence between groups.

Conclusion
Early, multi-disciplinary action on patients with CDI increased the proportion of patients undergoing active specialty consultation and improved use of concomitant antibiotics. A larger sample size is needed to determine the effects of such a team on other clinical outcomes.

Disclosures
All authors: No reported disclosures.
The Impact of Diagnostic Stewardship on Clostridium difficile Infections
Authors: Bischoff Werner , Bubnov Andrey , Palavecino Elizabeth , Beardsley James , Williamson John , Johnson James , Luther Vera , Ohl Christopher , El Helou Guy , Huang Glen , Stehle John , Sanders John 
Published: October 2017

Abstract

Background
Clostridium difficile infections (CDI) pose a growing threat to hospitalized patients. This study assesses the impact of changing from a nucleic acid amplification test (NAAT) to a stepwise testing algorithm (STA) by using an enzyme immunoassay (GDH and toxin A/B) and confirmatory NAAT confirmation in specific cases.

Methods
In an 885 bed academic medical center a 24 month pre-/post design was used to assess the effect of the STA for the following parameters: rates of enterocolitis due to C.diff (CDE), NHSN C.diff LabID events, CDI complications, mortality, antimicrobial prescription patterns, cluster occurrences; and testing, treatment, and isolation costs. Inpatient data were extracted from ICD-9/10 diagnosis codes, infection prevention, and laboratory databases.

Results
The STA significantly decreased the number of CDE ICD9/10 codes, HO, CO, and CO-HCFA C.diff LabID event rates by 65%, 78%, 75%, and 75%, respectively. Similar reductions were noted for associated complications such as NHSN defined colon surgeries (-61%), megacolon (-64%), and acute kidney failure (-55%). CDE unrelated complication rates for colon surgeries and acute kidney failure remained constant while the diagnosis of megacolon decreased but not significantly (-71%; P &gt; 0.05). Inpatient mortality did not change with or without CDE. Significant reductions were observed in the use of oral metronidazole (total: -32%; CDE specific: -70%) and vancomycin (total: -58%; CDE specific: -61%). There were no clusters detected pre-/post STA introduction. The need for isolation decreased from 748 to 181 patients post-intervention (-76%; P &lt; 0.05). Annual cost savings were over $175,000 due to decreases in laboratory testing followed by isolation, and antibiotic use.

Conclusion
The switch to an STA from NAAT did not affect the diagnosis, treatment, or control of clinically relevant CDI in our institution. Benefits included avoidance of unnecessary antibiotic treatment, reduction in isolation, achieving publicly reported objectives, and costs savings. Selection of clinically relevant tests can help to improve hospitalization and treatment of patients and should be considered as part of diagnostic stewardship.

Disclosures
All authors: No reported disclosures.
Antibiotic Exposure and Risk of Community-associated Clostridium difficile infection (CA-CDI): A Self-Controlled Case Series Analysis
Authors: DiDiodato Giulio , Fruchter Lauren 
Published: October 2017

Abstract

Background
CA-CDI accounts for up to 50% of all CDIs. Case–control studies (CCS) have been used to estimate the odds ratio (OR) of CA-CDI associated with antibiotic exposure. These ORs demonstrate significant heterogeneity across studies. Unlike CCS, a self-controlled case series (SCCS) design can be used to control for all time-invariant confounders leading to less biased effect estimates.

Methods
Adults (≥18 years) registered (N = 139,670) with the Barrie and Community Family Health Team (BCFHT) were included in the study. Cases were defined as any patient with an incident case of CA-CDI and ≥1 antibiotic exposure occurring between January 1, 2011 and December 31, 2016. The SCCS model was used to estimate the association between antibiotic exposure and CA-CDI. The SCCS model yields estimates of the relative incidence rate of CA-CDI in exposure periods relative to non-exposure periods within a case. Exposure periods were defined as starting two days after any antibiotic prescription and ending 60 days later. Multiple exposure periods and time-varying confounders due to calendar year were included in the final model. The relative incidence rate ratio (IRR) was estimated using conditional poisson regression analysis. Proton pump inhibitor (PPI) use was included as an effect modifier. Antibiotics were divided into high-risk (fluoroquinolone, clindamycin, and cephalosporin) and low-risk exposures. Research ethics approval was obtained from the BFCHT research ethics board.

Results
Among 544 total CDI cases, N = 189 CA-CDI cases met the inclusion criteria. Any antibiotic exposure increases the risk by ≥2-fold, with no difference observed between high and low-risk groups (IRR=1.11, 95% CI 0.53–2.36) (Table 1).

Conclusion
Antibiotic exposure increases the risk of CA-CDI, with IRR estimates similar to those observed for healthcare-associated-CDI. This, along with the control of all time-invariant confounders by the SCCS method suggests a less biased effect estimate previously reported from CCS.

Disclosures
All authors: No reported disclosures.
Predictors of 30-day All-cause Mortality in Veterans with First Recurrence of Clostridium difficile Infection (CDI)
Authors: Morrill Haley , Beganovic Maya , Caffrey Aisling , LaPlante Kerry 
Published: October 2017

Abstract

Background
Recurrent CDI is an important cause of mortality, however few studies have evaluated independent predictors of mortality in patients with recurrent CDI.

Methods
We conducted a case–control study nested in a national cohort of adult Veterans with a CDI episode (defined as a positive stool sample for C. difficile toxin(s) & receipt of &gt;2 days of CDI treatment [IV or PO metronidazole, PO or PR vancomycin, or fidaxomicin]) during an inpatient admission or outpatient encounter at a Veterans Affairs facility from 2010–2014. Only patients with a first recurrence were included, defined as a subsequent CDI episode within 30 days from the end of treatment of the first CDI occurrence. Cases were those that experienced 30-day all-cause mortality and controls included survivors matched to cases on year of episode, facility, and severity. Multivariable conditional logistic regression was used to identify predictors of mortality.

Results
110 cases were matched to 440 controls (1:4). Five predictors of mortality were identified including concurrent use of any antibiotic (OR 4.61, 95% CI 2.45–8.69), pulmonary heart disease (OR 4.707, 95% CI 1.30–17.06), the use of proton pump inhibitors within 7 days prior to CDI treatment (OR 3.59, 95% CI 2.01–6.42), nutrition deficiency (OR 2.62, 95% CI 1.28–5.38) and age (OR 1.04, 95% CI 1.02–1.07).

Conclusion
Increasing age, proton pump inhibitors, previous antibiotic exposure, and underlying comorbidities were important predictors of death among those with first recurrence of CDI. Our data is among the first to investigate predictors of morality in patients with first recurrence, and these data may assist healthcare providers in optimizing patient care.

Disclosures
H. Morrill, The University of Rhode Island: Investigator, Research grant; A. Caffrey, Merck: Grant Investigator, Research grant; The Medicines Company: Grant Investigator, Research grant; Pfizer: Grant Investigator, Research grant; K. LaPlante, Merck: Grant Investigator, Grant recipient; Pfizer: Grant Investigator, Grant recipient; Cempra: Scientific Advisor, Consulting fee; The Medicines Company: Grant Investigator, Grant recipient; Allergan: Scientific Advisor, Consulting fee; Bard/ Davol: Scientific Advisor, Consulting fee; Ocean Spray: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; Zavante: Scientific Advisor, Consulting fee; Achaogen: Scientific Advisor, Consulting fee
Genotypic Correlation between Cases of Clostridium difficile (CDI) with Community-Onset Diagnosis after Recent Hospital Discharge and Their Prior Unit-Based Contacts
Authors: Aslam Anoshé , Brite Jennifer , McMillen Tracy , Chow Hoi Yan , Babady N Esther , Kamboj Mini 
Published: October 2017

Abstract

Background
The incubation period of C. difficile infection (CDI) is highly variable. Infections may be diagnosed weeks after initial acquisition of bacterial spores. Such cases of CDI have onset in the community after a recent hospitalization, or upon readmission, and are characterized as community-onset healthcare-facility associated (CO-HCFA) by current surveillance methods.
Aim: With the application of multi-locus sequence typing (MLST), our study seeks to characterize genetic concordance between CO-HCFA cases and prior unit-based contacts (donors) sharing the same strain type (ST).

Methods
For all laboratory-identified cases of CDI from January 1, 2015, through December 31, 2016, patients with CDI onset within 8 weeks of hospital discharge were included in the study. Infection control database was queried to identify putative donors using the following criteria: previous unit occupants with CDI who had been discharged from the same unit less than 4 weeks, 4–8 weeks, and 8–12 weeks before admission of CO-HCFA cases. Intensity of exposure was further characterized by same room or same unit occupancy. Analysis was restricted to endemic strains at our institution (ST 1, 2, 3, 8, 11 and 42).

Results
During the two year period, 1330 cases were diagnosed with a new CDI episode, 425 community-onset (32%), 440 hospital-onset (33%) and 465 CO-HCFA (35%) cases. Among the 314 unique CO-HCFA patients due to endemic strains, there were a total of 92 same unit contacts with a concordant strain type, and 1035 same unit contacts with a discordant strain type. The proportion of concordant same unit occupants did not differ by time between cases (P = 0.8120).

Conclusion
CO-HCFA cases account for a third of all new cases of CDI. Genotypic concordance as potential donors was observed among 8% of all indirect unit based CDI contacts of CO-HCFA cases. This association did not vary significantly as the interval between potential exposure and CDI onset in CO-HCFA cases increased.

Disclosures
All authors: No reported disclosures.
Sorting the Wheat from the Chaff: Vaccine-Associated Rash Illness Occurring amidst a Large Measles Outbreak—Minnesota, 2017
Authors: Martin Karen , Mody Rajal , Desilva Malini , Banerjee Emily , Strain Anna , Holzbauer Stacy , Kenyon Cynthia , McMahon Melissa , Rota Paul , Gastanaduy Paul , Muscoplat Miriam , Hall Victoria , Ehresmann Kristen 
Published: October 2017

Abstract

Background
During April–June 2017, Minnesota experienced the state’s largest measles outbreak in 27 years. A vaccination campaign was implemented. Numerous vaccine-associated rash illnesses (VARI) were detected. VARI is non-contagious, but difficult to distinguish from measles clinically. Often, public health control measures need to be implemented before wild-type measles can be differentiated from VARI by viral genotyping. We compared clinical characteristics of VARI and confirmed measles cases to inform testing practices.

Methods
We defined measles cases per the Council of State and Territorial Epidemiologists. VARI was defined as a rash occurring in a person within 21 days after receipt of measles, mumps, and rubella (MMR) vaccine, and in whom a measles vaccine strain (genotype A) was detected in naso/oro- pharyngeal swab or urine samples. Minnesota’s immunization information system monitored MMR doses administered. We collected clinical information through routine case investigation.

Results
Over 42,000 MMR doses above expected were administered during the outbreak. We identified 71 measles cases and 30 VARI. The median age of VARI patients was 1.2 years (range 10 months–48 years) and for measles cases 2.8 years (range 3 months–57 years). VARI diagnosis increased with rising MMR administration (figure); rash onset occurred a median of 11 (range 7–18) days after MMR receipt. Most VARI (97%) occurred following first MMR dose. The presence of fever was similar among VARI and measles cases (97% of VARI vs. 100% of measles cases; P = 0.12), but differences were seen in the proportion with cough (30% vs. 96%; P &lt; 0.001), coryza (47% vs. 85%; P &lt; 0.001), conjunctivitis (23% vs. 68%; P &lt; 0.001), and exposure to infectious measles cases (0% vs. 96%).

Conclusions
Surges in MMR administration and heightened community awareness during a measles outbreak can result in a large number of VARI, consuming considerable public health resources. When evaluating the need to suspect measles among patients with febrile rash, clinicians should consider time since MMR administration, clinical presentation, and history of measles exposure. Collecting appropriate specimens for timely virus genotyping could inform appropriate public health action.

Disclosures
All authors: No reported disclosures.
Predictive Coding of Novel versus Familiar Stimuli in the Primary Visual Cortex
Authors: Homann Jan , Koay Sue Ann , Glidden Alistair M. , Tank David W. , Berry Michael J. 
Published: October 2017

AbstractTo explore theories of predictive coding, we presented mice with repeated sequences of images with novel images sparsely substituted. Under these conditions, mice could be rapidly trained to lick in response to a novel image, demonstrating a high level of performance on the first day of testing. Using 2-photon calcium imaging to record from layer 2/3 neurons in the primary visual cortex, we found that novel images evoked excess activity in the majority of neurons. When a new stimulus sequence was repeatedly presented, a majority of neurons had similarly elevated activity for the first few presentations, which then decayed to almost zero activity. The decay time of these transient responses was not fixed, but instead scaled with the length of the stimulus sequence. However, at the same time, we also found a small fraction of the neurons within the population (∼2%) that continued to respond strongly and periodically to the repeated stimulus. Decoding analysis demonstrated that both the transient and sustained responses encoded information about stimulus identity. We conclude that the layer 2/3 population uses a two-channel predictive code: a dense transient code for novel stimuli and a sparse sustained code for familiar stimuli. These results extend and unify existing theories about the nature of predictive neural codes.