bluuebunny/crossref_metadata_2025_split huggingface dataset:
125. The Clinical Impact of 16S rRNA Bacterial Sequencing in Infective Endocarditis
Authors: El-Dalati Sami , Cinti Sandro , Owczarczyk Anna , Riddell Jamie , Fagan Christopher , Chanderraj Rishi , Fukuhara Shinichi 
Published: October 2019

Abstract

Background
Cases of possible and/or culture-negative endocarditis continue to be a diagnostic challenge. Performing bacterial 16S ribosomal RNA polymerase chain reaction (rRNA PCR) sequencing on cardiac valves now allows providers to make microbiologic diagnoses that were previously unobtainable (sensitivity 66–80.5%). However, few publications address how the PCR results impact clinical management in endocarditis patients.

Methods
Between July 1, 2014 and December 31, 2018, the results of all 16S rRNA PCR tests collected from cardiac valves at the University of Michigan were reviewed. Samples were sent to the University of Washington for sequencing. Each chart was then reviewed by two independent ID physicians to determine whether patients’ medical plans were impacted by the PCR results.

Results
41 patients were identified with associated 16S rRNA PCR testing from cardiac valves. 16 cases met Duke Criteria for definite endocarditis, 22 for possible and 3 were rejected endocarditis. Overall, 18 (43.9%) samples were positive. Of these, 10 patients had concordant positive blood cultures. In 8 patients a previously unsuspected organism was identified. Twenty-four out of 41 patients were considered to have culture-negative endocarditis with October 24 (41.7%) who had positive PCR results. Twenty-two patients were noted to have operative findings consistent with infection with 16 (72.7%) having corresponding positive PCR results. 4/41 (9.8%) patients had their management plans changed based solely on the PCR findings. In 23/41 (56.1%) cases the PCR result was never referenced by any medical provider in the electronic medical record. There were 7 (17.1%) cases where patients received 6 weeks of antibiotics despite presenting with possible culture-negative endocarditis, noninfectious operative findings and negative valve PCRs which were not reviewed.

Conclusion
16S rRNA PCR sequencing is a useful tool for obtaining a microbiologic diagnosis in cases of possible or culture-negative endocarditis. The test has significant potential to impact individual patient care and in a subset of cases may be used to de-escalate antibiotic therapy. However, testing delays and cumbersome resulting methods impede bacterial sequencing from reaching its full potential as a diagnostic modality.

Disclosures
All authors: No reported disclosures.
2325. Relationship Between Neighborhood Census-Tract-Level Poverty and Respiratory Syncytial Virus Infection in hospitalized Adults in the San Francisco Bay area, CA 2015–2017
Authors: Holmen Jenna , Cikesh Bryanna , Kim Lindsay , Reingold Art 
Published: October 2019

Abstract

Background
In the United States, respiratory syncytial virus (RSV) is a leading cause of admission for adults with respiratory illness. In adults > 50 years of age, it accounts for up to 12% of medically-attended acute respiratory illnesses and has a case fatality proportion of ~6–8%. Poverty can have an important influence on health. Few studies have evaluated the relationship of RSV incidence and poverty level, and no identified studies have evaluated this relationship among adults. We evaluated the incidence of RSV-associated hospitalizations in adults in the San Francisco Bay Area, CA by census-tract-level poverty.

Methods
Medical record data abstraction was conducted for all adults with a laboratory-confirmed RSV infection who were admitted to a hospital within the 3 counties comprising the catchment area (Alameda, Contra Costa, and San Francisco counties) during the 2015–2016 and 2016–2017 RSV seasons. Patient addresses were geocoded to their corresponding census-tract (CT). Census tracts were divided into four levels of poverty based on American Community Survey data of percentage of people living below the poverty level: 0–4.9%, 5–9.9%, 10-–9.9%, and ³20%. Incidence rates were calculated by dividing the number of RSV cases in each CT poverty-level (numerator) by the number of adults living in each CT poverty level (denominator), as determined from the 2010 US census, and standardized for age.

Results
There were 526 RSV case-patients with demographic characteristics as outlined in Table 1. The highest incidence of RSV-associated hospitalization was in CTs associated with the highest levels of poverty (>20%). However, the second highest incidence of RSV-associated hospitalization occurred among adults living in CTs with <5% poverty (Figure 1 and Table 2).

Conclusion
The incidence rate of RSV-associated hospitalization in adults appears to be positively correlated with highest census-tract level of poverty; however, there is a high incidence among adults living in the lowest poverty census-tracts.

Disclosures
All authors: No reported disclosures.
2338. Early Predictors of Mortality in Neonatal Disseminated Herpes Simplex Virus Infection
Authors: Ouellette Christopher , Mejias Asuncion , Shimamura Masako , Marzec Laura , Salamon Doug , Leber Amy , Sanchez Pablo J 
Published: October 2019

Abstract

Background
Disseminated neonatal herpes simplex virus (dHSV) infection is associated with substantial morbidity and an estimated case fatality rate of ~25% despite antiviral therapy. Contemporary data on predictors of mortality among infants with dHSV infection are limited.

Methods
From January 2012 to December 2018, neonates with HSV infection were identified by the Virology database at Nationwide Children’s Hospital. Demographic, clinical, laboratory, and radiographic data were obtained from the infants’ electronic healthcare records to identify cases of dHSV infection and to determine possible predictor(s) of mortality. dHSV was defined as detection of HSV DNA by polymerase chain reaction (PCR) in blood, cerebrospinal fluid, or skin/eye/mouth, and evidence of hepatitis, pneumonitis, sepsis, or coagulopathy, with or without central nervous system involvement.

Results
Of 43 neonates with HSV infection, 12 (28%) infants (median [IQR] age: 8.5 [7–11] days) had dHSV and 6 (50%) died. Clinical and laboratory findings of neonates who survived vs. those who died are presented in Table 1. The median duration of symptoms at presentation was 1.5 [1–2] days. Among infants who died, the median duration of hospitalization to time of death was 1.5 days (range, 0 to 4 days). Clinical signs at presentation and blood semiquantiative viral loads (cycle threshold, Ct) were not different between infants who survived (Ct 18.0 [15.4–23.3]) and those who died (16.6 [13.4–23.3]; P > 0.05). Initial serum alanine aminotransferase (ALT), INR or lactate were not different between the two groups. However, initial serum median albumin concentration was lower among those who died vs. survivors (1.8 g/dL vs. 2.7 g/dL, P = 0.004). To assess the sensitivity and specificity of potential laboratory predictors of mortality, serum laboratory values were evaluated as follows (sensitivity, specificity): ALT > 800 (67%, 80%), INR > 2.7 (67%, 80%), serum lactate > 3 mmol/L (80%, 100%), and initial serum albumin < 2 g/dL (100%, 100%).

Conclusion
Albumin concentrations < 2 g/dL at presentation correlated highly with mortality in neonatal dHSV infection, suggesting that hypoalbuminemia may reflect components of both viral sepsis and poor synthetic liver function. Larger cohorts of neonates with dHSV infection are needed to confirm this result.

Disclosures
All authors: No reported disclosures.
2339. Clostridioides difficile: Impact of Active Screening of Asymptomatic Carriers and Testing Stewardship
Authors: Beth Graham Mary , Buchan Blake W , Singh Siddhartha , Revolinski Sara , Ledeboer Nathan A , Huerta Susan M , Pintar Paula , Savage Sabrina , Behrens Elizabeth , Munoz-Price L Silvia 
Published: October 2019

Abstract

Background
We recently implemented a hospital-wide C. difficile testing algorithm and screening/isolation of C. difficile asymptomatic carriers primarily in heme-onc units. We aim to evaluate the impact of these interventions on the epidemiology of C. difficile + tests.

Methods
This retrospective cohort was performed in a 600-bed hospital in Milwaukee, WI, from January 1, 2016 to March 31, 2019. All clinical C. difficile tests included nucleic acid amplification (NAAT; Xpert C. difficile, Cepheid). On February 2017, all NAAT+ tests had toxin (tox) checked (Quick check complete, Alere). Testing algorithm (Figure 1) started mid 2016 until now. Screening phases included: Phase 1 (September 2016–May 2017): C. difficile screening cultures shared with units but not placed in electronic medical records (EMR). Patients + placed on enteric precautions (gown, gloves, hand hygiene). Phase 2 (May 2017–January 2018): C. difficile screening (NAAT) performed on admission and weekly thereafter, results placed in EMR, NAAT+ patients placed on enteric precautions. Phase 3 (January 2018–present): C. difficile screening (NAAT) on admission, results placed in EMR, NAAT+ patients placed on enteric precautions. Federal reporting changed to only reporting NAAT+tox+. Tests (NAAT+, NAAT+tox+, and NAAT+tox-) were analyzed using Poisson regression offsetting for log of patient-days using SAS, v9.4.

Results
Hospital-wide C. difficile tests decreased from 21 to 10.9 tests per 1,000 patient-days (P < 0.0001; Figure 2). This effect was seen in heme-onc units (41 to 15.7; P < 0.0001; Figure 3) and in all other units (18.9 to 9.9; P < 0.0001). All NAAT+ results decreased from 2.99 to 1.94 per 1,000 patient-days hospital wide (P < 0.0001) but remained unchanged in heme-onc units (4.6 to 3.7, P > 0.05). NAAT+tox+ results remained unchanged hospital wide and in heme-onc units (0.8 to 0.7 and 1.1 to 1.2, respectively; both P > 0.05); however, the frequency of NAAT+tox− tests decreased hospital wide (1.8 to 1.3; P = 0.0003) and in heme-onc units (3.8 to 2.4; P = 0.05).

Conclusion
A C. difficile testing algorithm was successful decreasing the number of C. difficile tests performed and had a hospital-wide reduction of NAAT+tox− tests. The rate of NAAT+tox+ cases in heme-onc units and hospital wide remained unchanged despite active screening and isolation in selected units.

Disclosures
All authors: No reported disclosures.
2342. Elimination of Reflexive C. difficile PCR Testing Among Inpatients Resulted in Cost Savings Without Adverse Events
Authors: Sullivan Eva , Majumdar Rohit , Ortiz Courtney , Riggs Patricia K , Crum-Cianflone Nancy 
Published: October 2019

Abstract

Background
Diagnosis of C. difficile infection is imperfect and various algorithms have been proposed. While PCR is sensitive for detecting toxin-carrying C. difficile, it leads to overdiagnoses resulting in antibiotic overuse and potentially unnecessary healthcare costs.

Methods
We performed a study of C. difficile cases after changing the testing protocol from reflexive vs. physician-requested PCR in cases of indeterminant EIA testing (antigen +, toxin −). The study was conducted among inpatient adults at four large hospitals in the southern California area and evaluated two 6-month periods: pre-intervention: (September 5, 2016–March 5, 2017) and post-intervention (3/6/2017–9/6/2017). Only the first C. difficile test during a period per patient was evaluated. Primary outcome was change in number of C. difficile diagnoses. Secondary outcomes included adverse events (missed cases of C. difficile and 30-day readmissions) and cost savings (accounting for PCR, isolation, and treatment costs).

Results
A total of 500 EIA indeterminant C. difficile test results were evaluated, 281 pre- and 219 post-intervention. There were no statistically significant differences in demographics, laboratory values (WBC, Cr), or hospital site between the study periods. A PCR was performed in 99.6% (280/281; one not performed due to an inhibitor) and 66% (144/219) in the pre- vs. post-intervention periods (P < 0.01); the PCR was positive in 65% (n = 182 and n = 94, respectively) in both periods. The change in testing strategy resulted in a 49% reduction in PCR testing and 48% fewer C. difficile cases. There were no differences between study periods in 30-day readmissions for all-cause (P = 0.96), GI-related illness (P = 0.93) or C. difficile (P = 0.47), nor in new or recurrent C. difficile cases (P > 0.99). No patient without a PCR and not treated was later diagnosed with C. difficile infection. Each reflexive PCR avoided led to a cost savings of $4,384/patient.

Conclusion
Diagnostic stewardship is an emerging area that can potentially reduce overdiagnosis and overtreatment of a variety of infectious diseases. Our study showed that changing C. difficile PCR testing among EIA-indeterminant cases from reflexive to requiring a physician order resulted in valuable cost savings without associated adverse events.

Disclosures
All authors: No reported disclosures.
2347. Impact of Multidisciplinary Review of Clostridioides difficile Testing
Authors: Foreman Jena , Belter Neha , Thannum Stephanie 
Published: October 2019

Abstract

Background
Minimizing Clostridioides difficile infections (CDI) is an important patient safety goal due to significant cost and disease burden with CDI causing 15,000 deaths annually in the United States. Diagnosis of CDI is complicated when DNA amplification assay will return positive for both colonization and active infection of C. difficile, so testing clinically symptomatic patients with at least 3 loose stools per day is paramount to obtaining accurate reporting rates and starting proper treatment for CDI.

Methods
Due to economic considerations, the study was a single-center retrospective review of inpatients ≥ 18 years old who had C. difficile tests ordered from November 2017 to February 2019. Baseline characteristics collected include age, sex, white blood cell (WBC) count, fever, past C. difficile infections, recent antibiotic use, recent laxative use, and tube feeding status. Data were analyzed using descriptive statistics. The primary objective of this study was to look at the appropriateness of C. difficile tests pre and post-implementation of multidisciplinary review. Criteria for appropriateness of testing included 3 or more loose stools in addition to one additional factor including fever, elevated WBCs, immunocompromised status, or severe sepsis/septic shock. Secondary objectives include evaluating hospital-onset CDI rates and cost analysis.

Results
Baseline characteristics were similar between the two groups with the exception of statistically fewer patients with 3 or more liquid stools found in the post-implementation group (P = 0.0003). After implementation of a multidisciplinary review, the number of C. difficile tests ran significantly declined from 79% to 56% (P = 0.0001). The number of negative tests also were significantly reduced from 60% to 43% (P = 0.0001), with patients who had less than 3 stools per day being tested less frequently in the post-implementation group. Inappropriate test avoidance resulted in an annual savings of $1,550 in testing supplies alone, not including isolation or labor costs. There was no significant difference in hospital-onset CDI.

Conclusion
Implementation of a multidisciplinary review of C. difficile testing avoids clinically inappropriate tests and results in cost savings with no effect on incidence of hospital-onset CDI.

Disclosures
All authors: No reported disclosures.
2367. Selecting Testing Frequency for Estimation of Incubation Periods: A Simulation Study Based on Clostridioides difficile Observations
Authors: Wilson Brigid , Ascha Mustafa S , O’Hagan Justin , Donskey Curtis 
Published: October 2019

Abstract

Background
Estimates of the incubation period (time between pathogen transmission and symptom onset) for an infection inform infection control and prevention measures. However, observation of the exact transmission and onset times rarely occurs and “coarse,” or doubly interval-censored, data about these exact times are typically used for estimation. The effect of coarseness on the required number of symptomatic cases and the uncertainty of the estimates is unknown, prompting a simulation study informed by data from an investigation of the incubation period of Clostridioides difficile.

Methods
We simulated incubation period data assuming a log-normal distribution, a true median incubation period of 7 days, and a standard deviation of 1 day for sample sizes of 50 to 300 symptomatic cases. For each sample size, we simulated 1000 datasets and examined the impact of testing frequencies, considering intervals between tests of 0.25 to 2 times the median incubation period (1.75 to 14 days) about both transmission and symptom onset times. With these doubly interval-censored observed values, we fit accelerated failure time models to estimate the median incubation time and its 95% confidence interval (CI). Comparing the coverage of the true median and the widths of the CIs, we summarized simulation results across sample sizes and testing frequencies.

Results
Model results from all combinations of sample sizes and testing frequencies yielded median incubation period CIs close to the target 95% coverage level (Figure 1). The width of the 95% CI about the median decreased with larger sample sizes and shorter times between tests (Figure 2). Thus, similar estimates and confidence intervals would be observed from 100 symptomatic cases with a testing frequency of 3.5 days as from 200 symptomatic cases tested every 14 days.

Conclusion
The frequency of testing is a key factor in planning studies to estimate incubation periods for infectious diseases. To achieve a desired degree of certainty in estimation, increased frequency of testing can reduce the number of symptomatic cases required. We showed that simulations can assist in planning natural history studies, and these methods could be extended to include population data (e.g., transmission incidence) and cost constraints.

Disclosures
All authors: No reported disclosures.
2371. A Multicenter Cohort Study of the Natural History of Clostridioides difficile Colonization and Infection
Authors: Curry Scott R , Hecker Michelle , O’Hagan Justin , Kutty Preeta K , Alhmidi Heba , Karen Ng Wong Y , Cadnum Jennifer , Jencson Annette , Gonzalez-Orta Melany , Saldana Carlos S , Wilson Brigid , Donskey Curtis 
Published: October 2019

Abstract

Background
Asymptomatic carriage of toxigenic Clostridioides difficile strains is common in healthcare settings. However, the natural history of C. difficile colonization and infection is not well understood, particularly for patients with new acquisition of carriage.

Methods
In 3 tertiary care hospitals and affiliated long-term care facilities (LTCFs), we conducted a 6-month cohort study to identify patients with new acquisition of rectal carriage of toxigenic C. difficile and determined the duration and burden of carriage. Asymptomatic carriage was defined as transient if only 1 culture was positive with negative cultures before and after or persistent if 2 or more cultures were positive; clearance was defined as 2 consecutive negative rectal cultures.

Results
Of 4180 patients with negative initial cultures, 144 (3%) acquired asymptomatic carriage of toxigenic C. difficile, and 19 (13%) of these carriers subsequently were diagnosed with CDI. Of 50 asymptomatic carriers analyzed for duration of carriage, 33 (66%) had transient carriage of toxigenic C. difficile and 17 (34%) had persistent carriage. For persistent carriers, the estimated median time to clearance of colonization was 76 days (range, 41 to 95 days from acquisition). Ten of 17 (59%) persistent carriers had a high burden of carriage (defined as > 25 colonies recovered from 1 or more swabs) vs. only 1 of 33 (3%) transient carriers (P < 0.001).

Conclusion
Acquisition of asymptomatic carriage of toxigenic C. difficile carriage was common among patients in healthcare facilities, but most carriers had transient low-level carriage. Additional studies are needed to determine whether a higher burden of carriage predicts subsequent risk of transmission.

Disclosures
All authors: No reported disclosures.
2373. Impact of a Change in Testing Strategy for Clostridioides difficile Infection on a Publicly Reported Metric and Treatment Days of Therapy
Authors: Miller Ryan , Morillas Jose A , Sitaras Joanne , Bako Jacob , Neuner Elizabeth A , Gordon Steven M , Brizendine Kyle D , Fraser Thomas G 
Published: October 2019

Abstract

Background
In an effort to optimize diagnostic testing for Clostridioides difficile infection (CDI) our health system changed from stand-alone PCR testing to a “2-step” approach wherein all positive PCR results reflexed to an EIA. We report the effects of this change on publicly reported CDI metrics and treatment days of therapy (DOT).

Methods
The setting includes 10 Cleveland Clinic Health System hospitals in northeast Ohio and one in Florida. On June 12, 2018, 9 NE Ohio hospitals changed from PCR alone to PCR followed by EIA. Stand-alone PCR testing remained at one and GDH / EIA / PCR for discordant for another. Testing volumes were obtained from the microbiology laboratory. C. difficile LabID event SIRs were obtained from NHSN. Public reporting interpretative categories were identified based on SIR for second half of 2018. DOT for CDI agents were obtained from an antimicrobial stewardship database.

Results
Among hospitals that changed strategy the volume of PCR testing and the percent PCR + was similar between time periods. EIA positivity ranged from 23% to 53%. 4/11 hospitals improved their public reporting category: 3/9 that changed testing strategy and 1/2 that did not (Table 1). Two of 3 that changed strategy and improved public reporting also had a decrease in DOT. DOT increased in the 2 hospitals that did not change strategy.

Conclusion
Six months after adopting a 2-step CDI testing strategy 7 of 9 hospitals had a lower SIR with 3 also demonstrating an improvement in public reporting category favorably impacting reputational and reimbursement risk for our healthcare system. CDI agent DOT was similar before and after the change. The impact of choice of test on publicly reported metrics demonstrates the difficulty of utilizing a proxy for hospital onset CDI, the CDI LabID event, as a measure of quality of care provided.

Disclosures
All authors: No reported disclosures.