bluuebunny/crossref_metadata_2025 huggingface dataset:
662. Using Machine Learning to Aid in the Diagnosis of Multisystem Inflammatory Syndrome in Children
Authors: Soneji Maulin , Tan John , Wong Emily
Published: December 2021

Background

Multisystem inflammatory syndrome in children (MIS-C) is a newly recognized inflammatory syndrome that occurs post Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection. It affects multiple organ systems - particularly cardiac, gastrointestinal, dermatologic and neurologic. Clinicians may have difficulty diagnosing MIS-C due to its novelty and similarity to Kawasaki disease. Our goal was to use machine learning to predict whether children would have MIS-C based on symptoms and laboratory values.

Methods

A retrospective review was conducted of patients admitted to Loma Linda University Children’s Hospital who were suspected of having MIS-C. Demographic, symptom (such as fever, abdominal pain, diarrhea, shock, etc), and laboratory data were collected from the electronic medical record. For the 115 patients and 20 laboratory values, there was a total of 130 missing values (5.7%). Missing laboratory values were imputed using the median value based on the presence or absence of MIS-C. The data were split into a training (93 patients, 80%) and testing (22 patients, 20%) set. The training set was used to train a random forest model and the testing set was used to evaluate model performance. R 4.0.2 was used for modeling with the following packages: tidymodels and randomForest.

Results

There were 115 patients of which 49 were females, and 77 were diagnosed with MIS-C. The median age of the patients with MIS-C was 115 months and 79 months for those without MIS-C. In the testing set, all 15 patients with MIS-C were classified correctly but of the 7 without MIS-C, the model predicted 4 of the patients correctly. This gives a sensitivity of 100% and specificity of 57%. When changing the seed and testing set, the sensitivity remained 100% but the specificity improved to 86%. The random forest algorithm showed that the most important features were pro-calcitonin, ferritin, pro-BNP, and CRP.

Conclusion

During the height of the SARS-CoV-2 pandemic, many children were being admitted with suspected MIS-C, but clinicians struggled to confirm the diagnosis. We have found a model predicting which of these patients had MIS-C with high sensitivity. This model is a first step of many toward creating the foundation of personalized medicine for children.

Disclosures

All Authors: No reported disclosures
664. Clinical Impact of Cell-Free DNA Metagenomics in Diagnosing Infectious Diseases in Pediatrics: A Single-Center Experience
Authors: Otto William , Dumm Rebekah , Fatemi Yasaman , Swami Sanjeev K
Published: December 2021

Background

Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA has significant potential to improve infectious diseases diagnostics through unbiased detection of pathogens. However, the optimal patient population or clinical condition for this testing has not been determined.

Methods

We performed a retrospective review of all orders for plasma cell-free DNA mNGS using the Karius test (Karius, Redwood City, CA) from The Children’s Hospital of Philadelphia from 7/1/19-4/30/21. Chart review then determined if the test had a positive, negative, or no clinical impact.

Results

25 mNGS tests were ordered on 24 unique patients. The majority of tests were ordered on immunocompromised patients (Table 1). Most mNGS tests were ordered after completion of routine microbiological testing (17/25, 71%). Three tests were not completed as ordered. Most completed tests (18/22, 82%) had no impact on clinical care as they confirmed the known diagnosis or were not acted upon (Figure 1). mNGS testing had a positive impact in 2 cases. For one patient with congenital heart disease presented with persistent fever and concern for endocarditis despite negative infectious workup, a negative mNGS result allowed for continued monitoring without therapy. Another patient with a lymphatics disorder had mNGS performed due to persistent clinical instability; testing was positive for Candida parapsilosis, allowing for early initiation of antifungal therapy. However, test results had a negative clinical impact in 2 other patients. In a patient with congenital heart disease and fever, identification of two organisms led to prolonged antibiotic therapy for endocarditis without resolution of symptoms. In a patient with leukemia, report of a dematiaceous mold led to further diagnostic testing, including a lumbar puncture, as well as treatment with antifungal therapy despite no clear diagnosis.

Table 1

Conclusion

In this study, the majority of plasma cell-free mNGS tests had no impact on clinical care. mNGS testing did positively impact care in 2 patients, but did had a negative impact on care in 2 instances, leading to further testing and unnecessary treatment. Further investigation is needed to determine the ideal population or clinical condition for testing and the ideal time of sending plasma cell-free mNGS tests.

Disclosures

All Authors: No reported disclosures
665. Clinical and Financial Impact of Next Generation Sequencing (NGS) in addition to Conventional Microbiology Testing in our Urban Referral Health Center
Authors: Saini Vikram , Jaber Tariq , Como James D , Abdulmassih Rasha , Min Zaw , Bhanot Nitin
Published: December 2021

Background

Clinical microbiology traditionally relies on culture methodology and serological testing, that have inherent limitations. Newer diagnostic techniques such as Next Generation Sequencing (NGS) have shown promise to improve microbial identification. In select scenarios, we send clinical specimens to reference laboratories for NGS testing in addition to current standard of care (SOC) diagnostics. We wanted to determine how this diagnostic approach has impacted patient care. We also wanted to review the financial burden through cost-benefit analysis for these ‘send-out’ tests.

Methods

We performed a retrospective chart review of all cases over a 3-year period in which NGS was submitted. Data, including demographics, comorbidities, antimicrobial use, and diagnosis (by SOC and NGS) were gathered. We delineated how often there was concordance or discordance between SOC and NGS. We also obtained information on financial cost (direct and indirect) and turnaround time (TAT) for NGS results.

Results

A total of 33 clinical specimens from 25 patients were sent for NGS. The majority of specimens comprised joint tissue/fluid, organ tissue and CSF.

Concordance occurred between SOC and NGS testing in 75.8% (25/33) of samples; of those, 88% excluded infection. NGS identified a pathogen in 20% (5/25) patients in which concomitant SOC testing was negative. A subsequent change in antimicrobial management occurred in 16% (4/25) of patients. The mean TAT was 14 days and average cost per specimen was &821.52 (range: &573-&1590).

Table 1. Pathogens identified by NGS with negative traditional microbiological test results

Figure 1. Distribution of specimen site (in %) sent for NGS

Conclusion

NGS can provide additional diagnostic sensitivity in infectious diseases, which at our institution identified a new pathogen in 20% and a resultant treatment change in 16% of our patients. This testing may also allow physicians to reaffirm the absence of an infection diagnosis. A larger NGS testing population may reveal more significant benefits. While the attributable cost of NGS was substantial, it should be measured against the costs of administration of unnecessary antibiotics, inaccurate diagnosis, and adverse patient outcomes that may result from SOC testing alone. Considering its financial cost and extended TAT, in-house NGS testing may be warranted to facilitate a higher volume of testing.

Disclosures

All Authors: No reported disclosures
667. Next Generation Sequencing of Microbial Cell Free DNA in the Diagnosis and Treatment of Infectious Disease in Children: When Does the Result Justify the Cost?
Authors: Quick Rachel Downey , Martinez Kelli A , Russo Susan M , McGwier Sarah E , Quirt Rachel A , Hauger Sarmistha Bhaduri , Fernandez Mariosl , Murphey Donald
Published: December 2021

Background

Pathogen testing using next-generation sequencing of microbial cell-free DNA (NGS cfDNA) is a promising diagnostic tool to identify pathogens that might not be detected using conventional lab evaluation. Considering the cost of this test, it is important to determine when it is most useful to the plan of care (POC).

Figure 1. Unit of admission among cases

Figure 2. Patient characteristics in cases determined to be valuable and not valuable to the plan of care (POC)

Methods

In this retrospective study, we collected data from the medical charts of 50 consecutive NGS cfDNA tests in a free-standing children’s hospital. We evaluated patients for demographics, underlying conditions, diagnosis at time of testing, conventional laboratory testing and timing, medical treatment, and NGS cfDNA test results for clinical relevance or false negative results compared to conventional testing. The primary goal was to identify patients for whom the NGS cfDNA testing affected the POC. Charts were reviewed, and determinations regarding whether the result influenced the POC were confirmed by a provider.

Results

We were unable to differentiate patients with clinically valuable NGS cfDNA results (Fig 1 & 2). Among those with NGS cfDNA results valuable to the POC (n=22), both negative and positive testing guided POC (13 valuable negative vs. 9 diagnostic cases). In the total sample, 5 cases (10%) had a clinically relevant pathogen identified through conventional testing, but not through NGS cfDNA and 2 cases had antimicrobial resistance on culture, which is not detected by NGS cfDNA.

Conclusion

While we did not find a specific clinical profile for NGS cfDNA use, positive results were essential to the diagnosis in 18% of cases with otherwise negative laboratory evaluation for the pathogen identified in NGS cfDNA. Negative tests affected the POC in 26% of cases by avoiding unnecessary antimicrobials in high risk immunocompromised patients and patients that presented with low-risk of infection, but unclear disease process.

Caution must be exercised with reliance on this test with respect to antimicrobial resistance and risk of false negative results.

Disclosures

All Authors: No reported disclosures
668. Restricting Ordering of Multiplex Gastrointestinal Panel Improves Test Utilization
Authors: Tai Don Bambino Geno , Misra Anisha , Sampathkumar Priya , O'Horo John C
Published: December 2021

Background

The multiplex gastrointestinal pathogen panel (GIP) is a convenient and quick diagnostic test for determining the infectious etiology of diarrhea. It identifies several of the most common pathogens associated with gastroenteritis. However, it is expensive, and test results may not impact care, given that several of the pathogens in the panel are managed expectantly. We describe our experience with a diagnostic stewardship initiative to resolve the overuse of this testing method.

Methods

We performed a pre/post study of GIPs ordered for inpatients 18 years old and older from December 19, 2018, to December 18, 2020, at Mayo Clinic hospital in Rochester, Minnesota. GIP orders for inpatients were limited to the first 72 hours of hospitalization starting December 19, 2019. Orders after 72 hours were encouraged to be changed to Clostridioides difficile NAAT testing or sent to an infectious disease provider to override on a case-by-case basis. Our hospitals used BioFire® FilmArray® Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City, Utah).

Results

A total of 2,641 GIPs were performed during the study period. There were 1,568 GIPs (3.3/100 hospitalizations) in the pre-intervention period compared to 1,073 (2.6/100 hospitalizations) post-intervention, representing a drop of 21.2%. The most common pathogen detected was C. difficile (toxin A/B) (48.8%, n=402), followed by norovirus (17.5%, n=144). The overall test positivity rate was 27.9% (n=736). The test positivity rate decreased 1.8% from 28.6% (n=448) to 26.8% (n=288) after the restriction (p=0.33). The proportion of C. difficile among all pathogens detected increased from 48.5% to 49.7% (p=0.67).

Table 1. Pre- and Post-Intervention Test Positivity Rate of Specific Pathogens in GIP

Conclusion

Our study showed that restricting the ordering of GIP to the first 72 hours of hospitalization and directing providers to standalone C. difficile NAAT testing resulted in a reduction of GIPs performed. There were marginal changes in the test positivity rate of GIP. A limitation of our study is that the timing of post-intervention coincided with the COVID-19 pandemic, which had unpredictable effects on hospital practice and patient admissions. Ideally, future quality improvement projects should increase the test positivity of pathogens other than C. difficile while lowering the GIP use in diagnosing C. difficile colitis.

Disclosures

John C. O'Horo, Sr., MD, MPH, Bates College and Elsevier Inc (Consultant)
670. Precision Metagenomic (PM) Sequencing Outperforms Conventional Urine Culture in Detecting Clinically Relevant Microorganisms
Authors: Stinnett Rita C , Kent Bethany , Mangifesta Marta , Kadam Anagha , Xie Heng , Stauffer Stacie , Lemon Jamie , Briggs Benjamin , Farnaes Lauge , Schlaberg Robert
Published: December 2021

Background

Morbidity from urinary tract infection (UTI) is high. Urine culture is the reference method for UTI diagnosis. Its diagnostic yield is limited as prior antibiotic use prevents growth of established uropathogens, many emerging uropathogens do not grow under routine culture conditions, and results interpretation can be subjective. Faster, more comprehensive diagnostics could help manage recurrent and/or drug-resistant infections. We evaluated the diagnostic yield of a precision metagenomic (PM) workflow for pathogen detection & antimicrobial resistance (AMR) characterization directly from urine.

Methods

Residual urine samples from symptomatic adults evaluated by culture & susceptibility were identified by a combination of consecutive & stratified random sampling (n=480; 79% culture positive). DNA was extracted with modifications to the Quick-DNA Urine Kit (Zymo). Libraries were generated with Illumina DNA Prep with Enrichment for clinically relevant targets (191 pathogens, 1976 AMR markers) with the Explify Urinary ID/AMR Panel (UPIP, IDbyDNA). Enriched libraries were sequenced on the NextSeq550 (Illumina) and data analyzed with the Explify UPIP Data Analysis Solution (IDbyDNA).

Results

For bacterial uropathogens, 94% positive agreement was observed between this PM workflow and culture. PM detected fastidious and/or anaerobic potential uropathogens in 30% and 7% of samples reported as culture-negative or positive for other bacteria, respectively. Total agreement between AMR marker detection and phenotypic resistance was 78%. Notably, PM predicted phenotypes of ESBL E. coli and K. pneumoniae (10/10), MRSA (9/9), and vancomycin-resistant E. faecium (4/5). PM also detected pathogens associated with sexually-transmitted infection (C. trachomatis, HSV) and bacterial vaginosis (G. vaginalis). PM produced complete results within 24-36 hours of sample receipt (vs culture & susceptibility: 42-72 hrs).

Conclusion

The sensitivity of PM for uropathogen detection was noninferior to culture (Δ = 0.05; Nam RMLE; p < 0.0005). PM predicted antimicrobial resistance phenotypes for common uropathogens and identified potential pathogens not detected by conventional culture. Future studies should assess the impact of PM-guided management on clinical outcomes.

Disclosures

Rita C. Stinnett, PhD, MHS, IDbyDNA (Employee) Marta Mangifesta, PhD, IDbyDNA (Employee) Anagha Kadam, PhD, IDbyDNA (Employee) Heng Xie, PhD, IDbyDNA (Employee) Stacie Stauffer, BS, IDbyDNA (Employee) Jamie Lemon, PhD, D(ABMM), IDbyDNA (Employee) Benjamin Briggs, MD, PhD, IDbyDNA (Employee) Lauge Farnaes, MD, PhD, Cardea Bio (Advisor or Review Panel member)IDbyDNA (Employee) Robert Schlaberg, MD, MPH, IDbyDNA (Consultant, Shareholder, Co-founder)
674. Evaluation of the Access Bio CareStart™ Rapid SARS-CoV-2 Antigen Test in Asymptomatic Individuals Tested at a Community Mass-testing Program in Western Massachusetts
Authors: Matias Wilfredo , suliman Sara , Fulcher Isabel , Molano Francisco , Collins Shannon , Uceta Elizabeth , Zhu Jack , Paxton Ryan , Gonsalves Sean , Harden Maegan , Fisher Marissa , Meldrim Jim , Gabriel Stacey , Franke Molly , Hung Deborah , Smole Sandra , Madoff Lawrence , Ivers Louise
Published: December 2021

Background

Point-of-care antigen-detecting rapid diagnostic tests (RDTs) to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represent a scalable tool for surveillance of active SARS-CoV-2 infections in the population. Data on the performance of these tests in real-world community settings will be paramount for their implementation to combat the COVID-19 pandemic.

Methods

We evaluated the performance characteristics of the CareStartTM COVID-19 Antigen Test (CareStart) in a community testing site in Holyoke, Massachusetts. We compared CareStart to a SARS-CoV-2 reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) reference, both using anterior nasal swab samples. We calculated the sensitivity, specificity, and the expected positive and negative predictive values at different SARS-CoV-2 prevalence estimates.

Results

We performed 666 total tests on 591 unique individuals. 573 (86%) were asymptomatic. There were 52 positive tests by RT-qPCR. The sensitivity of CareStart was 49.0% (95% Confidence Interval (CI): 34.8 – 63.4) and specificity was 99.5% (95% CI: 98.5 – 99.9). Among positive RT-qPCR tests, the median cycle threshold (Ct) was significantly lower in samples that tested positive on CareStart. Using a Ct less than or equal to 30 as a benchmark for positivity increased the sensitivity of the test to 64.9% (95% CI: 47.5 – 79.8).

Performance characteristics of CareStart test results benchmarked against the RT-qPCR gold standard (excluding undetermined results).

Examples of images of CareStart rapid test showing variable band intensities.

N2 gene RT-qPCR Cycle threshold (Ct) values corresponding to positive and negative CareStart rapid antigen test results for all RT-qPCR positive samples (n=52).

Conclusion

Our study shows that CareStart has a high specificity and moderate sensitivity. The utility of RDTs, such as CareStart, in mass implementation should prioritize use cases in which a higher specificity is more important, such as triage tests to rule-in active infections in community surveillance programs.

Disclosures

All Authors: No reported disclosures
675. Crimean-Congo Hemorrhagic Fever Beyond Ribavirin: A Systematic Review
Authors: Fabara Stephanie P , Tirupathi Raghavendra , Ortiz Juan Fernando , Patel Urvish , Srikanth Sashwath , Al-Tawfiq Jaffar A , Rabaan Ali A
Published: December 2021

Background

The Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne virus infection that has been reported in about 30 countries worldwide. Clinical presentation is divided into three phases: pre-hemorrhagic, hemorrhagic, and convalescence. Ribavirin is standard of care treatment for acute infection and prophylaxis. However, the use of other treatments beyond ribavirin is largely unknown.

Methods

We conducted a systematic review using MOOSE protocol. The inclusion and exclusion criteria are seen in the Prisma diagram. For Bias Analysis we use a Robin-1 tool.

Literature review algorithm

Results

We gathered a total of 10 studies, which included 4 therapeutic plasma exchange (TPE), 2 corticosteroids, 2 IVIG, and 1 with convalescent plasma (CP).

TPE in one study showed decreased mortality rate and increased efficacy in patients with severe CCHF. While the other study reported pulmonary embolism related to the use of TPE. Nevertheless, the patients had good outcome in the end. Two case reports used TPE plus ribavirin and supportive measures. Both were discharged home and recovered without sequela. Corticosteroids were found to be beneficial in one study were the case fatality rate was lower with the addition of corticosteroids to ribavirin in severely ill patients (p=0.0014). In a case series of six patients, who received the combination in early stages of the disease had good clinical outcomes with improved survival. IVIG was shown to increase platelet counts in two studies. In the first study, platelet count increased above 150,000/mL in 8.5 +/- 2.5 days. While in the other study the normalization of platelets was seen in 4 - 4.8 days, with no significant difference (P = 0.49). In addition, there was a decrease in the duration of symptoms but there was no statistically significant difference in mortality rates (P = 0.171). CP treatment showed a survival rate of 86% in treated patients. CP was more useful in high-risk patients, defined as having a viral load of 108 copies/mL or more. The main limitations of the studies were the sample size and heterogenicity among the outcomes of the studies.

Conclusion

TPE, CP, IVIG, and corticosteroids were effective in improving the clinical outcomes of the patients. The use of these treatments beyond ribavirin should be explored in future studies.

Disclosures

All Authors: No reported disclosures
677. Compliance and Performance Characteristics of Subject Collected Versus Health-care Worker Collected Nasal Swabs for Respiratory Viral Surveillance
Authors: Kautz Michelle , Epsi Nusrat J , Richard Stephanie A , Colombo Rhonda E , Ganesan Anuradha , Collins Limone , Burgess Timothy , Maves Ryan C , Maves Ryan C , Markelz Ana E , Geaney Casey , Seshadri Srihari , Utz Gregory , Mende Katrin , Hrncir David , Modi Jitu , Fries Anthony C , McClenathan Bruce , Schofield Christina , Montgomery Jay R , Skerrett Catherine , Spooner Christina , Coles Christian L , Lalani Tahaniyat
Published: December 2021

Background

Self-collection of mid-nasal swabs (SCNS) at home is a convenient alternative to health-care worker-collected nasal swabs (HCWC) for determining the pathogen-specific epidemiology of influenza-like illness (ILI). We evaluated the compliance and performance characteristics of SCNS vs. HCWC for respiratory pathogens during 2019-2020 flu season.

Methods

Adult Military Health System (MHS) beneficiaries were enrolled in an influenza vaccine effectiveness trial (PAIVED). Following vaccination, subjects were instructed on SCNS and completion of a symptom diary and were contacted weekly to ascertain ILI symptoms (fever, sore throat, and/or cough). In the event of an ILI, subjects completed the symptom diary and SCNS and were scheduled a clinic visit for HCWC. Swabs were tested with the Luminex NxTAG® Respiratory Pathogen Panel. We evaluated compliance with swab collection, positive percent agreement (PPA) of SCNS using PCR detection from either HCWC or SCNS as the reference standard, and agreement between paired swabs using the Cohen Kappa coefficient (Κ).

Results

1808 ILI were reported by 972 participants enrolled during the study period. Compliance with HCWC was higher than SCNS (58% [1042] vs. 42% [766]; p< 0.001). SCNS were associated with a shorter interval from symptom onset (median: 4 days [IQR:2-6 days] vs. clinic collect: 7 days [IQR:4-9 days]; p < 0.001). 663 paired swabs were available for 609 participants (Table 1). The overall detection rate was higher in SCNS (36%) than HCWC (26%; p< 0.001) (Figure 1). The overall PPA was 85.7% and a PPA of approximately 80% of greater was observed for influenza, rhino/enterovirus, parainfluenza and respiratory syncytial virus. Agreement between paired swabs was poor due to the lower detection rates in HCWC.

Table 1. Demographics and swab collection data for 609 participants who provided 663 paired swabs

Figure 1. Detection by pathogen in 663 paired swabs

Conclusion

SCNS were associated with higher detection rates compared to HCWC, likely due to the shorter interval between symptom onset and swab collection. Strategies to improve compliance with SCNS and minimize the interval between symptom onset and swab collection are needed to optimize detection of respiratory pathogens in this MHS cohort.

Disclosures

Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) Jitu Modi, MD, GSK (Speaker's Bureau)
679. Infective Endocarditis and Septic Emboli-Related Complications; Epidemiology and Impacts on Hospital Outcomes
Authors: Park Hansang , Majmundar Monil , Roy Soumyajit , Velasquez-Espiritu Maria Rosa , Ghosh Kuldeep , Kadeishvili Khatuna , Chaudhari Shobhana , Lopez Eliana A
Published: December 2021

Background

Infectious endocarditis (IE) remains a disease of high mortality, complications and a severe burden to the healthcare system despite advances in diagnostic techniques and treatments. There are several investigations of IE using a nation-based population cohort, however, with limited focus on septic emboli-related complications.

Figure 1. Flowchart of the study cohort. IE=Infective Endocarditis

Methods

We used the 2016 to 2018 National Readmission Database (NRD) to identify a primary diagnosis of admissions among adults (Age≥18) with IE. International Statistical Classification (ICD-10) codes were used to identify patients with a primary diagnosis of IE who experienced in-hospital septic emboli-related complications. Primary outcomes were mortality, length of stay, total cost and 30-day all-cause readmission. Uni- and Multivariate Linear, Logistic and Cox regression were used to assess statistical significance and a two-sided p-value less than 0.05 was considered significant.

Results

A total of 30,870 patients were admitted with a primary diagnosis of IE from 2016 to 2018 (December admissions were omitted). After excluding the patients with omitted information, 30,289 patients went into analysis. Baseline characteristics are shown in Table 1. Septic emboli-related complications were seen in 42.6% of the patients; about 10% had central nervous system (CNS) complications, 7% had cardiac complications and 20.2% had respiratory complications. Embolic complications of any kind were associated with higher mortality (Odds Ratio = 2.11 [1.74 – 2.54]), a longer length of stay (5.72 days [5.17 – 6.27]) and higher total costs (21,812 dollars [19,856 – 23,769]) while adjusted for baseline characteristics. Multivariate Cox regression to assess the risk of 30-day readmission was not statistically significant. Predictors of 30-day all-cause readmission among baseline characteristics and subgroups of embolic complications are shown in table 4 and table 5, respectively.

Conclusion

The prevalence of septic emboli-related complications was up to 42.6% of patients admitted with the primary diagnosis of IE. These complications significantly impact hospital outcomes; including mortality, length of stay and total cost. Further studies are required to clarify the relationship between 30-day all-cause readmissions and embolic complications.

Disclosures

All Authors: No reported disclosures
680. Month Long Fungemia due to Candida auris Endocarditis
Authors: khan Haseeba , Varughese Christy , Gonzalez Hemil
Published: December 2021

Background

Candida auris (C. auris) is a multidrug resistant Candida species, reported to cause persistent fungemia along with a multitude of invasive fungal infections. We report the first case of C. auris fungemia due to endocarditis.

Methods

61 year old man with a history of diverticulitis that required sigmoid resection and was complicated by abdominal abscesses due to multi drug resistant organisms warranting heavy antibiosis. Prolonged hospitalisation for that surgery was followed by a stay at a long term acute care hospital. He was readmitted at an outside hospital with sepsis where blood cultures grew C.auris. Upon evaluation, was found to have aortic valve endocarditis. Per patient’s preference, surgery was initially deferred. Despite escalation of therapy with a combination of antifungals, he remained fungemic for five weeks with repeat blood cultures showing changing antifungal susceptibility patterns. Patient eventually underwent surgical intervention at our facility, with valve cultures being positive for C.auris. After the surgery he was treated with 6 weeks of intravenous combination antifungal therapy.

Results

C.auris’s pathogenicity stems from multiple mechanisms with multi drug resistance being most pertinent. What adds to the complexity of the management is the absence of C.auris specific minimum inhibitory concentration breakpoints. Therefore treatment is based on Center for Disease Control’s (CDC) proposed breakpoints that have been extrapolated from other Candida spp. It is further complicated by lack of C.auris specific data showing essential agreement among different commercially available antifungal susceptibility testing (AFST). Heteroresistance of the microbial population is an issue that must be considered in such protracted fungemia.

Conclusion

Invasive infections due to Candida auris presents as a diagnostic and therapeutic challenge to clinicians.

Disclosures

All Authors: No reported disclosures
681. Penicillin Plus Ceftriaxone Against Enterococcus faecalis In Vitro Time-Kill Studies
Authors: Khan Ruhmazia , Shah Zeel , Huang Vanthida , Cusumano Jaclyn
Published: December 2021

Background

Synergistic ampicillin plus ceftriaxone (AC) for Enterococcus faecalis infective endocarditis outpatient use is precluded by ampicillin’s poor room temperature stability. Penicillin has superior stability and has been combined with ceftriaxone (PC), however there is a lack of studies to demonstrate synergy.

Methods

AC and PC were evaluated, in duplicate, for synergy utilizing 24-hour in vitro time-kill assays with a starting inoculum of 106 colony forming units (CFU)/mL. Six clinical E. faecalis blood isolates and one wild-type E. faecalis isolate (JH2-2) were included. All isolates were susceptible to ampicillin and penicillin, with minimum inhibitory concentrations (MICs) ranging from 0.5-1 µg/mL and 2-4 µg/mL, respectively. Ampicillin and penicillin were tested at subinhibitory concentrations (0.25x and 0.5xMIC) as monotherapy and in combination with ceftriaxone average steady state concentrations for a dose of 2g IV q12hr (CPss 17.2 µg/mL), as all ceftriaxone MICs were high due to intrinsic resistance (MICs 128-2048 µg/mL). Synergy was defined as a ≥ 2 log10 decrease in CFU/mL at 24 hours from the most active single agent.

Results

An average increase in bacterial density from the starting inoculum was observed for all isolates against ampicillin 0.25xMIC alone, penicillin 0.25x and 0.5xMIC alone, and ceftriaxone alone (+1.60 ± 0.62, +1.91 ± 0.37, +1.48 ± 0.42, and +1.84 ± 0.46 log10 CFU/mL, respectively) [Table 1]. Ampicillin 0.5xMIC alone average increase in bacterial density from starting inoculum for all but two isolates (e2008 and e2009) was +1.21 ± 0.59 log10 CFU/mL. Isolates e2008 and e2009 were the only isolates with a higher penicillin MIC of 4 µg/mL, and did not display synergy for all AC and all PC combinations. AC synergy was observed for all other isolates, with only one isolate (e2012) displaying synergy at 0.5xMIC. PC synergy was observed for four isolates at 0.5xMIC (-3.47 ± 0.94 log10 CFU/mL) and for only one isolate (e2014) at 0.25xMIC but the change in bacterial density was -0.38 ± 0.24 log10 CFU/mL.

Conclusion

PC synergy against E. faecalis was observed with higher penicillin concentrations. AC and PC did not demonstrate synergy against isolates with a higher penicillin MIC of 4 µg/mL. Further research is warranted to better understand PC synergy against E. faecalis.

Disclosures

All Authors: No reported disclosures
682. Implantable Cardioverter-Defibrillator Lead Vegetation with Long-Standing Actinomyces neuii Bacteremia
Authors: Irwin Mark , Tilem Steven , Ervin Charlie , de la Serna Fernando , Sampath Rahul
Published: December 2021

Background

Endocarditis caused by Actinomyces species is uncommon with only 30 cases reported in contemporary literature.

Methods

We present a novel case of cardiovascular implantable electronic device (CIED) endocarditis secondary to infection by Actinomyces neuii – a unique non-branching member of the species that grows in both anaerobic and aerobic media.

Results

Our patient, a 51-year-old female, with a history of implantable cardioverter-defibrillator (ICD) placement 17 years prior for heart failure, presented with six weeks of fevers and rigors. She was referred to the infectious disease clinic for evaluation of pyrexia of unknown origin. Her examination was unremarkable, and the ICD pocket was uninflamed. Her initial labs revealed mildly elevated inflammatory markers and renal insufficiency. Blood cultures were positive for slow-growing non-branching gram-positive rods in both aerobic and anaerobic media. These were identified as Actinomyces neuii by mass spectrometry. Review of outside records showed positive blood cultures with Actinomyces neuii at another facility two weeks prior to our evaluation which were not acted upon and thought to be bacterial contamination. The patient was further evaluated with a transesophageal echocardiogram that demonstrated a 3.3 x 2.2cm mobile vegetation attached to the ICD lead. She subsequently underwent removal of her Saint Jude cardiac resynchronization therapy defibrillator and leads using laser and snaring techniques, but the tail end of the ventricular lead fractured and could not be retrieved. The ICD pocket was also found to be infected. A planned 6-week course of IV ampicillin was interrupted by 2 weeks of ceftriaxone for treatment of an intercurrent lower respiratory tract infection. The patient regained her baseline health and was discharged 2 weeks after ICD removal with a LifeVest. She is to complete 12 months of oral amoxicillin therapy after completion of IV antibiotics in view of retained lead fragment, and long standing Actinomyces bacteremia - consistent with published management strategies.

Figure 1. Transesophageal echocardiogram demonstrating size of vegetation.

Figure 2. Three-dimensional view demonstrating vegetation on the ICD lead.

Conclusion

Here we describe the first known case of Actinomyces neuii CIED endocarditis with a large lead vegetation and long-standing bacteremia, presenting as pyrexia of unknown origin.

Disclosures

All Authors: No reported disclosures
684. Diagnostic Yield of Echocardiography in Coagulase Negative Staphylococcus Bacteremia
Authors: Nagarakanti Sandhya , Bishburg Eliahu , Okoh Alexis , Grinberg Sagy , Suryadevara Madhu
Published: December 2021

Background

Coagulase negative Staphylococcus (CoNS) bacteremia is a common clinical finding, but is less commonly associated with infective endocarditis (IE). Echocardiography (Echo) is utilized when clinicians suspect the diagnosis of IE. We sought to evaluate the utilization and yield of Echo in patients who had 1 or ≥ 2 (+) blood cultures (BC) for CoNS, and correlate Echo results with a diagnosis of IE.

Methods

A retrospective review in a tertiary care hospital between 2013-2020. Patients with or without cardiac device, who had either 1 or ≥ 2 BC positive for CoNS and who underwent Echo were included. Modified Duke’s (MDC) criteria was used for the diagnosis of IE. Logistic regression was used to examine the association between BC positivity, device existence and the presence of a vegetation on Echo.

Results

We included 116 patients, median age 58 (41-70) years, 64 (55%) women. Cardiac device was present in 69 (59%): Automated implantable cardioverter defibrillator in 49 (71%), pacemaker in 11(16%), ventricular assist device in four (6%), intra-aortic balloon pump in five (7%). CoNS isolated from 1 BC in 53(46%) patients and from ≥ 2 in 63(54%) patients. Trans- thoracic Echo (TTE) was performed in 42(36%), trans- esophageal Echo (TEE) in 39 patients (33.6%). Sequential Echo (TEE after TTE) was performed in 34 patients (29%). “Definite” IE was diagnosed in none, “possible” IE in 30 (26%), the diagnosis was “rejected” in 86 (74%). Vegetations were noted on device lead in 13(43%) and on valves in 17(57%). Overall yield in patients classified as “possible” IE (n=30) was similar in patients with device (n=26) to those without a device (n=4) (22% vs. 3%; p=0.149). For patients with 1 BC positive for CONS, the presence of a device was not associated with a positive Echo yield (OR, 95% C.I: 1.8 (0.3, 12.9); p=0.474). Patients who had ≥ 2 BC for CoNS had the same Echo yield with or without a cardiac device (15% vs. 24% p=0.243).

Conclusion

In our medical center, patients with CoNS bacteremia, no patients had a “definite” diagnosis of IE. Yield of Echo was similar in patients with either one or ≥ 2 positive BC and there was no significant association with the presence of a device.

Disclosures

All Authors: No reported disclosures
685. Evaluating the Role of Medication-assisted Treatment (MAT) in the Management of Infectious Endocarditis in People Who Inject Drugs (PWID)
Authors: Gorseth Allison , Nolan William , Cluff Monica , O'Sullivan David , Dempsey Casey J
Published: December 2021

Background

An estimated 1.29-2.59 million people practice intravenous drug use (IVDU) in the United States making it a growing risk factor for infective endocarditis (IE). In people who inject drugs (PWID), IE accounts for 5-10% of total yearly deaths. IE often requires weeks of intravenous therapy with extensive medical follow-up. The purpose of this study was to evaluate if medication-assisted treatment (MAT) increased treatment retention and survival to optimize addiction assistance and IE treatment efforts.

Methods

A single-center, retrospective chart review was approved for patients admitted with an ICD-10 code of IE. A multidisciplinary group was created in April, 2019 aimed to improve endocarditis patient outcomes, formed of complex case coordination, infectious disease, cardiology, and pharmacy pain management service members. The historical period was January 1, 2018-March 31, 2019 and the IE pathway (IEP) group was April 1, 2019-June 30, 2020. Patients were excluded if there was no documentation of IVDU (Figure 1). The primary outcome was successful endocarditis therapy, defined per study protocol. Secondary outcomes include: against medical advice (AMA) departures, discharge naloxone prescriptions, clinical opioid withdrawal score (COWS) and patient reported pain.

Figure 1. Study Population

Methods for study population inclusion and exclusion

Results

A total of 419 IE patients were evaluated with 166 patients meeting inclusion criteria. The primary outcome was achieved in 51.2% of historical group and 48.8% of the IEP group (p=0.302). AMA departures and inpatient mortality were similar between the two groups. There was increased presence of the pharmacy pain management service with decreased time to consult in the IEP group (Figure 2). Last documented COWS were increased in the IEP group (p=0.002), while last reported patient pain scores decreased (p=0.030). More patients were started on MAT and discharged with naloxone in the IEP group (Table 3). Readmission was found to be higher in the IEP group (p=0.046). Post hoc analysis evaluating outcomes for patients seen by the endocarditis pathway team were similar between the two groups (Table 4).

Figure 2. Secondary Outcome (Consult Services)

The secondary outcomes of the study population are described comparing the presence and time to various consult services. **P-value indicates statistical significance. Abbreviations: n, number; ID, infectious disease; CT, cardiothoracic

Table 3. Secondary Outcomes

Table 4. Post Hoc Analysis

Conclusion

The multidisciplinary group was effective helping to guide the inpatient care of PWID and improve symptom management, but this did not translate to increased successful IE therapy or fewer readmissions.

Disclosures

All Authors: No reported disclosures
686. Comparing Treatments of Methicillin-Resistant Staphylococcus aureus Infective Endocarditis by People Who Inject Drugs
Authors: Rebold Nicholas , Alosaimy Sara , Lagnf Abdalhamid M , Holger Dana , Rybak Michael J
Published: December 2021

Background

People who inject drugs (PWID) are at high risk for infective endocarditis (IE) with high-mortality pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Stigma against PWID may cause differences in treatment and outcomes between these patients infected with MRSA IE.

Methods

Single center retrospective cohort study from August 2006 to February 2021 that includes adult patients diagnosed with IE. Primary outcomes included 90-day all-cause mortality, 60-day MRSA recurrence, 60-day readmission, and hospital length of stay (LOS). Statistical analysis was performed by chi-square, t-test, and Mann-Whitney-U as appropriate.

Results

A total of 214 patients were diagnosed with MRSA IE; 89 PWID and 125 non-PWID. The mean (SD) age was 47.4±12.4 years (PWID) vs 59.3 ±16.0 years (non-PWID) (p< 0.001). Patients were primarily male (56%), but differed in terms of race 34% African-American (AA) (PWID) vs 66% AA (non-PWID) (p< 0001). Mean APACHE II scores differed between groups: 16(±9.9) (PWID) vs 19(±8.1) (non-PWID) (p< 0.008). Among patients who cleared bacteremia, mean (SD) duration was 5.7(±3.9) days and was not significant between groups (p< 0.64). Valve-type was 93% native and 7% prosthetic and not different between groups (p< 0.16). Infectious Diseases consult did not differ at 96% overall (p< 0.31), but pursuit of source control nearly reached significance at 27% for PWID vs 41% non-PWID (p< 0.06). Similarly, use of combination therapy daptomycin and ceftaroline was nearly significant: 21% (PWID) vs 12% (non-PWID) (p< 0.09). Odds ratio of PWID and combination therapy remained non-significant after regression: 0.39(0.14-1.1,p< 0.07). Primary 90-day mortality was lower in PWID vs non-PWID (15% vs 30%) respectively (p< 0.01), but did not differ in 60-day MRSA recurrence (p< 1.0) at 9%, 60-day readmission (p< 1.0) at 33%, or median LOS (IQR) (p< 0.46) at 15 (10-24) days overall.

Conclusion

While PWID are significantly younger, less critically ill, and have lower mortality compared to non-PWID, they have similar LOS, MRSA recurrence, and readmission rates. Analyses suggest a potential difference in the pursuit of source control and combination therapy among PWID, however more studies may be needed to achieve significance.

Disclosures

Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)
687. Use of Dalbavancin in Gram-positive Infective Endocarditis: Review of Current Literature
Authors: Fazili Tasaduq , Bansal Ekta , de la Espriella Mariana Gomez , Garner Dorothy C
Published: December 2021

Background

Dalbavancin is a long acting, semisynthetic derivative of teicoplanin that is currently approved for treatment of acute bacterial skin and skin structure infections. Its efficacy and role of in the treatment of invasive infections, in particular infective endocarditis, is not well known.

Methods

We reviewed the English-language literature for the use of Dalbavancin in the treatment of endocarditis due to Gram-positive organisms, using Pubmed.

Results

15 publications were reviewed. All the publications were retrospective in nature, with relatively small numbers of patients, including a few case reports.

A total of 159 patients received Dalbavancin for endocarditis. The mean age was 47 years. The main reasons for using Dalbavancin were non-feasibility of a standard outpatient regimen (mainly due to drug use) or the need for a simpler regimen. 75 patients had infection of a native valve, 44 of a prosthetic valve and 19 of a cardiac device. The type of infection for the rest of the patients was not specified. The tricuspid valve was the most frequently reported. The etiologic organisms causing endocarditis were Staphylococcus species, followed by Streptococcus species and Enterococcus species, with Staphylococcus aureus being the most common. All, but one, patients received Dalbavancin as sequential therapy, after receiving other intravenous antibiotics initially. The duration of antibiotics received prior to initiation of Dalbavancin was variable, with the median being 3 weeks. The median duration of Dalbavancin use was 2.7 weeks. The dosage regimens varied, with the more common ones using a loading dose of either 1500 mg or 1000 mg, followed by one or more weekly doses of 500 mg. The overall clinical efficacy was around 89%. Adverse events were mild, including nausea, vomiting, rash, headache and reversible acute kidney injury. None of the patients had to discontinue the drug because of adverse events. Two publications evaluated the cost effectiveness of Dalbavancin and found it to save about &9000 per patient, the saving being mainly due to reduced length of hospital stay.

Conclusion

Dalbavancin appears to be an efficacious, safe and cost-effective option for sequential treatment of endocarditis caused by Staph aureus and other Gram-positive organisms.

Disclosures

All Authors: No reported disclosures
688. Incidence and Risk Factors for Prosthetic Valve Endocarditis Following TAVR: 2015-2019
Authors: de Oca Jamison Montes , Kenney Rachel , Wyman Janet F , Wang Dee Dee , O'Neill Brian , Eng Marvin , Lee James , Villablanca Pedro F , To Long
Published: December 2021

Background

Transcatheter aortic valve replacement (TAVR) is increasingly used for lower risk patients. Incidence of TAVR endocarditis ranges from 0.2% to 3.3%. The purpose of this study was to determine local incidence and risk factors of prosthetic valve infective endocarditis (PVIE) in a contemporary cohort.

Methods

IRB approved retrospective, nested case-control study evaluated the 1-year incidence and risk factors for PVIE among TAVR recipients from 2015 to 2019. Inclusion: ≥ 18 years, TAVR procedure at Henry Ford Health System. Exclusion: repeat TAVR. PVIE cases were matched with controls who did not experience PVIE. PVIE defined as diagnosis documentation in the electronic medical record.

Figure 1. Study Design

Results

23/1266 patients were identified as cases corresponding to a 1-year incidence of 1.82%. The median time to PVIE was 127 days and 35% occurred within 60 days. The most frequently isolated organisms were streptococci (26%), MRSA (13%), and MSSA (13%). Baseline demographics and comorbidities for 23 PVIE cases and 161 controls are displayed in Table 1. Significant risk factors for PVIE in bivariate analysis included STS-PROM (Society of Thoracic Surgeons Predicted Risk of Mortality), median: 4.1 controls and 6.4 cases (p = 0.012). Age, BMI, and comorbidities were not significantly different. Diabetes was notably more frequent among cases (36% vs 48%, p = 0.274). Patients with PVIE had more post-op RBC transfusions (5% vs 21.7% p = 0.003), ECG changes (23% vs 43.5%, p = 0.035), heart block (15.5% vs 34.8%, p = 0.038), longer length of stay (2 days, range 1 to 4 vs 4 to 11, p = 0.004), and thirty-day readmission (10.6% vs 52.2%, p < 0.001). Results displayed in Table 2.

Table 1. Patient Characteristics and Risk Factor Analysis

Table 2. Additional Outcomes

Conclusion

The results from this study give insight to the local incidence, microbiology, and risk of PVIE following TAVR. Future directions include a larger evaluation of modifiable risks such as diabetes management and examining the heart block patients who received permanent pacemaker implants.

Disclosures

Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder) Janet F. Wyman, DNP, CNS-BC, FACC, Edwards Lifesciences (Consultant) Dee Dee Wang, MD, Edwards LifeSciences (Consultant) Brian O'Neill, MD, Edwards Lifesciences (Consultant)