bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified model reference adaptive observer‐based control without assumptions on uncertain parameter bounds
Authors: Faramin Mostafa , Turner Matthew C.
Published: November 2023

This paper proposes a Modified model reference adaptive controller and observer (MMRACO) for unknown linear time‐invariant (LTI) systems. The recent literature, and in particular the so‐called MRACO approach, has demonstrated how some deficiencies in standard model reference adaptive control can be overcome by using a combination of modified reference models and observers, but this is done at the expense of knowing bounds on certain unknown parameters. Here, a novel adaptive observer/controller combination is presented which removes the need to know the above bounds but preserves the other desirable features of the MRACO approach. A Lyapunov analysis of the closed‐loop system ensures asymptotic convergence of both tracking and observer errors, with uniform boundedness of parameter estimation errors. A key advantage of the scheme is that the design involves only solutions of two Lyapunov equations (or linear matrix inequalities) and does not require the selection of a “high gain” parameter. The effectiveness of the approach is illustrated in some numerical examples.
Point cloud semantic segmentation based on local feature fusion and multilayer attention network
Authors: Wen Junjie , Ma Jie , Zhao Yuehua , Nie Tong , Sun Mengxuan , Fan Ziming
Published: November 2023

Semantic segmentation from a three‐dimensional point cloud is vital in autonomous driving, computer vision, and augmented reality. However, current semantic segmentation does not effectively use the point cloud's local geometric features and contextual information, essential for improving segmentation accuracy. A semantic segmentation network that uses local feature fusion and a multilayer attention mechanism is proposed to address these challenges. Specifically, the authors designed a local feature fusion module to encode the geometric and feature information separately, which fully leverages the point cloud's feature perception and geometric structure representation. Furthermore, the authors designed a multilayer attention pooling module consisting of local attention pooling and cascade attention pooling to extract contextual information. Local attention pooling is used to learn local neighbourhood information, and cascade attention pooling captures contextual information from deeper local neighbourhoods. Finally, an enhanced feature representation of important information is obtained by aggregating the features from the two deep attention pooling methods. Extensive experiments on large‐scale point‐cloud datasets Stanford 3D large‐scale indoor spaces and SemanticKITTI indicate that authors network shows excellent advantages over existing representative methods regarding local geometric feature description and global contextual relationships.
A comparative study on deep feature selection methods for skin lesion classification
Authors: Golnoori Farzad , Zamani Boroujeni Farsad , Monadjemi Seyed Amirhassan
Published: November 2023

Melanoma, a widespread and hazardous form of cancer, has prompted researchers to prioritize dermoscopic image‐based algorithms for classifying skin lesions. Recently, there has been a growing trend in using pre‐trained convolutional neural networks for detecting skin lesions. However, the features extracted from these classifiers may include irrelevant elements, emphasizing the importance of implementing effective feature selection methods. Nevertheless, there has not been a comprehensive study on feature selection methods to enhance the performance of skin lesion detection to date. To identify the most efficient methods, a diverse set of feature selection techniques, including filter, wrapper, embedded, and dimensionality reduction, were applied to images from two well‐known datasets, namely ISIC 2017 and ISIC 2018. According to the results, models trained with features chosen by wrapper techniques outperformed those trained with features chosen by filter and embedded methods. Achieving an accuracy of 0.8333 and an F1‐Score of 0.8291 for the ISIC 2017 dataset, and an F1‐Score of 0.9324 and an accuracy of 0.9350 for the ISIC 2018 dataset, the classification using features obtained via the GWO feature selection technique performed the best.
Ein Rekord, den niemand will
Authors: Schwencke Silja
Published: November 2023

Die diesjährigen Rekordwerte kranker Pflegender sind nicht überraschend. Dennoch haben wir uns gefragt: Warum genau sind so viele Pflegende krank? Und noch viel wichtiger: Was kann man dagegen tun? Lesen Sie hier einige Lösungsvorschläge.
Therapeutic Drug Monitoring in Inflammatory Bowel Disease
Authors: Neto Manoel Alvaro de Freitas Lins , Rolim João Otávio Moraes , Jatobá Diogo César Maurício de Oliveira , de Meira Júnia Elisa Carvalho , Filho Luís Henrique Salvador , Lins Lucas Correia , Peçanha Jorge Artur Coelho
Published: November 2023

Inflammatory bowel disease (IBD) is a problem that directly affects the quality of life of patients suffering from this condition. Monitoring the serum level of infliximab (IFX) (TDM) is an important tool for guiding therapeutic decisions in IBD patients. The purpose of this study was to determine the significance of quantitatively measuring the serum level of IFX (TDM) and antibody to IFX (ATI). Methods and materials: Prospective observational study involving 40 IBD patients on IFX therapy, including 14 Proactive (week 06 of the induction phase) and 26 Reactive (maintenance phase). Immediately prior to the infusion, blood samples were drawn and measured using a Bulhlmann rapid test instrument. Serum concentrations of IFX were categorized as supratherapeutic (>7.0 micrograms/ml), therapeutic (between 3.0 and 7.0 micrograms/ml), and subtherapeutic (3.0 micrograms/ml). When the serum concentration of IFX was 3 mcg/ml (subtherapeutic), the ATI was measured. 25 patients with CD and 15 patients with UC were evaluated. Only three of the twenty patients with subtherapeutic serum levels had a positive ATI, and both were reactive; two had CD and one had UC. There was a statistically significant difference between reactive and proactive patients with respect to levels of CRP (p = 0.042), with proactive DNS patients suffering greater alterations in CRP and albumin.
The effectiveness of visual instructions in the memorization of Chinese Semantic Radicals by Beginners
Authors: Tian Tian , Santos Lonsdale Maria dos , Cheung Vien
Published: November 2023

The acquisition of Chinese Characters (CCs) is challenging for learners. Chinese Semantic Radicals (SRs) are semantic components of CCs. The memorization of SRs facilitates the acquisition of CCs when learning Chinese as a second language. This study investigates the effectiveness of Visual Instructions (VIs) in the memorization of SRs by beginners. A preliminary study and three other studies have been conducted. The results have shown that the use of color-coded illustrations helps learners remember the meanings, shapes, and positions of SRs. This could be seen in the significantly increased accuracy of the responses in memory tests. These findings are an important contribution to research on VIs and on the memorization of SRs by beginners.
Disalignment in the EU
Authors: Franceschi Valeria
Published: November 2023

European Union (EU) institutions are highly multilingual environments where international communication is very
goal-oriented, as they produce and define policies and regulations applied to all member states. This paper aims at exploring how
disagreements and conflicting opinions are conveyed in such contexts through the qualitative analysis of debates in recorded
meetings of the European Parliament Committee on the Environment, Public Health and Food Safety. Two meetings from two different
parliamentary terms (2014–2019 and 2019–2024) will be analyzed. The study will adopt a pragma-rhetorical approach, drawing on
studies on politeness and conversation analysis techniques and focusing especially on the management of Face Threatening Acts in
English turns. Attention will also be paid to language choice, codeswitching, and to the international use of English. Results
show that conflict and overt disagreements in the data are very rare, with speakers displaying instead careful mitigation of the
language used, especially when English is employed.
Generalized 𝑞-Fock spaces and structural identities
Authors: Alpay Daniel , Cerejeiras Paula , Kaehler Uwe , Schneider Baruch
Published: November 2023

Using

q
q

-calculus we study a family of reproducing kernel Hilbert spaces which interpolate between the Hardy space and the Fock space. We give characterizations of these spaces in terms of classical operators such as integration and backward-shift operators, and their

q
q

-calculus counterparts. Furthermore, these new spaces allow us to study intertwining operators between classic backward-shift operators and the q-Jackson derivative.
Incomplete inverse problem for Dirac operator with constant delay
Authors: Wang Feng , Yang Chuan-Fu
Published: November 2023

In this work, we consider Dirac-type operators with a constant delay less than two-fifths of the interval and not less than one-third of the interval. For our considered Dirac-type operators, an incomplete inverse spectral problem is studied. Specifically, when two complex potentials are known a priori on a certain subinterval, reconstruction of the two potentials on the entire interval is studied from complete spectra of two boundary value problems with one common boundary condition. The uniqueness of the solution of the inverse problem is proved. A constructive method is developed for the solution of the inverse problem.
Twisted Kuperberg invariants of knots and Reidemeister torsion via twisted Drinfeld doubles
Authors: López Neumann Daniel
Published: November 2023

In this paper, we consider the Reshetikhin-Turaev invariants of knots in the three-sphere obtained from a twisted Drinfeld double of a Hopf algebra, or equivalently, the relative Drinfeld center of the crossed product

Rep
(
H
)
⋊
Aut
(
H
)

\text {Rep}(H)\rtimes \text {Aut}(H)

. These are quantum invariants of knots endowed with a homomorphism of the knot group to

Aut
(
H
)

\text {Aut}(H)

. We show that, at least for knots in the three-sphere, these invariants provide a non-involutory generalization of the Fox-calculus-twisted Kuperberg invariants of sutured manifolds introduced previously by the author, which are only defined for involutory Hopf algebras. In particular, we describe the

S
L
(
n
,

C

)

SL(n,\mathbb {C})

-twisted Reidemeister torsion of a knot complement as a Reshetikhin-Turaev invariant.
85. Efficacy of Sulbactam-Durlobactam (SUL-DUR) Compared to Colistin (COL) against Acinetobacter baumannii-calcoaceticus Complex (ABC) Monomicrobial and Polymicrobial Infections in a Phase 3 Trial
Authors: Miller Alita , McLeod Sarah , Shapiro Adam B , Rana Khurram , Altarac David
Published: November 2023

Background

Recently, a global, active-controlled Phase 3 trial evaluated the efficacy and safety of SUL-DUR vs. COL for patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections, including multidrug resistant strains. Both arms were dosed on a background of imipenem/cilastatin (IMI) to treat co-infecting Gram-negative pathogens. 33% of infections in the primary efficacy population were polymicrobial.

Methods

The minimal inhibitory concentrations (MICs) of SUL-DUR, colistin and imipenem against baseline isolates were determined by broth microdilution using CLSI guidelines. The primary efficacy endpoint was 28-day all-cause mortality (ACM) in patients with carbapenem-resistant ABC at baseline (CRABC m-MITT). Clinical and microbiological outcomes were evaluated at Test of Cure (TOC).

Results

28D ACM, clinical and microbiological outcomes were similar for patients in the SUL-DUR arm with either monomicrobial or polymicrobial ABC infections while patients in the COL arm with monomicrobial ABC infections had higher mortality rates with worse clinical and microbiological outcomes compared to those with polymicrobial infections (Table 1). Of the 12 patients in the SUL-DUR arm who did not survive to 28 days, 4 (33.3%) were attributed to the index infection (2 of 6 [33.3%] for both monomicrobial and polymicrobial ABC infections). Of the 20 patients in the COL arm who did not survive to 28 days, 10 (50%) were attributed to the index infection (7 of 15 [46.7%] with monomicrobial ABC infections and 3 of 5 [60%] with polymicrobial ABC infections) (Table 2).

Conclusion

SUL-DUR was equally efficacious in patients with monomicrobial vs. polymicrobial ABC baseline infections and an equal percentage of deaths (33%) were attributable to the index infection in each sub-group. Although fewer patients in the COL arm died with polymicrobial ABC infections (5 of 20, 25%) than monomicrobial ABC infections (15 of 20, 75%), 60% of the former (3 of 5) were attributable to polymicrobial ABC infections while 46.7% of the latter (7 of 15) were attributable to monomicrobial ABC infections. These results suggest that, if approved, the use of SUL-DUR plus a carbapenem could be an effective approach to treat polymicrobial infections that include ABC.

Disclosures

Alita Miller, PhD, Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds Sarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds|Innoviva Specialty Therapeutics: Stocks/Bonds Adam B. Shapiro, Ph.D, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Full Time Employee
91. Implementation of a blood culture algorithm in emergency department patients as a diagnostic stewardship intervention
Authors: Seidelman Jessica , Theophanous Rebecca , Ramos John , Calland Alyssa R , Krcmar Rachel , Shah Priya , Tarabal da matta Lucas , Shaheen Stephen , Wrenn Rebekah
Published: November 2023

Background

Blood cultures (BCx) are commonly ordered for patients at low risk of bacteremia. Liberal ordering can increase false-positive results due to contamination, along with increasing length of stay, excess antibiotics, and unnecessary diagnostic procedures. We implemented an algorithm for appropriate blood culture obtainment (Figure 1) in an academic tertiary care emergency department (ED) and assessed the intervention’s impact on various operational, clinical, and safety metrics.Figure 1:ED Blood culture algorithm

Methods

We performed a prospective cohort study in the Duke University Hospital ED from 12/2022 to 3/2023 using historical controls from 12/2020-11/2022. The BCx algorithm was disseminated in-person, electronically, and accessible online. Weekly chart review of all eligible patients for algorithm adherence was completed by 7 ED clinicians with monthly feedback provided to all ED providers. We defined a BCx event as 1 or more BCx sets within 24 hours. We excluded patients < 18 years, absolute neutrophil count < 500 109/L, and heart and lung transplant recipients. We measured BCx order volume, indication, algorithm adherence, BCx positivity rate, antibiotic days of therapy (DOT), and 30-day hospital readmission.

Results

Average monthly BCx volume was 1387 pre-intervention compared to 1226 post-intervention (p= 0.046). An increase in culture positivity was see post-intervention with a rate of 13.9% compared to 11.23% in the pre-intervention group (Figure 2, p< 0.001). The majority of the 2168 BCx adhered to the algorithm. (Figure 3). The most common reasons for non-adherence were isolated fever or leukocytosis (29%), non-severe community-acquired pneumonia or healthcare-associated pneumonia (6.9%) and non-severe cellulitis (4%). No change in DOT (786 vs. 783 days of therapy per 1000 patient days, p-value 0.85) (Figure 4) or monthly 30-day hospital readmission (21.1% vs 19.6%, p-value 0.30) was observed.Figure 2:Blood cultures drawn per month and % appropriate pre/post-intervention (N=2168)Figure 3:Algorithm Adherent vs. Algorithm Non-Adherent blood cultures per month (N=2168)Figure 4:Emergency Department anti-bacterial days of antibiotic therapy per 1000 patient days

Conclusion

Introduction of a BCx algorithm in an academic tertiary care ED, resulted in a decrease in BCx volume, increase in BCx positivity rate, and no increase in DOT or readmission was observed. (Table 1)Table 1:Blood culture volume, positivity rate, days of antibiotic therapy, and 30-day readmission

Disclosures

Jessica Seidelman, MD, MPH, Uptodate: content editor for pelvic osteomyelitis page
94. Rapid Diagnostic Testing is Associated with Decreased Broad Spectrum Antibiotic Use in Streptococcal Blood Stream Infections
Authors: Tate Tyler , Viehman Alex , Shields Ryan K
Published: November 2023

Background

Rapid diagnostic testing (RDT) allows antimicrobial stewardship programs (ASP) to intervene early in the setting of sepsis and septic shock leading to lower rates of death. Combining RDT with ASP results in faster antibiotic de-escalation compared to RDT alone; however, the utility of this approach for Streptococcal bacteremia is unproven. The objective of this study was to evaluate the impact of RDT with real-time ASP intervention on blood cultures growing Streptococcal species.

Methods

Retrospective, observational study comparing patients with Streptococcus spp. bacteremia over two 6-month periods. During the pre-RDT period, patients were prospectively followed by ASP who provided recommendations based on gram-stain and organism identification results. During the post-RDT period, blood cultures were tested by GenMark ePlex BCID-GP that identifies S. agalactiae, S. anginosis group, S. pneumoniae, S. pyogenes and Streptococcus spp. within 90 minutes which were reported directly to ASP for recommendations on antibiotic discontinuation, de-escalation, and additional diagnostic testing.

Results

94 patients were included in the analysis, 50 pre- and 44 post-RDT. Across cohorts, patient demographics, clinical characteristics, and severity of illness were comparable (Table 1). The median ages were 58 and 56, 62% and 68% were men, and a total of 12% and 16% were immunocompromised. The mean qSOFA scores were 1.9 and 2. The most common Streptococcus spp. was S. mitis (figure 1). Prior to RDT, the median time to antibiotic de-escalation was 88 hours. Following implementation of RDT, median time to de-escalation was 42 hours (P=0.002). De-escalation to targeted therapy improved from 50% to 86% in post-RDT (P< 0.01). Transition to oral antibiotics increased from 14% to 30% (P=0.08). There were no differences in hospital re-admission or acute kidney injury. A trend toward decreased 30-day mortality was identified in the post-RDT period (P=0.06).

Conclusion

Our study highlights the impact of RDT with ASP intervention on clinical outcomes for patients with Streptococcal bacteremia. We noted significant reductions in broad-spectrum antibiotic use and a trend towards lower mortality. Larger studies are needed to demonstrate the full potential of this approach.

Disclosures

Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support
95. What To Do With Prolonged Bacteremia in Staphylococcus aureus Osteoarticular Infection? A Retrospective Analysis at Two Children's Hospitals
Authors: McNeil Jonathon C , Joseph Marritta , Vallejo Jesus G , Hulten Kristina G , Kaplan Sheldon L , Boyle Mary G , Fritz Stephanie A
Published: November 2023

Background

Staphylococcus aureus is the most frequent cause of osteoarticular infection (OAI, including hematogenous osteomyelitis and septic arthritis) in children and is commonly associated with bacteremia. Current guidelines suggest that persistent bacteremia may warrant more aggressive treatment, however, data supporting this are limited. We retrospectively evaluated the management and outcomes of children with S. aureus OAI with respect to bacteremia duration.

Methods

Cases were identified through prospective S. aureus surveillance studies at Texas Children’s and St. Louis Children’s Hospitals. Children < 18 years old with OAI secondary to S. aureus from 2011-2021 were eligible. Prolonged bacteremia was defined a priori as the upper quartile of duration. Orthopedic complications included pathologic fractures, avascular necrosis, angular deformity and chronic osteomyelitis.

Results

Overall, 532 cases were identified of which 343 (64.5%) had ≥1 positive blood culture; 61 developed orthopedic complications (11.4%, Figure 1). The median duration of bacteremia in the cohort was 1 day (IQR: 1-3 days). Patients with prolonged (≥ 3 days) and non-prolonged bacteremia were similar in terms of demographics. Children with prolonged bacteremia had a longer duration of fever in hospital (median 6 vs. 3 days, p< 0.001), more often had MRSA, pyomyositis and venous thromboses and were less often transitioned to oral therapy (Figure 2). Duration of bacteremia also influenced discharge antibiotic choice (Figure 3). Within the subset of patients with prolonged bacteremia, those who were transitioned to oral therapy had similar outcomes to those treated with prolonged intravenous antibiotics; such patients received a median of 11.5 days (IQR: 6-23) of IV therapy prior to discharge (median 7 days [IQR: 4-20] after last positive blood culture).

Conclusion

Prolonged bacteremia in the setting of S. aureus OAI greatly impacts management and should prompt evaluation for other foci of infection. However, our data show that a subset of children with S. aureus OAI and prolonged bacteremia can be safely transitioned to oral antibiotics after a period of IV therapy. Additional work is needed to delineate optimal management of OAI with prolonged bacteremia.

Disclosures

Jonathon C. McNeil, MD, Allergan: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support Kristina G. Hulten, PhD, Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria
104. Accuracy of ChatGPT for UTI Diagnosis and Management Questions
Authors: Gupta Kalpana , O’Brien William , Strymish Judith
Published: November 2023

Background

Artificial Intelligence chatbots such as ChatGPT are increasingly being utilized for medical information by the public as well as by medical professionals, including researchers. We investigated the accuracy of information and citations generated by this search engine for a common medical condition, UTI.

Methods

This was a qualitative pilot evaluation of an artificial intelligence chatbot for answering and referencing clinical questions on UTI. We created 5 clinical questions (Table) related to UTI diagnosis and treatment. Two clinical infectious diseases experts graded the responses on a Likert scale as to accuracy of the response. The gold standard for responses was derived from IDSA guidelines and/or evidence based electronic resources (e.g. UpToDate). Citations were checked for accuracy using PubMed searches, Google Scholar and also, in one case, direct communication with the purported author.

ChatGPT Performance on UTI Questions

Results

ChatGPT answered 3 of the 5 questions mostly correctly (Likert scale 4 out of 5). The response to one question was rated as only half correct (Likert scale 3 out of 5). One question was answered 100% correctly. Incorrect information was primarily related to diagnostic approaches to urine cultures for both asymptomatic and symptomatic patients (Table), and did not reflect answers found in current guidelines.

When prompted for supportive evidence of answers, ChatGPT created plausible, yet fabricated studies. The authors were real and well-known experts in the field, but the combinations of authors, journal title and paper title were often false. Citations were incorrect for all 5 questions and fabricated in 12 of 24 provided citations.

Conclusion

ChatGPT performed surprisingly well on correctly answering basic diagnosis and management questions on UTI, a commonly encountered condition with a large body of literature to train from. The lack of current information from guidelines hampered accuracy and could be a barrier to appropriate use of this technology for real-time learning or clinical decision-making. The inaccuracy of citations limits its use for supporting evidence-based research and publications.

Disclosures

Kalpana Gupta, MD MPH, GSK: Advisor/Consultant|Iterum Therapeutics Limited: Advisor/Consultant|Qiagen, Inc.: Advisor/Consultant|UpToDate Wolters Kluwer Health: Royalties
962. Impact of Care Bundle Element Compliance on Clinical Outcomes for Pediatric Patients with Staphylococcus aureus Bacteremia
Authors: Pallotta Raneem , Davidge Karen , Riggsbee Daniel , Tribble Alison , Nagel Jerod
Published: November 2023

Background

Staphylococcus aureus bacteremia (SAB) is a major cause of morbidity and mortality in children. The Infectious Disease Society of America (IDSA) outlines standards of care for patients with SAB known to positively impact morbidity and mortality, which have been validated in numerous studies within the adult population. However, there is limited data evaluating the clinical impact of compliance with these standards in pediatric patients. The primary objective of this study was to evaluate the impact of compliance with seven key bundle elements for the treatment of SAB in children.

Methods

This was a retrospective, single-center, cohort study of pediatric patients aged 18 years or younger with SAB admitted to Michigan Medicine from 2019–2022. The seven bundle elements evaluated included timely initiation of antibiotics, appropriate targeted antibiotic therapy, ID consultation, documented culture clearance, an echocardiogram for high-risk patients, source control, and appropriate duration of therapy. To be considered fully compliant, patients had to meet all seven elements. The primary endpoint was a composite endpoint of mortality and 30-day infection-related readmission rates.

Results

A total of 73 patients were included; 40 (54.8%) met the fully compliant bundle definition, and 33 (45.2%) were partially compliant. Fully compliant patients had a significantly lower incidence of combined mortality and readmission (7.5% vs. 24.2%; p = 0.0466). Lack of appropriate targeted therapy and lack of source control in patients with a removable source were the most common reasons for not meeting full bundle compliance (Table 1). Appropriate duration of therapy was met in 78.8% of patients in the partially compliant group (26/33, p = 0.0026).Table 1.Bundle Element Compliance.Bundle element compliance between the two cohorts (fully bundle compliant vs partially bundle compliant)Table 2.Primary OutcomeCombine primary outcome of 30-day mortality and 30-day infection-related readmission (fully bundle compliant vs partially bundle compliant)

Conclusion

Adherence to all bundle elements was associated with lower incidences of mortality and readmission. The results of this study will assist in quality improvement interventions at Michigan Medicine.

Disclosures

All Authors: No reported disclosures
964. Real-world dalbavancin use for serious gram-positive bacterial infections: comparing outcomes between people who use and do not use drugs
Authors: Zambrano Sarah , Paras Molly L , Suzuki Joji , Pearson Jeffrey C , Schrager Harry , Mallada Jason , Dionne Brandon , Fairbank-Haynes Katie , Kalter Marlene , Szpak Veronica , Prostko Sara , Solomon Daniel A
Published: November 2023

Background

Dalbavancin has been used off label to treat invasive gram-positive bacterial infections due to its long half-life, eliminating the need for long term IV access and prolonged hospital stays. It is a particularly useful option in vulnerable populations such as people who use drugs (PWUD) who face unique challenges with long term IV antibiotics. This large, retrospective, multi-site study examined outcomes at 90 days in PWUD vs non-PWUD after treatment with dalbavancin for bacteremia, endocarditis, osteomyelitis, epidural abscess and septic joint infections.

Methods

Patients at three university-affiliated hospitals who received dalbavancin for an invasive gram-positive infection between March 2016 and May 2022 were included for analysis. Characteristics of PWUD and non-PWUD were compared using chi-square for categorical variables, t-test for continuous variables, and non-parametric tests where appropriate. A logistic regression model was created where clinical cure at 90 days was assessed according to PWUD status with adjustments for age, housing status, and type of infection. For all analyses alpha was set to 0.05.

Results

There were a total of 176 patients. Of those, 78 were PWUD and 98 were non-PWUD. PWUD were more likely to be younger (40.4 vs 56.2 years old; p< 0.0001), experiencing homelessness (24.4% vs 2%; p< 0.0001), and have a history of hepatitis C (65.4% vs 2%; p< 0.0001). Endocarditis, vertebral osteomyelitis, and epidural abscesses were more common infections among PWUD vs non-PWUD (20.5% vs 5.1%, 9% vs 0, and 9% vs 1%, respectively; P< 0.05 for all). There was no significant difference in length of hospital stay between the two groups. PWUD were more likely to have a patient directed discharge (27.3% vs 3.1%; p< 0.0001) and be lost to follow up (21.8% vs 6.1%; p < 0.002). Survival (78.2% vs 81.6%) and cure (71.8% vs 75.5%) at 90 days were not different between PWUD and non-PWUD, respectively. When controlling for age and housing status, the adjusted OR for clinical cure at 90 days among PWUD was 0.78 (95% CI 0.34-1.80).

Conclusion

Dalbavancin was an effective treatment option for invasive gram-positive infections in our patient population. Despite higher rates of patient directed discharge and loss to follow up, PWUD had similar rates of clinical cure at 90 days to non-PWUD.

Disclosures

Molly L. Paras, MD, Angiodynamics: Honoraria|Angiodynamics: Honoraria Joji Suzuki, MD, Indivior: Grant/Research Support
971. Pharmacokinetic Estimation Analysis of Multi-Dose Regimens of Dalbavancin for Treatment of Osteomyelitis or Bacteremia
Authors: Volk Cecilia , Hutson Paul , Rose Warren
Published: November 2023

Background

The management of multi-drug resistant gram-positive infections such as methicillin-resistant Staphylococcus aureus (MRSA) is a complicated task. This is made more difficult when prolonged treatment durations are required, such as for bacteremia, endocarditis, osteomyelitis, or other deep-seated infections. Dalbavancin (DAL) is a long-acting lipoglycopeptide increasingly being used for these infections and is a favorable option when clinicians desire to avoid central catheter placement. Despite the increasing use of DAL for prolonged therapy, there is a lack of consensus on optimal dosing and pharmacokinetic attainment.

Methods

An in silico pharmacokinetic/pharmacodynamic simulation was performed to assess the predicted DAL concentration resulting from either two 1500mg doses separated by one week, or a 1000mg loading dose followed by 5 weekly doses of 500mg. Single dose population PK parameters describing concentrations in serum as well as two tissue compartments were used to determine parameter estimates. Both the time above the MIC and 24-hour free DAL AUC/MIC were assessed as the PD target goals. The PK target for DAL was a 24-hour fAUC/MIC of 27.1 µg/mL.

Results

The two dose DAL dosing regimen (1500mg x2) maintained simulated free serum concentrations above the breakpoint (0.25 ug/mL) for a median of 56 days (lower 95%CI = 33 days) and above the MIC90 (0.06 ug/mL) for > 56 days (lower 95%CI = 43 days). Six dose DAL regimen (1000mg, then 500mg weekly) maintained simulated free serum concentrations above the breakpoint for a median of > 56 days (lower 95%CI = 53 days) and above the MIC90 for > 56 days (lower 95% CI = > 56 days). Both tissue compartments in the 3 compartment PK model demonstrated very similar drug levels to serum. The lower 95th percentile of 24h fAUC/MIC90 was maintained above 27.1 for > 56 days with both the 2-dose and 6-dose regimens.

Simulated free serum concentration of dalbavancin for modeled dosing regimens

Conclusion

Based on these simulations, the majority of patients maintain therapeutic DAL levels for at least 8 weeks using both modeled dosing regimens. These results, when combined with the observational data reporting clinical success, support the use of DAL when long durations of therapy are required, as for osteomyelitis or bacteremia.

Disclosures

Paul Hutson, PharmD, MS, Revive: Grant/Research Support Warren Rose, PharmD, MPH, Basilea: Honoraria|Ferring: Honoraria|Merck: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Honoraria
973. Pharmacokinetic/Pharmacodynamic Evaluation and Dose Optimization of Daptomycin in Pediatric Patients with Staphylococcus aureus Bacteremia
Authors: Olney Katie B , Howard Joel I , Burgess David
Published: November 2023

Background

Optimal dosing of daptomycin (DAP) in pediatric patients has not been elucidated in clinical practice. This study was conducted to examine DAP exposures achieved with package label dosing (PLD) and identify dosing regimens necessary to optimize efficacy and mitigate toxicity in pediatric patients being treated for Staphylococcus aureus bacteremia.

Methods

Pharmacokinetic/pharmacodynamic (PK/PD) models were constructed using age-specific pediatric PK parameters from previously published clinical trials in children to determine the probability of target attainment (PTA) for each of the following age cohorts: 3 to 6 months, 7 to 12 months, 13 to 24 months, 2 to 6 years, 7 to 11 years, and 12 to 17 years. Achievement of area under the curve over 24 hours (AUC0-24) ≥ 666 mg*hr/L was used as the PD target to determine the PTA for efficacy (PTAE). The probability for which the trough concentration (Cmin) exceeded 24.3 mg/L was the PD target used to determine the PTA for toxicity (PTAT). These PD targets were selected based on prior adult data correlating DAP exposure with efficacy and safety outcomes. Optimal dosing regimens were considered to be those which achieved the combined target of PTAE ≥ 90% and PTAT ≤ 5%.

Results

If targeting previously validated efficacy (AUC0-24 ≥ 666 mg*hr/L) and safety (Cmin < 24.3 mg*hr/L) endpoints, current pediatric dosing regimens do not achieve adequate DAP exposure for treatment of Staphylococcus aureus bacteremia. PLD failed to achieve adequate PTAE in all age groups with only 26.3% PTAE in children 13 to 24 months, 39.5% PTAE in children 2 to 6 years, 30.1% PTAE in children 7 to 11 years, and 50.1% PTAE in children 12 to 17 years of age. Optimal dosing regimens, defined as achieving at least 90% PTAE with PTAT ≤ 5%, are displayed in Table 1.

Conclusion

Current PLD of DAP resulted in inadequate exposure for all pediatric patients evaluated. If using validated PD targets for efficacy and safety, adequate PTAE and minimal PTAT were achieved with DAP at dosages of 20 mg/kg every 24 hours in children 3 months to 6 years of age, 18 mg/kg every 24 hours in children 7 to 11 years of age, and 10 mg/kg every 24 hours in children 12 to 17 years of age. Clinical studies evaluating these augmented dosages need to be conducted.

Disclosures

Katie B. Olney, PharmD, BCIDP, The Society of Infectious Diseases Pharmacists (SIDP): Grant/Research Support
975. Age and Body Mass Index Impact Optimal Vancomycin Model Selection for Bayesian Dosing: Results from a Large Multi-site Retrospective Study of Adult Patients
Authors: Hughes Maria-Stephanie , Lee Tiffany
Published: November 2023

Background

Vancomycin population pharmacokinetic (popPK) models embedded in Bayesian software are crucial to informing optimal initial dosing. Since pharmacokinetics (PK) vary based on patients’ age and body mass index (BMI), pharmacists are faced to select the best model amongst many for their patients. To aid in model selection, we used a large multi-site database to determine which models were the most accurate across age and BMI categories.

Methods

Data on adult patients receiving intravenous vancomycin therapy during January 1, 2022 - December 31, 2022, at healthcare organizations across the U.S. were queried from a Bayesian software database. Data collected included age, weight, height, serum creatinine, sex, vancomycin doses received, and vancomycin concentration levels. The a priori root mean square error (RMSE) for six well-performing and previously validated models was calculated for each patient to measure what the accuracy would have theoretically been if each were used. The average RMSE value per model was calculated and compared between age and BMI categories shown in Table 1. Each age-BMI combination’s most accurate model was reported.

Results

There were 79,600 patient treatment courses included across 84 health systems. The results for the most accurate model for each age-BMI combination are reported in Table 2. The lowest RMSE was 3.91 mg/L using the modified Goti model in patients > 80 years with BMI < 18.5 kg/m2. The highest RMSE was 7.86 mg/L using the Carreno model in patients < 35 years with BMI > 30 and < 35 kg/m2. A relationship was observed where older age categories lead to better model performance.

Conclusion

Age and BMI categories influenced which vancomycin popPK models performed best a priori within a Bayesian software when studied within a very robust dataset. These findings may help pharmacists choose which model to use for the most accurate PK calculations and thus inform optimal initial pop-PK vancomycin dosing. It also highlights that adults under 35 years, which tend to be underrepresented in model development populations, showed higher prediction error. Further research is needed on how to best implement these findings into practice.

Disclosures

Maria-Stephanie Hughes, PharmD, InsightRX: Stocks/Bonds Tiffany Lee, PharmD, InsightRX: Employment
978. Association of oral anticoagulation therapy with dabigatran and the incidence rate of Staphylococcus aureus bacteremia among patients with atrial fibrillation
Authors: Hasegawa Shinya , Ohl Michael , Vaughan-Sarrazin Mary , Perencevich Eli N , Goto Michihiko
Published: November 2023

Background

Dabigatran, a univalent direct thrombin inhibitor, is used as a direct oral anticoagulant (DOAC) for patients with high-risk conditions for thrombosis, such as atrial fibrillation (AF). In-vitro and animal model studies suggest dabigatran (but not other DOACs) might also reduce the virulence of Staphylococcus aureus by inhibiting staphylothrombin, and a recent study from Denmark reported lower incidence of S aureus bacteremia (SAB) among people on dabigatran compared to other DOACs (Butt et al. CID 2021). However, clinical data for this phenomenon in other populations are still sparse. We aimed to evaluate the incidence rate of SAB among patients in the United States Veterans Health Administration (VHA) treated with dabigatran compared with those treated with other DOACs or warfarin.

Methods

This retrospective cohort study examined medication and microbiology data for all patients with AF who started new oral anticoagulation therapies in VHA in 2011-18 and followed for the duration of the first anticoagulation therapy. We calculated crude incidence rates of SAB as the number of events per 10,000 person-years, stratified by the type of oral anticoagulation therapy.

Results

Among 45,023 patients starting anticoagulation for AF during the study period, the total person-years of exposure were 5,384 for dabigatran (5,052 unique patients), 12,613 for non-dabigatran DOACs (15,449 unique patients), and 38,964 for warfarin (31,415 unique patients). There were 11 SAB events among patients on dabigatran, 52 among patients on non-dabigatran DOACs, and 194 among patients on warfarin. The crude incidence rates of SAB in each group were 20.43 (95% confidence interval [CI], 8.37-32.49), 41.23 (95%CI, 30.04-52.41), and 49.79 (95%CI, 42.80-56.78) events per 10,000 person-years, respectively (dabigatran vs non-dabigatran DOACs: p=0.043, dabigatran vs warfarin: p=0.004).

Conclusion

The crude incidence rate of SAB among Veterans with AF who were on dabigatran was lower than those on other DOACs or warfarin. This supports the prior Danish study reporting lower SAB incidence among patients on dabigatran. Further studies are needed to assess this potential association while accounting for other patient-level factors and longer follow-up durations.

Disclosures

Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support
979. A Cluster-randomized Controlled Trial of Enhanced Carbapenem-resistant Enterobacteriaceae Prevention Program at General Medicine Wards, Siriraj Hospital
Authors: Taweesuk Apiradee , Rachakhom Siriporn , Wangchinda Walaiporn , Thamlikitkul Visanu , Assanasen Susan , Rattanaumpawan Pinyo
Published: November 2023

Background

Carbapenem-resistant Enterobacteriaceae (CRE) colonization is an important risk factor for CRE infection. Most of Infection prevention control (IC) strategies to reduce CRE colonization were recommended to implement in a private room setting. Data on effectiveness of IC program in general medicine wards is limited.

Methods

During February-October 2021, a cluster-randomized controlled trial was conducted among high risk for CRE-adult patients at six general medical wards, Siriraj Hospital. Six wards were randomized to receive either the standard IC care (sIC) or the enhanced CRE prevention program (eIC) plus sIC. The active CRE surveillance of stool or rectal swab specimen was performed in both groups within the first 72 hours of enrollment and then every 7 days. The eIC included a monthly healthcare education and feedback session, a real-time alert of CRE-acquisition from the active surveillance, and the CRE contact precaution visual reminder. The sIC included the cohorting and contact precaution of a CRE-acquisitioned patient, and a real-time alert of CRE-acquisition from the clinical specimen.

Results

There were 174 patients (with 1684 patient-days) in the intervention group and 189 patients (with 1517 patient-days) in the control group. Baseline characteristics were comparable between two groups. The cumulative incidence of CRE-acquisition was slightly lower in the intervention group (36.8% (64/174) vs. 46.6% (88/189);p=0.059). The incidence rate of CRE-acquisition was significantly lower in the intervention group (0.038 vs. 0.058;p=0.007). The median [range] of CRE-acquisition free time (6 days [1-73] vs. 5 days [1-81];p=0.84) were comparable. K. pneumoniae was the most common CRE pathogen isolated from the surveillance and clinical specimens. No difference in all-cause mortality and length of stay between the two groups was observed.

Conclusion

The incidence of CRE acquisition at our institute was remarkably high. The eIC could reduce the incidence of CRE-acquisition and lengthen the CRE-acquisition free time. Future study should be done to explore the benefit on morbidity and mortality outcomes.

Disclosures

All Authors: No reported disclosures
984. Detection of Mycobacterial Species from Specimens Submitted for Metagenomic Analysis
Authors: John Joseph F , Schmidt Michael G , Jarvis Courtney L , Diaz Niccole , Martin Rick
Published: November 2023

Background

A national U.S. epidemic of non-tuberculous mycobacterial (NTM) infections is occurring at rates unseen over earlier decades, resulting in substantial numbers of pathogenic sequelae. Culture of mycobacteria is laborious, often requiring weeks for cultivation and speciation. Next generation sequencing (NGS) to detect NTM from clinical specimens has advantages over culture methods. From January 2018 to June 2022 we queried a large national NGS database to detect NTM rates and species.

Methods

DNA was isolated from 431,716 patient specimens collected from a variety of body sites: sputum, urine, sinus, wound or an unspecified swabs. Employing an Illumina’s 16S and ITS targeted-gene, deep sequencing approach, bacterial and/or fungal species resident in the specimen were determined. The identity and relative abundance of mycobacterial DNA recovered for each specimen were reported by species as the primary outcomes.

Results

Of the 431,716 specimens analyzed in this 4.5 year retrospective study, 0.001% (468) contained mycobacterial DNA. Forty different species of mycobacteria were detected with the most common frequency including: M abscessus, 40%; M mucogenicum, 13%; M. tuberculosis, 8.5% and M immunogenum 4.6%. M. avian and M. intracellulare were each detected in only 4% of the positive NTM specimens. 15% were other NTM species and 15% were not speciated NTM. Between 2018-2022 of the 468 NTM, the annual number of M. abscessus was 38, 53, 41 and 41, respectively. The concentration or relative abundance of mycobacterial DNA within each specimen varied from 4 to 100% of the total bacterial DNA recovered.

Conclusion

Over 4.5 years , NGS performed at a national molecular diagnostic laboratory detected 40 NTM species with a predominant fraction as M. abscessus (40%), supporting the clinical concern for an epidemic increase in M. abscessus infections during the last half decade. These data support the view that NGS metagenomics can uncover NTM epidemiological trends and implicate NTM infections.

Disclosures

Joseph F. John, Jr., MD, FACP, FIDSA, MicroGenDx: Advisor/Consultant Michael G. Schmidt, PhD, MicroGenDx: Advisor/Consultant Courtney L. Jarvis, PhD, MicroGenDX: Employee Niccole Diaz, BS, MicroGenDX: Advisor/Consultant Rick Martin, BS, MicroGenDX: Ownership Interest