bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt; 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

Abstract

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 &lt; 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&lt; 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

Abstract

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

Abstract

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

Abstract

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&lt; 0.0001), experiencing homelessness (24.4% vs 2%; p&lt; 0.0001), and have a history of hepatitis C (65.4% vs 2%; p&lt; 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&lt; 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&lt; 0.0001) and be lost to follow up (21.8% vs 6.1%; p &lt; 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

Abstract

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 &gt; 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 &gt; 56 days (lower 95%CI = 53 days) and above the MIC90 for &gt; 56 days (lower 95% CI = &gt; 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 &gt; 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

Abstract

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 &lt; 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

Abstract

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 &gt; 80 years with BMI &lt; 18.5 kg/m2. The highest RMSE was 7.86 mg/L using the Carreno model in patients &lt; 35 years with BMI &gt; 30 and &lt; 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