Ristagno, Elizabeth H.

Abstract Background Pharmacokinetics of beta-lactams vary widely in neonatal and pediatric patients due to developmental biology and critical illness. Cefepime (FEP), meropenem (MEM), and piperacillin/tazobactam (TZP) are highly susceptible to pharmacokinetic changes as hydrophilic, small molecules with renal clearance. Subtherapeutic levels are associated with clinical and microbiologic failure, and supratherapeutic levels associated with toxicity. Beta-lactam therapeutic drug monitoring (TDM) may optimize the effectiveness and safety of these agents. The purpose of this investigation is to describe the % of pediatric and neonatal patients with beta-lactam serum levels within target range. Methods In August 2023, TDM launched at the Mayo Clinic Children’s Center for select patients treated with FEP, MEM, or TZP with expected durations ≥ 48 hours, or who were on kidney replacement therapy (KRT), extracorporeal membrane oxygenation (ECMO), weighed > 120 kg, had a BMI > 95th percentile, or at the discretion of pediatric ID team. Validated drug assays were performed daily, Monday through Friday. A two-level sampling strategy was preferred with a peak 1 hour after the end of the infusion and a trough 30 minutes before the next dose. Empiric trough target ranges were set at FEP 8-50 mg/L, MEM 2-30 mg/L, and piperacillin 16-150 mg/L. These target ranges were adjusted with confirmed microbiology to a time above the minimum inhibitory concentration of the organism for 100% of the dosing interval (100%T > MIC). Results From August 2023 to April 2024, 74 episodes of TDM were performed on 45 patients. Thirty-seven (82%) patients were in an intensive care unit (ICU) at the time of TDM, 8/45 (22%) of whom were in the neonatal ICU. Target range was achieved in 67% of patients on FEP, 50% on MEM, and 52% on TZP. Median (IQR) trough values were 22.1 (8.6, 44.2) mg/L for FEP, 0.6 (0, 4.1) mg/L for MEM, and 15.5 (3.8, 27.1) mg/L for TZP. Seven levels were above target for FEP and 0 for MEM and TZP. Seven levels were below target for FEP, 4 for MEM, and 11 for TZP. Conclusion Implementation of a TDM program for FEP, MEM and TZP in pediatric and neonatal patients revealed drug levels frequently outside target range. TDM may facilitate dose individualization to optimize medication efficacy and minimize toxicity. Disclosures Raymond Stetson, MD, MS, Moderna: Grant/Research Support Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member Erin F. Barreto, PharmD, MSc, Baxter Health: Advisor/Consultant|Wolters Kluwer: Advisor/Consultant

Abstract Background Prolonged and recurrent fevers in pediatric outpatients often require specialist consultations, presenting a challenge in accurately triaging to the correct pediatric subspecialty. This study aims to develop an artificial intelligence (AI)-based model to accurately direct pediatric patients to appropriate subspecialties.Table 1.Patient characteristics and the department confirming the final diagnosis Table 1. Patient characteristics and the department confirming the final diagnosis Methods A retrospective study was conducted at the Mayo Clinic, Rochester, from December 1, 2020, to January 1, 2023, involving pediatric patients aged 0 to 18 referred for recurrent fever or fever of unknown origin. Six machine learning models, including gradient boosting, random forest, support vector machines (SVM), k-Nearest Neighbor (KNN), logistic regression (LR) and decision tree, were developed using 7 variables (demographics, chief complaints, referral sources, departments of same-day initial visit, and lab tests results within 30 days before initial visits). Data were extracted from external electronic health records (EHR) using Mayo Data Explorer and Lab Information Management Systems. Precision, Recall, F1 Score, and area under the curve (AUROC) were selected to measure the performance.Table 2.Performance of six machine learning models Table 2. Performance of six machine learning models Results The study evaluated 87 pediatric patients with a median age of 10.2 years (IQR: 4.6-13.8), including 43 (49%) females (Table 1). External provider referrals were noted in 40 (46%) patients. Musculoskeletal pain was the most common chief complaint, identified in 29 (33%) patients, in addition to prolonged or recurrent fever. Infectious disease and rheumatology divisions jointly saw 43 (49%) patients during the initial visit. Sub-optimal performance was observed in six machine learning models (Table 2). The random forest model showed the best results (Accuracy=0.39, Precision=0.34, Recall=0.39, F1 Score=0.35, AUROC=0.60) (Figure).Figure.ROC curves for various models Figure. ROC curves for various models Conclusion This study demonstrates the potential of AI-based models for outpatient triage prediction in pediatric patients with recurrent fever, using EHR data to optimize health resource utilization. This data serves as the groundwork to expand and refine this AI triage tool. Disclosures All Authors: No reported disclosures

Abstract Background 16S ribosomal RNA (rRNA) gene PCR and sequencing may serve as an adjunctive diagnostic tool in complex infections, identifying bacteria in patients on antibiotics whose cultures may be negative. Data on the optimal clinical settings for utilizing this type of testing are limited. This study reviews a single center's 16S rRNA PCR/sequencing experience in children to identify clinical syndromes and optimize specimen choice for higher yield, leading to testing of appropriate patients. Methods A retrospective study was performed at Mayo Clinic, Rochester involving children aged 0 to 18 years whose normally sterile tissue or fluid samples underwent 16S rRNA gene PCR/sequencing. The assay involved an up-front real-time PCR assay, reported as negative or submitted to Sanger or next-generation sequencing depending on Ct values. Data was collected on patient characteristics and results of 16S rRNA gene PCR/sequencing and conventional tests. Impact on clinical decision-making was assessed as to whether the advanced molecular diagnostic changed antimicrobial therapy. Results A total of 162 tests were performed on 124 patients, including 47% females (58/124) with a median age of 9.6 (range, 2.2-15.0) years. Overall, 33/162 (20%) of tests were positive in 24/124 (19%) patients. 58% of positive tests (19/33) were from samples with negative bacterial cultures. Cerebrospinal fluid was the most common specimen tested (n=38; 31%). Positive results were more likely from fluid compared to tissue samples (OR [95% CI]: 3.1 [1.3, 7.1], p=.007; OR [95% CI]: 0.3 [0.1, 0.8], p=.007, respectively). Testing was positive in 5/10 (50%) pleural fluids tested, a higher positivity rate than any other specimen type (OR [95% CI]: 5 [1.3, 19.0], p=.011). No significant changes in antibiotics were made within 24 hours of reporting positive 16S rRNA gene PCR/sequencing results. Conclusion This study highlights the importance of selecting appropriate sample types for 16S rRNA gene PCR/sequencing in pediatric patients. The assay is most likely to yield positive results in children with pleural effusion and in other fluid samples such as subdural and synovial fluid. Further implementation science research is needed to achieve impact on clinical practice. Disclosures Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria

Abstract Background SARS-CoV-2 vaccination has been shown to prevent severe disease and subsequent secondary infections in immunocompromised patients. This study assessed the rate of SARS-CoV-2 vaccinations among pediatric solid organ transplant (SOT) recipients at a single transplant center.Figure 1.SARS-CoV-2 vaccination status among pediatric solid organ transplant recipients for all ages and by age group. Methods We retrospectively reviewed medical records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN between January 2011 and December 2023. All SARS-CoV-2 vaccine doses administered on or before April 1, 2024 were recorded. Up-to-date (UTD) status was based on current CDC recommendations for immunocompromised patients for each age group. Deceased patients, those no longer following at Mayo Clinic and whose vaccine records were unavailable were excluded. We also assessed whether patients had been seen by an ID physician in the year prior to collection stop date. Results The study included 136 patients: 48 kidney, 58 heart and 30 liver transplant recipients; 52.9% were male. Two patients subsequently received organs of a different type. Mean age was 16.1 years. Since authorization in 2020, 90 patients (66.2%) received at least one SARS-CoV-2 vaccine. This varied by age group, with 72.8% of > =12 year olds, 40.0% of 5-11 year olds and 62.5% of under 5 year olds (p = 0.007 [Figure 1]). Seventy-three patients (53.7%) completed at least three doses. Based on current recommendations that include the 2023-2024 formulation, 30 patients (22.0%) were UTD. This did not differ between age groups (p = 0.717) or by transplanted organ type (p = 0.21). Patients that saw ID were significantly more likely to be UTD (p = 0.001). Among partially immunized patients, 95% (n = 57) needed one additional dose to be UTD. Conclusion Despite simplified guidelines with fewer doses needed, a third of pediatric SOT recipients remain unvaccinated against SARS-CoV-2 and only 22% are UTD based on current recommendations. The proportion of unvaccinated patients was highest in the 5-11 year old age group and lowest in the oldest. Those that recently saw ID were significantly more likely to be UTD. Our data suggest that continued care provided by ID physicians may increase vaccine uptake, but reasons for undervaccination and strategies to counteract this should be further explored within this vulnerable population. Disclosures All Authors: No reported disclosures

Abstract Background Although infectious diseases present significant challenges in pediatric care, formal training in pediatric infectious diseases is not mandated in categorical pediatric residency training. This research seeks to examine the self-assessed confidence levels of general pediatric residents in Washington DC in managing common infectious diseases. The study specifically compares the confidence levels of residents who have undergone elective infectious diseases training with those who have not. Subjective Confidence in the Management of Common Infectious Diseases Encounters Methods A cross-sectional study was conducted using voluntary surveys distributed among pediatric residents from various programs in Washington DC. The surveys aimed to assess subjective confidence levels in managing common infectious disease conditions and to explore motivation to pursue infectious disease training. Effect of infectious diseases elective rotation on interest in infectious diseases as a career. Are you more or less likely to pursue infectious diseases fellowship? Results Analysis of 20 completed surveys revealed that residents who completed infectious diseases rotations demonstrated significantly higher confidence levels in managing infectious disease conditions compared to their counterparts (P: < 0.001). Notably, residents with specialized training showed increased confidence in antibiotic selection and in their diagnostic abilities. Additionally, they exhibited enhanced confidence in managing specific presentations such as sexually transmitted diseases, fever of unknown origin, and central nervous system infections (all with P < 0.05). Finally, 22% of respondents expressed an increased likelihood of pursuing a career in infectious diseases following their rotation. Effect of infectious diseases rotation on the confidence in the management of inpatient and outpatient infectious diseases encounters Conclusion These findings underscore the potential benefits of incorporating infectious diseases rotations into pediatric residency programs, as evidenced by improved skills in antibiotic selection, diagnosis, and management of specific infectious disease scenarios. Additionally, the observed increased interest in pursuing a career in infectious diseases among a subset of residents highlights the positive impact of such training on career trajectory and specialty choice. Investigators plan to distribute the questionnaire more broadly across the US to see if these results are more widespread. Disclosures All Authors: No reported disclosures

Abstract Background Specialty societies, including the Infectious Diseases Society of America, strive to address gender and racial inequities in professional advancement. Microaggressions remain a persistent and pervasive barrier to these goals. Nonprofessional speaker introductions are a manifestation of race- and gender-based microaggressions, which have not been previously assessed at IDWeek. We assessed disparities in speaker introductions at IDWeek over a 7-year period that included formal gender equity initiatives introduced in 2016. Methods We conducted a retrospective observational study of video-recorded IDWeek speaker introductions from 2013 to 2019. Trained coders reviewed presentation video archives to assess a primary outcome of nonprofessional introductions: when a speaker's professional title was not used as the first introduction. We used descriptive statistics, Fisher exact tests, Cochrane-Armitage trend tests, and multivariable logistic regression to characterize relationships between speaker introductions and presentation year, speaker demographics, and speaker-moderator demographic concordance. Results Of 1940 videos reviewed, 48.9% of IDWeek speakers received nonprofessional introductions during and before 2016 vs 41.5% of speakers after 2016 (P = .0013). There was an increasing linear trend in the frequency of professional introductions by speaker age group from 47.1% for age <40 years to 65.3% for age >60 years (P < .0001). White moderators more frequently used nonprofessional introductions than moderators from backgrounds underrepresented in medicine (47.7% vs 29.1%, P = .0014). Women-men speaker-moderator pairs had more nonprofessional introductions (54.6%, P < .001). Conclusions In the largest assessment of microaggressions in speaker introductions at a national medical specialty conference, we highlighted some progress over time and ample opportunity to further standardize equitable speaker introductions, especially for women and junior speakers

Abstract Background An escape room is a cooperative game that has been adapted into medical education and major academic conferences. Methods We describe the design, development, and implementation of an educational ID-themed escape room activity entitled “Out-BREAK!” at an international conference, IDWeek 2023. An anonymous survey was conducted to collect demographic data, assess participant satisfaction with the escape room puzzles, and gauge participant interest in game-based learning. Results Thirty escape room sessions were held over 3 days and included 201 participants. Escape room survey respondents (n = 132) were younger and more likely to be trainees compared with in-person IDWeek attendants. Among 131 responses, all respondents enjoyed the experience and would recommend the escape room activity to friends. Survey respondents enjoyed the puzzle solving (93%), medical content (92%), and team building (79%) components. Only 35% of the respondents had ever previously participated in game-based learning; 95% thought the escape room was a valuable teaching method. Among the 72 survey respondents involved in medical education, almost all (90%) said they were interested in incorporating escape rooms into medical education. Conclusions The Out-BREAK! escape room at IDWeek 2023 was successfully implemented and well received. Despite only a third of participants having prior experience with game-based learning, almost all respondents perceived the escape room to be an effective teaching method.

ABSTRACT Chronic nonbacterial osteomyelitis (CNO) is an uncommon autoinflammatory disorder. Significant effort has recently been spent to better define and treat this disorder including development of consensus treatment protocols, validate disease activity tools, and refining classification criteria. However, the underlying immunopathogenesis of the disease remains elusive. In this report, we describe the simultaneous onset of CNO in siblings. A pathogenic gene mutation was not identified, and these sisters lacked a similar biomarker profile. This report highlights that if a genetic predisposition for CNO exists, it may be related to complex polygenic or multifactorial mechanisms of disease evolution.

ABSTRACTIntroductionThere is a lack of data regarding SARS‐CoV‐2 vaccination rates and tixagevimab‐cilgavimab (TC) uptake among pediatric solid organ transplant recipients. The purpose of our study was to assess these rates.Materials and MethodsWe reviewed vaccination records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN, who received a transplant between January 2011 and December 2021. All SARS‐CoV‐2 vaccines and doses of TC received on or before September 1, 2022, the date of approval of the bivalent SARS‐CoV2 vaccine, were included. We also assessed whether patients had been seen by an infectious diseases physician (ID) in the preceding 6 months.ResultsOur study included 110 patients: 47 kidney, 36 heart, and 27 liver transplant recipients. All vaccine doses recorded were monovalent SARS‐CoV‐2 vaccines. Sixty‐eight (61.8%) patients received at least one vaccine. This varied by age group, with f of ≥12 years olds, 40.9% of 5–11 year olds and 14.3% of under 5 year olds (p = 0.001). Seven patients (6.4%) were up‐to‐date (UTD) for age. There was no difference in UTD status by organ type (p = 0.335). Patients who saw ID were significantly more likely to be UTD (13.2% versus 2.8%; p = 0.047). Among those eligible, 14 (18.2%) received TC, with rates not different based on transplanted organ type (p = 0.158) or whether they saw ID (p = 0.273).ConclusionsDespite the availability of vaccines, nearly 40% of pediatric solid organ transplant recipients remained unvaccinated against SARS‐CoV‐2 at time of the bivalent vaccine release. Less than a fifth of eligible patients received TC. Strategies to increase uptake of SARS‐CoV‐2 vaccines as well as adjunctive agents among this vulnerable group should be further explored.

Abstract Background Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As Staphylococcus aureus is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule. Methods We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and recurrence of disease after completion of therapy. Results There were 59 patients included in the study. There was similar occurrence of adverse effects in patients receiving cefadroxil and cephalexin, although use of cefadroxil coincided with more gastrointestinal adverse effects and leukopenia and use of cephalexin with more rash and neutropenia. One secondary treatment failure occurred in our study, in a patient receiving cephalexin for treatment of septic arthritis. Conclusions Cefadroxil may be a reasonable alternative oral therapy for methicillin-susceptible S aureus or culture-negative AHO in pediatric patients, particularly when a less frequent dosing schedule is desired. Future study with a larger sample size is warranted.