bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1122. Impact of an Antimicrobial and Diagnostic Stewardship Program in Children with Lower Respiratory Tract Infection admitted to Intensive Care Unit in Argentina
Authors: Perez Guadalupe , Carmona Rodrigo , Zuazaga Marcela , Ansio Carolina , Kijko Ivana , Gonzalez Gabriela , Velardez Daniel , Isasmendi Adela , Tevez Agustina , Borgnia Daniela , Taicz Moira , Rosanova Maria Teresa , Bologna Rosa 
Published: January 2025

Abstract

Background
Lower respiratory tract infection (LRTI) is a common cause of admission and antibiotic (ATB) overuse in children. Adequate use of diagnostic methods and ATB prescription in intensive care units (ICU) remain a challenge for antimicrobial stewardship programs.

Aims
to evaluate the impact of a multilevel intervention to improve diagnostic testing and ATB use in children with LRTI admitted to ICU.

Methods
Quasi-experimental, before-after study. Patients admitted to ICU from April to June 2023 (Pre Intervention period: PreI) and July to October 2023 (Post Intervention: PostI) with community acquired LRTI were included. Intervention consisted in educational activities, daily review and feedback of ATB prescription, development and dissemination of an institutional Guideline of ATB use in LTRI, including a Clinical Score to distinguish viral from bacterial pneumonia.

Results
95 patients were included. Median age was 11 months (IQR 4-19).Fifty eight (61%) had any underlying condition, including: previous bronchiolitis N:16 (17%), Asthma N:8(8%) and Neurological Disorders N:7 (7%). Clinical diagnosis upon ICU admission was: bronchiolitis (N:42, 44%), asthmatic crisis (N: 33, 35%) and Pneumonia (N: 11, 12%). A viral etiology was documented in 76 patients (80%). The most common was RSV (N: 52, 55%) followed by Rhinovirus (N: 19, 20%). Viral coinfection was detected in 15 patients (16%). Sixty-three patients were admitted during PreI and 32 during PostI. Children admitted to ICU during PreI were more frequently healthy (PreI: 48% vs PostIn 22%, p 0.015), with bronchiolitis as admission diagnosis (PreI 56% vs PostI 23%, p 0.002) and confirmed respiratory infection (PreI 87% vs PostI 66%, p 0.01). In PreI more Blood cultures (PreI 61% vs PostI 51%, p 0.06) and tracheal aspirate cultures (PreI 48% vs PostI 22%, p 0.04) were performed. Empirical ATB were started on admission in 39 patients (62%) during PreI, and in 13 patients (41%) in PostI (p: 0.04). Adequate ATB prescription increased from 14% in the PreI to 37% in the PostI (p 0.01). Patients in PostI had shorter hospital length of stay (8 vs 14 days, p 0.02)

Conclusion
A multilevel intervention in children with LRTI on admission to ICU improved the use of blood and tracheal aspirate cultures and ATB prescription. Length of stay decreased in PostI.

Disclosures
All Authors: No reported disclosures
417. Should We Be Doing This? Evaluating Pleural Fluid Inoculation into Blood Culture Bottles
Authors: Fraker J Hunter , Lee Matthew S 
Published: January 2025

Abstract

Background
Sterile fluid inoculation into blood culture (BCx) bottles has primarily been shown to be beneficial with peritoneal fluid. However, we have observed widespread expansion of this practice for other sterile fluid specimens at our institution. We investigated whether there was a clinical benefit to inoculating pleural fluid specimens into BCx bottles.

Methods
This was a retrospective chart review of patients who had pleural fluid inoculated into BCx bottles from July 1, 2021 through June 30, 2023. Clinical, microbiologic, and pharmacy data were extracted from medical records of patients that had at least one organism isolated from these samples and had a routine (non-blood culture bottle inoculation) pleural fluid culture sent from the same procedure. The primary outcome was the proportion of clinically relevant organisms based on evaluation by the primary or a consultant team.

Results
A total of 334 pleural fluid specimens were inoculated into BCx bottles during the study period; positive cultures were found in 12.2% (41/334). Five patients were excluded as they did not have a concomitant routine pleural fluid culture, leaving a study cohort of 36 patients.
In the study cohort (n=36), 61.1% (22/36) had the same organism(s) isolated from both BCx inoculated and routine pleural fluid cultures, while 38.9% (14/36) had additional organisms from the BCx bottle inoculated specimens that were not isolated on the routine pleural fluid culture.
Of the 14 patients with additional organisms from BCx bottle inoculation (Table 1), 4 were deemed contaminants. Ten patients had clinically relevant organisms and 4 of these led to changes in antimicrobial management (change in agent or duration).
Overall, 3% (10/334) of specimens with pleural fluid inoculated into BCx bottles had a clinically relevant organism that was not isolated in routine culture. 1.2% (4/334) of specimens led to a change in clinical management based on the additional organism(s) isolated.

Conclusion
In our single-institution study, we found widespread practice of inoculating pleural fluid into blood culture bottles. The practice may slightly increase microbiological yield over routine fluid cultures, but few patients had a change in clinical management at our institution.

Disclosures
All Authors: No reported disclosures
P-1152. Cefepime, Meropenem, and Piperacillin Therapeutic Drug Monitoring in Neonatal and Pediatric Patients
Authors: Dinnes Laura , Ristagno Elizabeth H , Brumbaugh Jane E , Stetson Raymond , Levy Emily Ruth , Lee Grace , Rivera Christina G , Smith Brandi , Thurber Gregory , Gullickson Taylor , Barreto Erin F 
Published: January 2025

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 &gt; 120 kg, had a BMI &gt; 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 &gt; 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
P-1165. Factors Associated with Initial Antifungal Choice for Invasive Candidiasis
Authors: Said Amira , Banerjee Ankona , Dutta Ankhi 
Published: January 2025

Abstract

Background
The Infectious Disease Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Disease (ESCMID) recommend an echinocandin (EC) for first line initial therapy for candidemia. No randomized clinical trial has demonstrated superiority for any antifungal (AF) over another for invasive candidiasis (IC). The EC have become preferred agents due to their favorable side effect profile and early fungicidal activity. Despite current recommendations, there are variabilities in prescribing practices of AF in children with IC. Our goal was to investigate factors influencing initial choices of AF for children with IC.

Methods
We performed retrospective analysis of de-identified data collected as part of the Pediatric Antifungal Comparative Effectiveness Study (PEACE), a collaborative effort by the International Pediatric Fungal Network, conducted 2014 to 2017. 750 patients from 35 centers were included. We looked at demographics, clinical features, risk factors (underlying diagnosis, neutropenia, immunosuppressive medications, stem cell or organ transplant, parenteral nutrition etc) which determine the initial choice of AF within the first 72 hours of IC.

Results
Males comprised 55.6% and White race 58.3%. Majority were non-Hispanic ethnicity (67.7%). Triazoles (TZ) (40.1%) were the most used initial AF followed by EC (33.7%) and amphotericin B (AmB) (17.9%). When EC use was compared to other AF, there was no difference in age or gender. Multivariate logistic regression showed that patients with prior steroid use were more likely to receive AmB than EC. However, patients who had solid tumor malignancy, gastrointestinal insufficiency, neutropenia, prior steroid use and on vasopressors were more likely to receive EC than TZ. Patients who identified as Black were more likely to receive combination AF than an EC alone (OR 2.36, 95% CI 1.03-5.43, P=0.016). The most common reason for changing AF from the initial therapy was for step-down therapy followed by treatment failure.

Conclusion
Combination AF use was higher in Black patients. Though overall use of TZ was higher among children with IC, presence of risk factors like steroid use, underlying solid tumor malignancy, neutropenia or vasopressors was associated with EC use. AmB use was not as common as anticipated.

Disclosures
All Authors: No reported disclosures
422. Household Economic Burden and Social Consequences of Childhood Severe Pneumonia in India: A Cost of Illness based Pharmacoeconomic Analysis
Authors: Tom Maria , Raju Jomel 
Published: January 2025

Abstract

Background
Childhood pneumonia stands as a leading cause of mortality among young populations. Providing care for pediatric pneumonia poses significant challenges in resource-constrained regions, where caregivers often bear treatment expenses directly. This study aimed to evaluate the burden, social impact, and economic ramifications of childhood pneumonia, as well as to identify associated risk factors.

Methods
An incidence-based Cost of Illness (COI) study was conducted, focusing on one episode of severe childhood pneumonia from a household perspective. The study was carried out across three distinct sites in the South Indian state of Kerala, India. Through face-to-face interviews, data on socioeconomic status, resource utilization, and associated costs were gathered from caregivers of children aged between 1 month and 6 years. Utilizing a micro-costing bottom-up methodology, medical, non-medical, and time-related costs were computed. Multiple regression analysis was employed to examine factors influencing COI, while sensitivity analysis was conducted to assess the robustness of cost estimations.

Results
A total of 436 children with severe pneumonia were enrolled between January 2022 and December 2023. The mean age of participants was 14 months (SD ±9.1), with males constituting 58.7% (256). The average household cost per episode amounted to USD 149 (95% CI; 139.7 - 155.9), with indirect costs serving as the primary cost drivers (65%, USD 98). While household expenses for the poorest income quintile were lower in absolute terms, they represented a higher proportion of monthly income. Notably, COI was significantly higher for treatments sought at urban health facilities compared to rural counterparts (difference USD 54.3, 95% CI 73.3 to 96.3). Additionally, factors such as age, parental education level, and healthcare facility location emerged as significant predictors of household COI.

Conclusion
This study underscores the substantial economic burden imposed on households by severe childhood pneumonia, with cost differentials evident across various socioeconomic strata. In light of these findings, tailored management strategies should be devised for resource-limited settings to enhance treatment affordability and alleviate household economic strain.

Disclosures
All Authors: No reported disclosures
P-1211. Early Infections Predict Weight Gain and Obesity in US Children
Authors: Taylor Zackary W , Lin Jane 
Published: January 2025

Abstract

Background
An unexplained link between early viral infection and later weight gain has been observed in the US and internationally. In our population of children at Kaiser Permanente Southern California, we seek to confirm this association and determine the magnitude of the absolute weight increase.

Methods
In a retrospective cohort of children born 2008 – 2012, frequency of infection in infancy (≤12m), timing of first infection (&lt; 6m vs 6-12m), and antibiotic use, class, timing, and frequency were assessed relative to absolute weight and body mass index (BMI) at age 4-6 and 10 years. Patients with low birthweight and prematurity were excluded. Maternal BMI, breastfeeding, birthweight, delivery type, and race/ethnicity were included in multivariable regression; height was also included when absolute weight was the outcome variable. Weight outcomes were compared in uninfected vs infected without antibiotic treatment in infancy (IWOT); and IWOT vs those infected who received antibiotic treatment (IWAT), using logistic regression analysis for obesity outcomes and linear regression for absolute weight.

Results
We identified N=66,687 children at 4-6y and N= 46,462 at 10y for analysis. Of the latter, 7,918 had been uninfected, 18,144 had IWOT, and 20,400 had IWAT. The IWOT group had higher rates of obesity vs uninfected (24% vs 19% at 10y; see figure 1), reflected in multivariable analysis at 4-6y (OR 1.11 [1.03-1.2]; p=0.004) and 10y (OR 1.14 [1.06-1.22]; p &lt; 0.001), in a "dose-dependent" manner (Figure 2). The corresponding absolute weight increase (+0.55 kg [+0.3-0.8] at 10y; p&lt; 0.001) was also dose-dependent (Figure 3). Compared to untreated infections, the additional contribution of antibiotic use to future obesity was minimal (OR 1.05 [0.99-1.1]; p=0.09) and not dose-dependent. Of the 10 year olds, most had upper respiratory infections (27,562 patients had at least one URI; 59%), ear infections (16,404 patients; 35%), or infections without a specified site (including viral syndromes; 11,822; 25%) in infancy.

Conclusion
A significant (14% at 10y) increase in obesity after early infection is confirmed, with a small (+0.55kg) corresponding increase in average weight. Prospective study in specific subgroups or with specific viruses of interest would be warranted.

Disclosures
All Authors: No reported disclosures
P-1269. Non-Vaccine Group B Streptococcus Serotypes in Clinical Samples
Authors: Taffet Allison A , Job Megan , Haldeman Sydney , Tettelin Hervé , Ratner Adam J 
Published: January 2025

Abstract

Background
Group B Streptococcus (GBS) is a common colonizer of the gastrointestinal and genitourinary tracts and a major cause of neonatal infection. Currently, pregnant individuals are screened for GBS colonization in late pregnancy and given intrapartum antibiotics if positive, but this approach is resource-intensive and incompletely effective. GBS has also emerged as a pathogen in non-pregnant adults. A hexavalent vaccine candidate (GBS6) that protects against 6 of the 10 known GBS serotypes (vaccine-type [VT] serotypes: Ia, Ib, II-V; non-vaccine type [NVT] serotypes: VI-IX) is in phase II/III trials. However, emergence of NVT serotypes could threaten the overall impact of GBS6. Previous studies have estimated that &lt; 2% of GBS isolates are NVT.
A. Serotype distribution for all isolates, from both colonization and sterile sites. B. Distribution of NVT isolates.

Methods
We conducted laboratory-based surveillance for GBS isolates from sterile sites and rectovaginal colonization samples from May 2021 – December 2023. Urinary samples were not included. GBS whole genome sequencing was used to determine serotype, multilocus sequence type (ST), and clonal complex (CC). We performed retrospective chart review to gather demographic and clinical data.

Results
For this interim analysis, 873 isolates were successfully sequenced, of which 868 had a detectable serotype (Figure). 5.3% of isolates were NVT. NVT isolates were present among both colonization (6.8%) and sterile-site isolates (4.1%). The majority of NVT isolates (40/46; 87%) were serotype VI. Serotypes VII – IX were rarely observed. Of the serotype VI isolates, almost all (37/40; 92.5%) were CC1. 34 serotype VI isolates had antibiotic susceptibility data available from the microbiology lab. 79% of these were susceptible to tetracycline, compared to the all-serotype average of 18%. 79% were susceptible to clindamycin, higher than the all-serotype average of 49%. All isolates from neonatal invasive disease (N=15) were VT.

Conclusion
The majority of clinical colonization and sterile-site GBS isolates have serotypes contained in GBS6. However, NVT rates are higher than previously estimated, primarily driven by serotype VI. Serotype VI merits further study and consideration for addition to future GBS vaccine candidates.

Disclosures
Hervé Tettelin, PhD, Merck, Sharpe & Dohme: Advisor/Consultant
P-1285. Particularities Of Non-Osteoarticular Brucellosis In Comparaison With Osteoarticular Cases
Authors: Hammami Fatma , Rekik Khaoula , Smaoui Fatma , Chakroun Amal , Marrakchi Chakib , Koubaa Makram , Jemaa Mounir Ben 
Published: January 2025

Abstract

Background
Osteoarticular (OA) brucellosis represent the most frequently described form of the sub-acute brucellosis. We aimed to study the clinical, laboratory and evolutionary features of non-osteoarticular (NOA) brucellosis in comparaison with OA cases.

Methods
We conducted a retrospective study including all patients hospitalized in the infectious disease department for sub-acute brucellosis between 1995 and 2022. Standard agglutination test titer &gt; 1/160 and/or positive blood cultures to Brucella spp confirmed the diagnosis of brucellosis.

Results
We encountered 108 cases among which 30 cases had NOA brucellosis (27.8%). In total, NOA cases included neurobrucellosis (60%), Brucella endocarditis (23.3%) and genitourinary brucellosis (16.7%). Patients with NOA were significantly younger (30[21-44] years vs 52[37-60] years; p&lt; 0.001). Vomiting (30% vs 2.6% ; p&lt; 0.001) and nausea (16.7% vs 3.8%; p=0.036) were significantly more frequent among NOA cases, while night sweats (46.7% vs 70.5%; p=0.021) was significantly less frequent among NOA cases. Fever (86.7% vs 80.8%; p =0.471), weight loss (24.1% vs 38.5%; p= 0.166), myalgia (13.3% vs 23.1%; p=0.26) and asthenia (53.3% vs 44.9%; p=0.43) were noted among NOA and OA cases. Hepatomegaly was significantly more frequent among NOA cases (13.3% vs 2.6% ; p=0.049). A negative C-reactive protein (67.9% vs 24.2%; p&lt; 0.001) and a normal erythrocyte sedimentation rate (75% vs 50.7%; p=0.027) were significantly more frequent among NOA cases. Leucopenia (6.7% vs 7.8%; p=1), thrombopenia (13.3% vs 6.4%; p=0.244) and hepatic cytolysis (6.7% vs 10.3%; p=0.723) were noted among NOA and OA cases. Treatment duration was significantly shorter among NOA cases (4[3-6] months vs 6[4-9] months; p&lt; 0.001). Sequelae were significantly less frequent among NOA cases (3.3% vs 20.8%; p=0.37). A favorable disease evolution (83.3% vs 90.9%; p=0.311) and relapse (3.3% vs 9.1%; p=0.437) were noted among NOA and OA cases.

Conclusion
Clinical presentation of NOA brucellosis included vomiting and nausea more frequently, the presence of hepatomegaly and the absence of inflammatory markers, among younger patients. The treatment duration was significantly shorter in comparaison with OA brucellosis cases.

Disclosures
All Authors: No reported disclosures
P-1304. Public Health Impact of Changes to Meningococcal Vaccination Platform in the United States
Authors: Schley Katharina , Presa Jessica , Snow Vincenza , Dooling Kathleen , Cane Alejandro D , Peyrani Paula , Farkouh Raymond , Sullivan Shannon M , Jaime Caro J 
Published: January 2025

Abstract

Background
In the US, vaccination recommendations for the prevention of Invasive meningococcal disease (IMD) include routine MenACWY vaccination at 11-12 years (y) of age and a booster at 16 y and two doses of MenB vaccine as shared clinical decision making from 16-23 y. Recently a MenABCWY vaccine became available and was recommended when both MenACWY and MenB are to be given at the same visit. The aim of this study is to assess the public health impact of various alternative vaccine strategies compared to current ACIP vaccine recommendations.

Methods
A static longitudinal cohort model was developed to estimate the impact of various vaccination strategies on IMD cases and deaths. A cohort of 11-y-olds was simulated for 50 y after vaccination. Vaccine uptake differed according to age and vaccination strategy.

Results
The current strategy results in 364 cases (82 cases due to MenB and 282 cases due to MenCWY) in one cohort of 11-y-olds. Keeping the dose of MenACWY vaccine at 11 y and switching to two doses of MenABCWY vaccine at 16 and 17 y would additionally prevent 15 MenB and 6 MenCWY cases over 50 y compared to the current strategy. Removing the dose of MenACWY vaccine at 11 y and using two doses of MenABCWY vaccine at 16 and 17 y would prevent 22 additional MenB cases but lead to 73 additional MenCWY cases compared to the current strategy. In contrast, offering one dose of MenABCWY at 11 y and one dose at 16 would prevent 26 additional MenB cases and 4 additional MenCWY cases compared to the current strategy. Offering two doses of MenABCWY at 13 y (instead of 11) and 17 y would prevent 14 MenB cases while leading to 22 additional MenCWY cases.

Conclusion
Our model suggests adding protection against serogroup B at 11 y would prevent additional cases of disease, while delaying adolescent protection against all serogroups of meningococcal disease will result in additional cases in the unprotected populations.
Funding: This study was funded by Pfizer Inc.

Disclosures
Katharina Schley, Dr. rer pol., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Jessica Presa, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Vincenza Snow, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Kathleen Dooling, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Alejandro D. Cane, MD, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company) Paula Peyrani, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Raymond Farkouh, PhD, Pfizer: Stocks/Bonds (Public Company) Shannon M. Sullivan, PhD, Evidera: Employee|Pfizer: Advisor/Consultant J. Jaime Caro, MDCM, FRCPC, FACP, Evidera: Employee|Pfizer: Advisor/Consultant