bluuebunny/crossref_metadata_2025_split huggingface dataset:
1637. Safety Evaluation of the Novel Oral Polio Vaccine Type 2 during a National Supplementary Immunisation Activity in Uganda, a Multipronged Approach: January–March 2022
Authors: Nsubuga Fred , Gilani Zunera , Tobolowsky Farrell A , Longley Ashley T , Greene Sharon A , Ntale Ismail , Hellen Ndagije , Kisakye Annet , Ampaire Immaculate , Kyabayinze Daniel , Gidudu Jane F 
Published: November 2023

Abstract

Background
Data from clinical trials show that novel oral poliovirus vaccine type 2 (nOPV2) is safe. However, nOPV2 is under emergency use listing, and continued vaccine safety monitoring is required to support licensure and World Health Organization (WHO) prequalification. In January 2022, Uganda introduced nOPV2 in a national supplementary immunization activity (SIA) in response to a circulating vaccine derived poliovirus outbreak, vaccinating 9.8 million children &lt; 5 years old. We sought to identify and characterize safety events following nOPV2 vaccination

Methods
We evaluated the safety of nOPV2 following the SIA in Uganda using a multi-pronged approach: 1) routine passive surveillance for adverse events following immunization (AEFI), 2) active hospital-based surveillance for adverse events of special interest (AESI) 3) active acute flaccid paralysis (AFP) surveillance, and 4) active, cohort event monitoring (CEM) among a nationally representative sample of 2000 households in 200 enumeration areas for 42 days following administration of the nOPV2 vaccine. The national AEFI committee conducted causality assessment for all reported serious AEFI and pre-specified AESI conditions using global guidelines.

Results
During 14 January–11 March 2022, 1,157 adverse events were identified: 43 (3.7%) from passive surveillance, 5 (0.43%) from hospital-based surveillance, 157 (14%) from AFP surveillance, and 952 (82%) from CEM. The most commonly reported adverse events identified through CEM 0-3 days post-vaccination were fever (n=377, 40%), diarrhea (n=147, 15%), and malaise (n=107, 11%). Through all surveillance systems, 171 events underwent causality assessment. Among these 7 (4%) were classified as vaccine product-related reactions (1 acute disseminated encephalomyelitis, 1 encephalitis, 1 fever, 3 gastro-enteritis, and 1 painful lower limbs), 101 (59%) were classified as coincidental events, and 63 (37%) were downgraded.

Conclusion
The majority of identified serious AEFI were classified as coincidental events. No unexpected safety signals were identified among children &lt; 5 years old during the nOPV2 SIA in Uganda. This evaluation provides critical data to contribute to the vaccine’s safety profile and informs recommendations for use, pre-qualification, and licensure.

Disclosures
All Authors: No reported disclosures
1642. Vancomycin AUC24 Estimation Using First Order Pharmacokinetic Methods in Pediatric Patients
Authors: Wallace Katie L , Burgess David , Olney Katie B , Brandon Hope 
Published: November 2023

Abstract

Background
The 2020 guidelines for the monitoring of vancomycin emphasize the importance of timely assessment of AUC24 for both efficacy and safety in pediatric patients. However, real-world data supporting the feasibility of vancomycin AUC24 in pediatric patients using first-order equations is lacking.

Methods
This is a single-center, retrospective cohort study of hospitalized pediatric patients (&lt; 18 years) receiving intravenous (IV) vancomycin between 1/1/2020 and 8/20/2022. Patients were included if they received at least 24 hours of IV vancomycin with peak and trough concentrations obtained in the first 96 hours of therapy. Patients with baseline renal dysfunction were excluded. First-order equations were utilized to estimate Ke, Vd, Cl, and AUC24.

Results
Overall, 219 patients (68% male, 87% Caucasian, 24% critically ill, median age of 6 years (IQR 1-12)) met inclusion criteria. Of the total patients, 9% were neonates (age ≤ 28 days), 11% were infants (age 29 days to &lt; 1 year), 58% were children (age 1 to 12 years), and 22% were adolescents (age 13 to 17 years). The pharmacokinetic parameters for each group are outlined in Table 1. The estimated AUC24 was within the therapeutic range of 400-600 mg*hr/L for the majority of patients. However, when comparing age groups, adolescents had the lowest (53%) while neonates had the greatest (79%) percentage of patients within the therapeutic range

Conclusion
Our results reinforce the variability in vancomycin PK seen across pediatric age groups, confirming the need to tailor empiric dosing regimens by patient age. For patients with AUC24 outside the therapeutic range, more patients had SUPRAtherapeutic rather than SUBtherapeutic AUC24. In response to results of this study, institutional empiric vancomycin dosing will be decreased for all age groups outside the neonatal group to better align with the 2020 guideline recommended AUC24 of 400 - 600 mg*hr/L for pediatric patients.

Disclosures
Katie B. Olney, PharmD, BCIDP, The Society of Infectious Diseases Pharmacists (SIDP): Grant/Research Support
1644. Quantifying Empiric Vancomycin Overuse in Two Tertiary Care Pediatric Intensive Care Units
Authors: Chiotos Kathleen , Newland Jason , Starnes Luke , Meyahnwi Didien , Same Rebecca G , Lautenbach Ebbing , Szymczak Julia E , Gerber Jeffrey S 
Published: November 2023

Abstract

Background
Vancomycin is among the most commonly prescribed antibiotics in US children’s hospitals. When used empirically for sepsis, vancomycin primarily targets methicillin-resistant Staphylococcus aureus (MRSA). We aimed to quantify empiric vancomycin overuse among critically ill children with suspected sepsis.

Methods
We performed a cross sectional study including all episodes of suspected sepsis in two tertiary care pediatric intensive care units (PICUs) between 11/2020 and 10/2022. Suspected sepsis was defined as collection of a blood culture and administration of one or more broad spectrum antibiotics within 12 hours. Episodes with prior broad-spectrum antibiotic use or transfers from an outside hospital within 7 days were excluded, as were episodes occurring within 14 days of a preceding sepsis episode. The frequency of MRSA among episodes of suspected sepsis was calculated based on the results of sterile site, respiratory, and wound cultures collected within 24 hours of the sepsis episode. MRSA history was defined as a positive clinical or screening culture or PCR within 6 months before the suspected sepsis episode. As a secondary analysis, we quantified the frequency of any vancomycin-requiring organism (Table 1).

Results
We identified 1859 suspected sepsis episodes. Of these, 1135 (61%) received empiric vancomycin for a median of 3 days (IQR 2,3). MRSA was identified in 37 (2%) and any vancomycin-requiring organism was identified in 101 (5%). Among 1790 episodes with no history of MRSA, 1080 (60%) received empiric vancomycin and MRSA was identified in 17 (&lt; 1%). MRSA was infrequent in community onset sepsis (21/1324 episodes, 2%) and in patients without central lines (18/1397, 1%) (Table 2). The proportion of episodes receiving empiric vancomycin differed between the two centers (70% vs 44%, P&lt; 0.01), as did the proportion with a history of MRSA (3% vs 5%, P=0.03), whereas identification of MRSA (1% vs 0.9%, P=.77) did not.

Conclusion
Vancomycin was administered to 61% of critically ill children initiated on broad-spectrum antibiotics, but MRSA was identified in just 2%. Reducing empiric vancomycin overuse for community onset sepsis and in patients with no history of MRSA or central venous catheter is an actionable target for antimicrobial stewardship efforts in the PICU.

Disclosures
Jason Newland, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support
1651. Utility of Staphylococcus aureus Nares Screening in Hospitalized Children with Osteomyelitis
Authors: Sands Ashley , Iacono Denise E , Hagmann Stefan 
Published: November 2023

Abstract

Background
Antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) are frequently started empirically in children diagnosed with osteomyelitis. At our institution clinicians increasingly obtain at time of admission a PCR-based staphylococcal nares screen (SNS) which can differentiate methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA. We aimed to evaluate the utility of SNS for antibiotic optimization in pediatric inpatients with osteomyelitis.

Methods
A retrospective chart review was conducted of children (&lt; 20 years) admitted for osteomyelitis (January 01, 2021 to December 31, 2022) who had a SNS and a clinical culture (i.e. site of infection or blood) performed as part of their diagnostic work up.

Results
A total of 36 children were included, median age (range) of 8.5 years (0-19). Etiologic diagnosis was established in 52.8% (n=19), most infections were with MSSA (n=12), followed by MRSA (n=4), and MRSA/MSSA (n=1). The prevalence of nasal MRSA and MSSA colonization was 8.3% (n=3) and 47.2% (n=17), respectively. The sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive values (NPV) of the SNS test to predict a MRSA and a MSSA infection were 40.0%, 96.8%, 66.7%, 90.9%, and 75.0%, 66.7%, 52.9%, 84.2%, respectively. When including only patients with site specific cultures (n=25), SE, SP, PPV and NPV of the SNS test to predict MRSA and MSSA infection were 40%, 100%, 100%, 86.9%, and 70%, 60%, 53.8%, 75.0%, respectively. Of those whose SNS test was negative (n=16), infection with MSSA was found in some (n=3) but none had documented MRSA infection.
In about half (15/32, 46.9%) anti-MRSA therapy was discontinued during the hospitalization, de-escalation solely in response to a negative MRSA SNS occurred in some (n=3, 20.0%).

Conclusion
We found that children with osteomyelitis have a disproportionate high rate of nasal colonization with MSSA which was also the primary etiologic cause for the infection in this cohort. The SNS was noted to show a high NPV for MRSA infection which may help encourage clinicians to de-escalate potentially toxic anti-MRSA therapy in a timely fashion, especially in non-critical patients. Further prospective study is warranted.

Disclosures
All Authors: No reported disclosures
1652. Impact of the 2022-2023 Amoxicillin Shortage on Antibiotic Prescribing for Acute Otitis Media: A Regression Discontinuity Study
Authors: Khazanchi Rohan , Brewster Ryan , Butler Alex , O’Meara Daniel , Bagchi Devika P , Michelson Kenneth 
Published: November 2023

Abstract

Background
On October 28th, 2022, the U.S. Food and Drug Administration (FDA) announced a national shortage of amoxicillin powder for liquid suspension. The extent to which drug shortages affect prescribing patterns has been poorly described. To characterize the causal impact of the amoxicillin shortage, we performed a quasi-experimental analysis of antibiotic prescribing for uncomplicated acute otitis media (AOM).

Methods
We retrospectively analyzed encounters for children &lt; 18 years old diagnosed with AOM from May 15th, 2022 to April 14th, 2023 at an urban children's health system. Exclusion criteria included a prior episode of AOM within 30 days, presence of concomitant respiratory infections (sinusitis, pharyngitis, pneumonia, and conjunctivitis), and penicillin or amoxicillin allergy. We used a sharp regression discontinuity design with logistic regressions to evaluate the causal impact of the FDA shortage on the odds of being prescribed amoxicillin, amoxicillin-clavulanate, cefdinir, other antibiotics, or no antibiotic.

Results
We identified 3076 encounters with 1677 (54.5%) occurring after the amoxicillin shortage (Table 1). The mean patient age was 4.1 years (SD 3.5), and most patients were male (n=1695, 55.1%), Hispanic (n=1252, 40.7%), and seen in the emergency department (n=1900, 61.8%). The most prescribed antibiotics were amoxicillin (n=1662, 54.0%), amoxicillin-clavulanate (n=671, 21.8%), and cefdinir (n=263, 8.6%).
The odds of being prescribed amoxicillin decreased by 91% after the FDA shortage declaration (OR 0.09 [95%CI 0.07-0.12]) (Fig. 1A). The odds of being prescribed amoxicillin-clavulanate or cefdinir increased 7-fold and 9-fold (7.90 [5.59-11.31] and 9.25 [5.27-17.17]), respectively (Fig. 1B/1C). Management without antibiotics (0.82 [0.55-1.23]) and prescriptions for other antibiotics (1.73 [0.96-3.19]) did not significantly change (Fig. 1D/1E).Table 1.Encounter Characteristics for Patients Diagnosed with Acute Otitis Media During the Pre-Shortage (May 15, 2022 - October 27, 2022) and Shortage (October 28, 2022 - April 14, 2023) PeriodsFigure 1.Regression Discontinuity Plot of Antibiotic Prescriptions Before and After the FDA Amoxicillin Shortage Declaration (October 28, 2022).

Conclusion
The amoxicillin shortage had an immediate, sweeping impact on prescribing patterns. To mitigate future clinical, economic, and antimicrobial resistance consequences, the FDA should increase oversight of manufacturers responsible for critical medications, require supply issue resolution timelines, and incentivize antibiotic production to mitigate their low profitability.

Disclosures
Kenneth Michelson, MD, Moderna: Stocks/Bonds|Pfizer: Stocks/Bonds
1659. Prokinetic Antibiotic Agents in the Neonatal Intensive Care Unit: Ripe for Antibiotic Stewardship Efforts!
Authors: Magers Jacqueline , Prusakov Pavel , Storey Michael , Sanchez Pablo J J 
Published: November 2023

Abstract

Background
Intolerance to enteral nutrition among infants in the neonatal intensive care unit (NICU) may lead to the use of prokinetic agents to improve gastric emptying and feeding tolerance. Two such oral prokinetic agents are erythromycin and amoxicillin-clavulanate that have been used in cases of dysmotility due to intestinal failure. However, dosing strategies vary and the recommended duration of therapy has not been determined. Moreover, the use of these oral antibiotics in the NICU may fall under the radar of neonatal antimicrobial stewardship programs. Our objective was to quantify their use in the Level 4 outborn NICU at Nationwide Children’s Hospital, Columbus, OH in order to inform antibiotic stewardship efforts.

Methods
This was a retrospective cohort study of all infants who received enteral erythromycin or amoxicillin-clavulanate in the NICU. The number of doses of each antibiotic was obtained from the Nationwide Children’s Hospital Pharmacy database. Pertinent clinical, laboratory, and outcome data were obtained.

Results
From January 1, 2022 to April 30, 2023, 15 infants in the NICU received ≥1 dose of erythromycin ethylsuccinate and 19 infants received ≥1 dose of amoxicillin-clavulanate enterally. Erythromycin was always used to improve motility while amoxicillin-clavulanate served as a prokinetic agent in 53% of infants in whom it was prescribed. Demographics and reason for initiation are provided in Table 1. The median (IQR) doses per patient for erythromycin was 64 (28, 125; dosing interval varied from every 6 to every 8 hours) and for amoxicillin-clavulanate was 50 (9, 105) doses per patient (majority of doses were given on a BID schedule).
Characteristics of infants who received prokinetic agents in the NICU

Conclusion
Enteral erythromycin and amoxicillin-clavulanate have not been the target of antimicrobial stewardship programs. These antibiotics may contribute to dysbiosis and adverse events in NICU infants. An automatic stop time with a time-out when ordered in the electronic health record may be a viable strategy to reduce overutilization of these antibiotics.

Disclosures
Pavel Prusakov, PharmD, Merck & Co: Grant/Research Support|Merck & Co: Employee Michael Storey, PharmD, MS, CSL Behring: Advisor/Consultant|Sarepta Therapeutics: Advisor/Consultant
1682. Clinical Characteristics and Outcome of Acinetobacter Bacteremia in Children
Authors: Gashgarey Deema , Alsuhaibani Mohammed , Alhajjar Sami , Alyabes Ohoud Abdulrahaman , Alhuthil Raghad 
Published: November 2023

Abstract

Background
Acinetobacter is a gram-negative bacterium that can cause several infections, particularly in hospitalized and immunocompromised patients. Invasive Acinetobacter infection in pediatrics can lead to significant morbidity and mortality. This study aims to investigate Acinetobacter bacteremia clinical characteristics and outcome in pediatric patients.

Methods
This is a retrospective study conducted in a tertiary-care center in Riyadh, Saudi Arabia, including pediatric patients (0-14 years) with a confirmed blood culture of one of the Acinetobacter species from January 2015 to December 2022. Medical charts were reviewed for demographics, clinical data, and outcomes. IRB approval number (2231132).

Results
Forty-two pediatric patients with Acinetobacter bacteremia were identified. The median age was 10.5 [interquartile range (IQR): 2-48] months, and 25 (59.52%) were males. Over half of the episodes were hospital-acquired infections 26 (61.90%). The most reported subspecies were Acinetobacter calcoaceticus–Acinetobacter baumannii complex 34 (81.13%), then Acinetobacter lwoffii 4 (9.52%). Polymicrobial infection was found in 15 patients (35.71%), most commonly Enterococcus faecalis 4 (26.67). The antimicrobial susceptibility showed that all isolates were susceptible to Colistin, and (68%) to Cefepime and Meropenem. Most of the patients were previously hospitalized 32 (76.19%), exposed to antimicrobial therapy 26 (61.90%), and underwent invasive procedures 23 (54.76%) one month prior to the bacteremia episode. The median duration of treatment was 15 days [IQR: 12-21]. Two patients (4.76%) had relapse (while on treatment), and two (4.76%) had recurrent infection. The overall 14-day crude mortality rate was (11.90%). Interestingly, non-survivors were significantly younger than survivors (median age: 2 [IQR: 1-2] vs. 18 [IQR: 3-48] months respectively.

Conclusion
Acinetobacter spp. are important emerging nosocomial pathogens. Most of the mortalities were associated with younger age. Previous hospitalization, prior antimicrobial therapy, and invasive procedures were common features for mortality in this study. Further multi-centers studies might be needed to investigate the mortality related risk factors.

Disclosures
All Authors: No reported disclosures
1686. Bacteremia associated with intravascular catheter colonization with Gram-negative rods in children
Authors: Hisano Hina , Shoji Kensuke , Matsui Toshihiro , Kato Hiroki , Fukui Kana , Kano Motohiro , Yamada Yuji , Gocho Yoshihiro , Ishiguro Akira 
Published: November 2023

Abstract

Background
Patients with Staphylococcus aureus colonization of an intravascular catheter, but without bacteremia, had a 14% chance of developing subsequent S. aureus bacteremia after removing the central venous catheter. However, information on the frequency and outcomes of subsequent bacteremia due to Gram-negative rods (GNRs) is limited, particularly in children.

Methods
We conducted a single-center, retrospective, case-control study. Clinical information including age, sex, immune status, bacterial culture results from both catheter tips and the blood, and outcomes were extracted from electronic medical records. Patients were included if the central venous catheter tip culture was positive for GNRs, but the concurrent blood culture (within one day before or after catheter removal) was negative. Subsequent bacteremia was defined as bacteremia caused by the same organism(s) as the catheter tip culture within six months of catheter removal. Clinical characteristics were compared between patients with and without subsequent GNR bacteremia.

Results
During the study period, 49 cases &lt; 18 years of age that were positive for central venous catheter tip culture but negative for concurrent blood cultures were identified. Median (interquartile range) age was 0 (0-4.5) years and male sex was 44.9%. Pseudomonas aeruginosa was the most common isolate (n=18, 36.7%), followed by Escherichia coli (n=8, 16.3%) and Klebsiella spp. (n=8, 16.3%). Subsequent GNR bacteremia developed in 6 (12.2%) patients. The median (range) days between catheter removal and the occurrence of subsequent GNR bacteremia was 16.5 (3-35) days. The median age and the proportion of immunocompromised cases were higher in patients with subsequent bacteremia than in those without subsequent bacteremia (8 years vs 0 years, P=0.011 and 6 [100%] vs 21 [48.8%], P=0.027, respectively). The presence of antibiotic treatment at catheter removal was similar between these two groups (n=4 [66.7%] vs n=25 [58.1%], P=1.0).

Conclusion
The frequency of subsequent GNR bacteremia in children was 12.2%. Immunocompromised patients may be at higher risk for developing subsequent GNR bacteremia.

Disclosures
Kensuke Shoji, MD, PhD, AstraZeneca K.K.: Honoraria|Gilead Sciences, Inc.: Honoraria|KYORIN Pharmaceutical Co.,Ltd.: Honoraria|Meiji Seika Pharma Co., Ltd.: Honoraria|Nippon Becton Dickinson Company, Ltd.: Honoraria|Novartis Pharma Co., Ltd.: Honoraria|Viatrs, Inc: Honoraria
1714. Incidence of Sexually Transmitted Infections in Youth with HIV Pre-COVID and COVID Era
Authors: Khan Firdous , Loerinc Leah , Scheel Amy , Gillespie Scott , Camacho Andres 
Published: November 2023

Abstract

Background
Adolescents and young adults (AYAs) living with HIV have high rates of co-sexually transmitted infections (STIs). During the COVID pandemic, STI prevention strategies including access to testing and treatment facilities, availability of public health practitioners and healthcare workers, and condom availability may have decreased. The aim of this study was to determine if differences in STI incidence for first infection and re-infection existed between the pre-COVID and COVID eras in a cohort of AYAs living with HIV in Atlanta, GA.

Methods
Retrospective chart review was conducted for all patients aged 13-24 at the Grady Ponce and Family Youth Clinic in Atlanta, GA. Two eras were identified: a pre-COVID era from 1/1/2009 – 12/31/2019 and a COVID era from 1/1/2020 – 6/30/2021. Patients could be followed in both eras, where follow-up for first and recurrent STI incidences were reinitiated at the start of the COVID era. STIs recorded included gonorrhea, chlamydia, human papillomavirus, syphilis, trichomonas, herpes simplex virus, lymphogranuloma venereum, hepatitis C, bacterial vaginosis, and chancroid. First and recurrent incidence rates for any STIs were reported.

Results
Our sample included 766 sexually active AYAs with HIV. The mean age of first observation was 18.91 (±2.86) years. 72.3% of our patients were male and 90.7% were black. 721 patients were included in the pre-COVID era and 583 (80.9%) had at least one STI. 337 patients were included in the COVID era, and 158 had at least one STI (46.9%). The overall first STI incidence rate increased from 42.47 to 58.67 per 100 person-years from the pre-COVID to the COVID era (p&lt; 0.001). Gonorrhea, trichomonas and syphilis had significantly higher rates during the COVID era (Table 1). The recurrent STI incidence rate for any STI also significantly increased from 121.50 to 169.85 per 100 person-years (p&lt; 0.001) (Table 2).

Conclusion
Our study demonstrated significantly higher incidence rates of first and recurrent STIs in AYAs living with HIV in the COVID era compared to the pre-COVID era. Reallocation of resources during pandemics should emphasize continuation of existing STI prevention programs to avoid secondary clinical and economic adverse effects of increased infections.

Disclosures
All Authors: No reported disclosures