bluuebunny/crossref_metadata_2025_split huggingface dataset:
1673. Time to positivity of blood cultures in a pediatric hospital: more tools to reconsider empirical treatment in suspected infections.
Authors: Andrade-Fernandez Joam C , Gutierrez-Tobar Ivan Felipe , Londono-Ruiz Juan Pablo 
Published: November 2023

Abstract

Background
Blood cultures are essential for diagnosing bacterial infections. Positivity time (TP) measures the time from incubation to bacterial growth detection. Understanding TP for different pathogens and age groups can guide empirical treatment duration. Our aim is to describe microbiological characteristics of blood culture isolates by TP, causative germ, and patient age.

Methods
This retrospective and observational study analyzed all blood culture isolates obtained from a pediatric reference center in Colombia between 2015 and 2021, using the automated BD Phoenix™ detection system. Data was extracted from WHONET and analyzed for average positivity time, patient age, and microorganism type.

Results
A total of 1258 positive bottles were analyzed: 32.9% [414] were Gram-negative, 65.5% [824] were Gram-positive, and 1.6% [19] were yeast. The overall median positivity time was 14.5 [10.9-20.6] hours, for Gram-positive organisms, the median growth time was 17.2 [13.2-21.6] hours, and for Gram-negative organisms it was 10.8 [8.9-14.1] hours [p=&lt; 0.0001]. 65.7% of Gram-negative organisms were identified within the first 12 hours, compared to 17.7% of Gram-positive organisms. (Figure 1). The pathogen with the fastest median growth time was S. agalactiae with 8.3 [6.7-10.3] hours [n=11], followed by K. pneumoniae with 9.5 [8.3-10.9] hours and S. pyogenes with 9.9 [7.7-12.1] hours [n=9]. Among clinically significant bacterial microorganisms with slower median positivity times were Haemophilus influenzae with 22.7 [14.8-23.9] hours [n=9], followed by coagulase-negative Staphylococcus species with a median of 19.6 [17.1-23.2] hours, then non-fermenting Gram-negative bacteria with a median of 16.4 [13.1-23.2] hours, and Salmonella spp with 16.3 [13.7-28.3] hours [n=22].
Distribution of positivity according to time intervals (Gram positive vs. Gram negative)
Proportion of microorganisms isolated according to age group
Positivity time in hours according to different groups of organisms

Conclusion
Based on the study findings, it can be concluded that in pediatric patients with suspected bloodstream infection, empiric antimicrobial regimens can be shortened to 24-36 hours. The results of the study support this conclusion by demonstrating that the time to blood culture positivity was typically less than 24 hours. However, it would be beneficial to include additional data on the time of positivity associated with severity and clinical outcomes in pediatric patients to further support this conclusion.

Disclosures
All Authors: No reported disclosures
1676. PK, Safety and Tolerability of VABOMERE® (meropenem-vaborbactam) in Infants, Children and Adolescents
Authors: Bokesch Paula M , Arrieta Antonio C , Bradley John S , Hoover Randall K , McCurdy Sandra 
Published: November 2023

Abstract

Background
The worldwide spread of serine carbapenemases threatens carbapenems. VABOMERE (combination of meropenem and vaborbactam (MV), is a new class of beta-lactamase inhibitors including inhibition of Klebsiella pneumoniae. The PK, safety, and efficacy data of MV in adults support study in pediatrics.

Methods
Phase 1, open-label, dose-finding study. Pediatric subjects, 3 mos. to &lt; 18 yrs already on antibiotics received a single-dose weight based infusion of MV over 3 hr. Blood samples were drawn pre-dose, 3,4, and 6 hr. for PK parameters. Population PK model included weight as a covariate. Safety assessments included AEs, vital signs, safety labs, physical exams, infusion tolerance, ECG. A DSMB reviewed safety and PK data before enrolling next cohort.

Results
MV was well-tolerated and safe in all age groups. Clearance per kg body weight of both M and V increased with decreasing body weight over all age groups suggesting an allometric relationship.

Conclusion
Targeted AUC0-8 efficacious in adult trials ranges of 91.7-513 mg•hr/L (meropenem) and 131-494 mg•hr/L (vaborbactam) were achieved in all pediatric cohorts.

Disclosures
Paula M. Bokesch, MD, Melinta Therapeutics: Advisor/Consultant Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support Randall K. Hoover, Ph.D., Melinta Therapeutics: Advisor/Consultant Sandra McCurdy, MS, Melinta Therapeutics: Employee
1679. Successful Control of MSSA Bacteremia Outbreak in Neonatal Intensive Care Unit
Authors: Cho Youngmin , Choi Sujin , Jung Young Hwa , Choi Chang Won , Shin Myoung-jin , Park Jeong Su , Song Kyoung-Ho , Kim Eu Suk , Kim Hong Bin , Lee Hyunju 
Published: November 2023

Abstract

Background
Staphylococcus aureus outbreaks in the neonatal intensive care units (NICU) have been reported with the great majority due to methicillin-resistant Staphylococcus aureus. We describe successful control of an outbreak caused by methicillin-susceptible S. aureus (MSSA) in the NICU.

Methods
We report a MSSA bacteremia outbreak which occurred in the NICU at a tertiary level hospital from November 29, 2020 to January 6, 2021. Molecular typing of MSSA isolates were performed including multi-locus sequence typing (ST) and spa typing.

Results
A total of 5 MSSA bacteremia cases occurred in 39 days. Outbreak investigation was initiated after the 5th case. Infection control measures, including isolation of cases, contact precaution and universal 0.5% chlorhexidine bathing of all NICU patients, were implemented. Surveillance cultures of patients (n=36) and health care workers (HCW) (n=60) were performed. Excluding bacteremia patients, 13% (4/31) of neonates and 32% (19/60) of HCW were identified as MSSA nasal carriers and targeted decolonization with intranasal mupirocin was performed. After implementation of control measures and decolonization, there were no new cases. Molecular analysis identified two strains [ST15 spa type t593 (n=3) and ST101 spa type t4171 (n=2)] as the cause of this bacteremia outbreak. Among MSSA nasal carriers, all 4 neonates colonized the ST15 spa t593 strain. ST15 spa t593 strain was also colonized in one HCW, however antibiotic susceptibility pattern differed. The rest of HCWs colonized many different types of MSSA. All MSSA isolates were negative for Panton-Valentine Leucocidin toxin gene.

Conclusion
Molecular analysis identified two different MSSA strains in this outbreak. MSSA colonization was prevalent among HCWs, however molecular analysis showed variance in distribution. Although outbreak strains were not found in HCWs, one strain was colonized among other neonates, suggesting horizontal transmission and potential of further cases. The outbreak was successfully controlled with reinforcement of precautions, universal chlorhexidine bathing and surveillance cultures with targeted decolonization. Early recognition and prompt implementation of control measures are important for outbreak control in NICU.

Disclosures
All Authors: No reported disclosures
1688. Naturally-induced Serum Antibody Levels in Children to Pneumococcal Polysaccharide 15B that Correlate with Protection from Nasopharyngeal Colonization but Anti-serotype 15B Antibody has Low Functional Cross-reactivity with Serotype 15C.
Authors: Kaur Ravinder , Gonzalez Eduardo , Pham Minh , Pichichero Michael 
Published: November 2023

Abstract

Background
Pneumococcal infections caused by non-vaccine serotypes, including serotype 15B and 15C, emerged after the introduction of pneumococcal conjugate vaccines (PCVs). Serotypes 15B and 15C have been added to new different pneumococcal-conjugate vaccines (PCV20 and V116, respectively). We sought to derive a serum anti-15B antibody level that would be a correlate of protection (COP) against acute otitis media (AOM) and nasopharyngeal colonization and assess functional cross-reactivity against serotype 15B and 15C in children following natural immunization.

Methods
Method: IgG antibody to serotype15B polysaccharide was measured by ELISA in 402 sera from 6-36 month olds collected before, at the time of, and after pneumococcal culture-confirmed AOM and colonization caused by serotypes 15B and 15C. 153 serum samples from 6-36 month olds where no colonization with either 15B or 15C was observed were included as controls. A two-step method was used for the construction of COP models: a generalized estimating equation followed by logistic-regression. Opsonophagocytic (OPA) assays were used to assess functional cross-reactivity between serotypes 15B and 15C.

Results
The COP for prevention of colonization was 1.41µg/ml for 15B and 0.63µg/ml for 15C with a predictive probability of 80%. Significantly higher anti-15B antibody levels were measured in children who had AOM caused by serotype 15B compared to control children and compared to children who had AOM caused by serotype 15C (p&lt; 0.03). Consequently, a COP for serotypes 15B and 15C could not be calculated for AOM. ELISA-measured antibody levels did not correlate with OPA titers. Thirty percent of child samples, with varying moderate to high amounts of ELISA-measured antibody, showed no OPA titer against either serotype 15B or 15C. For the remaining samples, very low or no functional cross-reactivity between serotypes 15B and 15C was measured.

Conclusion
Conclusions: A COP for prevention of colonization in young children based on naturally-induced antibody levels was derived for serotype 15B and 15C that differed. A COP for AOM could not be derived. ELISA-measured antibody levels correlated poorly with OPA titers and low functional cross-reactivity between serotypes 15B and 15C in child sera was observed.

Disclosures
All Authors: No reported disclosures
1698. Activity of ceftolozane/tazobactam in vitro against Gram-negative isolates from pediatric patients: SMART 2017-2021
Authors: Mu Xinli , Fu Ying , Li Pengcheng , Yu Yunsong 
Published: November 2023

Abstract

Background
The study aims to evaluate the in vitro activity of ceftolozane/tazobactam (C/T) and other common-used antibiotics against clinical Gram-negative bacterial (GNB) isolates obtained from Chinese pediatric patients using data from The Study for Monitoring Antimicrobial Resistance Trends (SMART).

Methods
From 2017-2021, 554 Gram-negative isolates were collected from 16 pediatric departments across China. GNB isolates from pediatric departments were mainly derived from bloodstream (n = 135), intraperitoneal (n = 129), lower respiratory tract (n = 198) and urinary tract (n = 92) infections (Figure 1). The minimum inhibitory concentrations (MICs) were tested using a Trek Diagnostic System (Thermo Fisher Scientific). Susceptibility was determined by CLSI broth microdilution and interpreted with CLSI M100 (2021) breakpoints.

Results
E. coli (34.30%) and K. pneumoniae (27.62%) were the most common pathogens, followed by P. aeruginosa (15.34%). Susceptibility of species with more than 20 isolates were showed in Table 1. The susceptibility of P. aeruginosa to C/T was 89.41%, which was the highest among beta-lactams and was second only to amikacin. The susceptibilities of E. coli and K. pneumoniae isolates to C/T were 92.63% and 58.17%, respectively. When exclude carbapenem-resistant E. coli and K. pneumoniae, the susceptibility to C/T increased to 96.17% and 86.14%. C/T showed similar activities to E. coli and K. pneumoniae isolated from pediatric patients &lt; 1 year (Table 2). Thirteen P. aeruginosa isolates were collected from patients &lt; 1 year and 13/13 were susceptible to C/T (Table 3).

Conclusion
P. aeruginosa and E. coli obtained from pediatric patients in China showed a high susceptibility to C/T. When excluding carbapenem resistant isolates, C/T also showed good activities against K. pneumoniae.

Disclosures
Pengcheng Li, M.D., MSD China: Employee of MSD China
1712. Reduction of Neonatal Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections After Implementation of a S. aureus Screening and Decolonization Protocol
Authors: Weber Rachel , Wharry Jeananne , Malczynski Michael , Lehman Jennifer , Caldarelli Leslie , Bolon Maureen K 
Published: November 2023

Abstract

Background
Staphylococcus aureus (SA) is an endemic, clinically important organism in Neonatal Intensive Care Units (NICUs). An 86-bed level III NICU at an academic medical center saw an increase in patients with methicillin-susceptible SA (MSSA) bloodstream infections (BSIs) from October-December 2020, as well as a cluster of patients with MSSA skin infections associated with intravenous catheters, which led to the intervention described.

Methods
We created a multidisciplinary team and reviewed infection prevention measures in our NICU, national recommendations and published literature. Previous state, NICU patients were screened for methicillin-resistant SA (MRSA) on day of life 7 or upon admission from an outside hospital or home. On 11/1/2021, we implemented weekly screening cultures for MRSA and MSSA among all NICU patients, performed using a composite swab of the bilateral anterior nares, axilla, peri-umbilical area, and perianal area. Decolonization of SA-colonized patients was performed with mupirocin (MUP) and chlorhexidine gluconate (CHG) bathing. MUP was applied to nares twice per day for 5 days for all colonized patients and 5 days of CHG bathing was administered only to patients greater than 48 weeks postmenstrual age. Patients were decolonized up to 2 times. Incidence rates (IR) and incidence rate ratios (IRR) were calculated.

Results
Between 11/1/2021 – 1/30/23, 1186 unique patients were screened with 177 unique patients colonized with MSSA and 9 unique patients colonized with MRSA. Of those colonized with MSSA, 126 (71.2%) patients were treated, with 123/126 treated with MUP only and 3/126 treated with MUP and CHG. Table 1 describes SA outcomes in the 15 month pre- and post-intervention periods. In the post-intervention period we observed a 73% decrease in MSSA BSIs (IRR, 0.27, 95% CI (0.05, 1.03)).

Conclusion
Implementation of a SA screening and decolonization protocol in our NICU resulted in a statistically non-significant decrease in MSSA BSIs. Future work will seek to identify risk factors for colonization, factors associated with successful decolonization and genomic sequencing of MSSA isolates to characterize the spread of MSSA among neonates.

Disclosures
All Authors: No reported disclosures
1720. Immunogenicity of COVID-19 Vaccines in Youth with Inflammatory Bowel Disease
Authors: Cirks Blake T , Parsons Emily , Samuels Emily , Laing Eric D , Rajnik Michael , Malloy Allison M 
Published: November 2023

Abstract

Background
Youth with special healthcare needs or on immunosuppression are at increased risk for severe COVID-19, yet evaluation of the immunogenicity of SARS-CoV-2 vaccines in this population has been limited. A quarter of individuals with inflammatory bowel disease (IBD) are diagnosed in childhood and require chronic immunosuppressive therapy. Describing the quality and duration of the humoral and cellular responses to novel mRNA vaccines in this population can improve implementation and protection for this vulnerable population.

Methods
This ongoing single-center, prospective, longitudinal cohort study enrolled children aged 6–21 years at-risk for severe COVID-19 beginning in January 2023. On enrollment and at pre-specified times after vaccination peripheral blood samples, epidemiologic and clinical data were obtained. Total SARS-CoV-2 spike (S) and receptor binding domain (RBD)-specific IgG antibodies, as well as endemic coronavirus (eCoV) antibodies, were measured using a multiplex microsphere immunoassay. SARS-CoV-2 specific T cell responses were measured with intracellular cytokine staining (ICS) after peptide stimulation.

Results
11 SARS-CoV-2-immunized children with IBD treated with anti-tumor necrosis factor (TNFα) therapy were enrolled (Table 1). The seroconversion rate was 100% (Figure 1). Anti-S IgG levels increased with more exposures (r =.81 p =.003) and decreased over time with a negative correlation between anti-S IgG and days since last exposure (r = -.691 p =.02), as well as a significant difference in anti-S IgG when grouped by time since last exposure (p =.02) (Figure 2). ECoV antibody levels did not significantly correlate with anti-S IgG. 63% and 81% of participants developed SARS-CoV-2 specific CD4+ and CD8+ T cell responses, respectively, though response magnitude was low (Figure 1). A majority of participants demonstrated measurable antibody (100%) and T cell (90%) responses &gt; 12 months after their last vaccination.
Table 1
Demographics of Enrolled Research Subjects
Figure 1
Cohort Humoral and Cellular Responses. Antibody levels (left) of SARS-CoV-2 wild type plus Delta and Omicron variants in BAU/mL. ECoV antibody levels in U/mL. T cell response (right) evaluated by frequency of CD4+ and CD8+ IFN-γ+ T cells following stimulation with wild type SARS-CoV-2 S, N, M peptides.
Figure 2
Humoral Immune Durability and Response. Significant correlation between SARS-CoV-2 S IgG and days since last exposure (left) and SARS-CoV-2 S IgG and number of exposures (right). Exposure = vaccination or infection. Shaded region 95% CI, n=11.

Conclusion
Our small, ongoing cohort study demonstrates both SARS-CoV-2 antibody and T cell responses can develop following vaccination in children with IBD on anti-TNFα therapy. While the humoral response decreased over time, a durable cellular response persisted at 12 months in most participants.

Disclosures
All Authors: No reported disclosures
1722. Impact of Universal Conjugate Pneumococcal Vaccination in Infants on the Incidence and Mortality of Pneumococcal Meningitis in the General Population in Uruguay, South America (2005 – 2022).
Authors: Delfino Marcos , Ferrer Monica Pujadas , Pírez María Catalina 
Published: November 2023

Abstract

Background
Universal vaccination of children with conjugate vaccines was introduced using the 7 – valent pneumococcal conjugate vaccine (PCV7), which was changed to PCV13 (2 + 1 schedule, years 2008 to 2010), with nationwide coverage of 95 %.
The objective of this study is to analyze the impact of universal children vaccination with PCV7 and PCV13 on the incidence and mortality of pneumococcal meningitis (PM) in the general population in Uruguay.

Methods
This is a descriptive, retrospective study that includes all cases (children and adults) reported to the Department of Health Surveillance of the Ministry of Public Health with a diagnosis of PM between January 1, 2005, and December 31, 2022. Variables: cases per year, sex, age (≤ 15 years and &gt; 15 years), identified serotype, and deaths by year. The average rates of cases per 100,000 inhabitants are described in two periods: Period 1 or pre – universal vaccination (P1) from 2005 to 2007 and Period 2 or post – universal vaccination (P2) from 2011 to 2022, with their respective confidence intervals. Statistical analysis were established based on frequency distribution and statistical significance tests as appropriate, considering a value of p equal to or less than 0.05 as statistically significant. The research was approved by the institutional Ethics Committee.

Results
The total number of cases (N) is 555, 56.5% are men. 102 cases from the vaccine introduction period (2008 to 2010) were excluded. The N for P1 is 149 (3 years), while for P2 it is 304 (12 years).
The main results of incidence and mortality are shown in Table 1 and in the attached graphs. Lethality remains high (26.5% average for the total period).
The vaccine serotypes (VS) decrease from 28.2% (95% CI: 20 to 35) in P1 to 12.2% (95% CI: 8.4 to 15) in P2, p: 0.00006. The non – VS increase from 18.1% (95% CI: 11 to 24) in P1 to 44.7% (95% CI: 39.1 to 50.3) in P2, p: 0.00000001.
The predominant VS in P1 is 14 (26.2%, 95% CI: 13-39); in P2 there are 8.1%, 95% CI: 0.7-16.9), p: 0.071. The predominant VS in P2 is 3 (46%, 95% CI: 30-62); in P1 9.5% (95% CI: 0.6-18), p: 0.0003.
The non – VS predominant in both periods is 12F.
Evolution of incidence rates of PM in the general population and in people under and over 15 years of age as a function of time (in years).
Mortality rates

Conclusion
The incidence and mortality of PM statistically decreased in children under 15 years old and in the general population, which can be attributed to herd immunity.

Disclosures
Marcos Delfino, Pediatrician, Pediatric Infectious Diseases, Pfizer: Finna María Catalina Pírez, Pediatrician, Pediatric infectologist, microbiologist Professor of pediatric, Degree V, Merck, Pfizer: Expert Testimony|Merck, Pfizer: Honoraria
1759. Maintaining Latin America Polio-Free: A Multidimensional Analysis of Polio Outbreak Risk in Argentina in the Period 2020-2022
Authors: Grisolia Veronica Lucconi , Barrios Rocio Nahir , Olavarría Janisse Requena , Cañete Juan León , Aranda María Jimena , Katz Nathalia , Elbert Raquel Gabriela , Neyro Silvina , Urruti Maria Eugenia , López María Victoria , Selent Carolina , Bertachini Octavia , De Prada Ana Martina , Rapaport Solana , Hernández Adriana Verónica , Pereira Andrés Martín , Bruggesser Florencia 
Published: November 2023

Abstract

Background
Argentina has eliminated the circulation of poliovirus (PV) in 1984, and from 2020 onward only inactivated vaccines (IPV) are included in its national immunization schedule (NIS) which consist of three doses and a booster. The persistence of PV in some countries and the regional use of attenuated vaccines allow for the risk of reintroduction of these viruses. Such risk can be estimated for each population based on the susceptibility to infection, the capabilities to identify an event and prevent its spread. Our main objective was to analyze the PV outbreak risk in Argentina since the exclusive use of IPV.

Methods
Descriptive study. We used the PV outbreak risk analysis model provided by the Regional Certification Commission for the Polio Endgame in the Region of the Americas (RCC). The data of the period 2020-2022 available in the records of the Ministry of Health of the Nation were synthesized. It includes the following dimensions: polio vaccination coverage, epidemiological surveillance, social determinants of health and the occurrence of other vaccine-preventable diseases.

Results
We analyzed the PV outbreak risk in the 512 departments of the country in 2020, 2021 and 2022. For each year, respectively, 83% (n: 425), 86.3% (n: 442) and 94.1% (n: 482) of the departments had high and very high risk. In these departments, the dimension of polio vaccination coverage contributed predominantly to the risk, with an average of 52.6% (SD: 8.9); 57.9% (SD: 7.9); 58.1% (SD: 8.6) in each series. In regards to the coverage in the last 5 years, with the third dose of IPV, 73.4%, 61.3% and 60.8% of the departments reached the average expected. In respect of the coverage with the second dose of IPV, only 26.6%, 16.7% and 29.5% reached as expected for each year. During the vaccination campaign 26.3% of the departments achieved the coverage expected.

Conclusion
Though the exclusive use of IPV in the NIS has represented a big step for Argentina, the multidimensional risk analysis shows a high PV outbreak risk, similar to that described for other Latin American countries. This is an essential tool in the making of national polio elimination programs. We must continue working in order to meet polio vaccination coverage goals and keep the population disease-free.

Disclosures
All Authors: No reported disclosures