bluuebunny/crossref_metadata_2025_split huggingface dataset:
961. Prevalence of Surgical Site Infections and Bacteremia in Pediatric Patients Receiving Extracorporeal Membrane Oxygentaion
Authors: Siraj Althagafi Samiyah , Abdullah Alsuhaibani Mohammed , Murdhi Alenzi Mashael , Abdulrahaman Alyabes Ohoud , Mohammed Beheri Reem , Khalid Alrawaf Fahad , Abdullah Almalki Afnan , Tariq Alhuthil Raghad 
Published: November 2023

Abstract

Background
Extracorporeal membrane oxygenation (ECMO) is a well-known type of advanced life support used in critically ill patients with serious heart and/or lung problems. ECMO treatment is associated with multiple life-threatening complications. The objectives of this study were to identify the prevalence of surgical site infections (SSI) and bloodstream infections (BSI) along with the associated risk factors and outcomes in patients on ECMO.

Methods
In this retrospective study, clinical charts of patients were reviewed from January 2012 to April 2023. All admitted pediatric patients 14 years or less who received ECMO treatment were enrolled. Mann-Whitney and Fisher exact tests were used to assess mortality-related risk factors.

Results
A total of 165 patients were included in the study, 79 (47.88%) females and 86 (52.12%) males, with a median age of 4 [IQR 0.8-24] months. BSI were found in 33 (20%) of them, 10 (30.30%) were gram-positive, 25 (75.75%) were gram-negative, and 6 (18.18%) were fungi. Furthermore, 33 (20%) developed SSI. The overall mortality rate in this study is (50.30%) with a median duration from ECMO procedure initiation to death being 11 [IQR: 5-26] days. Most of mortalities (78.31%) were noticed in infants aged ≤24 months. Compared with patient with neither SSI nor BSI, patients with SSI and BSI had a higher mortality rates of 19 (22.89%) and 16 (19.28%) respectively.
Additionally, other noted complications were mediastinitis 4 (2.42%), sternal osteomyelitis 2 (1.21%), infective endocarditis 4 (2.42%).
Younger age and thrombocytopenia were found to be a mortality related risk factors (P value 0.04 and 0.01 respectively).

Conclusion
Our study found a high rate of bacteremia and SSI in pediatric patients receiving ECMO. Younger age, thrombocytopenia were the potential risk factors associated with higher mortality rates in this group.

Disclosures
All Authors: No reported disclosures
987. Identification of Fungal Pathogens In Formalin-Fixed Paraffin-Embedded (FFPE) Tissues by Targeted Next-Generation Sequencing (NGS) Technology
Authors: Totten Marissa C , Morris Christopher P , Ariyaratne Pramila , Zhang Tony , Zhang Sean , Lee Charlie 
Published: November 2023

Abstract

Background
Histological presence of fungal organisms associated with tissue damage is the hallmark for invasive fungal diseases. Rapid and accurate identification (ID) of these fungal pathogens present is critical for initiating appropriate treatment without delay. We investigated an automated sample-to-answer targeted NGS workflow for the ID of fungi directly from FFPE tissues.

Methods
170 FFPE tissues (93 cases) from 2002 to 2022 at Johns Hopkins Hospital were selected based on histologic findings of the presence of fungal pathogens. Samples were run by PathoKey SQ Flex assay, (Vela Diagnostics) which includes automated extraction, library preparation and emulsion PCR followed by NGS on a Sentosa SQ301 and analyzed using Vela’s curated database. Two negative controls (NCs) were included on each run. To compare NGS results, 51 samples were extracted using the MagMAX™ FFPE DNA/RNA Ultra Kit (Applied Biosystems) followed by pan-fungal PCR (ITS1/ITS2/D1D2) and Sanger sequencing (SS) and analyzed through NCBI nucleotide blast for ID.

Results
116/170 (68%) samples had culture results: 69/116 (59%) were concordant with Vela NGS (VS) ID to the genus/species level; 18/28 (64%) samples were concordant with SS ID to the genus/species level. Among 54 samples with no/negative culture results: 26/54 (48%) were presumptive Mucorales, of which 23/26 (88.5%) were supported by VS ID and 5/12 (42%) supported by SS ID; 12/54 (22%) were presumptive aspergillus-like hyphae fungi, of which 10/12 (83%) were supported by VS ID and 4/9 (44%) supported by SS ID. 15/170 (8.8%) samples had no VS ID due to QC failures, and 15/26 (58%) with no VS ID had no organism seen or scant amount of fungal load in the histology slide.

Conclusion
VS detected fungal organisms in 76% (129/170) of FFPE tissues, of which it correctly ID-ed pathogens down to the genus/species level in 94% (102/129) of samples. VS is more sensitive to pathogen ID than SS. Samples with discordant or no results by VS were mostly due to small tissue input or low fungal loads present in histology. Environmental or human skin flora contamination reads overshadowing possible pathogens were observed in few cases; therefore, it is critical to include NCs in each run to distinguish them from clinically significant fungal pathogens.

Disclosures
Marissa C. Totten, MA, Vela Diagnostics: Grant/Research Support Pramila Ariyaratne, n/a, Vela Diagnostics: Employee Tony Zhang, n/a, Vela Diagnostics: Employee Sean Zhang, MD, PhD, Applied BioCode: Grant/Research Support|IMMY Diagnostics: Grant/Research Support|KARIUS: Advisor/Consultant|Pearl Diagnostics: Grant/Research Support|Scanogen: Grant/Research Support|T2 biosystems: Advisor/Consultant|Vela Diagnostics: Grant/Research Support Charlie Lee, Ph.D, Vela Diagnostics: Employee
1021. Semi-nested Molecular Method for the Diagnosis of Invasive Fungal Infections in Combat Injured
Authors: Ellis Graham C , Shaikh Faraz , Carson M Leigh , Sercy Erica , Stewart Laveta , Andrews Jared M , Campbell Wesley , Mende Katrin , Yabes Joseph , Bialek Ralf , Tribble David R , Wickes Brian , Ganesan Anuradha 
Published: November 2023

Abstract

Background
Among combat injured, invasive fungal infections (IFI) result in significant morbidity (eg surgical amputations). Primary diagnostic methods are limited as cultures are insensitive and time delayed, and histopathology often cannot provide genus level identification needed for directed treatment. We previously evaluated a panfungal PCR (PF) assay and it was 83% sensitive and 99% specific for angioinvasive IFI (AIFI). The PF assay requires substantial expertise and cannot be easily performed at all facilities. Thus, we evaluated less resource intensive semi-nested PCR (SN) targeted to clinically relevant fungi (order Mucorales and genus Aspergillus and Fusarium).

Methods
Formalin-fixed paraffin-embedded tissue (FFPE) specimens from a multicenter trauma IFI cohort (2009-14) were used. Cases were US military personnel injured in Afghanistan with histopathologic IFI evidence. Controls were patients with similar injury patterns and no laboratory IFI evidence (negative culture and histopathology). SN assays specific to Mucorales (V4/V5 regions of 18S rDNA), Aspergillus (P2/Asp2 regions of mitochondrial tRNA), and Fusarium (internal transcribed spacer [ITS]/28A regions of DNA) were compared to a PF assay amplifying the ITS2 region of rDNA and to histopathology. Performance characteristics and Cohen’s Kappa coefficients were calculated.

Results
Specimens from 92 injury sites (62 subjects) were compared to control specimens from 117 injuries (101 subjects; Fig 1). We observed substantial agreement between SN and PF assays overall and for order Mucorales (Table 1). Moderate agreement was observed at the genus level for Aspergillus and Fusarium. When compared with histopathology, sensitivity and specificity of SN assays were 64.7% and 96.6% respectively (91.7% and 96.6% when restricted to AIFI; Table 2). No statistically significant difference in performance between the SN and PF assays was observed.

Conclusion
Prior studies of SN molecular diagnostics have focused on culture-negative samples from immunocompromised patients. Our findings underscore utility of the SN approach in diagnosing IFI using FFPE samples, especially AIFI. Given the known DNA degradation with formalin fixation, sensitivity of SN assays may be higher in unfixed specimens and should be examined.

Disclosures
All Authors: No reported disclosures
1102. Pediatric Hepatitis C Screening by Maternal Hepatitis C Viral Load Status in Pregnancy
Authors: DiNicola Julia , Chappell Catherine , Rick Anne-Marie 
Published: November 2023

Abstract

Background
The rise of hepatitis C (HCV) infections among reproductive-age women increases the number of infants at risk for perinatal HCV infection, but screening remains low. It is unknown if maternal HCV viral load (VL) during pregnancy influences infant screening practices.

Methods
Using an existing retrospective cohort of mother-infant pairs with longitudinal well-child care from a single healthcare system, we included infants born from 2015 to 2019 with perinatal HCV exposure based on maternal or infant HCV-specific ICD diagnosis codes and/or laboratory testing and confirmed by reviewing electronic health records. Maternal HCV VL during pregnancy was classified as positive (+), negative (-) or unknown based on HCV RNA testing (or lack-thereof) obtained between 12 months before to 3 months after the infant’s birth date. Adequate infant screening included an HCV RNA test obtained ≥ 2 months of age or an HCV antibody test ≥ 12 months of age. We used univariate logistic regression to compare odds of infant screening based on maternal HCV VL during pregnancy.

Results
Of the 501 HCV-exposed infants, 139 (28%) were born to HCV+/VL- women, 100 (20%) to HCV+/VL unknown women, and 262 (52%) to HCV+/VL+ women. The proportion of screening tests ordered ranged from 68-82%, while test completion ranged from 64-70% (Figure 1). Overall, screening for HCV varied by maternal HCV VL (43% (60/139) HCV+/VL-; 50% (50/100) HCV+/VL unknown; 58% (152/262) HCV+/VL+). Perinatal HCV ranged from 1.7-6% depending on maternal HCV VL status (Figure 1). Infants born to HCV+/VL+ women were two times more likely to have a screening order compared to infants of HCV+/VL- women; but there was no difference for infants of HCV+/VL unknown women (Table 1). Among those with tests ordered, there was no difference in completion between groups (Table 1).Figure 1.Flow Diagram of Perinatal Hepatitis C Screening of Infants Exposed to Hepatitis C in utero.

Conclusion
Although infants born to HCV+/VL+ women are more likely to be screened for HCV, many, regardless of maternal HCV VL during pregnancy, are never adequately screened and pediatric HCV infections are going undetected. Efforts to increase caregiver and clinician awareness of infant HCV screening guidelines, including consideration of earlier RNA or office-based HCV screening, may improve screening rates and detection of HCV infected infants.

Disclosures
Catherine Chappell, MD, MSc, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Organon: Grant/Research Support
1945. Antibacterial activity of cefepime/enmetazobactam and comparator agents against U.S. Enterobacterales clinical isolates collected from 2019-2021
Authors: Belley Adam , Kothari Nimmi , Monti Federica , Hawser Stephen 
Published: November 2023

Abstract

Background
The investigational β-lactam/β-lactamase inhibitor combination of cefepime/enmetazobactam (FPE) met criteria for non-inferiority and superiority compared to piperacillin-tazobactam (PTZ) in a phase 3 clinical trial of adult patients with complicated urinary tract infections/acute pyelonephritis. FPE has demonstrated potent in vitro antibacterial activity against Gram-negative pathogens expressing extended spectrum β-lactamases (ESBL), the leading cause of resistance to 3rd-generation cephalosporins (3GC). In this study, the in vitro activity of FPE and comparator agents was assessed against Gram-negative clinical isolates obtained from the U.S. between 2019 and 2021.

Methods
Broth microdilution minimum inhibitory concentrations (MIC) were determined for 2,241 Enterobacterales clinical isolates following CLSI guidelines. For determination of phenotypic resistance to 3GC, isolates resistant to both ceftriaxone and ceftazidime but susceptible to the carbapenem meropenem (MEM) were selected. ESBL genotyping was performed using a multiplex PCR method. Cefepime breakpoints of susceptible (S) ≤2 µg/ml and susceptible-dose dependent (SDD) ≤8 µg/ml were used as provisional breakpoints for FPE.

Results
FPE demonstrated potent in vitro activity against the surveillance isolates obtained from US medical centers, with an MIC90 of 0.12 µg/ml that was comparable to those of MEM (0.06 µg/ml) and ceftazidime/avibactam (CZA; 0.25 µg/ml). When applying cefepime breakpoints, susceptibility to FPE was ≥98.4 µg/ml whereas susceptibility to 3GCs and PTZ was ≤85.8%. Against Enterobacterales with either an ESBL genotype or exhibiting a 3GC-resistant phenotype, FPE retained potent in vitro activity (MIC90 = 0.5 and 1 µg/ml) and provisional susceptibility was ≥95.6%. In contrast, susceptibility to 3GCs and PTZ ranged from 0.0 to 65.9%.
Summary of the in vitro activity of cefepime/enmetazobactam and comparator agents against US Enterobacterales clinical isolates collected from 2019-2021

Conclusion
These results demonstrate that diminished susceptibility to 3GCs and piperacillin/tazobactam has compromised their reliability as empiric therapies. Cefepime/enmetazobactam demonstrates potent in vitro activity comparable to meropenem against ESBL-producing Enterobacterales and is intended as empiric therapy in settings where ESBL are endemic.

Disclosures
Adam Belley, PhD, Allecra Therapeutics SAS: Advisor/Consultant Nimmi Kothari, PhD, Allecra: Allecra (study funding)|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Federica Monti, PhD, Allecra: Study funded|Innoviva Specialty Therapeutics, Inc.: Honoraria Stephen Hawser, PhD, Allecra: study funding|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C).
1163. Influenza Vaccination Coverage through December among Persons Ages Six Months and Older in the Vaccine Safety Datalink, 2017-18 through 2022-23 Influenza Seasons
Authors: Irving Stephanie , Groom Holly C , Belongia Edward , Crane Bradley , Daley Matthew F , Goddard Kristin , Jackson Lisa , Kenigsberg Tat’Yana A , Kuckler Leslie , Naleway Allison L , Patel Suchita A , Tseng Hung Fu , Williams Joshua T B , Weintraub Eric 
Published: November 2023

Abstract

Background
In the United States, annual vaccination against seasonal influenza is recommended for all people ages ≥ 6 months. Vaccination coverage assessments can identify populations with lower vaccination rates and help to tailor vaccination efforts. Within the Vaccine Safety Datalink population ages ≥ 6 months, we report influenza vaccination coverage through December of the 2022-23 influenza season and compare estimates to similar periods within the 2017-18 through 2021-22 seasons.

Methods
Using electronic health record data, we captured all influenza vaccines administered between August 1 and December 31 of each season. Crude, single-dose coverage was calculated for each season, overall and by sex; age group; race and ethnicity; and number of separate categories of diagnoses associated with an increased risk of severe illness and complications from influenza – these conditions were identified using ICD-10-CM diagnosis codes assigned in the year preceding each influenza season.

Results
Among cohorts of more than 11 million individuals each season, crude influenza vaccination coverage through December ranged from a high of 44% (2020-21) to a low of 37% (2022-23). In each of the six seasons, coverage was lowest among males, 18-49-year-olds (Figure), non-Hispanic Black people, and those without conditions associated with increased risk of severe illness and complications from influenza. While decreases in coverage in recent seasons were present in all age groups, the declines were most dramatic among children: during the 2022-23 season, coverage for children ages &lt; 9 and 9-17 years decreased 25% and 26% (12 and 10 absolute percentage points), respectively, from peak coverage in prior seasons (Figure).

Conclusion
Influenza vaccination coverage increased from the 2017-18 through 2020-21 seasons, then decreased to the lowest level in the 2022-23 season. Overall Vaccine Safety Datalink population estimates are far below United States vaccination targets. We identified persistent disparities in influenza vaccination coverage by sex, age, and race and ethnicity. The overall low coverage, disparities in coverage, and recent decreases in coverage raise significant public health concerns.

Disclosures
Edward Belongia, MD, Seqirus: Grant/Research Support Lisa Jackson, MD, MPH, Pfizer: Grant/Research Support Hung Fu Tseng, PhD MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support
1170. Follow-up of vaccine preventable disease hospitalisations in the ageing population: Loss of Independence
Authors: Salem Ahmed , Hartmann Maximilian , Servotte Nathalie , Aris Emmanuel , Doherty T Mark , Beck Ekkehard 
Published: November 2023

Abstract

Background
Influenza, pneumococcal infection, herpes zoster and pertussis are vaccine preventable diseases (VPDs) that cause significant burden for older adults (50+ years old). Downstream effects beyond the acute phase such as loss of independence have not been well characterised.

Methods
Using Optum’s de-identified Clinformatics® Data Mart Database, a retrospective claims database study was conducted to assess the impact of a VPD hospitalisation on subsequent loss of independence over 365 days of follow-up during the epidemiological years 2016–2018. Loss of independence is a composite endpoint defined as either a change in residence status from “living at home” to “long-term care facility” or the need of home health/home care (HHHC) which was not needed at baseline. Both were assessed over 365 days of follow-up after a VPD-hospitalisation. The VPD-hospitalised cohort were subjects hospitalised due to VPD as primary or secondary diagnosis or both. Controls were matched at baseline on variables like demographics, insurance, comorbidities, and Charlson Comorbidity Index (CCI) score. Results were stratified by age and CCI category at baseline and reported as mean difference between cohorts (with 95% confidence interval, CI).

Results
Subjects hospitalised for a VPD would experience at least 20% (18.9–21.5%, p&lt; 0.001) more LoI versus their matched counterparts over 365 days (Figure 1). Furthermore, at least 12% (10.0–13.2%, p&lt; 0.001) more subjects in the VPD-hospitalised cohort experienced a worsening in their residence status (Figure 2) at 365 days of follow-up. Finally, the need for HHHC was more pronounced for subjects hospitalised for a VPD where a mean difference of at least 9% (8.1–9.3%, p&lt; 0.001) and a maximum of 27% (25.0–28.7%, p&lt; 0.001) was observed compared to controls (Figure 3).Figure 1:Loss of inpendanceFigure 2:Proportion with worsening in residence statusFigure 3:Experiencing worsening in HHHC Status

Conclusion
Individuals hospitalized for a VPD were more likely to experience a loss of independence as defined by change in residence status and the need for home health care compared to matched controls. These findings highlight the potential burden of VPDs beyond the acute disease phase and can provide important motivation to improving preventive programs including vaccination.

Disclosures
Ahmed Salem, MSc, GSK: employee|GSK: Stocks/Bonds Maximilian Hartmann, PhD, GSK: Grant/Research Support Nathalie Servotte, PhD, GSK: employee|GSK: Stocks/Bonds Emmanuel Aris, PhD, GSK: employee|GSK: Stocks/Bonds T. Mark Doherty, PhD, GSK: employee|GSK: Stocks/Bonds Ekkehard Beck, PhD, GSK: employee|GSK: Stocks/Bonds
1171. Follow-up of vaccine preventable disease hospitalisations in the ageing population: onset of chronic comorbidities
Authors: Salem Ahmed , Hartmann Maximilian , Servotte Nathalie , Aris Emmanuel , Doherty T Mark , Beck Ekkehard 
Published: November 2023

Abstract

Background
Vaccine preventable diseases (VPD) such as influenza, pneumococcal infection, herpes zoster and pertussis pose a significant burden for adults 50 years and older. The disease burden beyond the acute phase (downstream effects) where a VPD can trigger or exacerbate comorbidities is less studied.

Methods
Using Optum’s de-identified Clinformatics Data Mart Database, a retrospective claims database study was conducted to assess the diagnosis of new comorbidities in older adults (50+) up to 365 days following an index hospitalisation with a VPD during the epidemiological years 2016 – 2018. A subset of outcomes is reported here, focusing on the new onset of myocardial infarction (MI) and congestive heart failure (CHF). Subjects hospitalised with a VPD were compared to matched controls without a VPD hospitalisation. Matching was conducted on the day of VPD hospitalisation based on baseline variables like demographics, insurance, comorbidities, and Charlson-Comorbidity Index (CCI) score. The study analysed the new onset of MI and CHF over 365 days following a VPD index hospitalisation stratified by age category and CCI score at baseline. Results are reported as mean change (95% confidence interval (CI)).

Results
At 365 days, there was a significant higher risk for a new MI observed in the VPD-hospitalised cohort compared to their matched controls (Figure 1) across all age groups and CCI categories. In particular, individuals without any comorbidity at baseline (CCI = 0) experienced an increased probability for a new MI diagnosis between 6% (4.9–7.4%, p&lt; 0.001) and 13% (11.6% - 14.3%, p&lt; 0.001). Furthermore, the VPD-hospitalised cohort also showed a significant higher risk for a new CHF diagnosis versus their non-VPD matched controls (Figure 2). Those without any comorbidity at baseline (CCI = 0) showed an increased proportion of new CHF diagnosis over 365 days between 12% (10–14%, p&lt; 0.001) and 25% (24–27%, p&lt; 0.001).

Conclusion
Results suggest that individuals hospitalised for a VPD were more likely to experience a new MI or CHF compared to their matched controls. Limitations exist around direct associations between the VPD hospitalisation and the onset of a new MI or CHF diagnosis, but the findings support the hypothesis that downstream effects of VPDs could trigger or exacerbate a comorbidity.

Disclosures
Ahmed Salem, MSc, GSK: employee|GSK: Stocks/Bonds Maximilian Hartmann, PhD, GSK: Grant/Research Support Nathalie Servotte, PhD, GSK: employee|GSK: Stocks/Bonds Emmanuel Aris, PhD, GSK: employee|GSK: Stocks/Bonds T. Mark Doherty, PhD, GSK: employee|GSK: Stocks/Bonds Ekkehard Beck, PhD, GSK: employee|GSK: Stocks/Bonds