bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-2097. Genomic basis of Oxacillin- and Cefoxitin-Susceptible PBP2a-Positive Staphylococcus aureus
Authors: Tao Lili 
Published: January 2025

Abstract

Background
Methicillin-resistance Staphylococcus aureus (MRSA) is resistant to all ß-lactam antibiotics except for the fifth-generation cephalosporin drug, ceftaroline. The mecA gene, which encodes an alternative penicillin-binding protein, PBP2a, is responsible for the high-level resistance to methicillin. However, mecA positive, oxacillin- and cefoxitin susceptible MRSA has been reported, with limited understanding of the genomic basis behind this contradictory phenomenon. Here, we studied the molecular base of a “stealth” MRSA from clinical specimen.

Methods
A MRSA isolate was routinely isolated from a deep wound specimen, which was positive for PBP2a by lateral flow assay but negative for cefoxitin screen test and susceptible to oxacillin (MIC of 0.5 ug/ml) by VITEK 2 AST-GP75 card. It was also susceptible to cefoxitin using disk diffusion method (diameter of 26 mm). The “stealth” MRSA isolate was sequenced on illumina NovaSeq 6000 platform using 150 bp paired end sequencing. Bacteria genome was assembled and annotated using pipelines on BV-BRC (https://www.bv-brc.org/).

Results
Genomic sequencing revealed a point mutation (G to A) in the mecA gene resulting in a Gly599Ser substitution located in the transpeptidase domain of PBP2a, which is close to the active site of Ser403 on the 3D structure of the protein. Additionally, an insertion in the methicillin resistance regulatory sensor-transducer mecR1 gene was identified, resulting in a frameshift mutation, and predicted to cause premature termination. However, the sequence of frame shift mutation in mecR1 has been described and was not associated with reversed cefoxitin susceptibility. Therefore, the point mutation in mecA gene is most likely responsible for loss of function of PBP2a, and lead to susceptible cefoxitin and oxacillin results despite a positive PBP2a reaction.

Conclusion
Whole genome sequencing is valuable to understand the genomic basis of unusual phenotypic testing results. The reversion of “stealth” MRSA strain to a high-level oxacillin- and cefoxitin-resistant strain has been reported, which highlights the importance of considering tests for mecA or PBP2a in routine laboratory practice to avoid the risk of missing such strains.

Disclosures
All Authors: No reported disclosures
P-2099. A Novel Anaerobic Activity Index to define the “anti-anaerobic” spectrum of antimicrobials
Authors: Mackow Natalie A , Aronoff David M , Young Vincent B , Bartelt Luther A , van Duin David 
Published: January 2025

Abstract

Background
While necessary for the treatment of anaerobic infections, use of antibiotics with anaerobic activity may be associated with poor patient outcomes including graft-versus host disease after bone marrow transplant and mortality in critically ill patients. However, we lack a uniform method to assess the relative anaerobic activity of antibiotics and have poor definitions of what it means for antimicrobials to be “anti-anaerobic”.

Methods
A PubMed search using terms “microbial sensitivity test”, “anti-bacterial agents” and “bacteria, anaerobic” yielded 575 papers published between January 2013-2024 (Figure 1). Papers with &lt; 100 isolates, non-human isolates, or without antimicrobial susceptibility testing (AST) were excluded. AST for an average of 17,709 anaerobic clinical isolates per antimicrobial from 56 publications were summarized. Anaerobes were categorized into 11 groups based on the literature (Table 1). For 16 commonly used antibiotics, values of 0, 1, or 2 were awarded for each group of anaerobes for average published susceptibility of ≤ 10%, 11-89.4%, and ≥ 89.5%, respectively, and tallied to create a composite score (0-22, Score A). Three alternative scores were created based on different susceptibility cutoffs (Scores B-D; Table 2).Table 1:Groups of anaerobes for which antimicrobial susceptibility was scored

Results
In Anaerobic Activity Index Score A, scores ranged from 11 for moxifloxacin to 22 for tigecycline, meropenem, and imipenem (Table 2). Anaerobic Activity Index scores were plotted against the Antibiotic Spectrum Coverage (ASC), a previously published antibiotic “broad” spectrum score (Figure 2). Varying susceptibility thresholds affected estimated anaerobic activity for some antibiotics, including clindamycin and vancomycin, but overall, there was good agreement across all scores (A-D). Moxifloxacin had the lowest overall scores due to high rates of resistance across all groups of anaerobes.

Conclusion
Antibiotic broad-spectrum scores have been proposed, but no valid score exists and no score assessing anaerobic activity has been developed. An Anaerobic Activity Index may improve the definition of “anti-anaerobic” antimicrobials for clinical care and research. Further studies are needed to validate this index as a potential tool to evaluate the effect of anaerobic antibiotic exposure on clinical outcomes.

Disclosures
Vincent B. Young, MD, PhD, Aimmune: Honoraria|American Society for Microbiology: Board Member|Debiopharm: Advisor/Consultant|Peggy Lillis Foundation: Board Member|University of Oklahoma COBRE: Advisor/Consultant|Vedanta: Advisor/Consultant|Vedanta Bioscience: Advisor/Consultant|Vedanta Bioscience: Grant/Research Support David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support
P-2102. Performance of the VITEK®2 Advanced Expert System (AES) as a Rapid Aid for Reporting Antimicrobial Susceptibility Testing in Pseudomonas aeruginosa and Acinetobacter spp
Authors: Hackel Meredith , Bailey-Person Mary 
Published: January 2025

Abstract

Background
The VITEK®2 Advanced Expert System (AES) is an automated antibiotic susceptibility testing (AST) system which provides rapid AST data by interpreting and checking each MIC against a database of phenotypes and MIC distributions and infers a resistance mechanism. AES provides a level of confidence for auto-releasing reports of green (consistent), yellow (consistent with correction), and red (inconsistent, MIC pattern not matching any phenotype). This study evaluated VITEK®2 AES reports compared to broth microdilution (BMD) on a set of Pseudomonas aeruginosa (PA) and Acinetobacter spp. (ABC).

Methods
A total 148 PA and 150 ABC were tested. Susceptibility was tested by VITEK®2 (N802 and XN15 AST cards) and CLSI reference BMD against 13 antimicrobials for PA and 17 antimicrobials for ABC applying 2021 CLSI breakpoints. Molecular characterization of isolates was based on WGS or PCR of β-lactamase genes. Permeability and gene expression were not evaluated.

Results
Among 143 ABC, AES reports were green for 131 (91.6%), and yellow for 12 (8.4%) isolates. Green reports agreed with BMD for 131 isolates (100%) and could have been automatically reported without further review. Among yellow reports, AES corrections were acceptable for 11 isolates (91.7%). Among 40 carbapenem-producing ABC, AES reports were green for 39 isolates (97.5%) and yellow for one isolate (2.5%). Green reports agreed with BMD for 37 isolates (94.9%) and could have been automatically reported. Of 148 PA, AES reports were green for 125 (84.5%), yellow for 18 (12.2%), and red for 5 (3.4%) isolates. Of 112 PA with molecular data, 64 (57.1%), 38 (33.9%), 6 (5.4%), 3 (2.7%), and one (0.9%) contained genes for intrinsic β-lactamases only (WT), MBL, GES carbapenemase, KPC, and ESBL genes only, respectively. Overall, the AES accurately reported phenotypes for 97/112 PA (86.6%). Among the MBL-positive PA, 37/38 (97.4%) were reported as green and all showed AES phenotype agreement with the genotype. Among the WT PA, 51/64 (79.7%) were reported as green and 82.4% showed AES phenotype agreement with the genotype.

Conclusion
The use of VITEK®2 AES for the confident release of AST results without additional review could have a positive impact on time savings in the laboratory and aid in antimicrobial stewardship.

Disclosures
All Authors: No reported disclosures
P-20. Estimating the Public Health Impact of Pertussis Decennial Booster Vaccination for German Adults
Authors: Soares Victoria G , Waize Maria , Marijic Pavo , Heiseke Alexander , Heinze Daniel , Jamet Nicolas , Shah Hiral , Deeywadaa Pavitra , Jacob Jorge , Oikonomou Stavros , Verelst Frederik , Biundo Eliana 
Published: January 2025

Abstract

Background
Pertussis is a highly contagious respiratory disease affecting both children and adults. Current vaccination strategies primarily target infants, young children, and pregnant women, shifting the disease burden towards adults, with age and comorbidities increasing the risk of severe disease. This study aims to estimate the potential public health impact of decennial booster vaccination in adults in Germany.

Methods
A dynamic transmission model (DTM) was developed to evaluate the public health impact of alternative strategies for pertussis booster vaccination in adults (≥ 18 years) and those at increased risk. Disease transmission dynamics occurred at total population level with high-risk and non-high-risk populations tracked in separate compartments. The DTM was populated with published German data sources for population, vaccination coverage and incidence. Incidence was adjusted with previously published under-reporting rates. The model evaluated the age-stratified incidence and impact on healthcare resource utilization over a 100-year horizon. As base case, a decennial booster strategy for all adults was assessed in replacement of the current recommendation of a single adult (≥ 18 years) booster. Vaccination strategies targeting only high-risk populations were tested in scenario analyses.

Results
Interim results for the decennial booster strategy in adults suggest that administering an incremental 171 million booster doses would prevent over 35 million symptomatic cases, 1.7 million hospitalizations and 215,000 cases with complications, over 100 years. The model predicts that 5 individuals need to be vaccinated to avoid a pertussis case and 100 to avoid hospitalization. At equilibrium, the population overall incidence (symptomatic and asymptomatic) is expected to decrease from around 1,480 cases to 930 cases (-38%) per 100,000 person-years.

Conclusion
Modelling results suggest that implementing adult decennial booster vaccinations can significantly alleviate the burden of pertussis in Germany.

Disclosures
Victoria G. Soares, MBA, GSK: Advisor/consultant Maria Waize, MSc, GSK: Employed by GSK Pavo Marijic, PhD, GSK: Employed by GSK Alexander Heiseke, PhD, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Daniel Heinze, PhD, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Nicolas Jamet, PharmD, GSK: Employed by GSK Hiral Shah, PhD, GSK: Employee of GSK|GSK: Stocks/Bonds (Public Company) Pavitra Deeywadaa, MBBS, MD, GSK: Employed by GSK|GSK: Stocks/Bonds (Private Company) Frederik Verelst, PhD, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Eliana Biundo, MSc, GSK: Employee|GSK: Stocks/Bonds (Private Company)
P-2126. ‘SPECIFIC’ First-In-Human Clinical Trial of 68Ga-triacetylfusarinine (TAFC) Siderophore PET/CT for Detection of Invasive Aspergillosis
Authors: Sim Beatrice Z , Levy Sidney , Haskali Mohammad , Decristoforo Clemens , Haas Hubertus , Emmerson Brittany , Kamil Usama , Slavin Monica , Hofman Michael , Douglas Abby 
Published: January 2025

Abstract

Background
Invasive Aspergillus spp. infections (IAI) confer high morbidity and mortality in immunocompromised patients. Diagnosis often requires invasive and risky sampling. 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) is useful in diagnosis but is non-specific.
Siderophores are pathogen-specific iron chelators which are a promising radiolabelling target for IAI diagnosis. Aspergillus fumigatus secretes 2 siderophores, fusarinine C and triacetylfusarinine (TAFC), which are upregulated during IAI. Gallium-68 (68Ga)-labelled TAFC is attractive due to its short half life, rapid renal clearance, and low radiation risk. Preclinical mouse studies demonstrate diagnostic potential of 68Ga-TAFC PET/CT with specific visualisation of A. fumigatus infection.Figure 1:68Ga-TAFC-PET/CT in a patient with leukemia and probable pulmonary A. fumigatus IAI. Specific infective uptake of known pulmonary lesions at around blood pool level intensity (SUVmax 3.5, SUVmean 2.3). There was minimal liver and marrow uptake, with progressive washout to 60 minutes.

Methods
We report the first result from a 10 patient pilot trial of 68Ga-TAFC PET/CT for IAI diagnosis (NCT06105411). Inclusion criteria are adults with pulmonary IAI within 2 weeks of diagnosis. Exclusion criteria are pregnant/lactating patients or those within a week of iron infusion.
68Ga-TAFC PET/CT was performed at 15, 62, and 209 minutes after IV 139 MBq 68Ga-TAFC administration. Findings pertinent to IAI and physiologic uptake were analysed.

Results
The patient had probable A. fumigatus IAI in the setting of leukemia. Galactomannan and Aspergillus fumigatus PCR were positive on bronchoalveolar lavage fluid. Empiric antifungal treatment was commenced with fever resolution at 72 hours.
68Ga-TAFC-PET/CT was performed 10 days after treatment start and 4 days after microbiological diagnosis. Blood pool activity (SUVmax at 15/60/209 mins: 4.1/2.7/1.9) was demonstrated with minimal liver, spleen and gastrointestinal tract uptake (SUVmax 2.7), early renal excretion, and no marrow or other organ uptake. There was focal uptake in multiple pulmonary lesions (SUVmax 3.5), similar to blood pool activity, with synchronous washout over time. No adverse effects occurred.

Conclusion
Very low background physiologic biodistribution was seen in the first participant in this study. Focal low grade pulmonary uptake was visualised, likely demonstrating specific activity for A.fumigatus. Trial recruitment continues.

Disclosures
Abby Douglas, MBBS, Gilead Sciences: Honoraria
P-2156. Impact of Metagenomic Next-Generation Sequencing of Plasma Cell-Free DNA on Infectious Diseases Management in Adult and Pediatric Patients
Authors: Tholt Olivia , Hammer Katie Lynn , Gajurel Kiran , Buckley Kevin S , Lefemine Amanda 
Published: January 2025

Abstract

Background
Plasma metagenomic next-generation sequencing (mNGS) is a noninvasive diagnostic test that uses cell-free DNA to identify a variety of pathogens. mNGS has the potential to identify difficult to detect pathogens and avoid invasive procedures while ensuring appropriate antibiotic use. However, the broad range of organisms detected makes it difficult to discern pathogens from colonization. The impact and ideal patient population for this test remain uncertain.Figure 1. Reason for Ordering mNGSNote: patients could have more than one reason for ordering mNGS

Methods
This was a retrospective evaluation of adult and pediatric patients who had mNGS ordered during their admission at Atrium Health's Carolinas Medical Center or Levine Children's Hospital from July 2019 through July 2023. The aim of this study was to characterize the use of mNGS including patient demographics, testing indication, result concordance with conventional testing and clinical impact of results. Figure 2. Suspected Site of InfectionNote: patients could have more than one suspected site of infection

Results
A total of 67 adult and 44 pediatric patients were included with 72 and 50 mNGS orders, respectively. Most of the patients were immunosuppressed including 72% of adult and 94% of pediatric patients. The most common reasons for ordering mNGS were probable infection with negative cultures, rule-out infection, and lack of improvement on current therapy (Figure 1). The suspected sites of infection are shown in Figure 2. There were 48 adult patients and 23 pediatric patients with a positive test. Of those that were positive, the results were fully concordant with conventional testing for 13% of adult and 26% of pediatric patients. At least one organism detected by mNGS was suspected to be the causative pathogen in 69% of adult and 43% of pediatric positive tests. Clinical impact was largely uncertain, and a negative impact was not identified in either group. The adult group had a positive impact in 33% of patients compared to 12% of pediatric patients. The most common positive impacts were confirmed and new diagnosis of which the most frequent suspected sites were cardiac and respiratory.

Conclusion
mNGS was used primarily in immunocompromised patients with suspected, indeterminant infections. This data suggests mNGS may assist in the identification of organisms causing deep-seated infections or infections caused by pathogens otherwise difficult to detect but remains non-contributory to management in a majority of cases.

Disclosures
All Authors: No reported disclosures
P-2160. Where Does Karius Testing Have a Clinical Impact? A Retrospective Analysis of Next Generation Sequencing
Authors: Prado Antonio , Ewens Elise , Shephard Emily , Bhagat Hita , Won Regina 
Published: January 2025

Abstract

Background
Karius testing, a commercially available microbial cell-free DNA assay, has emerged as a new diagnostic tool for clinicians, particularly for management of culture negative infections and in immunocompromised patients. There remains uncertainty regarding the clinical impact of next-generation sequencing in patient management.
Figure 1

Methods
This was a retrospective multi-site observational cohort study over a five-year period from 2018 to 2023 at a community hospital system. Patients were included if they had a Karius test ordered with results available to treating clinicians during the time period. The primary outcome was a change in clinical management defined as either the addition or removal of antibiotics, based on results from Karius testing.

Results
391 patients met inclusion criteria, with 283 (72%) in immunocompetent and 108 (28%) in immunocompromised patients. An infectious diseases (ID) consult was obtained in 355 (91%) cases. Fifty-two percent of Karius tests were positive, with an average of 1.1 pathogens reported. Concordance rate between positive cultures and Karius results was 12%. Pneumonia (24%), fever of unknown origin (FUO) (18%), and endocarditis (17%) were the most common indications for Karius orders (Fig 1). Testing changed management in 19% of all included individuals, and in 18% of immunocompromised patients. Karius testing was most impactful in neutropenic fever and endocarditis with 27% and 22% respectively changing management and least impactful when ordered for joint infection, where 12% resulted in a change in management (Fig 2).

Conclusion
The Karius test changed antibiotic treatment in 19% of patients. It was most clinically relevant in neutropenic fever and endocarditis management. Even with our sizeable sample population including both immunocompromised and immunocompetent patients across a large, multi-site community hospital system, findings remained consistent compared to other smaller studies. Further investigation would be beneficial to determine how best to incorporate this emerging tool in clinical practice.

Disclosures
All Authors: No reported disclosures
P-2168. The Intervention of Infectious Diseases Physicians Might Enhance the Value of Broad-Range 16S rRNA Gene Polymerase Chain Reaction in the Clinical Aspect
Authors: Fukuoka Risa , Nakagawa Hidenori , Kato Masaru , Shirano Michinori 
Published: January 2025

Abstract

Background
Evaluation of Broad-Range 16S rRNA gene polymerase chain reaction (BRPCR) has been reported to aim in diagnosing infection by detecting and identifying bacterial genes in clinical specimens from patients with suspected infections. However, collecting the right specimens at the right time and determining whether the bacteria detected by BRPCR are the true cause or contamination requires infectious disease expertise. We investigate whether there is an association between the detection of bacteria that caused infection using BRPCR and intervention by Infectious Diseases (ID) physicians.

Methods
We reviewed the patients who underwent BRPCR at Osaka City General Hospital between April 2017 and March 2024. The collected items are age, sex, bacteria detected by BRPCR, determination of whether the bacteria if detected, caused infection, or were contaminated, and with or without the intervention of ID physicians (consultation to ID physicians). Then we analyzed the correlation between the intervention of ID physicians and the identification of the bacteria that caused the infection by BRPCR using Fisher's exact test. We also investigated whether the BRPCR results had affected the final diagnosis.

Results
There was a total of 149 clinical specimens from 138 patients. Of these, 84 (60%) were male, with a median age of 48 years (IQR 6-72). Bacteria were identified in 101 (67.7%) clinical specimens. In 70 specimens of them, the identified bacteria were presumed to have caused the infection. Of the 70 specimens, 56 had interventions by ID physicians. Whereas there were 79 specimens in which bacteria were identified but were presumed to be contaminants, and in which bacteria were not identified, of which 49 had intervention by ID physicians. The results showed an association between the intervention of ID physicians and the identification of the bacteria that caused the infection by BRPCR (p=0.0196). In 29 (19.4%), the final diagnosis changed from infectious to non-infectious based on the results of BRPCR.

Conclusion
Interventions by ID physicians might relate to identifying the bacteria causing an infection using BRPCR, and that might lead to enhancing the value of BRPCR.

Disclosures
All Authors: No reported disclosures