bluuebunny/crossref_metadata_2025 huggingface dataset:
385. Sepsis-Associated Encephalopathy and Dementia Outcome: A Retrospective Cohort Study of 30,378 Adult Sepsis Inpatient Survivors at a Tertiary Medical Center in Taiwan
Authors: Lin Yu-Chao , Chang Yi-Ching , Lin Che-Chen , Kuo Chin-Chi , Chiang Hsiu-Yin
Published: January 2025

Background

Sepsis-associated encephalopathy (SAE) is commonly observed in critically ill patients without identifiable causes, potentially leading to neurological sequelae. Prior studies have associated the long-term risk of dementia with sepsis or in-hospital infections, or the short-term risk of mortality with SAE, rather than the short-term dementia risk with SAE. We aimed to assess the association between SAE and the 1-year risk of dementia among sepsis survivors.Figure 1.Flowchart of the selection process of adult sepsis inpatient survivors (n = 30,378).

Methods

This cohort included inpatients aged ≥ 18 years with first-time sepsis during 2010-2019, no prior dementia or central nervous system (CNS) infections, Glasgow Coma Scale (GCS) measurements within 7 days of sepsis, and who survived the index hospitalization (Figure 1). Sepsis was identified using Sepsis-3 criteria. SAE was defined as having at least two GCS measurements of either < 7 for patients with endotracheal tubes, tracheostomies, or aphasia, or < 12 for the remaining patients within the 7 days of sepsis. Dementia at 3 months and 1 year was defined by the presence of ICD-9 and ICD-10 diagnosis codes from 7 days to 3 months, and from 3 months to 1 year post-sepsis onset, respectively. Multivariable Cox models were used, considering death as the competing risk.

Demographic, clinical characteristics, and outcomes of adult sepsis inpatient survivors, stratified by SAE status.

Results

Of 30,378 eligible sepsis inpatient survivors, 6.4% developed SAE within 7 days of sepsis onset. Patients with SAE tended to be older, female, and have more comorbidities compared to those without SAE (Table 1). Dementia occurred more frequently in patients with SAE than those without (10.9% vs 3.9% within 3 months; 3.6% vs 2.1% within 1 year). Similar patterns were observed in mortality rate. SAE was significantly associated with an increased risk of dementia for 3-month (adjusted hazard ratio [aHR] 1.81; 95% confidence interval [CI] 1.55-2.12) and for 1-year (aHR 1.54; 95% CI 1.18-2.01), compared to patients without SAE (Table 2). This association was significantly stronger among patients without chronic pulmonary disease, stroke, and with a qSOFA < 2, regarding the 3-month dementia risk (Figure 2).

Risk of dementia and all-cause mortality associated with SAE among adult sepsis inpatient survivors.

Conclusion

Determining whether SAE is a trigger for the disease itself or merely triggers more intensive dementia surveillance requires more studies with standardized SAE diagnostic criteria and post-sepsis follow-up strategies.

Subgroup analyses of the risk of dementia and all-cause mortality associated with SAE.

Disclosures

All Authors: No reported disclosures
P-1018. A comprehensive strategy identifies Candida albicans genes and biologic processes that contribute to pathogenesis of intra-abdominal candidiasis (IAC)
Authors: Clancy Cornelius J , Cheng Shaoji , Nguyen Minh-Hong
Published: January 2025

Background

IAC pathogenesis is poorly understood.Figure 1.C. albicans transcription factor mutants attenuated during IAC.

Methods

We used RNA-Seq to measure C. albicans SC5314 gene expression during early peritonitis (30-min), late peritonitis (24-hr) and abscesses (IAA; 48-hr) of mice. ≥2-fold differences were significant (false discovery ≤0.01). We screened duplicate signature-tagged, homozygous deletion libraries for 165 C. albicans transcription factors (TFs) in 72-hr IAA.

Results

The 50 genes most highly expressed during early peritonitis were associated with pH (e.g., RIM101, PHR1), oxidative stress responses (e.g., SOD4-6), and adhesion/hyphal growth (e.g., ALS3, HWP1, ECM331, SAP6). The corresponding 50 late peritonitis genes were associated with phagocyte responses and nutrient acquisition (glyoxylate cycle, fatty acid β-oxidation, iron homeostasis). Responses within IAA included DNA damage and iron metabolism. Null mutants for genes involved in adhesion (ALS1, ALS3), transport (OPT8, SGE11), biofilm (ZCF23), DNA damage responses (RFX1, RFX2, DDI1), cell wall responses (DAP2) and copper metabolism (CCC2) were attenuated during peritonitis and/or IAA [Table 1]. 21 TF mutants were significantly attenuated for virulence in both libraries [Fig 1]. Biologic processes over-represented were regulation of pH responses, biofilm, hyphal formation, echinocandin responses, and copper metabolism. 9 pH response regulators were confirmed to contributed to virulence, including RIM101, STP2 (alkaline), ASH1, SFL1, SFL2 (neutral), MNL1, SKO1, PHO4 (weak acid), and CSR1 (acid) [Fig 2]. Over-expression of aspartyl protease SAP5 in rim101 restored virulence during IAA at 3, 7, and 10 days. Over-expression of either SKO1 or PHO4 in mnl1 restored weak acid responses in vitro [Fig 3] and virulence (not shown).Figure 3.Over-expression of PHO4 or SKO1 in mnl1 rescues weak acid responses

Conclusion

Numerous C. albicans environmental response genes make temporal-spatial contributions to IAC. pH response regulators RIM101 and MNL1 contribute to virulence during peritonitis and IAA, in part by regulating SAP5 and PHO4/SKO1, respectively. Other processes and genes involved in IAC pathogeneses are adhesion, transport, biofilm, DNA damage responses, cell wall responses and copper metabolism.

Disclosures

Cornelius J. Clancy, MD, Cidara: Grant/Research Support|Gilead: Honoraria|Merck: Grant/Research Support|Scynexis: Advisor/Consultant|Shionogi: Advisor/Consultant|Venatorx: Advisor/Consultant
P-1019. Incidence And Risk Factors for Invasive Fungal Infections in Pre-Transplant and Transplant-Ineligible Multiple Myeloma in the U.S.: A Claims Analysis (2017-2021)
Authors: Rogers Daniel , Baker Aubrey N , Xu Jianing , Chen Xianyan , Henao Martínez Andrés F , Chastain Daniel B
Published: January 2025

Background

Current research on risk factors for invasive fungal infections (IFIs) in multiple myeloma (MM) has limitations due to heterogeneous patient populations, including post-transplant, or reliance on subgroup analyses. This study aimed to address this gap by evaluating the incidence of IFIs and identifying risk factors in patients with MM receiving treatment before or ineligible for transplant.

Methods

We analyzed data from the Merative MarketScan Database (2017-2021) to identify adults (≥ 18 years) diagnosed with and treated for MM with proteasome inhibitors, lymphodepleting agents, thalidomide or derivatives, anti-SLAMF7 monoclonal antibodies, or exportin 1 inhibitors, with or without dexamethasone. We evaluated the incidence and risk factors for IFIs following anti-MM therapy initiation. All patients were followed for at least one year. Patients without an IFI were censored at the end of the study period.

Results

Among 3054 individuals with MM, 6% (n=195) were diagnosed with an IFI. Candidiasis was most common (87%), followed by pneumocystis (6.2%) and aspergillosis (3.6%). Patients with an IFI were younger with a higher burden of comorbidities compared to those without an IFI (table 1). Notably, neutropenia, thrombocytopenia, chronic heart failure, chronic liver failure, hypercalcemia, and hyperglycemia were significantly more common in the IFI group. Anti-MM therapies were similar between groups, with a high prevalence of both thalidomide or derivatives and dexamethasone (table 2). Antifungal prophylaxis was uncommon while nearly half of each group received antibacterial prophylaxis. Patients with an IFI were more likely to have received multiple lines of anti-MM therapy. Multivariate analysis identified recent dexamethasone use (HR 5.85, 95% CI: 4.08-8.40), neutropenia (HR 2.77, 95% CI: 1.87-4.11), and a greater number of anti-MM therapies within the preceding year (HR 2.15, 95% CI: 1.71-2.69) as significant risk factors for IFI.

Conclusion

Candidiasis was the most common IFI in patients with MM. Younger age, higher comorbidity burden, and neutropenia were associated with IFIs. Additionally, recent dexamethasone use and a higher number of prior anti-MM therapies significantly increased the risk of IFIs.

Disclosures

All Authors: No reported disclosures
P-1040. Clinical Outcomes of Micafungin for Invasive Fungal Infections in the Obese and Nonobese
Authors: Moran Ryan , Cady Beth
Published: January 2025

Background

The efficacy and safety of echinocandins make them favorable first-line options for many fungal infections. Current guidelines do not recommend dose adjusting echinocandins for obesity. Increasing evidence suggests pharmacokinetic goals may be difficult to attain with standard echinocandin dosing in obese populations but clinical outcomes data is scarce. The purpose of this study is to investigate if obese patients given micafungin for invasive fungal infection (IFI) have worse outcomes compared to nonobese patients.

Methods

This retrospective study compared obese and nonobese patients receiving micafungin for IFI. Primary outcome was favorable clinical response in obese patients compared to nonobese patients with IFI at the end of antifungal therapy. Inclusion criteria were age ≥ 18, suspicion of IFI, and receipt of micafungin for ≥ 72 hours. Doses other than micafungin 100 mg were excluded. Patients were placed into one of two groups. Patients with a body mass index (BMI) < 30 kg/m2 were assigned to the nonobese group and those with a BMI ≥ 30 kg/m2 were assigned to the obese group.

Results

600 patients were evaluated resulting in 378 being included with 177 and 201 in the obese and nonobese groups, respectively. There were minor variations in baseline characteristics. The primary outcome occurred in 49% in the obese group and 51% in the nonobese group (p=0.76).

Conclusion

These results do not show a difference in clinical outcomes using micafungin in obese and nonobese patients and do not support use of higher doses of micafungin in the obese. It is unknown whether there is truly no difference or if no difference was seen due to small sample size. Additional research is needed to further evaluate echinocandins and clinical outcomes in obese patients.

Disclosures

All Authors: No reported disclosures
P-1044. Physician's Compliance to Clinical Practice Guidelines and Outcomes of Patients with Invasive Candidiasis at A University Hospital in Thailand
Authors: Pirogard Nantaporn , Chongtrakool Piriyaporn , Chayakulkeeree Methee
Published: January 2025

Background

Compliance to the clinical practice guidelines (CPG) has shown to reduce mortality in patients with invasive candidiasis (IC). This study aimed to evaluate the physician’s compliance to locally developed CPG after implementation of care bundles and patient’s outcomes.

Methods

This is a quasi-experimental study using historical cohort control. Candidemia patients admitted during November 2021 to April 2024 were enrolled. The CPG for IC was implemented in the prospective cohort. Care bundles were implemented. Each eight CPG item was given a value for poor to good compliance ranging from 0 to 2, and the compliance score was calculated. Compliance score < 8 was considered as poor compliance. Physician’s compliance and all cause 30-day mortality were analyzed.

Results

A total of 109 patients were included, 56 in historical control and 53 in prospective intervention group. Patients in both groups showed similar baseline characteristics and risk factors for candidemia. After the implementation of the CPG and care bundles, the physician’s compliance increased significantly, including early treatment within 24 hours (OR = 5.63, 95% CI [2.25-14.01], p-value < 0.001), receipt of appropriate antifungal therapy (OR = 8.67, 95% CI [1.05-71.88], p-value 0.03), source control within 48 hours (OR = 34.70, 95% CI [4.36-276.10], p-value < 0.001), obtaining blood culture every other day (OR = 17.93, 95% CI [6.90-46.82], p-value < 0.001), antifungal therapy at least 14 days after negative blood culture (OR = 2.76, 95% CI [1.20-6.33], p-value 0.02), echocardiography (0% vs 17%, p-value 0.001), and fundoscopy (OR = 5.25, 95% CI [1.78-15.45], p-value 0.001). There was significant improvement in compliance score of ≥ 8 in the intervention group (OR = 5.07, 95% CI [1.86-13.84], p-value 0.001). Mean ± SD of the compliance score was 8 ± 2 in the control group and 11 ± 2 in the intervention group (p-value 0.001). All cause 30-day mortality rate significantly decreased from 55.4% in the control group to 35.8% in the intervention group (OR = 0.45, 95% CI [0.21-0.97], p-value 0.04).

Conclusion

CPG and care bundles for IC significantly improved physician’s compliance and patient’s survival, encouraging the implementation of the CPG and care bundles for the management of IC.

Disclosures

All Authors: No reported disclosures
P-1069. Comparative Antibacterial Activity of Hypochlorous and Polygalacturonic + Caprylic Acids in an In Vitro Wound Biofilm Model
Authors: Gerges Bahgat Z , Raad Issam I , Jiang Ying , Rosenblatt Joel , Truong Y Lan
Published: January 2025

Background

Therapeutic agents which impart minimal inflammatory responses are needed to disinfect microbially contaminated chronic wounds. Polygalacturonic + caprylic (PG+CAP) and hypochlorous (HOCl) acids have been shown to be well tolerated potent antimicrobial agents for eradicating a broad range of microbial biofilms in standard in vitro biofilm models. However, standard microbiologic biofilm eradication models do not present the complex natural environments of chronic wound beds which contain significant quantities of human proteins. In this study we compared the efficacy of PG+CAP and HOCl against resistant wound biofilm bacterial pathogens in a 3-dimensional fibrin gel wound biofilm model, which is more realistically simulates a colonized chronic wound.

Methods

A fibrin gel biofilm eradication model was used to quantify antibacterial efficacy. Forty-eight hours mature biofilms of Staphylococcus aureus and Pseudomonas aeruginosa were allowed to form on fibrin gels creating wound biofilm models. They were then exposed to 1% PG+ 0.8% CAP or 400 ppm HOCl for three hours. Following exposure, the wound gels were sonicated in neutralizer broth, then serially diluted, plated and counted to enumerate viable colonies (CFU/mL). Positive controls were not exposed to antimicrobial agents. Statistical comparisons of six-replicates for each group were performed using Wilcoxon rank sum test (p<0.05 is considered statistically significant).

Results

Figure 1 presents the median number of CFU/mL recovered from controls and wound biofilms exposed to PG+CAP, and HOCl.

Conclusion

PG+CAP completely eradicated S aureus biofilms with greater than 7-log reduction in CFU/mL versus positive control, while HOCl produced a 4.2 log reduction. The CFU/mL difference between PG+CAP and HOCl was significant (P= 0.0028). For P. aeruginosa, PG+CAP and HOCl produced 8.28 and 2.32 log reductions versus positive control respectively with a significant difference in CFU/mL between them (P= 0.0043). These results suggest microbiologic testing in wound biofilm models may be important to realistically test the efficacy of antimicrobial agents for chronic wound care. These results suggest PG+CAP merits further testing for disinfecting contaminated chronic wounds.

Disclosures

All Authors: No reported disclosures
P-1081. Activity of Aztreonam-Avibactam against Enterobacterales Isolated from Patients with Intra-Abbdominal Infection from United States Medical Centers (2019-2023)
Authors: Sader Helio S , Doyle Timothy , Mendes Rodrigo E , Winkler Marisa , Castanheira Mariana
Published: January 2025

Background

Aztreonam-avibactam (ATM-AVI) is being developed for the treatment of Gram-negative infections, including those caused by metallo-β-lactamase (MBL) producers. We evaluated the activity of ATM-AVI against Enterobacterales (ENT) isolated from patients with intraabdominal infections (IAI) in United States (US) medical centers.

Activity of β-lactamase inhibitor combinations against Enterobacterales from intra-abdominal infections

Methods

2,036 isolates (1/patient) were consecutively collected from patients with IAI in 63 US hospitals in 2019-2023. Susceptibility testing was performed by broth microdilution method. ATM-AVI was tested with AVI at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤8 mg/L was applied for comparison. Carbapenem-resistant ENT (CRE) were screened for carbapenemases (CBase) by whole genome sequencing. Comparator agents included ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), and cefiderocol (CRE only), among others.

Results

The most common ENT species were E. coli (47.1%), K. pneumoniae (18.7%), and E. cloacae species complex (9.8%). Only 1 ENT exhibited ATM-AVI MIC >8 mg/L (MIC50/90, ≤0.03/0.12 mg/L), an E. coli with ATM-AVI MIC of 16 mg/L. The most active agents against CRE were ATM-AVI (93.3% inhibited at ≤8 mg/L) and cefiderocol (93.3% S); CAZ-AVI, MEM-VAB, and IMI-REL were active against 86.7% of CRE (Table). A multidrug-resistant (MDR) phenotype (non-S to ≥3 classes) was observed in 21.4% of ENT (n=436) and the most active β-lactamase inhibitor combination (BLIC) against MDR isolates were ATM-AVI (99.8% inhibited at ≤8 mg/L), MEM-VAB (99.5% S), and CAZ-AVI (99.3% S). Piperacillin-tazobactam (PIP-TAZ) was active against 87.2% of ENT and 50.2% of MDR, and meropenem was active against 92.2% of ENT and 96.1% of MDR. A CBase was identified in 9 isolates (60.0% of CRE), and included KPC-2 (3 isolates), KPC-3 (4), and NDM-5 (2). All CBase producers were inhibited at ≤8 mg/L of ATM-AVI and were cefiderocol-S; whereas susceptibility to CAZ-AVI, MEM-VAB, and IMI-REL were 77.8%.

Conclusion

ATM-AVI and the newer BLICs exhibited almost complete activity against ENT causing IAI in US hospitals. ATM-AVI may represent a valuable treatment option for IAI, including those caused by CRE and MDR ENT.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support
P-1082. Antimicrobial Susceptibility of Enterobacterales Causing Infection in the Elderly: Focus on Aztreonam-avibactam and Recently Approved β-Lactamase Inhibitor Combinations
Authors: Sader Helio S , Mendes Rodrigo E , Doyle Timothy , Winkler Marisa , Castanheira Mariana
Published: January 2025

Background

Infections account for about 1/3 of all deaths in people 65 years and older and this population has a higher risk of exposure to antimicrobial-resistant bacteria. We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) causing infection in elderly patients in United States (US) medical centers.

Activity of β-lactamase inhibitor combinations against Enterobacterales from elderly patients

Methods

Clinical isolates (1/patient) were consecutively collected from 72 US medical centers in 2021-2023 and susceptibility tested by broth microdilution. Results for 10,574 ENT isolates from elderly patients (≥65 years old) were analyzed and compared to 9,793 isolates from adult patients (age 18-64). Results were stratified by infection type and resistant subsets. Cefiderocol was only tested against carbapenem-resistant ENT (CRE). ATM-AVI was tested with AVI at fixed 4 mg/L and a PK/PD susceptible (S) breakpoint of ≤8 mg/L was applied for comparison. CRE isolates were screened for carbapenemases (CBase) by whole genome sequencing. Comparator agents included ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), and cefiderocol (CRE only), among others.

Results

All elderly isolates were inhibited at ATM-AVI MIC of ≤8 mg/L. CAZ-AVI (99.7% S) and MEM-VAB (99.8% S) were very active against ENT overall but exhibited limited activity against CRE (71.6% and 70.4% S, respectively; Table). The most active agents against CRE were ATM-AVI (100.0% inhibited at ≤8 mg/L) and cefiderocol (96.3% S). Multidrug-resistant (MDR; non-S to ≥3 classes) and ESBL phenotypes were observed in 19.8% and 12.3% of isolates, respectively, and ceftolozane-tazobactam (TOL-TAZ) and piperacillin-tazobactam (PIP-TAZ) showed limited activity against these organisms. Susceptibility to TOL-TAZ, PIP-TAZ, and ceftriaxone were lower among elderly isolates from pneumonia than BSI or UTI. The most common CBase were KPC (56.8% of CRE) and NDM (22.2%). A metallo-β-lactamase was identified in 24.7% of isolates. In general, susceptibility rates of isolates from the elderly were comparable (+/- < 2%) to those from the adult population.

Conclusion

ATM-AVI demonstrated complete activity (100.0% S) against ENT causing infection in the elderly, including CRE and isolates with ESBL or MDR phenotypes.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support
P-1091. Hydrogen peroxide generating electrochemical bandage for the treatment of wound biofilm infections - preliminary demonstration of device safety on healthy human skin
Authors: Kies Paige , Fleming Derek , Kim Won-Jun , Anoy Md Monzurul , Bozyel Ibrahim , Holtegaard Susan , Greenwood-Quaintance Kerryl , Beyenal Haluk , Patel Robin
Published: January 2025

Background

Wound biofilm infections impact ∼2% of the United States and at-risk individuals often have underlying morbidities such as diabetes. Antibiotics and topical approaches like debridement or silver dressings have had limited success, underscoring a need for strategies that efficiently target pathogens in wound beds.

Methods

We developed a hydrogen peroxide (H2O2) generating electrochemical bandage (e-bandage) composed of carbon fabric electrodes separated by cotton fabric with an Ag/AgCl reference electrode (RE) placed between cotton fabric layers. The e-bandage is controlled by a wearable micropotentiostat (MP); H2O2 is generated by O2 + 2H++ 2e- → H2O2. O2 is dissolved on a primary working electrode with negative polarity compared to the RE while a positively polarized secondary counter electrode generates H+ and e-. The H2O2 e-bandage/MP device has in vitro activity against mono- and dual-species bacterial and fungal biofilms. We showed that the H2O2 e-bandage decreased the burden of methicillin-resistant Staphylococcus aureus and/or Pseudomonas aeruginosa with difficult-to-treat resistance in a murine wound infection model. Given this, we initiated a H2O2 e-bandage safety assessment on healthy human skin. Here, testing of a non-polarized, circular (2 cm diameter) device pre-loaded with biocompatible hydrogel containing 0.9% NaCl is reported. Sterilized e-bandages assessed in a shelf-life study retained activity for two weeks. Adults with intact forearm skin were then recruited to the Clinical Research Trials Unit at the Mayo Clinic. Consented individuals had a non-polarized e-bandage covered by Tegaderm placed on their forearm. A MP enclosed in a biocompatible case was connected to the e-bandage and secured using skin tape. One day later, the device was removed and a follow-up phone call made six days later to assess for adverse effects.

Results

Three volunteers wearing a non-polarized H2O2 e-bandage experienced no discomfort, irritation, allergic reaction, or skin discoloration after device removal and seven days post device placement.

Conclusion

These preliminary studies combined with the previously performed murine bacterial biofilms work support further studies of this novel device for treating wound infections caused by antimicrobial resistant pathogens.

Disclosures

Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria
P-1108. Efficacy and Safety of Investigational Therapeutic Microbiome SER-109 in Recurrent Clostridioides difficile Infection: A Systematic Review
Authors: Fabara Stephanie P , Alok Akankcha , Kalsi Harsimran , Bakhit Mohamed , Thomas Sanil
Published: January 2025

Background

Current therapies for recurrent Clostridioides difficile infection (CDI) often fail to address the disrupted microbiome contributing to C. difficile spore germination and subsequent toxin production. SER-109, an investigational therapeutic microbiome, is composed of purified Firmicutes spores and shows promise in treating recurrent CDI. Our aim was to evaluate the efficacy, safety and recurrence rate of CDI following administration of oral SER-109.Figure 1.Selection of studies using a PRISMA flow chart.

Methods

We systematically reviewed available literature on PUBMED using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for clinical trials involving SER-109 (Figure 1). We found three clinical trials that met our inclusion criteria and primary efficacy endpoint criteria (Table 1). For assessing bias, we used the Cochrane Collaboration's tool risk assessment of the clinical trials (Figure 2).Table 1.Inclusion criteria and primary efficacy endpoint

Results

Oral SER-109 was well tolerated with the rate of recurrent CDI remaining low, regardless of the number of prior recurrences or patient demographics. The diagnostic approach did not significantly impact the beneficial effect of SER-109. In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was mild and similar to that of placebo. Our findings are summarized in Table 2.Figure 2.Bias analysis of the clinical trials in the systematic review.

Conclusion

SER-109 holds promise as a safe and effective treatment for recurrent CDI. Further research is warranted to confirm its long-term efficacy and explore potential mechanisms underlying its impact on the disrupted gut microbiome.Table 2.Characteristics and outcomes of selected studies.

Disclosures

All Authors: No reported disclosures
P-1120. Antibiotics use among premature infants in three neonatal care Units in Brazzaville, Republic of Congo
Authors: Ekat Martin Herbas , Ibara Rolland Bienvenu Ossibi
Published: January 2025

Background

To evaluate the use of antibiotics in Congolese premature infants based on WHO recommendations in three neonatal care units in Brazzaville.

Methods

This was a cross-sectional study, premature infants admitted 72 hours after birth in three neonatals care units in Brazzaville, between January 2019 and November 2020, were included. Taking into account WHO recommendations, we grouped premature infants according to the presence or absence of maternal risk factors for neonatal infection (3 items), and each factor was rated 1. Risk factors for neonatal infection, such as early onset sepsis (EOS) specific to the newborn (7 items), were also used and rated 1 or 0 depending on whether it was present or not. Maternal risk had 4 categories (0, 1, 2 and 3) and EOS risk had 8 categories (0, 1, 2, 3, 4, 5, 6 and 7). Premature newborns were first classified according to maternal risk followed by EOS risk for each maternal risk category, then the proportion of premature infants placed on antibiotics was determined.

Results

Aa total of 448 premature newborns were included. The proportion of antibiotic therapy depending on the categories was as follows: maternal risk 3 (EOS risk 2, 3 and 5 were 100% and INBP risk 4 67%), maternal risk 2 (INBP risk 1, 2, 3, 4 and 5: 0%, 64%, 92%, 91% and 100% respectively), maternal risk 1 (EOS risk 1, 2, 3, 4, 5 and 6: 88%, 66%, 88%, 93%, 100% and 100% respectively), maternal risk 0 (INBP risk 1, 2, 3, 4, 5 and 6: 29%, 57%, 76%, 82%, 96% and 100% respectively). In multivariate analysis, the factors associated with the use of antibiotic therapy outside the WHO recommendations were: being born in a health structure different from that of hospitalization (OR: 0.16; 95%CI: 0.03 – 0.94 ), be born in an integrated health center (OR: 23; 95%CI: 2.9 – 190).

Conclusion

The Use of antibiotic therapy is only effective when all the maternal or premature newborn risk factors are present, contrasting with WHO recommendations. Other factors are involved in the use of antibiotics, such as being born in primary healthcare facility. The implementation of an antibiotic management program is a necessity.

Disclosures

All Authors: No reported disclosures
P-1129. Exploring Cost Savings through Reduced Sedation for Magnetic Resonance Imaging in Pediatric Osteomyelitis Diagnosis
Authors: Sumner Lauren , Downey Rachel , Hauger Sarmistha Bhaduri , Thoreson Lynn , Williams John , Kaufman Brian
Published: January 2025

Background

Magnetic resonance imaging (MRI) is essential for the diagnostic workup of pediatric osteoarticular infection. In the pediatric population, sedation is often required to mitigate motion artifact and improve imaging quality, which contributes to cost, resource utilization, and risk to the patient. In 2021, our hospital implemented an evidence-based update to the pediatric osteomyelitis guideline adjusting MRI imaging sequences, which reduced sedation age requirements from 8 years to 3 years of age. This change was initiated in September 2021. This study evaluates economic implications of sedation reduction strategies in pediatric osteomyelitis imaging.

Figure 1. Pre vs Post Guideline Sedation Rates.

Methods

This is a retrospective chart review study of pediatric patients evaluated for bone and joint infection by MRI at a free standing 299 bed hospital in Central Texas. Cases were pulled by MRI indication according to the hospital’s osteomyelitis guideline inclusion criteria between January 1, 2020 and December 31, 2023. Previously healthy children age 6 months to 18 years with physical exam suggestive of acute hematogenous osteomyelitis or septic joint and less than 14 days of symptoms were included. Cases were compared by year pre-guideline (2020-2021) and post-guideline (2022-2023) and reviewed for age, sex, need for sedation, and diagnosis after MRI. Cost savings estimates were based on an average per case cost of sedation. The cost of sedation was determined by hospital charges.

Figure 2. Pre & Post Guideline Sedated vs Non-Sedated Patients.

Results

279 patients were included, (98 pre guideline change; 181 post guideline change). 61.3% male, 38.7% female, median age 6, IQR 6.5. A statistically significant reduction in sedation usage was observed after guideline implementation (50%-33%, p=0.0087) (fig 1). Among patients 3-8 years of age, 21 of 34 patients (62%) pre-guideline and 15 of 78 patients (19%) post- guideline received sedation (p< 0.001) (fig 2). An average estimated cost savings of $270,215 per year was found. There was no increase in repeat MRI rates seen with the implementation of the age requirement change.

Conclusion

Lowering the required age for sedation allows for individualized assessment of sedation needs in the 3-8 age group. This leads to improved patient care through decreased patient risk, reduction in overall rate of sedation and results in cost savings.

Disclosures

Brian Kaufman, MD, Johnson & Johnson: Advisor/Consultant
P-1156. Procalcitonin Assay in Predicting Etiology in Young Febrile Infants Visiting the Emergency Department in Korea
Authors: Kim Haemin , Kim Min Young , Baek Jee Yeon , Lee Ji Young , Yoon Seo Hee , Kim Heeyeon , Kang Ji-Man
Published: January 2025

Background

There have been no studies conducted in Korea on the role of procalcitonin as a predictive factor for serious bacterial infection (SBI) in young febrile infants under 90 days of age, and it is not included in insurance reimbursement criteria despite its potential clinical utility. Our aim was to assess the role of the procalcitonin assay in distinguishing the etiology of fever, including SBI and simple urinary tract infection (sUTI), in young febrile infants in Korea.

The sensitivity and the specificity of procalcitonin (≥0.5 ng/mL) for SBI and sUTI

A. The sensitivity and the specificity of procalcitonin for SBI

B. The sensitivity of the specificity procalcitonin for sUTI

Methods

This retrospective study was conducted on patients under 90 days of age who visited the pediatric emergency department (ED) at Severance Children's Hospital and underwent procalcitonin assay from January 2019 to February 2024. Patients who visited the ED for reasons other than fever or were under 29 days of age were excluded. The SBIs were defined as cases of the identification of pathogens in sterile fluids such as blood and cerebrospinal fluid, while sUTIs were defined as UTIs without bacteremia. Viral infections were defined as cases where a virus was identified through testing or when symptoms or contact history clearly indicated viral infection; otherwise, they were classified as unknown. The cut-off value for procalcitonin was set at 0.5 ng/mL.

Results

A total of 633 patients were collected, of whom 131 were excluded, resulting in 502 individuals included in the analysis. Among them, half were aged between 29-60 days and the other half between 61-90 days, with six admissions to the intensive care unit and no fatalities. By etiology, there were 22 cases of SBI (4.4%), 161 cases of sUTI (32.1%), 147 cases of viral infection (29.3%), and 172 cases classified as unknown (34.3%). The median values of procalcitonin were 5.03 (range, 0.08-100) for SBI, 0.35 (range, 0.05-52.2) for sUTI, 0.13 (range, 0.04-53.3) for viral infection, and 0.15 (range, 0.04-100) for unknown. The sensitivity of procalcitonin (≥0.5 ng/mL) for SBI and sUTI was 81.8% and 42.2% respectively, while the specificity was 77.8% and 88.3% respectively. (see Figure)

Conclusion

In febrile young infants in Korea, the utility of procalcitonin as a predictor of SBI is significant, warranting consideration for its proactive integration into clinical practice.

Disclosures

All Authors: No reported disclosures
P-1158. Surgical Outcomes Following Paenibacillus Infant Infectious Hydrocephalus
Authors: Ericson Jessica E , Natukwatsa Davis , Ssenyonga Peter , Onen Justin , Mugamba John , Mulondo Ronald , Morton Sarah , Templeton Kelsey , Hehnly Christine , Mbabazi-Kabachelor Edith , Kulkarni Abhaya , Warf Benjamin , Broach James , Paulson Joseph , Schiff Steven
Published: January 2025

Background

We previously identified Paenibacillus species in the cerebrospinal fluid of 44% of infants presenting for neurosurgical evaluation with findings consistent with postinfectious hydrocephalus (PIH) in Eastern Uganda. Here we sought to compare outcomes among hydrocephalic infants with and without Paenibacillus detection at the time of hydrocephalus surgery.

Methods

In a prospective observational trial, 78 infants with PIH who underwent a cerebrospinal fluid (CSF) diversion had a positive CSF polymerase chain reaction result for Paenibacillus species (PP), and 111 had a negative result (PN). The primary outcome was diversion failure-free survival defined as being alive without diversion failure at the end of the observation period adjusted for age at the time of diversion and surgery type. Secondary outcomes included overall survival and diversion success.

Results

After a median follow-up period of 35.7 months, the primary outcome had occurred in 42 PP patients (54%) and in 76 PN patients (68%) (adjusted hazard ratio (aHR), 2.45; 95% confidence interval [CI], 1.42 to 4.22; P=0.001). PP patients who underwent endoscopic diversion had the worst primary event rate (aHR, 6.47; 95% CI, 2.40 to 17.42; P< 0.001). Death from any cause occurred in 16 PP patients (20%) and 9 PN patients (8%) (aHR, 3.47; 95% CI, 1.44 to 8.37; P=0.006). Diversion failure occurred in 28 PP patients (36%) and in 29 PN patients (26%) (aHR, 2.24; 95% CI, 1.31 to 3.85; P=0.003).

Conclusion

Paenibacillus detection in the CSF at the time of hydrocephalus surgery was associated with a significantly increased rate of the composite of diversion failure or death, death, and diversion failure, and was particularly increased for patients who had an endoscopic diversion. Preoperative testing and treatment of Paenibacillus infections may improve outcomes for surgical management of PIH.

Disclosures

Jessica E. Ericson, MD, MPH, Abbvie: Advisor/Consultant
P-1169. Disseminated Pediatric Coccidioidomycosis at an Academic Center in Southern Arizona (2013 - 2023)
Authors: Lacy Marian , Gotwalt Jordan , Ampel Neil M , Shehab Kareem W
Published: January 2025

Background

There have been few reviews of pediatric disseminated coccidioidomycosis, particularly regarding presentation. A better understanding of this may enable more timely diagnosis and improve management in children.

Methods

We identified 157 children with coccidioidomycosis seen in the pediatric infectious diseases practice at University of Arizona – Banner University Medical Center in Tucson, AZ, between 2013 – 2023. Criteria included: age under 18, seen by a pediatric infectious diseases specialist, with a diagnosis of coccidioidomycosis in the consultation note. This study includes the subset of children with a diagnosis of disseminated coccidioidomycosis. Cases were excluded if the electronic medical record did not document at least one of the following supporting diagnostics: positive coccidioidal IgM or IgG by EIA, culture positive for Coccidioides, or histopathological findings characteristic of coccidioidomycosis. Demographic, laboratory, and radiologic data as well as clinical characteristics were collected from review of the electronic medical record.

Results

Among 157 patients, 28 (17.8%) had disseminated disease. Median age at diagnosis was 11.7 years (range 7 months to 17 years of age). 64% were male. Musculoskeletal disease was the most common extrapulmonary organ system involved (15 patients), followed by skin (11), central nervous system (4), abdominal organs and viscera (2), pericardium (1) and bloodstream (1). Sixteen (57%) had no comorbidities. The chest radiograph was normal in 10 of 26 (38%) where it was performed. Seventeen (61%) had a negative coccidioidal EIA IgG serology, and 3 patients (11%) had negative IgM and IgG serologies on presentation. Only 3 (11%) had an elevated absolute eosinophil count (above 600/µL).

Conclusion

Disseminated coccidioidomycosis affects children of all ages and can involve many different organ systems, particularly musculoskeletal, skin, and central nervous system. It should be considered in the appropriate clinical setting even in patients with negative coccidioidal serologies, normal chest x-rays, normal eosinophil counts, or no underlying illness.

Disclosures

All Authors: No reported disclosures
P-1185. Targeting and Universal Congenital Cytomegalovirus Screening in a Neonatal Intensive Care Unit
Authors: Torriente Adriana Gonzalez , Randis Tara , Espinosa Claudia M
Published: January 2025

Background

Congenital cytomegalovirus (cCMV) infection, confirmed by urine or saliva CMV PCR within 3 weeks of life, affects 0.5 % of live births in the United States. This number varies in different populations, and it is affected by socio-demographic characteristics. In Neonatal Intensive Care Units (NICUs), higher prevalence has been reported in preterm and low birth weight infants, but timing of screening remains a challenge without universal screening because only 10% of cCMV are symptomatic. Regardless of symptoms, infected infants are at increased risk of adverse outcomes such as hearing loss. Thus, we sought to determine the incidence and associated characteristics of cCMV infection using targeting and subsequently universal screening in our NICU population

Methods

From Feb 1, 2023 to Apr 30, 2024, infants who were admitted at Tampa General Hospital (TGH) NICU and had a CMV PCR testing performed during admission were followed prospectively. Before Feb 28, 2024, cCMV screening was performed only in infants who were symptomatic (IUGR, microcephaly, thrombocytopenia) or failed hearing screen. After that, all infants born preterm < 33 weeks gestational age (GA) and all infants with anticipated NICU stay > 3 weeks were screened for cCMV at admission. Characteristics such as GA, birth weight, and race and ethnicity are recorded in a RedCap database. Descriptive statistics were used

Results

A total of 715 infants were screened for CMV while hospitalized in the TGH NICU during the study period. Most of the infants (68.2%) were screened after failing newborn hearing screen and only four (0.6%) were screened because of their symptoms. The characteristics of the infants with positive and negative saliva or urine CMV PCR are described in Table 1. Only three (0.4%) infants tested positive for CMV and were confirmed to have cCMV. Two infants with cCMV infection were screened because they were symptomatic

Conclusion

At TGH NICU, the incidence of cCMV using targeting and universal screening was comparable with the U.S. general population and lower than reported in other NICUs. We plan to perform association when statistically feasible, and compare incidence of cCMV between the targeting and universal screening periods

Disclosures

Claudia M. Espinosa, MD, MSc, AstraZeneca: Grant/Research Support|Clinetics: Grant/Research Support|Enanta: Grant/Research Support|Gilead: Advisor/Consultant|Jansen & Jansen: Advisor/Consultant|Kentucky Health Rural Association: Honoraria|Medimmune: Grant/Research Support|Melinta: Grant/Research Support|Merck: Grant/Research Support|Sanofi: Advisor/Consultant|Sanofi: Honoraria
425. Revealing Seasonal Patterns in the Post-Pandemic Era: A Comparative Analysis of Burden and Seasonality of Influenza and COVID-19 in Europe and the US
Authors: Shaikh Nabila , van Aalst Robertus , Harris Rebecca C , El Guerche-Séblain Clotilde
Published: January 2025

Background

The emergence of SARS-CoV-2 has profoundly impacted global healthcare systems, raising concerns about its interaction with seasonal influenza and the appropriateness of concomitant vaccination campaigns. This study aims to compare the burden and timing of COVID-19 and influenza-associated hospitalizations during the post-pandemic period.Figure 1:Evolution of Influenza and Covid-19 activity by season over 2022-2023 and 2023-2024

Methods

We retrospectively analyzed laboratory-confirmed hospitalization data from sentinel surveillance systems for influenza and COVID-19 across two seasons (2022-2023 to 2023-2024) in England, the US, and four European countries (France, Germany, Italy, Spain). We examined absolute hospitalization numbers in the EU, weekly rates in England, and both rates and numbers in the US to identify seasonal peaks and describe epidemiological trends.

Annual cumulative number of laboratory-confirmed hospitalizations in Germany, Spain and US by season (annual period defined as epi week 27 – epi week 26)

Results

Peak laboratory-confirmed hospitalizations in EU countries for COVID were higher than for influenza, ranging from 0 to 1,427 per week and 0 to 366 per week, respectively. Similarly in the US, hospitalizations for COVID-19 and influenza varied from 44,760 to 319,445 and 3,301 to 172,784, respectively. England had higher peak weekly rates for both influenza (18.1 per 100,000) and COVID (18.3 per 100,000) compared to the US (7.4 per 100,000 for influenza and 13.7 per 100,000 for COVID).

Across the EU, England, and the US, peak influenza activity occurred between Week 47 and Week 6 in both 2022-2023 and 2023-2024 seasons. While COVID-19 activity peaked alongside influenza, activity remained high beyond the winter seasons.

Annual cumulative hospitalizations for COVID-19 were 4, 5, and 12 times higher than influenza in the US, Germany, and Spain, respectively. Cumulative hospitalizations for other countries were not assessed due to missing data.

Conclusion

COVID-19 and influenza continue to pose a significant burden on healthcare systems. While differing testing practices between viruses and between countries introduces limitations to this analysis, our findings confirm that COVID-19 circulation is not restricted to winter seasonality, and surveillance and prevention measures should be reinforced year-round. Further research is also required to properly inform the validity of concomitant vaccination policy.

Disclosures

Nabila Shaikh, MSc, Sanofi: Stocks/Bonds (Public Company) Robertus van Aalst, PhD, MSc, Sanofi: Employee|Sanofi: Stocks/Bonds (Public Company) Rebecca C Harris, MBioch, MSc, PhD, Sanofi vaccines: Stocks/Bonds (Private Company) Clotilde El Guerche-Séblain, PhD, Sanofi vaccines: Stocks/Bonds (Private Company)
P-1228. Predictive Performance of Population Pharmacokinetic (Pop PK) Models in InsightRX® for Model-Informed Precision Dosing (MIPD) for Cefepime
Authors: Konig Christina , Kuti Joseph L , Fratoni Andrew J
Published: January 2025

Background

MIPD is a promising Bayesian tool to ensure therapeutic antimicrobial concentrations, with multiple models often available. Model selection and sampling strategy might generate different estimates for different populations. Herein, we assess performance of two models in InsightRX® to predict cefepime PK and exposure through differing sampling approaches.

Methods

Historic cefepime PK data were sourced from prospective-observational studies that used robust sampling to develop pop PK models in patients with diabetic foot infection (n=5), VAP (n=15), and supported on ECMO (n=6, 2 on CRRT) or CRRT only (n=4). Historic individual Bayesian estimates served as the reference standard. Two pop PK models (A; B) in InsightRX® were evaluated using four sampling scenarios 1) trough, 2) midpoint, 3) trough and midpoint and 4) peak, midpoint and trough. The median percentage error (MPE) and median absolute percentage error (MAPE) with acceptable defined as < ±20 and < 30%, respectively, were calculated as measures of bias and imprecision for clearance (CL) and volume of central compartment (Vc). Predicted categorical achievement of ≥ 70% fT > 8 mg/L was compared.

Results

Imprecision and bias for CL and Vc showed variability dependent on model and sampling strategy (Table 1). MAPE/MPECL for all models and sampling strategies were acceptable. Both models showed the lowest bias on CL for sampling scenario 4. In the full patient cohort, MAPE/MPEVc were >30 and > ± 20% for most tested scenarios. When excluding patients with extracorporeal support (i.e. ECMO or CRRT), bias and imprecision for Vc improved, with best prediction in model A using sampling scheme 4 and sampling 1 in model B. Using each model and sampling scheme, only 1 patient had discordant predicted categorical achievement of ≥ 70% fT >8 mg/L.

Conclusion

Among patient populations representative of the two studied PopPK models in InsightRX®, predicted PK parameters and achievement of relevant exposures demonstrated acceptable performance for clinical care. While all sampling scenarios were acceptable in predicting CL, increasing the number of samples up to three generally improved performance. Appropriate model selection for special populations such as ECMO and CRRT remains paramount as Vc was poorly predicted among this subgroup.

Disclosures

Christina Konig, PhD, Gilead Inc.: Honoraria|Pfizer Inc.: Honoraria|Shionogi Inc.: Honoraria Joseph L. Kuti, PharmD, Abbvie: Advisor/Consultant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi Inc: Advisor/Consultant|Shionogi Inc: Grant/Research Support|Shionogi Inc: Honoraria|Venatorx: Grant/Research Support Andrew J. Fratoni, PharmD, InsightRX: Grant/Research Support