Abstract: Abstract Background Imipenem/relebactam (I/R) demonstrates potent in vitro activity against multidrug-resistant (MDR) Pseudomonas aeruginosa. The objective of this study was to evaluate the effectiveness of I/R for treatment of MDR P. aeruginosa infections across the U.S.Table 1.Detailed inclusion and exclusion criteria for patients receiving I/R1 Pneumonia was defined as the presence of a new or progressive infiltrate with at least one of the following: purulent tracheal secretions, worsening cough or dyspnea, PaO2/FiO2 < 200 with PEEP ≥5 cm H2O, fever (≥38°C) or hypothermia (≤35°C), leukocytosis (≥10,000 white blood cells per µL), or tachypnea (respiratory rate >30 beats per minute).2 MDR was defined as non-susceptibility to at least one agent in three or more antibiotic classes.Table 2.Patient demographics, underlying diseases, severity of illness, and treatment characteristics of patients treated with I/R for pneumonia or bacteremia.*Other immunocompromising conditions included bone-marrow transplant, chronic steroid use, neutropenia, and AIDS.Abbreviations: IQR = interquartile range Methods This was a retrospective, multicenter, observational study of I/R for MDR P. aeruginosa pneumonia and bacteremia. Patients were included if they received I/R for >48h initiated within 7 days of the index MDR P. aeruginosa culture (Table 1). Clinical success was defined as survival, resolution of signs and symptoms of infection, completion of the intended treatment course, and the absence of a recurrent infection due to MDR P. aeruginosa. I/R susceptibility was determined by site-level microbiology labs; non-susceptibility was defined by the Clinical and Laboratory Standards Institute (CLSI) criteria.Table 3.Real-world characteristics of I/R use in pneumonia and bloodstream infections.1 I/R treatment was discontinued in one patient with acute interstitial nephritisTable 4.Clinical outcomes of patients treated with I/R for MDR P. aeruginosa pneumonia or bacteremia1 Non-susceptibility was defined as a categorical change from susceptible to non-susceptible as defined by CLSI interpretive criteria. Among the 16 cases meeting this criteria, non-susceptibility was identified by gradient strip testing and broth microdilution in 25% and 75%, respectively. The median I/R MICs for isolates categorized as susceptible and non-susceptible were 2 and 8 mg/L, respectively. Results 64 patients from 10 centers were included (Table 2); patients from 6 additional centers were screened and did not meet inclusion criteria. The overall cohort was critically-ill; 80%, 75%, and 48% were in the intensive care unit, receiving mechanical ventilation, and on vasopressors, respectively. The median (interquartile range; IQR) SOFA score was 7 (5 – 12). 53% received treatment with another new β-lactam for MDR P. aeruginosa infections prior to I/R. The median time to I/R initiation was 67 hours. I/R treatment was primarily prescribed based on susceptibility results in 75% of patients, including resistance to other novel β-lactam agents (Table 3). 63% of patients completed the intended I/R treatment course as planned. At day 7 and 30, 80% and 55% met criteria for clinical success, respectively (Table 4). The overall 30- and 90-day mortality rates were 17% and 30%, respectively. Recurrent infections were documented in 38% of patients within 90 days. Conclusion In this critically-ill patient population we found that I/R was often used following treatment with other novel β-lactams. Clinical outcomes were generally comparable to those previously reported in similar real-world studies for other novel β-lactam agents suggesting that I/R plays a role in treatment of MDR P. aeruginosa infections, particularly when other agents are not available or test resistant. Disclosures jason M. Pogue, PharmD, Entasis: Advisor/Consultant|Entasis: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support Alexander J. Lepak, MD, FIDSA, BioMerieux: Grant/Research Support William R. Miller, M.D., Merck: Grant/Research Support|UpToDate: Royalties, topic author Jeffrey C. Pearson, PharmD, InflaRx Pharmaceuticals, Inc.: Advisor/Consultant Emre Yucel, PhD, Merck & Co., Ltd: Stocks/Bonds (Public Company)

Abstract: Abstract Background Outpatient parenteral antibiotic therapy (OPAT) is a method of treatment that allows patients who would require inpatient admission for the duration of their IV therapy to receive it in the outpatient setting. Persons who use or inject drugs (PWUD/PWID) are not always offered OPAT due to concern for tampering of lines, nonadherence, and elopement. Implementation of addiction medicine consults has demonstrated reduction in readmission rates for PWUD. Medication-assisted treatment (MAT) has been shown to aid in completion of OPAT in case reports but data is lacking for this purpose. The goal of our study is to evaluate the OPAT completion rate between patients who accepted MAT versus those who did not accept MAT.Figure 1:Overall completion of OPATOPAT, Outpatient parenteral antibiotic therapy; MAT, Medication Assisted Treatment; n, Number of patients in categoryFigure 2:Overall Primary and Secondary EndpointsPWUD, Patients who use drugs, OPAT, Outpatient parenteral antibiotic therapy; MAT, Medication Assisted Treatment; n, Number of patients in category Methods This is a single-center retrospective cohort study comparing OPAT completion rates, readmission within OPAT period, and 30-day recurrence of infection for patients requiring OPAT for invasive bacterial infections from July 1, 2023 to June 30, 2024 who either accepted or declined MAT during hospitalization. Exclusion criteria included patients younger than 18, prisoners, and encounters that did not include both an OPAT and Addiction Medicine consult and MAT. Categorical variables were reported as counts and percentages using the Fisher exact test for comparison. Continuous variables were reported as medians and interquartile ranges (IQRs) from the 25th to the 75th percentiles and compared using the t test. A P value of < 0.05 was considered significant.Figure 3:PWID Primary and Secondary EndpointsPWID, Patients who inject drugs; OPAT, Outpatient parenteral antibiotic therapy; MAT, Medication Assisted Treatment; n, Number of patients in category Results 236 patients were identified as having had an OPAT and being offered MAT, and 117 were excluded based on criteria. Of the 119 patients included, 97 accepted MAT and 22 declined. There was not a significant difference in these measured outcomes between PWUD who either accepted or declined MAT during hospitalization. Subgroup analysis did show a significant reduction in recurrence of infection for PWID who accepted MAT (5.3% vs 25%). Conclusion We did not find a difference in patients who accepted MAT versus those who did not accept MAT and OPAT completion rates, however we did find a statistically significant decrease in 30-day recurrence of infection in the IVDU subgroup population. More studies are needed to better identify what other factors contribute to successful completion of OPAT therapy in patients who inject drugs. Disclosures All Authors: No reported disclosures

Abstract: Abstract Background Ventilator-associated pneumonia (VAP) has been considered as a healthcare-associated infection with high mortality. Acinetobacter baumannii is one of the most frequently isolated pathogens in hospitals worldwide, especially in critically ill patients who needed invasive mechanical ventilation. Acinetobacter ventilator associated pneumonia (AB-VAP) is associated with high case-fatality rates, reaching 70% in some studies, with controversy still existing on the ideal antimicrobial treatment. Methods We performed a descriptive, retrospective study. To meet the inclusion criteria, patients had to be adults admitted to the intensive care unit with VAP diagnosis treated with colistin monotherapy and isolation of Acinetobacter baumannii in lower respiratory tract samples as the sole pathogen between December 2016 and December 2023. We evaluated demographic variables, time between ICU admission and the clinical event, case-fatality rate and antimicrobial susceptibility profile. We calculated with RStudio the average (and standard deviation) or median (and interquartile range values) for quantitative variables and frequency for qualitative ones. The antimicrobial choice was influenced by local susceptibility patterns and the economic resources of our hospital. Results Data from 126 patients that met the inclusion criteria was analyzed. The mean age was 55.5 years (SD:16 years) and 68% were men. Median time between he ICU admission and VAP diagnosis was 14 days (percentiles 25-75%: 8-27 days). Median Charlson Comorbidity Index value was 3, with an interquartile range of 1 - 5. Case fatality rate at 14 days after the diagnosis was 30,4% (IC95%: 23-39), reaching 36,8% at 28 days (IC95%: 28,8-45,5).All microbiological isolates, except one, were susceptible to colistin and none to carbapenems Conclusion Although mortality in patients with AB-VAP remains high in our hospital, it does not reach the values described in the literature, even when treated with non-beta-lactam monotherapy. We also observed that the highest mortality is concentrated in the first 14 days after the infection diagnosis. Larger multicenter studies are needed to confirm our findings. Disclosures All Authors: No reported disclosures

Abstract: Primary spinal cord tumors (PSCTs) present diagnostic and management challenges, particularly in low-resource settings. This study assessed current diagnostic and treatment practices, with a specific focus on the use of standardized management algorithms for PSCTs in Yaoundé, Cameroon. A cross-sectional analysis was conducted on 67 consecutive patients with newly diagnosed PSCTs in Yaoundé between November 1, 2011, and December 31, 2023. Data collected included demographics (mean age 43.28 ± 9.8 years; 34% female), clinical parameters (median admission delay 405 days, interquartile range 248–541; 13.4% insured), tumor histology, and WHO grade. Five predefined management algorithms were used to classify care pathways, incorporating diagnostic imaging, staging, surgical intervention, and chemotherapy. We evaluated completion of the algorithmic care pathway and applied multivariate logistic regression to identify factors associated with adherence. Tumor histologies were ependymoma (41.2%), meningioma (23.5%), plasmacytoma/multiple myeloma (19.6%), and other types (15.7%). WHO grade II tumors predominated (76.5%). Overall, 76.1% of patients completed the prescribed algorithmic care pathway. In multivariate analysis, strong family support was the strongest predictor of algorithm completion (odds ratio 12.6, 95% confidence interval 2.45–64.8 for high vs. low support). Age, gender, and insurance status were not significantly associated with completion of care. Given the limited sample size and wide 95% confidence intervals, these associations should be interpreted as exploratory and hypothesis-generating rather than definitive. In Yaoundé, Cameroon, PSCT diagnosis and management were characterized by prolonged delays and limited insurance coverage, yet standardized algorithmic care was largely achievable. Importantly, family support substantially influenced algorithm completion. These findings highlight the need to integrate social support mechanisms and improve access to diagnostic and therapeutic resources to optimize PSCT care in low-resource settings.

Abstract: Abstract Background Postoperative infections remain a significant concern in pediatric patients following cardiac surgery. While inflammatory biomarkers such as procalcitonin (PCT) and C-reactive protein (CRP) may help with early detection of infection, their effectiveness in distinguishing infection from postoperative inflammation remains uncertain. Methods We conducted a retrospective analysis of pediatric patients (< 18 years) admitted to the PCICU after cardiac surgery between January 1, 2022, and December 31, 2024. We extracted and evaluated PCT and CRP levels obtained on the same day as the cultures. Positive blood cultures were defined using the National Healthcare Safety Network (NHSN) standardized definition, with single cultures for coagulase-negative Staphylococcus (CoNS) excluded. We calculated the median and interquartile ranges (IQRs) for CRP and PCT both overall and by organism. We used the Wilcoxon rank-sum test to compare CRP and PCT between positive and negative blood cultures. All analyses were performed using Stata, version 18.5.Table 1:PCT and CRP by organism. Results We identified 659 patients (731 admissions); the median age was 1.5 months, and 55% were male. During the study period, 150 patients had 459 blood cultures; of these, 29 samples from 21 patients were positive. Median procalcitonin (PCT) levels were higher in positive cultures [8.1 (IQR 0.87-29.7)] compared to negative ones [0.7 (IQR 0.23–2.08)]. Similarly, median C-reactive protein (CRP) was elevated in positive cultures [13.19 ( IQR 5.12-26.88)] versus negatives [IQR 2.59 (0.86-7.02)]. CRP and PCT values varied by organism with Enterococcus faecalis exhibiting the highest levels for both markers (Table 1). Both markers were significantly elevated in patients with positive cultures (p < 0.001). Conclusion Our findings indicate CRP and PCT are significantly elevated in PCICU patients with blood stream infection as compared to those with negative blood cultures. Additional studies will be needed to assess CRP and PCT in the context of other common infection sites. Disclosures Michael J. Smith, M.D., M.S.C.E, Pfizer: Grant/Research Support

Abstract: Abstract Background The significance of Candida species and other fungi isolated in diabetic foot infections (DFI) is unclear. Do these isolates require treatment? Antifungal treatment carries additional cost and risk of adverse events. In this study, we compared outcomes among patients with DFI that were treated vs. not treated for fungi isolated from surgical specimens. Methods We conducted a retrospective review of adults undergoing surgery for DFI with surgical cultures positive for fungi from Oct 1, 2019 to Sept 30, 2022, at a teaching hospital in Dallas, Texas. Patient outcomes were assessed up until last recorded visit or 12 months post-surgery. Descriptive statistics were used to describe the study cohort using medians and interquartile range (IQR) for continuous variables and percentages for categorical variables. To compare outcomes among treated versus untreated patients, Fisher’s Exact Test was used with α=0.05 (R v4.4.1). Results Forty-seven limbs from 46 patients had positive fungal cultures. Median age was 59 years, 68 % male, 62% white, 30% Hispanic, median HgA1c was 7.8%, with 52% having excisional debridements, 19% toe amputation, 13 % ray amputation, 15% transmetatarsal amputation and 2% above or below-knee amputation. Sixty percent of all cases had non-healing wounds. Yeast grew in 70% of specimens, with C. parapsilosis being most common (36%), followed by C. albicans (13%). Mold grew in 32% of specimens including dermatophytes in 19% of specimens. Most patients (68%) were not treated for fungal infection. When comparing patients treated vs. untreated for positive fungal cultures, there were no statistically significant differences in wound healing (53% vs 62%), subsequent amputation (27% vs 28%,) or all-cause mortality (47% vs 25%). Conclusion Our findings did not demonstrate significant differences in outcomes among patients that were or were not treated for positive fungal cultures in patients undergoing surgery for DFI. Compared to prior DFI studies, patient mortality rates were similar although rates of non-healing wounds were higher. While outcomes in DFI are dependent on multiple factors, further research is needed to determine the need/added value of treatment for fungal organisms isolated from surgical specimens in DFI. Disclosures All Authors: No reported disclosures

Abstract: Abstract Background Lower respiratory infections are a major contributor to morbidity after battlefield trauma. Between 2009-10, 8.5% of 423 US military casualties developed pneumonia (PNA) with a higher proportion (18.5%) in patients admitted to ICUs. Using a larger population, we examined characteristics associated with PNA after battlefield trauma.Characteristics of Wounded Military Personnel Who Did and Did Not Develop PneumoniaICU – intensive care unit IED – improvised explosive device; IQR – interquartile range1 Patients frequently sustained polytrauma, so the numbers will sum to more than the total number of patientsCharacteristics of Patients with Pneumonia Stratified by Isolation of Multidrug-Resistant (MDR) BacteriaICU – intensive care unit IED – improvised explosive device; IQR – interquartile range1 Patients frequently sustained polytrauma, so the numbers will sum to more than the total number of patients Methods Data were collected via the Trauma Infectious Disease Outcomes Study, an observational study of infections in wounded US military personnel (2009-2014). PNA was defined using standardized criteria. Chi-square (or Fisher exact) and Mann-Whitney U tests were used for categorical and continuous variables, respectively.Frequency of Isolates Recovered from First Respiratory Culture with Growth1 Other Gram-negative bacteria include Achromobacter spp., Acinetobacter spp. (non-baumannii), Burkholderia spp., Chryseobacterium spp., Elizabethkingia spp., Enterobacter non-cloacae spp., Haemophilus parainfluenzae, Haemophilus spp., Hafnia spp., Proteus spp. (non-mirabilis), Ochrobactrum spp., Ralstonia spp., Raoultella spp., Serratia spp. (non-marcescens), and unidentified Gram-negative bacteria2 Other Gram-positive bacteria include Corynebacterium spp. and Rothia dentocariosa3 Other fungal and yeast organisms include Hansenula anomala, Mycelia sterile, Penicillium spp., Trichosporon spp., and unidentified yeast Results A total of 2,687 wounded military personnel were assessed, with 324 (12%) patients developing PNA. The PNA patients had higher injury severity scores (ISS; median 38 vs 17; p< 0.001) with more injuries to the head/neck (66% vs 44%), thorax (55% vs 21%), abdomen (44% vs 16%), groin/perineum (23% vs 7%), spine (33% vs 19%), upper extremities (56% vs 36%), and lower extremities (69% vs 59%) than non-PNA patients (p≤0.001, Table 1). PNA patients also had more ICU admissions (98% vs 46%), greater mechanical ventilation requirements (91% vs 25%), longer hospitalizations (median 44 vs 19 days) and higher crude mortality 4% vs 0.7% (p< 0.001). Among PNA patients, 92 (28%) had multidrug-resistant (MDR) bacteria isolated and the MDR PNA group had greater median ISS (43 vs 32 p=0.003), blood units in 1st 24 hours of injury (median 22 vs 13 p=0.001), ICU admissions (100% vs 97% p=0.010), mechanical ventilation (99% vs 88% p=0.002), and hospital stays (median 54 vs 40 days p< 0.001) than PNA patients with non-MDR bacteria (Table 2). Most frequent bacteria were Pseudomonas aeruginosa (N = 269, 11% MDR) and Acinetobacter baumannii (N = 158, 82% MDR, Table 3). Conclusion Battlefield-injured patients who developed PNA had greater injury severity along with more frequent injuries to the torso than non-PNA patients. PNA patients with MDR isolates were more severely injured with higher crude mortality than those with susceptible pathogens. These data support developing interventions to prevent PNA in these patients. Further analysis of clinical factors to include imaging and symptom reporting is planned. Disclosures All Authors: No reported disclosures

Abstract: Cardiac Tamponade Complicating Type A Acute Aortic Dissection: Insights From 25 Years of Registry Research” (published in JACC: Advances in 2025) draws its primary data from the International Registry of Acute Aortic Dissection (IRAD), a well-established, multicenter, international collaborative registry founded in 1996. IRAD is widely regarded as one of the most authoritative and comprehensive sources for real-world data on acute aortic dissection, including type A cases (TAAAD). Key Data Sources and Methodology • Primary Source: IRAD DatabaseThe analysis includes all enrolled adult patients with TAAAD from January 1996 to August 2022 across 63 high-volume aortic centers (42 in North America, 16 in Europe, and 5 in Asia). This spans approximately 26–27 years of prospective data collection, often rounded to “25 years” in summaries. The total cohort comprised 6,014 patients with TAAAD, of whom 865 (14.4%) presented with preoperative cardiac tamponade (TMP).IRAD uses standardized data collection forms, with ongoing updates over time to capture evolving variables (e.g., clinical presentation, imaging, management, and outcomes). Comparisons between TMP and non-TMP groups employed statistical tests such as Fisher’s exact test for categorical variables and Wilcoxon rank-sum/Mood’s median tests for continuous variables. Multivariable modeling identified factors linked to TMP presence, and Kaplan-Meier survival curves assessed long-term outcomes (median follow-up: 35.8 months, interquartile range 11.6–59.4 months). • Registry Strengths for ValidationIRAD is a prospective, multicenter registry designed specifically for acute aortic syndromes, minimizing selection bias common in single-center studies. It has produced numerous landmark publications on TAAAD epidemiology, risk factors, management, and prognosis. Earlier IRAD analyses (e.g., from 2009) reported higher TMP incidence (~18.7%) and in-hospital mortality (~54% with TMP vs. ~24.6% without), providing historical benchmarks that the current study updates and refines with a much larger, more contemporary cohort. The lower TMP rate in this analysis (14.4%) may reflect improved early recognition, diagnostic imaging, or shifts in patient demographics over time. Evidence Supporting the Study’s Validity and Findings • Consistency with Prior IRAD and External DataThe findings align with established literature: TMP remains a high-risk feature in TAAAD, linked to older age, female sex (less male predominance), syncope, altered consciousness, and doubled in-hospital mortality (38.4% with TMP vs. 15.4% without; P < 0.001). Surgical management rates were similar between groups (~87.5–87.7%), and post-discharge long-term survival (e.g., 4-year) was comparable among hospital survivors (log-rank P = 0.767), emphasizing that TMP primarily impacts acute-phase outcomes.These results are consistent with prior IRAD reports and other studies on TAAAD complications, reinforcing the registry’s reliability. • Methodological RigorMulticenter design, large sample size, standardized definitions (e.g., preoperative TMP), and appropriate statistical adjustments enhance generalizability and reduce confounding. The study’s funding (partly from sources like W.L. Gore & Associates, common in aortic research) and author disclosures are transparently reported, with no evident conflicts undermining core conclusions. • Limitations Acknowledged in ContextSome variables may have incomplete entries due to evolving data forms over 25+ years, a common registry challenge. However, this does not invalidate the core comparisons or outcomes. Overall, the study’s reliance on IRAD—a gold-standard, collaborative registry with decades of validated output—provides robust, high-quality evidence. The findings offer updated, comprehensive insights into TMP as a predictor of acute mortality in TAAAD while highlighting the benefit of prompt surgical intervention for survivors. This positions the analysis as a credible extension of prior IRAD work rather than an outlier.

Abstract: Abstract Background Pediatric central nervous system tuberculosis (CNS-TB) accounts for 10% of all pediatric TB cases in India and carries the highest morbidity and mortality. However, data on pediatric drug resistant (DR) CNS-TB remains scarce. Regional data from Mumbai suggests that pediatric DR CNS-TB accounts for about 12% of all pediatric DR-TB cases. This dearth of epidemiological data translates to a lack of clinical studies on pediatric DR CNS-TB. This study aims to address this knowledge gap by analyzing the clinico-demographic profiles, laboratory findings, treatment regimens and outcomes, and adverse drug reactions (ADR) in a cohort of Indian children diagnosed with DR CNS-TB.Table 1:Clinical characteristics of the patients at presentationNote: SD- Standard deviation, IQR- interquartile range, TB- Tuberculosis, PTB- Pulmonary tuberculosis, EPTB- Extrapulmonary tuberculosis, LN- Lymph node, DR-TB- Drug-resistant tuberculosis, RR- Rifampicin resistant, MDR- Multidrug resistant, XDR- Extensively drug resistant.Table 2:CSF, microbiological, and blood investigations of the patients at presentationNote: CSF- Cerebrospinal fluid, SD- Standard deviation, TLC- Total leukocyte count, RR- Rifampicin resistant, RI- Rifampicin indeterminate, RS- Rifampicin sensitive, MGIT- Mycobacterial Growth Indicator Tube, ATT- Antitubercular therapy, LPA- Line probe assay, pDST- Phenotypic drug sensitivity testing, Hb- Hemoglobin, ALC- Absolute lymphocyte count, ESR- Erythrocyte sedimentation rate. Methods A retrospective study was conducted from May 2020 to April 2024 and included 44 children less than 18 years of age, diagnosed with DR CNS-TB, treated with second-line antitubercular therapy (ATT) regimens, and followed-up on an outpatient basis. Demographic, clinical, laboratory, treatment, ADR, and outcome data was collected and analysed.Table 3:Treatment details of the patientsNote: SD- Standard deviation, SLI- Second-line injectable, DLM- Delamanid, BDQ- Bedaquiline, IQR- Interquartile range, ATT- Antitubercular therapy.Table 4:ADRs of antitubercular therapy, thalidomide and steroidsNote: ADRs- adverse drug reactions, QTcF- QT interval corrected for heart rate by Fridericia's formula, BDQ- Bedaquiline, DLM- Delamanid, Cfz- Clofazimine, Mfx- Moxifloxacin, DILI- Drug-induced liver injury, Eto- Ethionamide, Cys- Cycloserine, PAS- Para-aminosalicylic acid, PZA- Pyrazinamide, Lzd- Linezolid. Results Mean age at presentation was 9.67±4.41 years.Sixteen (36.36%) patients presented with TB meningitis alone, 7 (15.91%) patients presented with tuberculomas alone, and 21 (47.73%) presented with both. Past exposure to ATT was seen in 1 (2.27%) patient. Neurological deficits were observed in 16 (36.36%) patients during therapy, of which 4 (25%) had hemiparesis ± cranial nerve palsies, 1 (6.25%) had paraparesis with facial palsy, 1 (6.25%) had monoplegia with motor aphasia, and 10 (62.5%) patients had isolated cranial nerve palsies. Visual abnormalities during treatment were seen in 7 (15.91%) patients and sensorineural hearing loss (SNHL) was seen in 11 (25%) patients during treatment. New tuberculomas while on treatment were seen in 26 (59.09%) patients. ADR were seen in 36 (81.82%) patients. Mean duration of ATT given was 22.57±13.13 months. Of the 16 patients who developed motor deficits, 6 (37.5%) had residual motor deficits (1 had blindness, 6 had SNHL, 1 had residual hemiparesis and facial palsy, 3 had cranial nerve palsies), 3 (18.75%) recovered, 5 (31.25%) were still ongoing treatment, and 2 (12.5%) were lost to follow-up. Conclusion Pediatric DR CNS-TB is difficult to treat with high rates of ADR, long treatment durations, and unfavourable neurological outcomes. Disclosures All Authors: No reported disclosures

Abstract: Abstract Background Prosthetic joint infection (PJI) is a severe complication of hip or knee arthroplasty, often necessitating invasive intervention and posing a high risk of adverse outcomes. Early diagnosis and tailored antibiotic therapy are critical for the effective management of PJI. This study evaluated the utility of cell-free deoxyribonucleic acid (cfDNA) extracted from synovial fluid to diagnose PJI and identify the causative pathogens.Figure 1.Comparison of Synovial Fluid cfDNA Concentration Between PJI and Non-PJI GroupsFigure 2.ROC curve for Determining the Optimal cfDNA Concentration Cut-Off for PJI diagnosiscfDNA concentration of 1.59 ng/ul or above indicates possibility of PJI. (sensitivity, 0.90; specificity, 1.00), respectively.cfDNA, cell-free deoxyribonucleic acid; PJI, prosthetic joint infection. Methods This prospective, single-center study included a PJI group consisting of patients with confirmed infections based on the European Bone and Joint Infection Society criteria and a non-PJI group comprising patients without suspected PJIs who underwent joint surgery or aspiration. Synovial fluid samples were collected from all patients, and various culture methods, including conventional synovial fluid, sonication, and tissue and blood cultures, were applied along with cfDNA analysis. Results A total of 35 patients were included, with 20 diagnosed with PJI and 15 classified as non-PJI. The median cfDNA concentration in synovial fluid was significantly higher in the PJI group (4.560 ng/μl, interquartile range (IQR) [3.320–6.348]) compared with the non-PJI group (0.028 ng/μl, IQR [0.009–0.273]) (p &lt; 0.001). The Youden index identified a cfDNA concentration ≥ 1.59 ng/μl as strong likelihood of PJI. Culture positivity rates in the PJI group were as follows: synovial culture (10/20, 50.0%), sonication culture (8/9, 88.9%), tissue culture (2/8, 25.0%), and blood culture (2/12, 16.7%). The bacterial detection rate of cfDNA was 65.0% (13/20). Conclusion cfDNA concentration was significantly higher in the PJI group, with synovial cultures showing substantial agreement. Additionally, cfDNA sequencing detected pathogens after antibiotic treatment and identified multiple pathogens in polymicrobial infections. These findings highlight cfDNA analysis as a valuable diagnostic tool for PJI, with the potential to enhance current diagnostic approaches. Disclosures All Authors: No reported disclosures

Abstract: Abstract Background Invasive fungal infections are a significant source of morbidity and mortality in immunocompromised and critically ill patients. Posaconazole and isavuconazole are commonly used for prophylaxis and treatment of invasive fungal infections in these populations. Oral therapy has many advantages over IV, including convenience and decreased IV-associated complications. Limited studies exist assessing the appropriateness of administering these medications via enteral feeding tube (EFT), but recent case series show feasibility in achieving therapeutic levels.Table 1.Primary and Secondary Outcomes Methods A single center retrospective chart review was performed for adult patients who received posaconazole or isavuconazole via EFT between January 1st 2020 and August 31st 2024. Key exclusion criteria included patients who received the antifungals via other routes of administration, no trough levels, or non-true trough levels (drawn too early or drawn before five days of therapy). For statistical analysis, continuous variables were reported as medians with interquartile ranges and compared using Mann-Whitney U tests. Categorical variables were reported as counts and percents and were compared utilizing Fisher’s exact tests. All statistical comparisons used a two-tailed alpha of 0.05. Results Eighty-six patients were reviewed for inclusion, and 29 patients were included in the final data analysis. Forty-nine percent of patients were receiving these medications for prophylaxis, and the remainder for treatment. Overall achievement of target trough levels was successful in 50% of patients who received posaconazole delayed release tablets (DRT), 56% of patients that received posaconazole suspension, and 100% of patients that received isavuconazole (p = 0.031; Table 1). Posaconazole patients also had lower rates of target trough attainment with first level drawn and took longer to achieve the first therapeutic trough level. No differences in 30-day mortality were found between treatment groups. Conclusion This study suggests that isavuconazole capsules, but not posaconazole, can be administered via EFT with adequate level attainment. Crushed posaconazole in DRT or suspension form was significantly less likely to reach therapeutic trough levels compared to isavuconazole when administered through EFT. Disclosures Emir Kobic, BCIDP, Shionogi: Honoraria

Abstract: Abstract Background Advanced molecular testing for pathogen identification has become a crucial part of the diagnostic toolkit for infectious disease (ID) physicians; however, several modalities and techniques are available. At our institution, we have access to broad-range PCR with reflex to Next-Generation Sequencing (NGS) (University of Washington, UW), multiplex PCR followed by targeted NGS sequencing (MicroGenDx), and microbial cell-free DNA NGS from plasma (Karius). The aim of this study was to evaluate the clinical utility of advanced molecular testing.Table 2:Variables Associated with Positive Advanced Molecular Diagnostic Tests Methods We performed a single-center retrospective chart review of our institution’s usage of the above diagnostic techniques between Apr 2022 to Dec 2023. Three separate ID physicians, blinded from results, evaluated the perceived appropriateness of each request. Clinical impact (positive, neutral or negative) on care was adjudicated. Demographics and clinical data were collected. Categorical variables were summarized as counts and frequencies; continuous variables as medians with interquartile ranges. We assessed group differences using Chi-square and Mann-Whitney tests.Table 3:Variables Associated with Positive Impact on Clinical Care Results We identified 76 samples for analysis, most of which were sent to UW (59%) with the rest sent to MicroGenDx (36%) and Karius (4%). Results from 17 (22%) samples were positive with one or more organisms with most (76%) of these concordant with a clinical syndrome. Figure 1 shows detected microbe groups. 80% of tests were deemed appropriate by ID physician consensus. Including negative and positive tests, most (62%) results had a neutral clinical impact and only 29% had a positive impact. A positive test was associated with being concordant with a clinical syndrome (p&lt; 0.001) and positive impact on clinical care (p&lt; 0.001). Gram stain with white blood cells and organisms, positive microbiological stain on pathology and receiving antibiotics within 72 hours were significantly associated with a positive result (Table 2). Positive gram stain/microbiology stain was significantly associated with positive impact (Table 3). Conclusion Although numerous commercially available technologies are accessible to identify causative pathogens, there is need to refine test selection criteria and develop evidence-based guidelines to maximize clinical benefit. Disclosures Zoe Weiss, MD, Alnylam Pharmaceuticals: Stocks/Bonds (Public Company)|Anvil Diagnostics: Advisor/Consultant|Anvil Diagnostics: Ownership Interest|Cartography: Stocks/Bonds (Private Company)|Denali Therapeutics: Stocks/Bonds (Public Company)|Indomo: Stocks/Bonds (Private Company)|Maze Therapeutics: Stocks/Bonds (Public Company)

Abstract: Abstract Background Traditional antimicrobial stewardship initiatives aimed at reducing drug acquisition expenditures may fail to capture overall healthcare costs including increased hospital length of stay (LOS). Meropenem (MEM) had historically been utilized at our institution for treatment of extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) bloodstream infections (BSI) due to the high cost of ertapenem (ETP). Drugs requiring multiple daily infusions like MEM are associated with additional expenses for nurse time, intravenous tubing, admixture fluids, syringes and waste disposal compared to once-daily ETP and have also been associated with increased LOS. We aimed to quantify differences in LOS and other associated healthcare costs for patients with ESBL-E BSI treated with MEM versus ETP following de-restriction of ETP for Infectious Diseases providers in the inpatient setting.Baseline patient characteristics.Abbreviations: BMI = body mass index; BMT = bone marrow transplant within the previous 12 months; CCI = Charlson Comorbidity Index; ETP = ertapenem; HIV = human immunodeficiency virus; ICU = intensive care unit; ID = infectious diseases; IQR = interquartile range; MEM = meropenem; NS = non-significant; SOT = any history of solid organ transplantLength of stay, antimicrobial use, and patient outcomes.Abbreviations: CDI = C. difficile infection; DOT = days of therapy; ETP = ertapenem; ICU = intensive care unit; IQR = interquartile range; LOS = length of stay; MEM = meropenem; NS = non-significant Methods This retrospective study included patients with ceftriaxone-resistant E. coli or K. pneumoniae BSIs between February 1, 2023 and March 31, 2025. Patients were included if they received at least 72 hours of therapy with ETP or MEM. Patients with polymicrobial bacteremia, those receiving combination therapy for &gt; 72 hours, or infections without documented source control were excluded.Raincloud plots of LOS for (a) overall and (b) non-ICU cohorts.a) LOS was significantly decreased in the ETP group for the overall study cohort (median 7 [IQR: 6-10] versus 10 days [IQR: 7-18], p &lt;0.004). b) LOS was significantly decreased in the ETP group for the subset of patients not admitted to the ICU (median 7 [IQR: 6-10] versus 10 days [IQR: 6-17], p &lt;0.037). Abbreviations: ETP = ertapenem; ICU = intensive care unit; IQR = interquartile range; LOS = length of stay; MEM = meropenemAssociated costs of treatment, dollars.a) Associated costs per day of MEM and ETP administration for a patient with normal renal function and BMI &lt;30; MEM is administered as 1 gram IV q8h over 3h and ETP 1 gram IV q24h over 30 minutes per institutional protocol. b) Total costs of MEM and ETP for all study patients based on dosing frequency and length of definitive therapy. Abbreviations: ETP = ertapenem; IV = intravenous; MEM = meropenem Results Of the 161 blood cultures reviewed, 82 patients met criteria for study inclusion, 46 in the MEM group and 36 in the ETP group. Baseline characteristics were comparable in both groups, except for more patients in the MEM group admitted to the ICU at the time of index culture (Figure 1). More than 63% of patients included had an immunosuppressive condition. LOS was decreased in the ETP group compared to MEM in the overall study population (7 versus 10 days, p &lt; 0.004) and in the subset of patients not admitted to the ICU (p &lt; 0.037) (Figures 2 and 3). Associated costs of administration were also decreased (Figure 4). Conclusion A change to de-restriction of inpatient ETP use for ESBL E.coli and K. pneumoniae BSI resulted in a significant decrease in patient LOS. Associated healthcare costs were also decreased despite the increased acquisition cost of ETP. Antimicrobial stewardship programs should look beyond traditional drug cost reduction initiatives to optimize overall healthcare savings and patient outcomes. Disclosures Lucy S. Witt, MD, MPH, Merck & Co: Grant/Research Support

Abstract: Abstract Background Lambda (C.37) was a variant originally identified in Peru, its impact on severe COVID-19 disease in children has not been adequately studied in Andean countries. Thus, this study aims to evaluate the risk of severe COVID-19 in hospitalized children during the predominance of the Lambda variant at a referral hospital in Lima, Peru.Figure 1.Cases of hospitalized children across periods of SARS-CoV-2 variant predominance a at Hospital Nacional Edgardo Rebagliati Martins in Lima, Peru, 2020–2022 (N=240).a. The type of SARS-CoV-2 predominance was defined as the period in which a variant was dominant (more than 70%) in Peru, according to CDC Peru and GISAID Data Science Initiative.Table 1.Clinical characteristics of hospitalized children with SARS-CoV-2 infection in Lima, Peru, 2020–2022.IQR: Interquartile range; ICU: Intensive care unit.a. Kruskal-Wallis test.b. Chi-square test.c. Fisher's exact t-test. Methods Retrospective cohort of patients &lt; 14 years hospitalized at Hospital Nacional Edgardo Rebagliati Martins, from April 2020 to April 2022. The type of SARS-CoV-2 predominance was defined as the period in which a variant was dominant (more than 70%) in Peru, according to CDC Peru and GISAID Data Science Initiative. Severe COVID-19 was defined if any of the following criteria was present: admission to the intensive care unit, use of vasopressors/inotropes, need for high-flow nasal cannula (HFNC) therapy, requirement for invasive mechanical ventilation, or death. Crude and adjusted relative risk with 95%CI were calculated using generalized linear models with a Poisson family, log link, and robust variance.Table 2.SARS-CoV-2 variants and severe COVID-19 in hospitalized children in Lima, Peru, 2020–2022 (N=240).ICU: Intensive care unit; RR: Relative risk; CI: Confidence Interval; NC: Not calculable.a. Not calculable because there is a zero value in one cell. Results 240 children were included; 18% were admitted during the period of Lambda variant predominance, median age was 89.5 months, and 54.2% with comorbidities. Severe COVID-19 occurred in 14.17%. No severe COVID-19 cases were reported during the Delta predominance, whereas 25.28% of children experienced severe disease during the Lambda predominance, with a higher use of HFNC (16.28%) compared to other variant predominance periods (p=0.031). However, the hospitalization during Lambda predominance was not associated with severe disease (RR 1.41, 95%CI:0.67–2.98; p=0.367), nor was it associated with other critical outcomes when compared to the Wuhan predominance period, adjusted for the Omicron predominance, age, male sex, and comorbidities. Conclusion In our cohort, hospitalization during the Lambda predominance was probably not associated with greater severity of COVID-19 disease. Large multicenter studies are needed to confirm our findings. Disclosures All Authors: No reported disclosures

Abstract: Abstract Background There is limited evidence to guide the diagnosis and treatment of urinary tract infections (UTIs) in men. In this study, we characterized clinicians’ diagnostic and treatment decisions for outpatient men with UTIs.Table 1:Clinician CharacteristicsCharacteristics of clinicians who responded to the survey. APP = advanced practice professional; IQR = interquartile range; IM = internal medicine. a APPs excluded.Characteristics Predicting Use of Misleading UTI Signs – Professional RoleMultivariate analysis with attendings used as the reference range. APPs were significantly more likely to view cloudy (Odds Ratio [OR] 3.623, Confidence Interval [CI] 1.289-10.179, p = 0.015) and foul-smelling urine (OR 2.933, CI 1.047-8.220, p = 0.041) as indicative of UTI. APP = advanced practice professional. N = 196 (cloudy urine), N = 199 (foul-smelling). Methods We surveyed clinicians on their diagnostic and treatment approaches to men with UTIs. Surveys were distributed to primary care and emergency medicine providers, urologists, and internal medicine residents. We analyzed clinician characteristics associated with identifying cloudy or foul-smelling urine as suggestive of UTI via logistic regression.Characteristics Predicting Use of Misleading UTI Signs – Primary Area of PracticeMultivariate analysis with outpatient (IM) used as the reference range. Clinicians practicing primarily in the ED were more likely to find cloudy (OR 4.935, CI 1.433-16.998, p = 0.011) and both cloudy and foul-smelling urine indicative of UTI (OR 4.411, CI 1.398-13.924, p = 0.011). ED = emergency department; IM = internal medicine. N = 196 (cloudy urine), N = 196 (both).Preferred Antibiotic Therapy Duration (N = 193)The preferred duration of therapy for outpatient men with UTIs according to survey respondents. Results Respondents (N=206) were trainees (53%), attendings (34%), and advanced practice professionals (APPs; 14%). Most physicians were internal medicine trained (79%), with a smaller proportion of family medicine (10%), urology (7%), or emergency medicine (4%). The most commonly reported symptoms and signs indicative of UTI were dysuria (96%) and suprapubic tenderness (91%). Most respondents also reported cloudy (59%) and foul-smelling urine (63%) as indicative of UTI. Across areas of practice, emergency department clinicians were significantly more likely than outpatient internal medicine clinicians to view cloudy or foul-smelling urine as indicative of UTI (Odds Ratio [OR] 4.07, Confidence Interval [CI] 1.32-12.52, p=0.01). Across professional roles, APPs were significantly more likely than attendings to identify cloudy urine (OR 3.62, CI 1.29-10.18, p=0.02) or foul-smelling urine (OR 2.93, CI 1.05-8.22, p=0.04) as indicative of UTI. For treatment, 87% of clinicians say they prescribe antibiotics for ≤7 days, and their most common empiric antibiotic choice was trimethoprim-sulfamethoxazole (68%). Conclusion Clinicians found little consensus on most signs and symptoms of UTI in men. Additionally, APPs and emergency department providers significantly relied on non-evidence based, misleading signs of cloudy and foul-smelling urine. There was also a lack of treatment consensus—no one antibiotic garnered more than 68% endorsement by clinicians as an appropriate empiric choice. The variable diagnostic and treatment approaches for UTIs in men highlights the need for clinical trials in this population to guide clinical practice. Disclosures All Authors: No reported disclosures