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Abstract Background Methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) is treated with antistaphylococcal penicillins (ASP) or cefazolin. Altered pharmacokinetics in the setting of hypoalbuminemia may reduce the likelihood of therapeutic success in patients receiving highly protein bound beta-lactams. ASPs and cefazolin are 94% and 80% protein bound, respectively. We assessed the impact of hypoalbuminemia (≤2.5 g/dL) on clinical outcomes in patients with MS-SAB treated with ASPs or cefazolin.Table 1:Unweighted and weighted analysis of full cohort by albumin statusTable 2:Weighted analysis of cefazolin and ASP cohorts by albumin status Methods This single center, retrospective study included adults (≥18 years) admitted with community-acquired MS-SAB between 1/1/2006 and 12/31/2019 who received ASPs or cefazolin and had a serum albumin obtained between the date of first culture positivity and 72 hours of definitive therapy. Exclusion criteria included receipt of ≥5 days of MSSA active empiric therapy prior to definitive, polymicrobial bacteremia, antibiotics for an indication other than MS-SAB, or central nervous system infection. The primary outcome was failure to clear blood cultures within 72 hours of definitive therapy initiation. Propensity score weighting was used to adjust for baseline differences between cohorts. Results 160 patients were included with 61 (38.1%) being hypoalbuminemic (Table 1). In the propensity score weighted analysis, the primary outcome occurred in 37% of patients with an albumin ≤2.5 g/dL vs. 10.2% with an albumin >2.5 g/dL (p< 0.001). This finding was consistent in both ASP and cefazolin subgroups (Table 2). Hospital length of stay was longer in hypoalbuminemic patients but did not represent a statistically significant difference in the weighted overall analysis (15.9 vs. 11.6 days, p=0.8). There was no difference in inpatient mortality in any of the cohorts analyzed. 90-day all-cause mortality was higher in hypoalbuminemic patients only in the cefazolin subgroup analysis (20.7% vs 4.9%, p=0.019). Conclusion The presence of hypoalbuminemia was associated with failure to clear blood cultures within 72 hours of definitive therapy initiation in patients with MS-SAB. While no significant difference in mortality was observed overall, the higher mortality in the cefazolin subgroup warrants further research on the impact of hypoalbuminemia on clinical outcomes in patients with MS-SAB. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties).

Abstract Background Spinal implant infections (SII) are serious complications following instrumented spinal fusion. Debridement with implant retention requires antibiotic therapy, yet the optimal duration remains unclear. We assessed whether longer antibiotic duration is associated with reduced risk of treatment failure. Methods We conducted a multicenter retrospective cohort study of adult patients diagnosed with acute postoperative SII (≤90 days from index surgery) between January 1, 2017, and December 31, 2022. All patients underwent debridement with implant retention. Treatment failure was defined as unplanned reoperation, clinical recurrence, or infection-related death. A Cox proportional hazards model assessed whether being on antibiotics was protective, treating antibiotic use as a time-dependent covariate, adjusting for relevant clinical variables, and including death not attributable to infection as a competing event. A second Cox model evaluated whether shorter antibiotic duration was associated with increased risk of failure with landmark analysis at six weeks. Results There were 531 patients included in the study. Patient demographics are described in Table 1. During a median follow-up of 1,168 days (IQR 576-1,817), 151 patients experienced treatment failure. There was a non-significant trend toward decreased hazard of failure while on antibiotics (HR 0.70; 95% CI 0.46–1.05; p=0.087). Among 363 patients without early failure, 60 (16.5%) received ≤6 weeks of antibiotics and 303 (83.5%) received >6 weeks. Longer antibiotic duration was not associated with a differential risk of failure (HR 0.75, 95% CI 0.43–1.33; p=0.34). Conclusion Continuing antibiotic therapy after debridement and implant retention may help reduce the risk of treatment failure in SII. However, it remains unclear whether extending antibiotic treatment beyond a certain duration continues to offer additional benefits. Prospective studies are needed to better define the optimal duration and approach to antibiotic therapy in these scenarios. Disclosures Sandra B. Nelson, MD, UpToDate Wolters Kluwer Health: Author, Editor

Abstract Background Colonization with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) is increasingly recognized in critically ill patients and impacts infection prevention practices and empiric antibiotic selection. However, contemporary United States estimates of ESBL-E prevalence at the time of ICU admission are limited.Table 1.ICU-Specific Prevalence of ESBL Colonization at Admission Confirmed by Whole Genome SequencingFigure 1.Distribution of ESBL Gene Variants Among ESBL-Producing Enterobacterales Isolates by Bacterial Species (n = 173) Methods We conducted a prospective molecular epidemiology study of ESBL-E colonization among adult and pediatric patients admitted to nine ICUs at The Johns Hopkins Hospital between March and August 2023. Routine rectal surveillance swabs (Copan Eswab) collected at ICU admission were plated on selective chromogenic media (HardyCHROM™ ESBL) to identify third-generation cephalosporin-resistant Enterobacterales (3GCRE). Species identification was performed using MALDI-TOF MS, and ceftriaxone resistance was confirmed by broth microdilution. Whole-genome sequencing (WGS) was performed on the first isolate of each species per patient to confirm ESBL gene carriage and assess molecular features. Results Among 3,278 ICU admissions, 328 (10%) had 3GCRE isolated on admission swabs. Of these isolates, 173 (5% of all admissions) were confirmed by WGS to harbor at least one ESBL gene—representing approximately 53% of all 3GCRE isolates. ESBL-E colonization was most prevalent in the medical (10%) and cardiac (8%) ICUs. The most common ESBL-E species were Escherichia coli (72%) and Klebsiella pneumoniae (19%). Dominant E. coli sequence types were ST131 (36%), ST1193 (7%), and ST38 (6%). Nearly all ESBL genes belonged to the blaCTX-M family (95%), with blaCTX-M-15 as the predominant allele (63%). Other ESBL genes included blaCTX-M-27 (17%), blaCTX-M-14 (5%), blaCTX-M-55 (5%), and blaSHV-12 (3%). Conclusion In this large, prospective cohort, 5% of ICU patients were colonized with ESBL-E at admission, most commonly E. coli and K. pneumoniae harboring blaCTX-M genes. Phenotypic detection of 3GCRE overestimated ESBL-E prevalence by nearly 90%, highlighting the need for molecular confirmation to accurately characterize resistance. These findings suggest ESBL-E colonization remains uncommon in the U.S., even at a major referral center, supporting non-carbapenem empiric therapy in low-risk patients and reinforcing the need for targeted surveillance. Disclosures All Authors: No reported disclosures

Abstract Background Cytomegalovirus (CMV) infection remains one of the most prevalent and important infections following solid organ transplant (SOT). Treatment is often challenging, especially when dealing with refractory and resistant CMV infections.Table 1:Univariable logistic regression analyses of associations with early refractory CMV infectionTable 2:Univariable logistic regression analyses of associations with resistant CMV infection Methods We performed a retrospective cohort study of SOT recipients with clinically significant CMV infection (csCMVi) at a tertiary transplant center in the US during 2010-2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Kaplan-Meier estimation, univariable logistic regression analysis, and multivariable Cox regression were used for outcome analysis.Table 3:Multivariable Cox regression analysis of associations with recurrent CMV infection after primary treatment endedNote: Refractory CMV was not included in the model for recurrent CMV as no patients with refractory infection had recurrence. Results A total of 145 SOT recipients with csCMVi were included. Most patients were recipients of liver (49%), followed by kidney (22.1%), heart (6.9%), lung (5.5%), and pancreas (4.1%). Multiple organ transplants accounted for 12.4% of the cohort. Most common induction was an anti-IL-2 antibody (43.9%) followed by ATG (29.5%). 82 (56.5%) had CMV D+/R- mismatch. In total, 34 (23.4%) had CMV syndrome, 38 (26.2%) had tissue-invasive CMV disease, while the rest (50.3%) were asymptomatic. After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R- mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48-0.95, p=0.029) while lower absolute lymphocyte count (ALC) was higher risk of early refractory csCMVi (OR 1.54; CI 1.01-2.44, p=0.048) (Table 1). Drug-resistant CMV occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2; CI 1.08-3.93, p=0.031) (Table 2). Of 144 patients with post-treatment follow-up, 25 (17.2%) experienced recurrent csCMVi within 6 months. Table 3 shows the associations with recurrence of csCMVi after initial treatment. 30 patients (20.7%) died during a median follow-up of 4 years, but refractory, resistant or recurrent CMV were not associated with mortality. Conclusion Refractory csCMVi is associated with low ALC and an earlier onset post-transplant. Resistant csCMVi is associated with high levels of initial CMV DNA. Recurrence of csCMVi is common and possibly associated with low ALC at the end of antiviral treatment. Disclosures All Authors: No reported disclosures

Abstract Background Hematopoietic cell transplantation (HCT) is associated with a net state of immunosuppression to enable graft acceptance and mitigate graft-versus-host disease risk1. Most of these patients require multiple prophylactic antimicrobials to prevent opportunistic infections during the post-transplant course2, including central nervous system (CNS) infections3. Brain abscesses are a form of CNS infection with a high incidence of morbidity and mortality4 Methods We conducted a retrospective cohort study of adults diagnosed with brain abscess following HCT between January 2009 and December 2024, including patients from all Mayo Clinic sites (Arizona, Florida, and Minnesota). The study was approved by our institutional review board with a protocol number 24-011428. The data was extracted from the electronic medical records into a secure database in REDCap. Statistical analyses were conducted using R version 4.4.1 (R Foundation for Statistical Computing). Results We identified 22 patients with brain abscess diagnosis following HCT. 50% of patients had leukemia. 81.8% of them received prior chemotherapy. 16 patients had prior allogeneic HCT, and 54.5% received a myeloablative conditioning regimen (table 1). 21 patients had neuroimaging available. More than one cerebral lobe was involved in 42.9% of the cases. 14 patients had extra-axial infection, the lung being the most frequently affected organ. Nocardia accounted for 40.9% of the brain abscesses (table 2). 45.5% underwent surgical intervention, and most of our patients were treated with a combination of intravenous and oral antimicrobials, many of them followed by long-term suppression. 54.5% of the brain abscesses resolved, with a median time to resolution of 156 days. All-cause mortality was 59.1%, with a median time to death of 540 days after brain abscess diagnosis (table 3). Conclusion Although rare, brain abscess is a devastating complication of HCT, with high morbidity and mortality. The most common pathogen encountered was Nocardia species. The required treatment is usually extensive, and these patients often need long-term suppression. Further investigation is required to determine risk factors for specific pathogen infection, non-resolution, and mortality. Disclosures All Authors: No reported disclosures

Abstract Background Despite effective therapy for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia with anti-staphylococcal penicillins (ASP; e.g., oxacillin, nafcillin) or cefazolin, persistent bacteremia is associated with poorer clinical outcomes and increased complications. Emerging strategies, such as combination therapy with an ASP or cefazolin and ertapenem, have demonstrated the potential to accelerate microbiologic clearance in persistent MSSA bacteremia. However, despite its increasing utilization in clinical practice, data on the effectiveness of this combination regimen remains limited. We sought to describe the clinical characteristics and outcomes of patients with MSSA bacteremia receiving combination therapy. Methods We performed a single-center, retrospective study of adult patients with MSSA bacteremia who received ASP or cefazolin and ertapenem combination therapy from 2019-2023. Time to blood culture clearance, in-hospital mortality, and 90-day relapse were examined. Results A total of 57 patients were included: median age of 65 years [IQR 53-73] with 75.4% male. MSSA bacteremia complicated by infective endocarditis and cardiac implantable electronic device infection occurred in 35.1% and 12.3%, respectively. The median length-of-stay was 16 days [IQR 12-28], and 57.9% required ICU admission. Forty (70.2%) patients underwent source control interventions such as valve replacement, device extraction or surgical debridement. The median duration of bacteremia prior to combination therapy initiation was 4 days [IQR 3-6]. Blood culture clearance occurred in a median of 1 day. The median duration of combination therapy was 4 days [IQR 3-6]. In-hospital mortality was 15.8%. None of the patients surviving the hospitalization experienced relapsed bacteremia within 90 days. Conclusion This study supports growing evidence that combination therapy may offer benefits in managing persistent MSSA bacteremia, specifically with regards to time to blood culture clearance. Further investigation is warranted to determine optimal timing of combination therapy and if known benefits of combination therapy translate into superior clinical outcomes as compared to monotherapy. Disclosures All Authors: No reported disclosures

Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with considerable clinical burden. Although increasing literature has described its features and associated treatment failure, large-scale cohorts with long-term follow-up remain limited. Herein, we evaluated a large cohort of patients with NVO to characterize the clinical manifestations, management, and long-term outcomes, and to further explore factors associated with treatment failure.Table 1.Baseline characteristics of patients with native vertebral osteomyelitisTable 2.Treatment, failure rates, and mortality in patients with native vertebral osteomyelitis Methods We conducted a retrospective multicenter cohort study of adults (≥18 years) with NVO across Mayo Clinic sites between 1999 and 2024. Data on demographics, clinical manifestations, antimicrobial therapy, and surgical intervention were collected. Cumulative incidence of treatment failure was estimated as a function of follow-up accounting for the competing risk of death. Independent predictors of treatment failure were evaluated in a multivariable Cox regression model with time-dependent covariates.Table 3.Multivariable predictors of treatment failure in patients with native vertebral osteomyelitisFigure 1.Cumulative incidence of death and treatment failure following diagnosis of native vertebral osteomyelitis(A) Short-term (12-month) cumulative incidence of death and treatment failure (magnified view of the first year from panel B).(B) Long-term (up to 7 years) cumulative incidence of death (dotted orange line) and treatment failure (solid blue line). Results Among 1,255 patients included (median age 67 years; 66% male), lumbosacral involvement was most common (65%), with multilevel vertebral involvement ( >2 levels) in 21%. Epidural abscesses were present in 43%, paravertebral abscesses in 42%, and psoas abscesses in 20%. Pathogens were identified in 77%, most commonly S. aureus (50%; MSSA 37%, MRSA 13%), followed by Streptococcus species (22%), and Gram-negative bacilli (11%) (Table 1). The median total antibiotic duration was 59 days (IQR, 42–132). Surgical intervention was performed in 13% after a median of 2 days (IQR, 1-5). Treatment failure occurred in 162 patients during a median follow-up of 2.8 years (6-month and 5-year cumulative incidence were 11% and 14%, respectively), with the median time to failure of 3.1 months. Cumulative mortality was 12% at 6 months and 33% at 5 years (Table 2, Figure 1). Diabetes (HR 1.90, 95% CI 1.16–3.12), multilevel vertebral involvement (HR 1.75, 95% CI 1.22–2.51), and MRSA infection (HR 2.11, 95% CI 1.06–4.18) were independently associated with increased risk of treatment failure (Table 3). Conclusion This 25-year study highlights the persistent burden of treatment failure in NVO and associated risk factors, underscoring the importance of early recognition of high-risk features to optimize outcomes. Disclosures All Authors: No reported disclosures

Abstract Background Clostridium difficile infection (CDI) remains a significant public health concern in the United States, contributing to considerable morbidity and mortality, particularly among hospitalized and elderly populations. This study examines the temporal trends in CDI-related mortality across the United States over recent decades.Figure 1A:Mortality trends among gender; B: Race; C: US Census Region; D: Metropolitan areas. Mortality ratio (Gender): Female = 58.15% Male = 41.85% Mortality ratio (Race): Hispanic = 5.53% Whites = 83.92% Blacks = 8.12% Others = 2.22% Mortality ratio (US Census Region): Northeast = 22.18% Midwest = 24.36% South = 33.13% West = 20.33% Mortality ratio (Metropolitan): Metropolitan areas: 83.78% Non-metropolitan areas: 16.22%Figure 2A:Trends in mortality rates caused by Clostridium Difficile in United States from 1999-2020; and B: from 2021-2023. Top 90th percentile States (crude mortality rate per 100,000 population): Rhode Island: 6.55 Maine: 4.61 Ohio: 4.58 Vermont: 4.21 West Virginia: 4.18 Missouri: 4.11 Bottom 10th percentile States (crude mortality rate per 100,000 population): Georgia: 1.59 Mississippi: 1.49 Louisiana: 1.32 Utah: 1.26 Alaska: 0.96 Hawaii: 0.77 Methods In CDC WONDER analysis, we used total US residents of any age from all 50 states who died due to CDI spanning from the years 1999-2023. The dataset employed demographic attributes, place of death, state-level information, as well as classification into census regions, and the distinction between metropolitan and non-metropolitan localities. The ethnic/racial groups used in our study were classified as Hispanic, Black/African American, White, and others (including American Indian/Alaskan Native, Asian/Pacific Islander) individuals as indicated on the death certificates. US Census regions were categorized into Northeast, Midwest, South, and West based on the definitions provided by the Census Bureau.Figure 3:Place of death among individuals infection with clostridium difficile. Place of Death: Medical Facility - Inpatient: 71.22% Medical Facility - Outpatient or ER: 1.56% Medical Facility - Dead on Arrival: 0.06% Medical Facility - Status unknown: 0.03% Decedent's home: 5.52% Hospice facility: 4.64% Nursing home/long term care: 15.03% Other: 1.72% Place of death unknown: 0.22%Figure 4:Crude mortality rate among States. Crude mortality rate is represented per 100,000 population from the years 1999 to 2023. Results There were a total of 216,311 deaths associated with CDI over the study span. Out of them, 58.1% were females, 41.9% were males, 83.9% were White individuals, 8.12% were Black/African Americans, 5.53% were Hispanics, and 2.22% belonged to other racial groups. About 33% (one-thirds) of the deaths occured in South region followed by 24.4% in Midwest, 22.2% in Northeast and 20.3% in West region. According to NCHS rural-urban scheme classification, 83.8% deaths occured in metropolitan areas and the rest 16.2% in non-metropolitan areas. Conclusion National surveillance data indicate a marked increase in CDI-associated deaths during the early 2000s, largely driven by the emergence of hypervirulent strains and increased antibiotic resistance. However, recent years have shown a gradual decline in mortality rates, attributed to improved infection control practices, antimicrobial stewardship programs, and heightened public awareness. Despite these gains, disparities persist among racial, geographic, and age-specific subgroups, highlighting the need for targeted interventions. This underscores the evolving landscape of CDI mortality and the importance of sustained preventive strategies to further reduce the burden of this infection. Disclosures All Authors: No reported disclosures

Abstract Background Native joint septic arthritis (NJSA) is a serious musculoskeletal infection requiring timely surgical intervention to prevent long-term morbidity. Although current guidelines recommend early surgical debridement, supporting data, particularly on long-term outcomes, remain scarce. Given this, we evaluated the association between surgical timing and 1-year clinical outcomes using the Desirability of Outcome Ranking (DOOR) framework, applied for the first time in NJSA.Table 1.Desirability of Outcome Ranking (DOOR) ordinal scaleTable 2.Baseline demographic, clinical characteristics, and treatment outcomes Methods We conducted a retrospective multicenter cohort study of adults (≥18 years) with NJSA who underwent surgery across Mayo Clinic campuses between 2012 and 2021. Clinical outcomes at one year were assessed using a 9-level DOOR scale, incorporating survival, treatment failure (relapse, reinfection, readmission, or significant surgical events), and joint recovery (full vs qualified) (Table 1). Time to surgery from hospital admission was analyzed both as a continuous variable and as categories: < 1, 1–2, or ≥3 days.Table 3.Associations between duration and outcomesFigure 1.Association Between Time to Surgery and DOOR Scores in Native Joint Septic Arthritis.A) Distribution of Modified DOOR Scores by Surgical Timing. B) Modeled Probability of DOOR Scores by Time to Surgery. Results Among 268 patients (median age 62 years, 61% male), 30% underwent surgery < 1 day from admission, 47% within 1–2 days, and 24% at ≥3 days. At 1 year, 57% achieved full recovery without unfavorable events (DOOR score 1), while treatment failure occurred in 34% (Table 2). In unadjusted analyses, longer surgical delay was significantly associated with higher DOOR scores (per IQR increase [from 0 to 2 days], OR: 1.5; 95% CI: 1.0–2.1; p = 0.026) and with increased 1-year mortality (HR: 1.7; 95% CI: 1.1–2.6; p = 0.019) and treatment failure (HR: 1.5; 95% CI: 1.1–2.0; p = 0.007). Similar results were obtained when delay was used as a categorical 3-level variable, with the highest risk observed in patients undergoing surgery after ≥3 days. After adjusting for age and Charlson index, only the association between surgical delay and treatment failure remained statistically significant (HR: 1.5; 95% CI, 1.1–2.0; p=0.016) (Table 3, Figure 1). Conclusion Delayed surgical intervention for management of NJSA was independently associated with higher risk of treatment failure at 1 year. These findings reinforce current guideline recommendations for timely operative management and further underscore the potential of the DOOR framework to capture clinically meaningful, multidimensional outcomes in NJSA. Disclosures All Authors: No reported disclosures

Abstract Background Despite advancements in vaccination, mortality from Pneumococcal blood stream infections remains high (∼20%). Risk factors include host comorbidities (e.g., immunosuppression, kidney disease, alcohol use, smoking) and certain serotypes. While intensive care unit (ICU) admission and septic shock are associated with poor outcomes, predictors of severe disease remain underexplored. Characteristics of patients with ICU admission within 24 hours of invasive pneumococcal disease diagnosis Epidemiology, clinical characteristics, metastatic complications and management of invasive pneumococcal disease (IPD) Methods We conducted a retrospective review of hospitalized adults with Streptococcus pneumoniae bacteremia between 2013-2023. Clinical comorbidities, laboratory values, vaccination status, microbiologic data, and treatment strategies were collected. Descriptive statistics and univariate logistic regression were used to assess predictors of ICU admission using R Studio v4.4.3 Univariate logistic regression analysis for predictors of ICU admission within 24 hours of diagnosis of streptococcus pneumoniae blood stream infection Rates of streptococcus pneumoniae blood cultures over the years- seasonality trends Results A total of 185 patients were included; the majority were male (60%) with a median age of 64 years (Table 1). Immunocompromising conditions were present in 60%, and only 43% were up to date with pneumococcal vaccination. Metastatic infection was identified in 28% of cases, most commonly meningoencephalitis (74%), musculoskeletal involvement (28%), and endocarditis (12%). ICU admission within 24 hours of presentation was required in 55% of patients (Tables 2 and 3). Predictors of ICU admission included active smoking (OR 2.20), substance use within the past five years (OR 3.45), presence of metastatic foci (OR 2.39), and neurologic complications (OR 6.10). Up-to-date pneumococcal vaccination demonstrated a trend toward a protective effect. 30-day and 90-day mortality rates were 18.9% and 25.4%, respectively. Other predictors of 30-day mortality included smoking history, higher Charlson comorbidity index (CCI), hemodynamic shock at admission, and lab abnormalities such as hypoalbuminemia and elevated liver enzymes. Among the 69 isolates with available serotype data, serogroups 22 and 15 were most frequently identified. Conclusion Pneumococcal bloodstream infections are associated with substantial mortality, particularly among patients requiring ICU admission. Smoking, recent substance use, and the presence of metastatic complications were significantly associated with severe disease and ICU admission. Up-to-date pneumococcal vaccination demonstrated a protective effect. Disclosures All Authors: No reported disclosures