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Abstract Background Staphylococci are the most frequent microorganisms in periprosthetic joint infection (PJI) and treatment remains challenging. Phage is being considered as a potential treatment. Here, the in vitro activity of phages SaMD07FSphi1or SaNSI1469phi1, alone and in combination with vancomycin against staphylococcal biofilms was evaluated. Figure 1 In vitro activity of phage SaMD07FSphi1 against S. aureus and S. epidermidis biofilms Figure 2 In vitro activity of phage SaNSI1469phi1 against S. aureus and S. epidermidis biofilms Methods Biofilms were grown at 37°C on 4 cm stainless steel K-wires in tryptic soy broth (TSB) with 106 cfu/ml of S. epidermidis or S. aureus (8 PJI isolates with phage activity against planktonically-grown bacteria). After 24 h, 3 K-wires were quantitatively cultured to define pre-treatment bacterial loads, with the remaining assigned to one of four treatment groups: TSB, phage (4 x 106 plaque forming units/ml), vancomycin (16 µg/ml) or phage/vancomycin. K-wires were incubated for 6 or 24 h at 37°C, rinsed, sonicated, and quantitatively cultured. Testing was performed in triplicate and on 3 separate days and mean log10 cfu/K-wire reduction factors (LRFs) versus TSB calculated. Results Phage SaMD07FSphi1 (Figure 1) plus vancomycin showed LRFs of 2.8 (p, 0.0003) and 2.3 (p, 0.0177) log10 cfu/K-wire at 24 h for S. aureus IDRL-6121 and S. aureus IDRL-8454, respectively, whereas phage alone showed was 3.1 (p, 0.0003) and 3.0 (p, 0.0003), respectively. All treatments were ≤1.0 log10 cfu/K-wire 24 h LRFs for S. aureus IDRL-6175, S. epidermidis IDRL-5966 and S. epidermidis IDRL-6108.This phage plus vancomycin showed LRFs of 0.6 log10 cfu/K-wire at 6 h for S. epidermidis IDRL-5966 and S. aureus IDRL-6175, with bacterial regrowth at 24 h. Phage SaNSI1469phi1 (Figure 2) plus vancomycin showed 24 h LRFs of 2.0 (p, 0.02) and 3.2 (p, 0.003) log10 cfu/K-wire for S. epidermidis IDRL-6955 and S. aureus IDRL-7299, respectively, whereas phage alone was 0.2 (p, 0.17) and 0.5 (p, 0.03) log10 cfu/K-wire, respectively. All treatments showed ≤1.0 log10 cfu/K-wire 24-hour LRFs log10 cfu/K-wire for S. epidermidis IDRL-10273. This phage alone showed 6 h LRFs of 1.0 and 1.3 for S. epidermidis IDRL-6955 and S. aureus IDRL-7299, with bacterial regrowth at 24 h. Conclusion Phages SaMD07FSphi1 and SaNSI1469phi1 alone and with vancomycin showed activity against staphylococcal biofilms formed by 4 isolates. Increased activity was observed at 6 h in some cases, with bacterial regrowth at 24 h. Disclosures Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection: a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection|MicuRx Pharmaceuticals and bioMérieux: Grant/Research Support|PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., Nostics, HealthTrackRx, bioMérieux and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course: Honoraria

Abstract Background A unified definition of prosthetic joint infection outcomes (PJI) is crucial for consistent data, study comparisons, and better care. This study systematically reviews how PJIs outcomes are defined, building on our prior research on native vertebral osteomyelitis and postoperative spinal infection.Figure 1Network plot illustrating the co-occurrence of outcome criteria in prosthetic joint infection studies. Edge thickness reflects the frequency of the co-occurrence of each criterion. Each plot highlights one criterion, namely (1) clinical signs, (2) imaging, (3) microbiology, (4) histopathology, (5) antibiotics-related, (6) surgical-related, (7) mortality. Methods We conducted a comprehensive search of the Cochrane, Embase, Medline, and Scopus databases for studies published after 2005 that clearly defined outcomes for PJI. Eligible studies included randomized controlled trials and cohort studies with a minimum of 10 patients diagnosed with PJI. Our methodology adhered closely to the PRISMA guidelines. Using a saturation approach, we extracted and grouped explicit definitions of PJI outcomes into thematic criteria. A network plot (Figure 1) was used to visualize how frequently these criteria appeared and how they co-occurred across the included studies. Results Out of 7,584 screened studies, 552 (7.3%) met the inclusion criteria. This pilot analysis included 49 randomly selected studies (8,162 patients), mostly retrospective (48/49, 98%), focusing on mixed joint replacements (25/49, 51%), two-stage exchanges (15/49, 31%), or mixed surgeries (24/49, 49%). Only 6/49 (12.2%) applied a society-endorsed definition, and 13/49 (26.5%) cited a reference for their outcome definitions. Overall, 32/49 (65.3%) explicitly defined "success," 35/49 (71.4%) defined "failure," and 16/49 (32.7%) defined both. Most studies (25/49, 51%) had follow-up periods over two years, and 14/49 (28.6%) included patient-reported outcomes, identifying 14 unique PROMs (most commonly UCLA, HHS, and KSS scores). Functional outcomes were assessed in 13/49 (26.5%) studies. We identified 16 distinct outcome criteria across seven categories: clinical signs, microbiology, imaging, histopathology, antibiotics-related, surgical-related, and mortality. Network analysis revealed strong links among clinical signs, microbiology, surgical factors, mortality, and imaging. Conclusion Our pilot study found major variation in PJI outcome definitions, with few standardized criteria. A consensus-driven approach is needed to strengthen evidence synthesis and advance patient care in PJI. Disclosures All Authors: No reported disclosures

Abstract Background Despite a total decrease in age-adjusted mortality rate (AAMR) for HIV across all demographic variables, a multitude of factors have accounted for this cumulative effect of reduction in AAMR, including HIV-related hospitalizations, as 59% of these deaths occur in a medical facility. This study’s main objective is to provide insights from the national in-patient database for the recent years regarding the trends of HIV-associated in-hospital mortality and their healthcare resource utilization.Figure 1:(A). shows age-distribution of HIV-related hospitalizations (n=289,095); (B). gender; (C). age-groups; (D). racial/ethnic groups; (E). Trends in age-adjusted mortality rates among gender; (F). Trends in age-adjusted mortality rates among racial/ethnic groups.(A). Histogram (age).(B). Pie-chart (frequency).(C). Distribution dot-plot (horizontal).(D). Bar graph (vertical).(E). Line graph (two-groups).(F). Line graph (four-groups).Figure 2:Trend analysis for crude mortality of in-hospital HIV mortality among gender (A), race (B); inflation-adjusted hospitalization cost from 2016-2022 among gender (C), and race (D); and length of hospital stay among gender (E) and race (F).The Cochrane-Armitage test is used for crude mortality rate trend analysis for the years 2016 up to 2022.The Jonckheere-Terpstra test is used for non-parametric distribution of trends in length of stay and hospitalization costs (inflation-adjusted). Methods The National Inpatient Sample (NIS) database was searched from 2016 to 2022 to identify patients with HIV (ICD-10 Codes: B20-B24). Hospital discharge weights for national representation were utilized. Baseline social and demographic characteristics along with hospital-level variables were analyzed subsequently using the odds ratio with multivariate regression analysis for mortality adjusted with age. Secondary outcomes included length of hospital stay and inflation-adjusted costs. For cost-based analysis, inflation adjustment was performed according to the inflation index for the Medical Care Consumer Price Index (CPI).Figure 3:A-Univariate analysis of sociodemographic variables associated with in-hospital mortality with HIV; B-Significant predictors of in-hospital mortality with HIV in patients with comorbidities; C- Top 20 listed primary causes of admission stratified by ICD-10 codes in HIV patients.Top 20 listed primary causes of hospitalization in HIV patients from the year 2016 to 2022:1. B20 = HIV-related conditions.2. A41.9 = Sepsis, unspecified organism.3. J18.9 = Pneumonia, unspecified organism.4. N17.9 = Acute kidney failure, unspecified.5. J44.1 = Chronic obstructive pulmonary disease with (acute) exacerbation.6. U07.1 = COVID-19 infection.7. Z51.11 = Encounter for antineoplastic chemotherapy.8. I13.0 = Hypertensive heart and chronic kidney disease (CKD) with heart failure and stage 1 through stage 4 CKD.9. I10.0 = Hypertensive heart disease with heart failure.10. I21.4 = Non-ST elevation (NSTEMI) myocardial infarction.11. A41.89 = Other specified sepsis.12. I13.2 = Hypertensive heart and chronic kidney disease (CKD) with heart failure and with stage 5 CKD, or end-stage renal disease.13. F25.0 = Schizoaffective disorder, bipolar type.14. F33.2 = Major depressive disorder, recurrent severe without psychotic features.15. J96.01 = Acute respiratory failure with hypoxia.16. F10.239 Alcohol dependence with withdrawal, unspecified.17. O98.72 = HIV disease complicating childbirth.18. F25.9 = Schizoaffective disorder, unspecified.19. I12.0 = Hypertensive chronic kidney disease (CKD) with stage 5 (CKD) or end-stage renal disease.20. K52.9 = Noninfective gastroenteritis and colitis, unspecified.Table 1:Baseline characteristics of the study population.ED: emergency; HMO: health maintenance organization; DRG: diagnosis related groups; LOS: length of stay; SNF: skilled nursing facility; AMA: against medical device; NCHS: National Center for Health Statistics. Results A total of 289,095 HIV-related hospitalizations were included, which represents a weighted size of 1,445,475 hospital discharges. The mean age was 50.24 years, with 68.3% males and 51.85% African Americans. A total of 2.59% in-hospital deaths occurred; AAMR was 7029 per 100,000 hospitalizations in males, which was higher than females (5644 per 100,000). AAMR was found to be highest in the Hispanic population, at 8184 per 100,000. Males had a 3% annual percent change from 2016 to 2022, while trends show an increase in deaths in other races, like Asians/Pacific Islanders/Natives. Most deaths occurred in the West region (OR=1.43), non-metropolitan areas (OR=1.40), and medium-large bed-size hospitals (OR=1.28). Conclusion HIV-related in-hospital mortality has posed a significant challenge across various demographic factors. Utilizing mortality data from large databases can serve as a valuable screening tool for targeted public health surveillance and allocation of resources to obtain further development of tailored health programs and interventions aimed particularly at allocation of resources in reducing the impact of HIV-related deaths. Disclosures All Authors: No reported disclosures

Abstract Background The increased frequency of spinal surgeries has led to a rise in postoperative spine infections (PSIs), now recognized as the third most common surgical complication. Currently, there is no standardized definition of PSI, complicating clinical management and research. This meta-epidemiological study aimed to develop clear diagnostic criteria to assist clinicians and researchers in identifying and reporting PSIs consistently. 2020 PRISMA flow diagram Sankey diagram showing the distribution of combination of criteria or definitions used by the authors. This refers to 21 articles that used a definition derived by the authors. Methods Following PRISMA guidelines, a comprehensive literature search was conducted by a medical librarian using Ovid MEDLINE (March 14, 2024). Studies were included if they reported on at least ten adult patients diagnosed with PSI and provided clear diagnostic definitions. The primary objective was to evaluate existing PSI diagnostic criteria and categorize them into thematic clusters. We constructed standardized diagnostic combinations using 13 predefined criteria derived from clinical practice guidelines and prior research (Table 1).Characteristics of the included studies*Total can be more than 100% since some variables can be present in multiple categories.This refers to 21 articles that used a definition derived by the authors. For articles #411 and #630 categorization was not possible as the definition provided only information about the depth of infection and not the criteria for diagnosis. Article #1148 was included as, defining “presumed aspetic” cases meant, by definition, also defining infectious cases.Abbreviations. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), Centers for Disease Control and Prevention (CDC), The National Healthcare Safety Network (NHSN), Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA), Magnetic Resonance Imaging (MRI) Results From an initial 1,466 studies screened, 101 were included (Figure 1). Most studies were retrospective (91/101, 92.1%), and a majority (77/101, 76.2%) relied on established criteria such as those from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) or the CDC. Seven studies combined predefined criteria with additional detailed explanations. Among the remaining studies using independent definitions, clinical signs and symptoms were the most common criteria (13/24, 54.2%) (Table 1). Criteria were grouped into clinical, microbiological, and radiological categories, with most studies primarily using clinical criteria alone or in combination with microbiological or imaging findings (Figure 2). Conclusion There was no clear consensus in the literature on what defines a PSI. Our findings emphasize the necessity of establishing a standardized PSI definition that integrates clinical, microbiological, and radiological criteria. Implementing such a unified framework could enhance diagnostic accuracy, address existing limitations associated with hardware complications, wound drainage interpretations, and imaging ambiguities, and improve upon the current shortcomings of surveillance systems. Disclosures Jeremy D. Shaw, MD, Globus: Grant/Research Support|Purgo Scientific: Advisor/Consultant|Purgo Scientific: Stocks/Bonds (Private Company)

Abstract Background Cardiac implantable electronic device infection (CIEDI) is a serious complication, occurring in approximately 1% of implantations. In addition to antimicrobial therapy, complete device extraction is considered essential for definitive cure. However, this may not always be feasible due to a variety of factors. In select cases, long-term chronic antibiotic suppression (CAS) has been used, yet clinical characteristics and outcomes of patients who received CAS have scarcely been reported. Methods A descriptive study analyzing all adult (age > 18) patients with definite CIEDI who received CAS between 2016 and 2023 across the Mayo Clinic Enterprise (Arizona, Florida, Minnesota, and Upper Midwest) was conducted. Patients with either ventricular assist devices or fungal infection were excluded. Results A total of 321 patients were diagnosed with definite CIEDI during the study period. A total of 37 (8.7%) patients received CAS due to device retention. The median age was 77.5 [IQR 70.5, 87.5] with 32.4% female. Permanent pacemakers were involved in most (64.9%) infections. Approximately one-third (32.4%) of patients had a prosthetic valve. The median time from initial device implantation to CIEDI was 10.6 years [IQR 4.8, 18.1]. CIED-related infective endocarditis was present in 70.3% of cases and 67.6% had lead involvement. The most commonly isolated organisms were Staphylococcus aureus (29.7%), coagulase-negative staphylococci (27%), Enterococcus faecalis (13.5%) and Streptococci (13.5%). Other pathogens or culture-negative cases comprised 16.3%. The primary reason for device retention and CAS was poor surgical candidacy. Doxycycline was the most commonly used agent for CAS, accounting for 37.8% of cases. The average length of suppression was 469.0 days [IQR158.0, 1264.0]. The rate of relapse was 8.1% with all occurring within 90 days of diagnosis. One year mortality was 27.0%. Conclusion CAS may be a feasible option for patients with device retention, although a small proportion experience CIEDI relapse. Unexpectedly, the pathogen distribution among CAS recipients differed from that seen in a general CIED infection population, highlighting selection bias and the distinct clinical characteristics of patients managed with CAS. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties).

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