Garcia, Sofia Molina

Abstract Background Chronic Q fever, caused by Coxiella burnetii, presents significant diagnostic and management challenges due to its variable presentation and high morbidity, especially among patients with underlying cardiac or vascular disease. In the United States, cases are rising, often without identifiable exposures, and diagnostic delays remain common. Methods We conducted a retrospective cohort study of chronic Q fever cases at the Mayo Clinic from 2007 to 2023. Patients with clinical evidence and a phase I IgG titer ≥1:1024 and/or positive PCR for C. burnetii were included. Data were abstracted from electronic health records, including demographics, exposures, clinical manifestations, diagnostics, treatments, and outcomes. Statistical analyses assessed factors influencing diagnostic delay and treatment response. Results We identified 33 patients with chronic Q fever (median age 56; 88% male). Median time to diagnosis was 99 days with 11.4 days between Infectious Diseases (ID) evaluation and diagnosis. Animal exposure was reported in 17 patients (52%), while eight (24%) had no identifiable exposure. Patients primarily presented with prosthetic valve endocarditis (n=14, 42%), or vascular graft infection (n=9, 27%). The majority were treated with doxycycline and hydroxychloroquine (n=25, 75%) and 14 patients (42%) required surgical intervention. Mortality attributable to chronic Q fever was 6% (n=2). Conclusions Chronic Q fever remains under-recognized, with substantial diagnostic delays prior to treatment. Cardiovascular infection predominates, and surgical intervention is often required despite prolonged antimicrobial therapy. Early specialist evaluation and standardized diagnostic pathways may improve outcomes.

Abstract Background Lyme arthritis is the most common late manifestation of disseminated Lyme disease in the United States. While most patients respond to antibiotic therapy, a subset develops postantibiotic Lyme arthritis (PALA), characterized by persistent noninfectious inflammatory arthritis. Data describing predictors of PALA and treatment patterns remain limited. Methods We conducted a retrospective observational cohort study of patients with polymerase chain reaction (PCR)−confirmed native joint Lyme arthritis treated at our institution from 2004 to 2025. Clinical, laboratory, imaging, treatment, and outcome data were abstracted from electronic health records. Continuous variables were compared using the Mann–Whitney U test, and categorical variables using Fisher's exact test. Results Seventy-seven patients with PCR-confirmed native joint Lyme arthritis were identified: 64 adults and 13 children. Children more frequently presented with fever and had significantly higher synovial fluid white blood cell counts compared with adults. Knee monoarthritis was the predominant presentation in both groups. Among adults, 41 (64%) achieved complete symptomatic resolution following antibiotic therapy, while 19 (29.7%) developed PALA. Adults who developed PALA had significantly lower synovial fluid white blood cell counts and more extensive joint involvement. The use of intravenous antibiotics and longer total antibiotic duration was more common among PALA patients without evidence of improved outcomes. Conclusions In this cohort of PCR-confirmed native joint Lyme arthritis, a substantial proportion of adults developed PALA. Failure to respond to initial antibiotic therapy and certain clinical features may identify patients at increased risk. These findings support judicious antibiotic use and early consideration of noninfectious mechanisms in persistent arthritis.

Background: Candidemia is a serious complication after gastrointestinal (GI) perforation and/or ischemia, yet most evidence pools candidemia with intra-abdominal candidiasis (IAC). We sought candidemia-specific risk factors after GI perforation and/or ischemia and evaluated associated outcomes. Methods: We conducted a single-center, retrospective matched case–control study of adults undergoing emergency surgical procedure for GI perforation and/or ischemia and admitted to a surgical intensive care unit. Cases with candidemia during index admission were matched 4:1 to controls by age, Charlson Comorbidity Index, and surgical procedure year. Conditional logistic regression assessed pre-specified risk factors, and exploratory outcomes included mortality, length of stay, and days on invasive ventilation. Results: Twenty-four cases were matched to 99 controls. Factors identified to be independently associated with candidemia include the presence of IAC (adjusted OR [aOR]: 5.51, 95% CI: 1.61, 18.89; p = 0.007), upper GI injury (aOR: 4.28, 95% CI: 1.52–12.08; p = 0.006), and diffuse intra-abdominal contamination, compared with contained/none (aOR: 3.21, 95% CI: 1.06–9.74; p = 0.040). Among candidemia cases, species distribution was Candida albicans 41.7%, C. glabrata 33.3%, C. parapsilosis 12.5%, with single cases of C. tropicalis, C. krusei , and C. dubliniensis . Candidemia was associated with a longer hospital length of stay (+13.97 d; 95% CI: 0.90–27.04; p = 0.036), without significant differences in ICU stay, duration of invasive ventilation, or mortality. Conclusions: After GI perforation and/or ischemia, the risk of candidemia is highest in patients with upper GI injury and diffuse contamination, independent of IAC. These readily identifiable operative features may guide targeted surveillance and selective early antifungal strategies. Prospective validation is warranted.

Abstract Background Candidemia can occur as a consequence of gastrointestinal (GI) injury. The mortality of candidemia is high, ranging 30-60%, even with treatment with antifungal agents. In this retrospective matched case-control study, we aimed to elucidate the medical and surgical risk factors of developing candidemia in patients who received emergency surgery for GI ischemia and/or perforation, and compare clinical outcomes in these patients with or without candidemia. Methods All patients ≥ 18 years of age who had emergency GI surgery at Mayo Clinic Rochester, MN, for the indication of GI ischemia and/or perforation between 01/01/2018 to 07/31/2024 were included. Cases were defined as patients who developed candidemia during index admission and had no alternative sources of candidemia. Controls and cases were matched 4:1 on age (± 5 years), Charlson Comorbidity Index (± 3), and year of surgery (± 2 years). The relationships between risk factors of interest and case/control were assessed using conditional logistic regression. Results Among medical risk factors, any shock requiring vasopressor (OR = 3.44, 95% CI 1.00, 11.97) or respiratory failure (OR = 8.20, 95% CI 1.04, 64.53) during hospitalization were associated with increased risk of candidemia. Among surgical risk factors, perforation in the upper GI tract was strongly associated with development of candidemia (OR = 16.99, 95% CI 2.11, 136.95) and perforation in the lower GI tract were less likely to lead to candidemia (OR = 0.06, 95% CI 0.01, 0.44). The patients who had diffuse intraabdominal contamination were more likely to develop candidemia compared to those who had no contamination or contained contamination (OR = 3.87, 95% CI 1.33, 11.25). The patients with candidemia showed signal towards higher in-hospital and 30-day mortality, and had significantly longer stay in the hospital. Conclusion Candidemia was more frequently identified in patients with shock, respiratory failure, upper GI perforation, and intra-abdominal contamination, and contributed to significant morbidity and mortality. Further analysis will include building a multivariate logistic regression model to implement prospective trial for early initiation of antifungal therapy for high-risk population. Disclosures All Authors: No reported disclosures

Abstract Background Lyme arthritis is a manifestation of disseminated infection with Borrelia spp., typically presenting as knee monoarthritis weeks to months after infection. Most patients respond to antibiotics, but some develop antibiotic-refractory Lyme arthritis (ARLA), characterized by proliferative or autoimmune synovitis despite clearance of active infection, with proposed risk factors including treatment delay, host genetics, and intra-articular steroid use prior to antibiotics. Table 1 Characteristics of cohort. IQR = interquartile range, ESR = erythrocyte sedimentation rate, CRP = C-reactive protein, WBC = white blood cell. Table 2 Comparison of characteristics and outcomes between ARLA and non-ARLA patients Methods We performed a retrospective chart review of adult patients with Lyme PCR-positive synovial fluid at our center between 01/2004 and 02/2025. ARLA was defined as persistent inflammatory arthritis despite ≥8 weeks of antibiotics and/or negative repeat PCR after antibiotics. Statistical analysis was done on R and STATA. Figure 1 Type of antibiotics administered during the first course (A) and the second course (B) Figure 2 Box plot comparing the median time from symptom onset and treatment initiation in patients who had complete symptomatic resolution with any duration of antibiotic therapy, and those that did not have symptomatic resolution with antibiotic therapy. Results Table 1 summarizes the characteristics of the study cohort. Definitive Lyme arthritis was diagnosed in 67 patients. Of these, 35 patients (52%) achieved complete symptom resolution after one course of antibiotics, and 45 patients (67%) achieved resolution after up to two courses. Doxycycline was used as first-line therapy in 97% of cases (Figure 1). Antibiotic-refractory Lyme arthritis (ARLA) developed in 20 patients (30%); of these, 7 required disease-modifying antirheumatic drugs (DMARDs), and 3 underwent synovectomy. ARLA was associated with incomplete response to a single antibiotic course and persistent joint effusion on post-treatment radiography (Table 2). Intra-articular steroid use prior to antibiotic therapy was associated with a threefold increased odds of ARLA, although this did not reach statistical significance. Patients who responded to antibiotics had a shorter median time to treatment (19 days) compared to non-responders (42 days) (Figure 2). Conclusion In this cohort, 30% of patients were ultimately diagnosed with antibiotic-refractory Lyme arthritis (ARLA), a rate notably higher than the previously reported 10%. Despite advancements in Lyme disease diagnostics, we observed significant delays in diagnosis and initiation of appropriate antibiotic therapy, as well as the use of intra-articular steroids prior to antibiotics. These factors may contribute to the development of ARLA. 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 Central nervous system (CNS) infections are significant causes of morbidity and mortality, especially when diagnosis is delayed. Traditional cerebrospinal fluid diagnostic methods for CNS infections have limited sensitivity. Metagenomic next-generation sequencing of cerebrospinal fluid (MSCSF) is a newer diagnostic tool capable of detecting a broad range of pathogens in a single assay. Methods This retrospective cohort study evaluated the first-year experience with MSCSF at Mayo Clinic. A total of 422 tests performed during calendar year 2024 on adult patients at Mayo Clinic facilities and those tested through Mayo Clinic Laboratories were analyzed, with a subcohort analysis of the 210 Mayo Clinic patients performed to define patient characteristics associated with positive results and clinical outcomes. Results The sensitivity of MSCSF for detecting neuroinfection in the subcohort was 64%, with 43% of confirmed neuroinfections diagnosed by MSCSF only. Subjects who were immunosuppressed (odds ratio [OR]: 3.5, P = .008) and those with a high pretest probability of CNS infection (OR: 20.1, P < .001) were more likely to have positive results. Also, those who tested positive were more likely to die within the ensuing 30 days than those who tested negative (OR: 5.2, P = .001). Conclusions MSCSF can be a valuable tool for diagnosing CNS infection but should not be used indiscriminately. It appears to be most beneficial when there is a high clinical suspicion of CNS infection and conventional diagnostics, and available molecular tests, yield negative results. Its integration into clinical practice should be guided by diagnostic stewardship to maximize cost-effectiveness and clinical utility.

Abstract Background Infective endocarditis (IE) is a life-threatening infection often challenging to diagnose, particularly in culture-negative cases. Plasma microbial cell-free DNA (mcfDNA) sequencing has shown potential for detecting pathogens in IE. However, its clinical utility, diagnostic impact, and limitations remain debated. This study evaluates its use in diagnosing and managing IE in a tertiary care setting. Methods This single-center retrospective cohort study included adult patients (≥18 years) who underwent mcfDNA sequencing via the Karius test for suspected IE at Mayo Clinic Rochester between December 2019 and February 2024. Diagnostic classification followed the 2023 Duke–International Society of Cardiovascular Infectious Diseases criteria. Data on demographics, clinical features, routine microbiologic workup, and mcfDNA sequencing results were collected. Statistical analysis was conducted to evaluate diagnostic utility and treatment impact. Results Among 141 patients, 66 had a diagnosis of IE, with mcfDNA sequencing identifying pathogens in 60.6% of them, compared with 39.4% with routine workup. mcfDNA sequencing was the sole microbiologic test with positive results in 33.3% of patients, leading to antimicrobial adjustments in 50.0% of that group. Clinically insignificant mcfDNA sequence detection occurred in 28.6% of patients without a diagnosis of IE. Conclusions mcfDNA sequencing is a valuable adjunctive tool for diagnosing culture-negative IE and guiding antimicrobial therapy when clinical suspicion is high. However, its utility depends on appropriate clinical context, highlighting the need for careful test interpretation and further prospective studies to assess patient-centered outcomes and cost-effectiveness.

Background/Objectives: Our study examined 5-year patient and graft survival outcomes among non-smokers, former smokers, and active smokers at the time of liver transplantation (LT) and immediate post-operative complications and short-term outcomes following LT. Methods: This was a retrospective study that examined all liver transplants occurring at Cleveland Clinic Main Campus between January 2015–October 2022. Kaplan–Meier curves examined survival outcomes, and Cox’s multivariate regression analysis was performed. Results: Over the 5-year period, patient survival did not differ statistically between patient groups (all p-values >0.05). However, graft survival was significantly lower in active smokers (p = 0.012). In the multivariate analysis, age (HR = 1.03, 95% CI 1.01–1.05, p = 0.002) and admission to the ICU (HR 1.68, 95% CI 1.13–2.50, p = 0.01) were positively associated with overall mortality. Immediate and short-term complications did not differ statistically between patient groups. Cardiovascular disease (22.5%) was the most common cause of death among all patients. Conclusions: Though our study did not show decreased patient survival outcomes, our findings are in line with previous studies that have shown that pre-transplant smoking is associated with overall reduced graft survival. Combined with the risk for de novo malignancy and cardiovascular events post transplant, smoking cessation before LT should be encouraged to ensure graft longevity.

Introduction Bispecific antibodies (BsAbs) have become a key component of treatment in relapsed/refractory multiple myeloma (MM). However, despite promising response rates demonstrated in clinical trials, BsAbs have been shown to have a distinct adverse event profile including increased risk of infections as compared with conventional treatment regimens. The aim of this study was to explore the infectious risk of MM patients on active treatment with Teclistamab. Methods This was a retrospective study of MM patients treated with Teclistamab at Taussig Cancer Center from December 16th 2022 to March 31st 2024. Patients who completed step up dosing and received at least one dose of Teclistamab at maintenance dose were included in the study. The study period spanned from the date of the first dose of Teclistamab up to 6 months after the last dose of Teclistamab, change in therapy or death. Infections which required inpatient hospitalization occurring during the study period were included in the study. Neutropenia was defined as absolute neutropenia count <1500 cells/uL. Hypogammaglobulinemia was defined as serum IgG levels below 700 mg/dL. Data were collected on baseline patient characteristics, MM disease characteristics, and infection characteristics. The primary endpoint was rate of infections per patient-year. Results A total of 58 MM patients who were treated with Teclistamab at Taussig Cancer Center were screened for the study. 46/58 (79.3%) of those patients met inclusion criteria and were included in the study. Among the 46 patients included in the study, there were 20 infectious episodes that required inpatient hospitalization, occurring among 18 patients. The median age of the 46 patients was 66 with an interquartile range (IQR) of 62-74. Patients had broad exposure to novel agents including proteasome inhibitors (46, 100.0%), immunomodulatory drugs (44, 95.7%) and monoclonal antibodies (44, 95.7%). Other notable treatment exposures included CAR T-cell therapy (15, 32.6%), and autologous stem cell transplant (3, 6.5%). 6/9 (66.7%) of patients who underwent previous CAR T-cell therapy and 2/3 (66.7%) of patients who underwent previous autologous stem cell transplant developed an infection requiring hospitalization. No statistically significant difference was found in patients with infection and prior CAR T-cell therapy or autologous hematopoietic stem cell transplant. The median number of lines of therapy from MM diagnosis to start of Teclistamab therapy was 7 (IQR: 5.5-8). The median time from start of Teclistamab therapy till first infectious episode was 84.5 days (IQR: 27-177). Bacterial infections were most common (12/20, 60%), with the most common organism being Streptococcus spp. (2/12, 17%). The most common source of infection was respiratory (10/20, 50%). Neutropenia was present at diagnosis for 5/20 (25%) infectious episodes with 4/5 (80%) of these episodes having Grade 4 neutropenia. Hypogammaglobulinemia occurred during the study period in 43/46 (93.5%) patients with a median IgG nadir of 168 (IQR: 118-320). 22/43 (51.2%) patients received intravenous immunoglobulin (IVIG) during the study period, with 3/22 (13.6%) of these patients going on to develop an infection that required inpatient hospitalization. Of the 21 patients not administered IVIG, 13/21 (61.9%) went on to develop an infection that required inpatient hospitalization (p-value .0016). The median length of hospital stay for all infectious episodes was 7.5 days (IQR: 4-12.5). 6/20 (30%) infectious episodes required ICU stay with a median length of stay of 4.5 days (IQR: 2-18). The overall rate of infections per patient-year was 0.82. The rate of infections per patient-year for the 22 patients with hypogammaglobulinemia who did receive IVIG was .28. The rate of infections per patient-year for the 21 patients with hypogammaglobulinemia who did not receive IVIG was 1.5 (p-value = .06). The overall infection-related mortality rate was 3/20 (15%). Conclusion Multiple myeloma patients treated with Teclistamab experienced a high rate of infections requiring hospitalization and ICU care while on active treatment regardless of prior CAR T-cell and autologous hemopoietic stem cell transplant. Preventive measures, such as administration of prophylactic IVIG to patients with hypogammaglobulinemia, improved outcomes and should be taken to reduce infectious risk in this susceptible patient population.