Kim, Myeongji

In this retrospective cohort study at a quaternary referral hospital, 829 adult patients supported by extracorporeal membrane oxygenation (ECMO) between January 1, 2014, and October 31, 2024, were screened for ventilator-associated pneumonia (VAP). The incidence of VAP in ECMO-supported patients was 17.7 per 1,000 ECMO days (venoarterial [VA] ECMO, 22.1 per 1,000 ECMO days; venovenous [VV] ECMO, 13.8 per 1,000 ECMO days). Median time from ECMO cannulation to diagnosis of VAP was 4 (interquartile range [IQR], 3–8; range 1–84) days. Gram-negative bacteria comprised most respiratory pathogens. A significant increase in minimum ECMO sweep was noted from 2 days before to 1 day after VAP diagnosis (0.79 L/min increase, p = 0.004). Only 38 of 153 patients (24.8%) met National Healthcare Safety Network (NHSN) VAP definitions. After creating a modified VAP definition, which included an ECMO sweep increase of 0.5 L/min as evidence of worsening respiratory status, 78 (51.0%) met the modified definition. Those who met the modified VAP definition had worse in-hospital (60.3% vs. 28.0%, p < 0.001), 30 day (33.3% vs. 17.3%, p = 0.023), and 90 day (53.8% vs. 25.3%, p < 0.001) mortality compared with those who did not meet the modified VAP definition. The incorporation of ECMO parameters into diagnostic criteria may improve detection sensitivity, but further validation is necessary before implementation.

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 Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is standard therapy for high-risk nonmuscle-invasive bladder cancer. However, M bovis infections can occur and are not well understood. We aimed to characterize clinical phenotypes, diagnosis, management, and outcomes of culture-confirmed M bovis BCG infections following intravesical therapy for urothelial carcinoma. Methods A retrospective single-center review of adults with culture-confirmed M bovis infection after intravesical BCG (May 2009–July 2024) was conducted, abstracting clinical, microbiologic, treatment, and outcome data. Results Twenty-two White male patients (median age, 77 years) were included; 8 (36.4%) had localized genitourinary infection, 6 (27.3%) had dissemination limited to blood, and 8 (36.4%) had dissemination to other organs. Patients with bloodstream-only infection presented acutely (median 1.5 days after last BCG), whereas those with localized or organ-disseminated disease presented months to years after BCG, with the longest diagnostic delays in organ-disseminated infection. Despite all cases had culture-proven M bovis BCG infection, acid-fast smear, Mycobacterium tuberculosis complex polymerase chain reaction, and histopathology had limited sensitivity. All isolates were susceptible to rifampin, isoniazid, and ethambutol; all were resistant to pyrazinamide. Median treatment duration exceeded 9 months, 94.7% achieved cure, and attributable mortality was 5.0% (1 vascular graft infection). Conclusions M bovis BCG infections following intravesical therapy have favorable outcomes but are often associated with diagnostic delays and prolonged treatment. Early suspicion, comprehensive diagnostic evaluation, and timely surgical source control when indicated are critical. Management strategies should be tailored based on the extent of disease dissemination and individual host factors.

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 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

Infective endocarditis (IE) remains a diagnostic challenge, particularly in cases where microbiological diagnosis is not established. Advances in molecular diagnostics have expanded the ability to identify causative pathogens beyond traditional culture-based methods. This review explores the role of molecular assays, including pathogen-specific PCR, multiplex PCR, broad-range PCR, and shotgun metagenomic sequencing, in diagnosing IE. These molecular techniques enhance pathogen detection, especially in patients with prior antibiotic exposure, and improve diagnostic accuracy in culture-negative IE. Broad-range PCR assays and metagenomic sequencing offer the untargeted detection of a wide spectrum of organisms. Despite their advantages, limitations such as availability, interpretation challenges, and a lack of antimicrobial susceptibility testing remain. A multimodal approach integrating molecular diagnostics with conventional methods is essential to optimize patient management. Further research is needed to refine diagnostic algorithms and improve cost-effectiveness in clinical practice.

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.

Abstract Background Plasma microbial cell-free DNA (mcfDNA) sequencing, commercially available from Karius® (Redwood City, CA), has been increasingly utilized in diagnosing endovascular infections. The 2023 updated Duke criteria incorporated detection of pathogen via metagenomic sequencing in its microbiologic criteria. We analyzed the clinical impact of mcfDNA sequencing in the diagnosis and treatment of suspected infective endocarditis (IE) cases. Methods We performed retrospective review of patients with suspected IE who underwent Karius® test at Mayo Clinic, MN, between 2017 to 2023. Results We preformed preliminary analysis of 25 patients. Analysis of baseline characteristics (table 1) revealed that these patients had significant predisposing factors for IE. Before accounting for mcfDNA sequencing, 3 (12%) met criteria for definite IE, 10 (40%) met criteria for possible IE, and 12 (48%) were rejected per 2023 Duke criteria. After incorporating mcfDNA sequencing result, 1 patient who was classified as possible IE was escalated to definite IE. This patient had previous infection of implantable cardioverter-defibrillator (ICD) with Streptococcus dysgalactiae. ICD was removed. She had development of endophthalmitis and stroke, 1 week and 2 weeks after the completion of IV antibiotics, respectively, with echocardiogram showing new tricuspid valve vegetation. Routine work-up was negative despite that she was not on any systemic antibiotics at the time of blood culture collection. mcfDNA sequencing detected Streptococcus dysgalactiae, making definite diagnosis of IE, leading to the physician’s decision to extend the IV antibiotic treatment (treatment escalation). Overall, after mcfDNA sequencing result, treatment decision was not impacted in 14 (56%), ongoing treatment was escalated in 4 (16%), de-escalated in 5 (20%), and antimicrobials was newly initiated in 2 (8%) (figure 1). Positive mcfDNA sequencing result often led to treatment escalation or initiation; negative result often led to treatment de-escalation (figure 2). Conclusion In challenging cases of suspected IE, mcfDNA sequencing led to alteration of antimicrobial treatment in 44% of cases. Further data collection and final analysis will include larger number of patients. Disclosures All Authors: No reported disclosures