Saleh, Omar Abu

Abstract Background Persistent candidemia (PC) occurs in a minority of Candida bloodstream infections (BSIs) but is associated with increased morbidity. Comparative data on patient profile, species distribution and outcomes are limited.Table 1Clinical profile and outcomes of patients with persistent candidemia in the primary study cohort. ANC = absolute neutrophil count. SD = standard deviation.Table 2Comparative analysis of persistent candidemia and non-persistent candidemia cases. Methods All candidemia episodes at three academic medical centers (2018-2025) were reviewed. Persistence was defined as ≥72 hours of positive blood cultures after appropriate antifungal initiation. Each PC case was matched 1:2 to non-PC controls who survived ≥72 hours. Demographics, Charlson Comorbidity Index (CCI), Candida species distribution, and outcomes were used for comparative analysis. Continuous variables were summarized as median (interquartile range [IQR]) and compared with Wilcoxon rank-sum, while categorical data (n%) were analyzed by Fisher’s exact test (species by χ²), yielding odds ratios (ORs) with 95% confidence intervals (CIs). Two-tailed p < 0.05 denoted significance. Results Each PC case (n = 46) was matched 1:2 to non-PC controls (n = 92). Clinical profiles and outcomes of PC cases are presented in Table 1. Most PC patients (54.3%) had an immunocompromising condition, and non-urinary intra-abdominal sources were the most frequently suspected infection source (21/46; 45.7%). All but one of 46 PC cases had antibiotic exposure within the preceding 90 days. Comparative demographics and outcomes for PC cases and non-PC controls are displayed in Table 2. PC patients were younger (median 62 yr, IQR 45–69 vs 68 yr, 57–76; p = 0.01), more often female (59% vs 30%; OR 3.3, 95% CI 1.5–7.1; p = 0.002), and had higher comorbidity (CCI 5, IQR 3–8 vs 3, 1–4; p < 0.001). Species distribution differed (χ² p = 0.04), driven by C. guilliermondii over-representation in PC cases (9% vs 0%) (Figures 1 and 2). Hospital stay was longer in PC cases (median 36 d, 24–54 vs 16 d, 8–28; p < 0.001) and time from admission to first culture greater (12 d, 3–26 vs 3 d, 1–10; p = 0.003). 90-day mortality was 54.3% (25/46) in PC cases versus 31.5% (29/92) in controls (OR 2.57, 95% CI 1.17–5.71; p = 0.016). Conclusion In this 7-year multicenter study, there were significant differences in demographics, microbiology, and clinical outcomes between PC and non-PC cases, including higher short-term mortality rates with PC in univariate analysis. Disclosures Paschalis Vergidis, MD, MSc, Current Fungal Infection Reports: Honoraria|F2G: Grant/Research Support|Merck Manuals: Honoraria|Mundipharma: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) is effective and cost-efficient, but 12%–63% of patients experience adverse events, requiring close monitoring. Therapeutic drug monitoring (TDM) is routinely used for vancomycin and aminoglycosides but is underutilized for beta-lactams (BLs) due to limited access, logistical barriers, and clinician inexperience. This study evaluated its use and clinical impact within a high-volume OPAT program. Methods This retrospective, single-center cohort included adult patients (≥18 years) enrolled in an OPAT program who received cefepime (CEF), piperacillin/tazobactam (TZP), or meropenem (MEN) and underwent BL TDM between April 2023 and April 2025. BL TDM was not protocolized within the OPAT program; however, institutional guidance supported its use in carefully selected patients. We aimed to describe TDM indications, lab trends, microbiological profiles, and the impact of TDM on treatment. Results During the study period, 25 OPAT patients underwent BL TDM. TDM was performed in patients receiving CEF (64%), TZP (20%), and MEN (16%). The most common indication for TDM was suspected beta-lactam toxicity (32%) (Figure 1). Post-TDM therapy adjustments were made in 52% (n = 13), including changes in dosing frequency (38.5%) and dosage strength (30.8%). Additional changes included infusion strategy modification or agent substitution (15.4% each). Subtherapeutic levels were the most common reason for adjustment (46.2%), followed by adverse effects, supratherapeutic levels, and changes in renal function (23.1% each). Skin, soft tissue, and musculoskeletal infections were most common (Figure 2). Positive cultures were present in 80%, with Pseudomonas spp most frequently isolated. Therapy was completed in 17 patients; 7 discontinued early, and 1 had treatment ongoing. Reasons for therapy discontinuation are detailed in Table 1. Conclusion BL TDM is contributing to a paradigm shift in OPAT practice by improving both efficacy and safety. While inpatient TDM typically targets efficacy, safety concerns more commonly motivate TDM in the OPAT setting. Although this review involved a small cohort, our experience adds to the growing body of evidence supporting BL TDM as a tool to enhance patient outcomes in the OPAT setting. Disclosures All Authors: No reported disclosures

Abstract Background Leishmaniasis is a rare protozoan parasitic disease transmitted through the bite of infected Phlebotomus and Lutzomyia sandflies. Clinical presentation is variable due to numerous species and host immunity differences. We present our clinical experiences with CL to guide timely diagnosis and treatment in returning travelers. Methods We retrospectively analyzed a cohort of adult patients 18+ years old who were diagnosed with CL from 2005 and 2025. We describe the demographic, clinical, and diagnostic features of CL. Results Biopsy-confirmed CL was diagnosed in 20 returning travelers (Table 1) from various endemic regions, most commonly Costa Rica (Fig. 1). The median time from travel to symptom onset was 36.5 days (SD 102), with an additional 75.5 days (SD 87) prior to biopsy diagnosis. All patients were evaluated by dermatology and 70% were evaluated by infectious disease (n=14). On initial presentation, lesions were described as ulcerated (50%, n=10), nodular (30%, n=6), painful (20%, n=4), and necrotic (10%, n=2; Fig. 2). Most lesions were located on the upper extremity (55%, n=11), followed by the face (35%, n=7), lower extremity (30%, n=6), and trunk (15%, n=3). 15% of individuals (n=3) had constitutional symptoms. No patients had definitive mucosal involvement, however, 10% (n=2) endorsed lip edema. No patients had visceral involvement. Species level identification occurred in 14 cases (70%), of which the most common was L.V. panamensis (50%), L.L. mexicana (21%), L. V. guyanensis (14%), L. L. tropica (7%), and L. V. braziliensis (7%). Initial treatments included azoles, liposomal amphotericin B (AmBisome), and miltefosine (each 20%); cryotherapy and parenteral pentamidine (each 10%); with compounded topical paromomycin added in 15% of cases. 35% of individuals (n=7) failed initial treatment and required additional treatment courses due to persistent lesions (57%) or relapse following initial resolution (14%). 10% (n=2) required a third treatment course due to persistent/recurrent lesions. Conclusion While CL in travelers has a variety of clinical manifestations, travel history, knowledge of key clinical features, and lesion patterns can aid in early diagnosis and treatment. CL is associated with early treatment failure rate for uncertain reasons. Disclosures All Authors: No reported disclosures

Abstract Background Good syndrome (GS) is an under-recognized adult-onset immunodeficiency characterized by the coexistence of thymoma and hypogammaglobulinemia. It is marked by recurrent infections, combined B- and T-cell immunodeficiency, and frequent autoimmune manifestations. Its rarity, unclear pathogenesis, and often delayed diagnosis contribute to its clinical complexity.Distribution of Infections by pathogen type in patients with Good Syndrome: the microbiological spectrumDemographics, clinical characteristics, thymoma classification with staging and management Methods We conducted a retrospective review of adults diagnosed with good syndrome at Mayo Clinic up until 2024. We assessed baseline characteristics, clinical features with a particular focus on infectious complications, immunological lab parameters, thymoma histopathology with staging, and management. Descriptive statistics were utilized for analysis.Immunological lab parameters and management of Good syndrome Results During the study period, Good syndrome was diagnosed in 32 patients; 78% were male, with a median age at diagnosis of 62 years (Table 1). All patients had thymoma, the majority of which were stage I (localized), and most underwent thymectomy as part of management. The median delay in GS diagnosis following thymoma diagnosis was 1,486 days (interquartile range IQR: 406.75–1,992.75). Infectious complications were observed in 30 of 32 patients (97%), most commonly sinopulmonary infections (87%) (Figure 1). Bacterial infections were documented in 29 patients (94%), viral in 14 (45%), fungal in 13 (42%), and mycobacterial in 3 (10%) (Figure 2). Immunologic data were available for 22 patients. Reduced CD4+ T-cell counts and severe B-cell lymphopenia were observed in 77%. IgM and IgG deficiencies were the most prevalent, present in 82% of cases. Most patients received monthly immunoglobulin replacement; additionally, 59% were prescribed oral antimicrobial prophylaxis due to their elevated risk of infections. All-cause mortality was 31% (n=10); among these, 3 deaths (10%) were directly attributable to complications of Good syndrome. Conclusion We observed a significant delay (Median of 4.07 years) in the diagnosis of Good syndrome following thymoma detection. Given the high risk of infectious complications and associated mortality, clinicians should maintain a high index of suspicion and consider early immunologic evaluation in adults with recurrent or opportunistic infections, particularly in the context of a known thymoma. Disclosures All Authors: No reported disclosures

Abstract Background Beta-lactam pharmacokinetics can be significantly altered in patients with malignancy. Therapeutic drug monitoring (TDM; i.e., drug level testing) may facilitate pharmacokinetic/pharmacodynamic (PK/PD) target attainment, but the data are limited. This study aimed to characterize PK/PD target attainment of anti-pseudomonal beta-lactams in hematology/oncology patients.Table 1:Case DescriptionGraph 1:Distribution of Beta-Lactam TDM Indications Methods We conducted a retrospective review of beta-lactam TDM performed between June 2022 and June 2024 in hospitalized adults with hematologic or solid organ malignancies. We included patients who underwent beta-lactam TDM during clinical care, typically for extracorporeal membrane oxygenation (ECMO), extremes of body weight, suspected augmented renal clearance, multidrug-resistant infection, or suspected dose-dependent beta-lactam toxicity. Primary outcomes were (1) the proportion achieving target beta-lactam concentrations and (2) the proportion undergoing antibiotic dose adjustment based on TDM results.Table 2:Institutional Dosing Guidelines Results There were 47 TDM episodes in 20 unique patients. Considering only the first TDM per patient, 10 (50%) patients achieved target concentrations, 2 (10%) were below target, and 6 (30%) were above target. Antibiotic dose adjustments were made in 8 (40%) patients in response to TDM results. The most common indication for beta-lactam TDM was concerns regarding accurate renal clearance, followed by extremes of weight. Conclusion Retrospective findings suggest that beta-lactam TDM facilitated individualization of therapy in 40% of patients with either hematological or solid organ malignancy, with dose adjustments often intended to improve antibiotic safety. Future studies should refine the criteria for beta-lactam TDM use in this population and determine the need for tailored PK/PD targets in patients with impaired host response to infection. 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 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 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

Abstract Background Although recent guidance recommends early surgical debridement for native joint septic arthritis (NJSA), supporting data, particularly on long-term outcomes, remains scarce. 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 1 year were assessed using a 9-level Desirability of Outcome Ranking (DOOR) scale, incorporating survival, treatment failure (relapse, reinfection, readmission, or significant surgical events), and joint recovery. Time to surgery from hospital admission was analyzed both as a continuous variable and as categories: < 1, 1–2, or ≥3 days. Results Among 268 patients, 30% underwent surgery <1 day from admission, 47% in 1–2 days, and 24% in ≥3 days. At 1 year, 57% achieved full recovery without unfavorable events (DOOR score 1), while treatment failure occurred in 34%. In unadjusted analyses, longer surgical delay was significantly associated with higher (worse) DOOR scores (per IQR increase [from 0 to 2 days], OR: 1.5; 95% CI: 1.0–2.1; P = .026), increased 1-year mortality (HR: 1.7; 95% CI: 1.1–2.6; P = .019) and treatment failure (HR: 1.5; 95% CI: 1.1–2.0; P = .007). Even after adjusting for age and Charlson comorbidity index, the association between surgical delay and treatment failure remained significant (HR: 1.5; 95% CI, 1.1–2.0; P = .016). Conclusions The finding that delayed surgical intervention is associated with an increased risk of treatment failure reinforces current expert recommendations for timely surgical management in NJSA.