Citations

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.

ABSTRACT Achromobacter species are Gram-negative bacilli that predominantly affect individuals with cystic fibrosis or those with immunocompromising conditions. Clinical and microbiologic data on Achromobacter species are limited due to the rarity of these organisms and challenges with species-level identification. We conducted a 10-year retrospective analysis (1 January 2013 to 14 March 2023) of all bloodstream and non-bloodstream Achromobacter isolates identified at three tertiary-care Mayo Clinic locations (Minnesota, Arizona, and Florida). Additionally, we examined clinical characteristics of adult patients with Achromobacter bloodstream isolates. A total of 1,598 Achromobacter isolates, encompassing 1,545 non-bloodstream isolates and 53 bloodstream isolates, were identified. The most frequently identified species was Achromobacter xylosoxidans , though species-level identification was not possible for many isolates. Among adult patients with Achromobacter bloodstream infection, the mean age was 58.3 years (standard deviation ± 16.7), 73.1% had a central venous catheter, and 59.6% were immunocompromised. All-cause mortality was 10.2% at 30 days and 18.4% at 90 days. Bloodstream isolates exhibited greater than 90% susceptibility to meropenem, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole. The respiratory tract was the most common source of non-bloodstream isolates (57.5%). Non-bloodstream isolates showed high susceptibility to imipenem (94.6%), piperacillin-tazobactam (92.8%), trimethoprim-sulfamethoxazole (92.1%), and meropenem (87.5%) while demonstrating significant resistance to fluoroquinolones and aminoglycosides. Our findings support the use of piperacillin-tazobactam, carbapenems, or trimethoprim-sulfamethoxazole as initial therapy for Achromobacter infections. Further research is needed to better define the clinical and microbiologic characteristics of Achromobacter infections. IMPORTANCE Achromobacter is a rare but important genus of bacteria that tends to cause infection in those with cystic fibrosis, recurrent healthcare exposures, and/or an immunocompromising condition. There is limited data on the clinical profile of Achromobacter infections as well as optimal antibiotic selection for affected patients. We conducted a retrospective study to improve understanding of the microbiologic and clinical characteristics of Achromobacter . Our study consists of a 10-year survey of all Achromobacter isolates processed by three Mayo Clinic tertiary-care centers in Minnesota, Florida, and Arizona from 2013 to 2023. We report multiple findings, including the clinical characteristics of patients with Achromobacter bloodstream infection, the number of different Achromobacter species identified, and the sources of isolates not obtained from blood cultures. We additionally present antimicrobial susceptibility results for Achromobacter isolates. Our study provides guidance to clinicians treating Achromobacter infections and, it is hoped, will facilitate ongoing study of Achromobacter .

Abstract Purpose No consistent recommendations exist on how best to educate pharmacists to facilitate implementation of new evidence-based practices. This study aimed to determine whether spaced learning was more effective than traditional education when learning a new evidence-based practice (β-lactam therapeutic drug monitoring, or TDM). Summary β-lactam TDM was implemented in a phased fashion at Mayo Clinic in Rochester. Two go-lives took place, separated by 6 months, which allowed for a natural experiment to test education delivery methods (traditional education in the first go-live group of pharmacists vs spaced learning in the second go-live group of pharmacists). Each group received the same base educational package, with pharmacists in the spaced learning group also offered monthly in-person sessions for 6 months before go-live to discuss key considerations and cases with experts. There was no difference between the spaced learning group and the traditional education group when assessing appropriate use of TDM as defined by (1) appropriate patient selection; (2) correct ordering of laboratory testing; (3) appropriate clinical action; and (4) completed documentation. Assessments of secondary knowledge transfer also showed no difference between the groups. Pharmacists in the different education groups had similar satisfaction scores related to the effect and utility of the education. Both spaced learning and traditional education were part of a comprehensive implementation plan for β-lactam TDM, which might have influenced the outcomes. Spaced learning for future pharmacist education efforts needs further study. Conclusion As part of a greater β-lactam TDM implementation effort, altering the education delivery method did not impact the degree of knowledge transfer.

This study aimed to determine if extended infusion (EI; over > 3 hr) beta-lactam therapy increased IV access requirements compared with traditional dosing (TD; over 30 min). Eighty-six adult ICU patients treated with TD anti-pseudomonal beta-lactams who underwent therapeutic drug monitoring (TDM) were included. Patients who transitioned from TD to EI after TDM (EI group) were matched 1:1 to patients who remained on TD. In the primary analysis, the median (interquartile range) total number of lumens in the 24 hours before TDM compared with the 48 hours after TDM were similar between groups (pre: TD 3 [2–5] vs. EI 4 [3–5]; p = 0.22 and post: TD 3 [2–4] vs. EI 4 [3–5]; p = 0.05). Delivery of beta-lactams via EI was not associated with a need for more IV access. Practical challenges such as access should not limit use of EI beta-lactams when indicated.

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.