Lahr, Brian D.

Abstract Background We investigated the relationship between cumulative, historical antibiotic therapy and the presence of ceftriaxone-resistant (CRO-R) Enterobacterales bloodstream infections (BSI) from urinary sources. Methods Adult patients established with primary care at Mayo Clinic with a first episode of monomicrobial Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis BSI from a urinary source from May 2019 to May 2023 were included. Antibiotic therapy over the year prior to BSI was quantified as days of therapy (DOT), cumulative modified Antibiotic Spectrum Index (mASI), and cumulative Days of Antibiotic Spectrum Coverage (DASC) using prescription data. Patients with CRO-R urinary pathogens prior to antibiotic therapy assessment were excluded. Results In total, 721 adults had monomicrobial gram-negative BSI, including 70 patients (9.7%) with a CRO-R pathogen and 651 patients (90.3%) with a ceftriaxone-susceptible (CRO-S) pathogen. In the 12 months prior to BSI, levels of antibiotic DOT, mASI, and DASC were significantly greater among patients with CRO-R BSI than CRO-S BSI (P < .001). The median time from blood culture collection to appropriate antibiotic therapy was significantly longer in the CRO-R group (24 hours, interquartile range [IQR] 16–48) than the CRO-S group (1 hour, IQR 0–2) (P < .001). Increasing cumulative antibiotic therapy prior to BSI, as quantified by the mASI, was significantly associated with increased risk of 1-year CDI after BSI (P = .027). Conclusions Patients with first episode CRO-R Enterobacterales BSI had significantly greater prior antibiotic exposure than patients with CRO-S BSI and experienced significant delay of appropriate therapy. Routine quantitation and reporting of prior antibiotic therapy may improve empiric prescribing.

Background: The relationship between vegetation characteristics in Staphylococcus aureus infective endocarditis (IE) and blood culture time to positivity (TTP) has not been investigated. This study evaluates the correlation between vegetation length and TTP in patients with S. aureus IE. Methods: A retrospective cohort study was conducted that included 164 definite cases S. aureus IE. Vegetation length was determined by transesophageal echocardiography (TEE), and TTP was measured in hours from the initial time of blood culture incubation to positivity. Correlations between vegetation characteristics and TTP were analyzed using Spearman’s rank correlation coefficient. Results: A modest but statistically significant negative correlation was observed between vegetation length and TTP (Spearman ρ = −0.18, p = 0.020), suggesting that larger vegetations were associated with shorter TTP. No significant correlations were found for other vegetation characteristics (e.g., vegetation mobility, location, or number) and TTP. Conclusions: Larger vegetation size in S. aureus IE was associated with shorter TTP. These findings highlight the importance of vegetation size in the pathophysiology of S. aureus IE and its role in bacteremia dynamics.

Background: The objective of this study was to describe thrombin generation in children undergoing cardiac surgery with cardiopulmonary bypass. Change in the endogenous thrombin potential (ETP) across three measurements before and after cardiopulmonary bypass (after protamine and at chest closure) was the primary outcome. Secondary analyses explored an association between thrombin generation and transfusion requirements and predictors of the thrombin generation decline. Methods: Blood samples of children (median age, 6.3 months; 68.5% weighed less than 10 kg) were collected intraoperatively three times: before administration of heparin (baseline), shortly after protamine, and at sternal closure. Platelet-poor plasma obtained after centrifugation of these samples was frozen at −80ºC. Thrombin generation and anti-Xa assays were performed in series on batches of thawed samples to evaluate thrombin generation parameters and functional activity of unfractionated heparin, which could have affected thrombin generation assay results. Results: Between August 2022 and May 2024, 162 plasma samples from 54 patients were collected and analyzed. Compared with baseline, mean ETP decreased by 1,911 nM (95% CI, 1,655 to 2,168) after administration of protamine and by 1,865 nM (95% CI, 1,609 to 2,122) at sternal closure (P < 0.001). Similar changes were observed in secondary thrombin generation parameters. Median unfractionated heparin activity was less than 0.1 U/ml at all three time points. Secondary analyses showed a strong negative correlation between ETP after protamine and volume of transfusion after bypass (ρ = −0.52, P < 0.001). Among five examined factors, only total heparin dose was independently associated with ETP decline, with a higher dose being predictive of greater ETP decline (P = 0.002). Conclusions: In children undergoing cardiac surgery, thrombin generation assay revealed significant and persistent decline in endogenous thrombin potential after cardiopulmonary bypass, despite hemostatic interventions. This reduced thrombin potential correlated with a higher volume of transfusions. Additionally, greater intraoperative heparin requirements could be linked to a more pronounced decline in thrombin generation.

Abstract Background There remains a lack of consensus regarding the postoperative treatment regimen in patients with native valve Staphylococcus aureus infective endocarditis who undergo surgical valve replacement or repair. Methods We conducted a multicenter retrospective review of patients with S aureus native valve endocarditis who underwent surgical valve replacement or repair at Mayo Clinic Enterprise (Minnesota, Florida, Arizona, and Mayo Clinic Health Systems) between 1 January 2012 and 31 December 2022. Postoperative treatment regimens were classified as either monotherapy with a methicillin-sensitive or methicillin-resistant S aureus active agent or combination therapy that included rifampin and/or gentamicin with either active agent. Results Of the 339 patients diagnosed with S aureus native valve endocarditis, 61 underwent surgical valve replacement or repair within the initial 6 weeks of antimicrobial therapy. A total of 12 (20.2%) patients died during the 1-year follow-up period. Between patients postoperatively treated with monotherapy (n = 33) and combination therapy (n = 28), a propensity score–weighted analysis revealed that combination therapy was associated with increased risk of 1-year mortality (P = .039), 6-month relapse (P = .016), and treatment-related adverse events (P &lt; .001). Conclusions Among patients treated for native valve infective endocarditis caused by S aureus after valvular surgical intervention, all study outcomes—adverse events and drug-drug interactions, 6-month infective endocarditis relapse, and 1-year mortality—were higher in the combination therapy group than the monotherapy group.

Abstract Background The Rochester Epidemiology Project (REP) has been used to examine numerous infectious and non-infectious entities in a population-based approach in Olmsted County, Minnesota. To further investigate patterns of enterococcal bloodstream infection (BSI), we used the Expanded Rochester Epidemiology Project (E-REP) to include additional surrounding counties to conduct a retrospective population-based study of adult patients who developed enterococcal BSI, with or without infective endocarditis (IE). Methods The E-REP population under study included eight counties in southeastern Minnesota (including Olmsted County), representing a total population of over 250,000 individuals. Adults (age ≥ 18 years) diagnosed with an initial episode of enterococcal BSI with or without enterococcal IE between January 1, 2018 and December 31, 2022 were included; patients with either polymicrobial BSI with enterococci or a previous bout of enterococcal BSI before the study period were excluded. Cases of enterococcal BSI and IE were identified using ICD-10 codes and underwent complete medical record review. Patient characteristics, microbiology, antibiotic regimens, infectious complications, and outcomes were collected. Results A total of 113 cases of enterococcal BSI were identified over the five-year study period. The age- and sex-adjusted incidence rate of enterococcal BSI was 6.9 per 100,000 person-years, with a significantly higher rate among males than females (Figure 1). BSI incidence rate varied by age, with patients 80 years or older having the highest incidence rate (Figures 1 and 2). Twenty-two cases of enterococcal IE were identified, yielding an overall IE prevalence of 20.8% (Figure 3). The cumulative mortality rate at 12 months was high at 41.7% (Figure 3). Five patients (4.4%) had a relapse of enterococcal BSI, defined as recurrence of BSI after negative follow-up blood cultures and within 12 weeks of the initial BSI. Conclusion This is the first population-based investigation that has focused on the epidemiology and clinical profile of patients with enterococcal BSI and complicating IE in a US population. This included an IE prevalence of 20.8%, which should be considered when evaluating and managing patients with enterococcal BSI. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties).

Background Echocardiographic evaluation of vegetations is crucial in infective endocarditis ( IE ). Although several studies have noted a link between larger vegetations and an increased risk of embolization, a more comprehensive evaluation of vegetation characteristics in a contemporary cohort has not been conducted. Our study aimed to define the short‐term risk of symptomatic embolization in patients with IE . Methods and Results The Mayo Clinic IE registry was screened to identify patients from 2015 to 2021 who had undergone transesophageal echocardiography. Multivariable subdistribution hazards regression analysis was used to identify factors associated with the cumulative incidence of symptomatic embolism over 30 days accounting for the competing risk of death. Overall, 779 patients with IE were included, of whom 517 (66.4%) were men, median age was 65.0 ( interquartile range, 52.9–74.8) years, and 89.3% were White. In total, 234 patients had a symptomatic embolic event, a 30‐day cumulative incidence of 30.2%. In multivariable analysis, a highly mobile vegetation was the strongest predictor of embolism ( P <0.001). Vegetation length with interaction of IE type was also associated with embolic risk ( P <0.001), with a stronger effect in native valve IE ( P interaction=0.001). Other associated factors included multiple vegetations, younger age, and Staphylococcus aureus . A nomogram that incorporated these factors was constructed to facilitate the prediction of embolic risk. Conclusions Highly mobile, larger vegetations are associated with embolic events. Embolic risk could be assessed by evaluating length as a continuous variable, alongside other echocardiographic findings, using a newly developed scoring tool; external validation is warranted.

Abstract Introduction Vulnerable populations experience a higher burden of cardiovascular disease.(1) However, the incidence of cardiovascular risk factors, such as diabetes, within these populations, is incompletely characterized. Recently, the United States Centers for Disease Control and Prevention (US CDC) developed the Social Vulnerability Index (SVI) to categorize counties that may be vulnerable to worse health outcomes. The SVI is composed of 4 themes: socioeconomic status (Theme 1), household composition & disability (Theme 2), minority status & language (Theme 3), and housing type & transportation (Theme 4).(2) We sought to evaluate the association of the 4 SVI themes with county incidence of diagnosed diabetes. Method We used CDC data (2004-2019; reported for 94% of US counties), on county incidence of diagnosed diabetes. The SVI themes were scored from 0 to 1 (low to high vulnerability) based on national percentile ranking. We used weighted least squares regression with restricted cubic splines to model the relationship between SVI themes and incidence of diagnosed diabetes (median data 2004−2019), adjusting for median age, sex ratio, state, percent uninsured, food environment index, healthcare providers, and rurality.(3) The partial effects of SVI themes and diabetes incidence were reported as F-statistics (P-values) and diabetes incidence rate ratios (IRR [95% confidence interval]), which were plotted for all values compared with the 50th percentile (SVI 0.5). For each theme, we also present the IRR for a 0.5-point increase when moving over the lower (SVI score 0.5 vs. 0.0) and the upper (1.0 vs. 0.5) half of the SVI score distribution. Results The 4 SVI theme rank scores were significantly associated with diabetes incidence (all, P&lt;.001). However, Theme 1 and 2 scores showed stronger associations with IRR than Theme 3 and 4 (Figure). For Theme 1, SVI score 0.5 vs. 0.0 was associated with a 15% higher incidence (IRR 1.15 [1.13–1.18]) and score 1.0 vs. 0.5 was associated with a 13% higher incidence (IRR 1.13 [1.11–1.16]). For Theme 2, SVI score 0.5 vs. 0.0 was associated with a 16% higher incidence (IRR 1.16 [1.14–1.18]), but there was no difference between rates for SVI score 1.0 vs. 0.5 (IRR 1.01 [0.99–1.03]). For Theme 3, there was no difference between SVI score 0.5 vs. 0.0 (IRR 0.98 [0.96–1.00]), but rates were 8% lower for SVI score 1.0 vs. 0.5 (IRR 0.92 [0.90–0.94]). For Theme 4, SVI score 0.5 vs. 0.0 was associated with a 3% lower incidence (IRR 0.97 [0.96–0.99]) and score 1.0 vs. 0.5 was associated with a 2% higher incidence (IRR 1.02 [1.01–1.04]). Conclusion In US counties, the strength and directionality of the association between SVI themes and diabetes incidence differed by theme and level of SVI scores. These themes, particularly socioeconomic status and household composition & disability may be leveraged to identify high-risk counties for primary prevention of diabetes, with implications for reduction in cardiovascular risk.

Aim: The association of echocardiographic findings and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. The aim of this study was to determine if transthoracic echocardiography (TTE) measurements are associated with the subsequent development of LS-NVE in patients without cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and predisposing cardiac conditions were excluded. Only patients who had a TTE performed 6 months to 3 years before the development of LS-NVE were included as cases. Controls were patients within the same Mayo location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson comorbidity index, and echocardiography date. Results: There were 148 cases and 431 matched controls. As compared to controls, infective endocarditis (IE) cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) (P < 0.001). Left ventricular outflow tract velocity (P = 0.017), left ventricular ejection fraction (P = 0.018), and E:e’ ratio (P = 0.050) were associated with LS-NVE. Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this pilot study. A larger cohort of LS-NVE patients, however, is needed to validate these findings.

Abstract We examined the effect of preoperative antibiotic exposure and duration on synovial fluid samples from patients with native joint septic arthritis of the hip/knee. While exposure before diagnostic arthrocentesis did not affect fluid parameters, increased duration was associated with a decreased total nucleated cell count, underscoring the complex antibiotic effects on synovial fluid parameters.

Introduction: We compared outcome of repeat CABG (RCABG) and PCI in patients with previous CABG. Hypothesis: RCABG may improve survival versus PCI. Methods: From 1993 through 2009, 3,058 patients underwent revascularization after previous CABG. RCABG patients (n=530) were grouped by the use of arterial grafts (n=396), or saphenous vein grafts (SVG; n=134). At previous CABG, 37% of RCABG patients received IMA graft. PCI patients (n=2,528) were grouped into balloon angioplasty (BA; n=491), bare metal stent (BMS; n=1,267), and drug-eluting stent (DES; n=769). PCI patients were further stratified by the treated target into native coronary artery (n=1,637), bypass grafts (n=674), or both (n=216). Propensity score analysis matched 287 patients. Results: RCABG had increased 30-day mortality compared with PCI (HR=3.92; 95% CI, 2.25-6.84; P <.001) in multivariable analysis, while in propensity matched analysis it did not ( P =.09). Overall survival, however, was greater for RCABG compared with PCI in multivariable analysis (HR=0.70; 95% CI, 0.59-0.83; P <.001), as well as in propensity matched analysis (10-year survival rates were 52% vs 37%, respectively [ P =.005]). Compared with RCABG, PCI involving bypass grafts had increased mortality (HR, 1.39; 95% CI, 1.09-1.78; P =.008), whereas PCI targeting only the native coronaries did not (HR, 1.12; 95% CI, 0.85-1.47; P =.43); BMS patients had increased mortality (HR, 1.34; 95% CI, 1.06-1.68; P =.013), but DES did not (HR, 1.28; 95% CI, 0.77-2.12; P =.35). At RCABG, 318 patients (60%) received an IMA graft and late survival was similar to those receiving SVG; The use of IMA in previous CABG was associated with improved survival (HR=0.82; 95% CI, 0.72-0.92; P <.001]. Conclusions: Long-term survival after previous CABG is improved with RCABG compared to PCI, especially when PCI involves bypass grafts. There is no difference in long-term survival between RCABG using arterial grafts vs SVG only if IMA is used in either previous or RCABG.