Citations

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.

Abstract Background Drugs use during pregnancy is a major social and medical issue, which may lead to significant pre- and post-natal complications, such as preterm birth and newborn mortality. Exposed newborns may have long-term behavioral, cognitive, and developmental problems. Accurate detection of in utero drug exposure is crucial for timely medical intervention for the newborn and the mother. Meconium is the ‘gold standard' matrix for detection of drugs in newborn which reflects drug exposure during pregnancy. This study aims to develop and optimize a clinical assay for simultaneous screening of 21 drugs in meconium using a custom biochip array. Methods Custom biochip array (Randox Laboratories Ltd.) included 21 discrete test regions (DTRs) for amphetamine, methamphetamine, opioids/opiates (targeting morphine, oxymorphone, oxycodone, hydrocodone, 6-monoacetyl morphine, tramadol, buprenorphine, fentanyl, and methadone), phencyclidine (PCP), cocaine (targeting benzoylecgonine), benzodiazepines (targeting oxazepam, lorazepam, and clonazepam), zolpidem, barbiturates (targeting phenobarbital), ethyl glucuronide, methylphenidate, and marijuana metabolite (targeting Delta-9-Carboxy-Tetrahydrocannabinol [THC-COOH]). Patient samples were obtained from the residual meconium samples that had been previously used for other tests. Blank meconium samples were spiked at in-house cutoff, negative and positive assay control levels. All samples were extracted in specimen diluent using Biotage® Lysera and centrifuged. The supernatant was analyzed on a fully automated Randox Evidence+® Analyzer. A robotic arm pipetted 60 µL sample on to a biochip and then the analyzer performed a competitive chemiluminescent immunoassay. The results were generated as relative light units (RLUs). Results The sample results were determined to be “positive” or “negative” based on average RLU of cutoff controls for each analyte on an assay. The intra-assay (CV ≤ 15%) and inter-assay (CV ≤ 18%) precision was 100% agreement for positive and negative controls and there was no observed carryover for any of the analytes. The sample recovery was excellent with minimal to no matrix suppression for all analytes. Accuracy was performed by comparing spiked analyte results from Randox Evidence+® Analyzer with the expected results and all the spiked samples matched (positive or negative). When authentic patient or spiked results were compared with external laboratory test results, some discordant results were obtained. However, the discrepancies could be explained based on the different cutoffs (e.g., the Randox assay had lower cutoffs) or the known assay cross reactivities within the analytes of same class. These deviations did not affect clinical utility of the assay. Conclusions We validated a novel and simple qualitative chemiluminescent immunoassay in meconium using a custom biochip array. Unlike other routine screening/ELISA methods, which require separate assays for detection of similar drug targets, the custom biochip array offers a convenient, rapid and efficient method that utilizes only a single sample preparation for the screening of all 21 drug targets. Therefore, this technology has potential to be utilized as high-throughput screening assay. Like all qualitative assays, the limitation of this test is that all positive results will need to be assessed quantitatively for a definitive interpretation.