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Background: Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear., Methods: We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020. Clinical characteristics, bacterial genotypes, and outcome were compared among Black and White patients with SAB. Multivariable logistic regression models were used to determine factors independently associated with the outcomes., Results: Among 3068 patients with SAB, 1107 (36%) were Black. Black patients were younger (median, 56 years vs 63 years; P < .001) and had higher rates of diabetes (47.5% vs 34.5%, P < .001), hemodialysis dependence (40.0% vs 7.3%, P < .001), and human immunodeficiency virus (6.4% vs 0.6%, P < .001). Black patients had higher rates of methicillin-resistant S. aureus (49.3% vs 44.9%, P = .020), including the USA300 hypervirulent clone (11.5% vs 8.4%, P = .007). White patients had higher rates of corticosteroid use (22.4% vs 15.8%, P < .0001) and surgery in the preceding 30 days (28.1% vs 18.7%, P < .001). Although the median Acute Physiology Score (APS) at the time of initial SAB diagnosis was significantly higher in Black patients (median APS, 9; interquartile range [IQR], 5-14 vs median APS, 7; IQR, 4-12; P < .001), race was not associated with 90-day mortality (risk ratio, 1.02; 95% confidence interval, .93-1.12), and rates of metastatic infection were lower among Black patients (37.2% vs 41.3% White, P = .029)., Conclusions: Despite differences in Black patients' higher APS on presentation and more risk factors, including a 5 times higher risk of hemodialysis dependence, 90-day mortality among Black and White patients with SAB was similar., Competing Interests: Potential conflicts of interest. V. G. F. reports personal consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases Society of America for service as associate editor of Clinical Infectious Diseases (2017–2022); a patent on sepsis diagnostics pending; and support from Contrafect to present phase 2 data at 2019 European Congress of Clinical Microbiology & Infectious Diseases. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility of microbial cell-free DNA (mcfDNA) as a tool to identify the microbial etiology of IE., Methods: Blood samples from patients with suspected IE were serially collected. mcfDNA was extracted from plasma and underwent next-generation sequencing. Reads were aligned against a library containing DNA sequences belonging to >1400 different pathogens. mcfDNA from organisms present above a statistical threshold were reported and quantified in molecules per milliliter (MPM). Additional mcfDNA was collected on each subject every 2-3 days for a total of 7 collections or until discharge., Results: Of 30 enrolled patients with suspected IE, 23 had definite IE, 2 had possible IE, and IE was rejected in 5 patients by modified Duke Criteria. Only the 23 patients with definite IE were included for analysis. Both mcfDNA and blood cultures achieved a sensitivity of 87%. The median duration of positivity from antibiotic treatment initiation was estimated to be approximately 38.1 days for mcfDNA versus 3.7 days for blood culture (proportional odds, 2.952; P = .02771), using a semiparametric survival analysis. mcfDNA (log10) levels significantly declined (-0.3 MPM log10 units, 95% credible interval -0.45 to -0.14) after surgical source control was performed (pre- vs postprocedure, posterior probability >0.99)., Conclusion: mcfDNA accurately identifies the microbial etiology of IE. Sequential mcfDNA levels may ultimately help to individualize therapy by estimating a patient's burden of infection and response to treatment., Competing Interests: Potential conflicts of interests. The authors of this manuscript have conflicts of interest to disclose. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche, and receives royalties from UpToDate. V. G. F. has received grants to his institution from the National Institutes of Health, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Basilea, Janssen. V. G. F. receives support for attending meetings and/or travel to present phase 2 data at 2019 ECCMID from Contrafect. V. G. F. has a sepsis diagnostics patent pending and has stock or stock options at ArcBio and Valanbio and is an Associate Editor at Clinical Infectious Diseases. A. A. A., N. D., E. R. S., and E. C. report they are employees at Karius Inc. D. Hong, D. Hollemon, C. D. V., C. H., L. B., S. D., and J. B. report they are former employees of Karius Inc. A. A. A. and N. D. report registration fees for conferences from Karius, and patents planned, issued or pending from Karius Inc. L. B. reports stock or stock options with Karius, Inc. S. D. reports consulting fees from Karius Inc. C. H. reports stock or stock options from Karius, Inc. D. Hong reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events as an employee of Vir Biotechnology and Janssen Biopharma. E. R. S. reports personal fees from Sema4 and is a former employee of Karius., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Microbial cell-free DNA (mcfDNA) sequencing of plasma can identify the presence of a pathogen in a host. In this study, we evaluated the duration of pathogen detection by mcfDNA sequencing vs conventional blood culture in patients with bacteremia., Methods: Blood samples from patients with culture-confirmed bloodstream infection were collected within 24 hours of the index positive blood culture and 48 to 72 hours thereafter. mcfDNA was extracted from plasma, and next-generation sequencing was applied. Reads were aligned against a curated pathogen database. Statistical significance was defined with Bonferroni adjustment for multiple comparisons (P < .0033)., Results: A total of 175 patients with Staphylococcus aureus bacteremia (n = 66), gram-negative bacteremia (n = 74), or noninfected controls (n = 35) were enrolled. The overall sensitivity of mcfDNA sequencing compared with index blood culture was 89.3% (125 of 140), and the specificity was 74.3%. Among patients with bacteremia, pathogen-specific mcfDNA remained detectable for significantly longer than conventional blood cultures (median 15 days vs 2 days; P < .0001). Each additional day of mcfDNA detection significantly increased the odds of metastatic infection (odds ratio, 2.89; 95% confidence interval, 1.53-5.46; P = .0011)., Conclusions: Pathogen mcfDNA identified the bacterial etiology of bloodstream infection for a significantly longer interval than conventional cultures, and its duration of detection was associated with increased risk for metastatic infection. mcfDNA could play a role in the diagnosis of partially treated endovascular infections., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Infective endocarditis (IE) is a rare but serious infection that complicates pregnancy. Little is known about IE management and outcomes in this population., Methods: The National Readmissions Database was used to obtain data between October 2015 and October 2018. Billing codes identified admissions for IE in female patients of reproductive age. Demographic characteristics, comorbidities, and outcomes were compared between patients with maternity-associated and nonmaternity-associated IE and obstetric patients who delivered with and without IE. Weighted regressions were used to examine outcomes in adjusted models., Results: We identified 12 602 reproductive-aged female patients with a diagnosis of IE, of which 382 (weighted national estimate, 748) were maternity-associated. Of these cases, 117 (weighted national estimate, 217) occurred during a delivery admission. Compared with patients with nonmaternity-associated IE, maternity-associated infection was associated with younger age (mean, 29.0 vs 36.6 years; P < .001), Medicaid coverage (72.5% vs 47.2%; P < .001), and drug use (76.2% vs 59.8%; P < .001). Mortality was comparable (8.1% vs 10.6%; adjusted rate ratio [aRR], 1.03; 95% confidence interval [CI]: .71-1.48). Compared with patients who delivered without IE, IE complicating delivery was associated with worse maternal and fetal outcomes, including maternal mortality (17.2% vs <0.01%; aRR, 323.32; 95% CI: 127.74-818.37) and preterm birth (55.7% vs 10.1%; aRR, 3.61; 95% CI, 2.58-5.08)., Conclusions: Maternity-associated IE does not appear to confer additional risk for adverse outcome over nonmaternity-associated infection. Patients who deliver with IE have worse maternal and fetal outcomes than those whose deliveries are not complicated by IE., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB)., Methods: All SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE). PFGE-indistinguishable pairs from 40 patients underwent whole genome sequencing (WGS). Acute phase plasma from R-SAB and S-SAB patients was matched 1:1 for age, race, sex, and bacterial genotype, and underwent cytokine quantification using 25-analyte multiplex bead array., Results: R-SAB occurred in 69 (9.1%) of the 756 study patients. Of the 69 patients, 30 experienced relapse (43.5%) and 39 reinfection (56.5%). Age, race, hemodialysis dependence, presence of foreign body, methicillin-resistant Staphyloccus aureus, and persistent bacteremia were individually associated with likelihood of recurrence. Multivariate risk modeling revealed that black hemodialysis patients were nearly 2 times more likely (odds ratio [OR] = 9.652 [95% confidence interval [CI], 5.402-17.418]) than white hemodialysis patients (OR = 4.53 [95% CI, 1.696-10.879]) to experience R-SAB. WGS confirmed PFGE interpretations in all cases. Median RANTES (regulated on activation, normal T cell expressed and secreted) levels in acute phase plasma from the initial episode of SAB were higher in R-SAB than in matched S-SAB controls (P = .0053, false discovery rate < 0.10)., Conclusion: This study identified several risk factors for R-SAB. The largest risk for R-SAB is among black hemodialysis patients. Higher RANTES levels in R-SAB compared to matched controls warrants further study., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)