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Background The 2023 Duke–International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required. Methods We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria. Results A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P <.001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P <.001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact. Conclusions The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE. [ABSTRACT FROM AUTHOR]

Introduction Recommended duration of antibiotic treatment of Staphylococcus aureus bacteremia (SAB) is frequently based on distinguishing uncomplicated and complicated SAB, and several risk factors at the onset of infection have been proposed to define complicated SAB. Predictive values of risk factors for complicated SAB have not been validated, and consequences of their use on antibiotic prescriptions are unknown. Methods In a prospective cohort, patients with SAB were categorized as complicated or uncomplicated through adjudication (reference definition). Associations and predictive values of 9 risk factors were determined, compared with the reference definition, as was accuracy of Infectious Diseases Society of America (IDSA) criteria that include 4 risk factors, and the projected consequences of applying IDSA criteria on antibiotic use. Results Among 490 patients, 296 (60%) had complicated SAB. In multivariable analysis, persistent bacteremia (odds ratio [OR], 6.8; 95% confidence interval [CI], 3.9–12.0), community acquisition of SAB (OR, 2.9; 95% CI, 1.9–4.7) and presence of prosthetic material (OR, 2.3; 95% CI, 1.5–3.6) were associated with complicated SAB. Presence of any of the 4 risk factors in the IDSA definition of complicated SAB had a positive predictive value of 70.9% (95% CI, 65.5–75.9) and a negative predictive value of 57.5% (95% CI, 49.1–64.8). Compared with the reference, IDSA criteria yielded 24 (5%) false-negative and 90 (18%) false-positive classifications of complicated SAB. Median duration of antibiotic treatment of these 90 patients was 16 days (interquartile range, 14–19), all with favorable clinical outcome. Conclusions Risk factors have low to moderate predictive value to identify complicated SAB and their use may lead to unnecessary prolonged antibiotic use. [ABSTRACT FROM AUTHOR]

Background Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias. Methods Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB. [18F]FDG-PET/CT was performed on clinical indication as part of usual care. Primary outcome was 90-day all-cause mortality. Effect of [18F]FDG-PET/CT was modeled with a Cox proportional hazards model using [18F]FDG-PET/CT as a time-varying variable and corrected for confounders for mortality (age, Charlson score, positive follow-up cultures, septic shock, and endocarditis). Secondary outcome was 90-day infection-related mortality (assessed by adjudication committee) using the same analysis. In a subgroup-analysis, we determined the effect of [18F]FDG-PET/CT in patients with high risk of metastatic infection. Results Of 476 patients, 178 (37%) underwent [18F]FDG-PET/CT. Day-90 all-cause mortality was 31% (147 patients), and infection-related mortality was 17% (83 patients). The confounder adjusted hazard ratio (aHR) for all-cause mortality was 0.50 (95% confidence interval [CI]:.34–.74) in patients that underwent [18F]FDG-PET/CT. Adjustment for immortal time bias changed the aHR to 1.00 (95% CI.68–1.48). Likewise, after correction for immortal time bias, [18F]FDG-PET/CT had no effect on infection-related mortality (cause specific aHR 1.30 [95% CI.77–2.21]), on all-cause mortality in patients with high-risk SAB (aHR 1.07 (95% CI.63–1.83) or on infection-related mortality in high-risk SAB (aHR for 1.24 [95% CI.67–2.28]). Conclusions After adjustment for immortal time bias [18F]FDG-PET/CT was not associated with day-90 all-cause or infection-related mortality in patients with SAB. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bacteremia (SAB) is a heterogeneous disease with changing epidemiology due to changing demographics and evolving clinical management. SAB is associated with high mortality, but the current fraction of infection-related mortality is less well quantified. Methods In a multicenter prospective cohort study of consecutive patients with SAB, we determined clinical features of SAB and determined 90-day mortality and risk factors of all-cause and infection-related mortality. Infection-related mortality was based on an adjudication committee evaluation. Results Four hundred ninety patients with SAB were included, with community-acquired (n = 166), health care–associated (n = 163), and hospital-acquired SAB (n = 161). Endocarditis (n = 90, 18.3%), peripheral intravenous catheter infection (n = 80, 16.3%), and septic arthritis (n = 58, 11.8%) were the most frequent diagnoses, but proportions differed for community, health care, and hospital acquisition. One hundred ninety-two patients (39%) had permanent implanted prosthetic material (eg, prosthetic joint, heart valve, pacemaker). Day 90 all-cause mortality was 33% (n = 161), with 60% adjudicated as infection-related, and 90% of infection-related deaths occurring in the first 30 days post-SAB. Infection-related deaths after 30 days were rare and mainly related to endocarditis. Determinants associated with day 90 infection-related mortality were age (odds ratio [OR], 1.09; 95% CI, 1.06–1.11), Charlson comorbidity index (OR, 1.13; 95% CI, 1.01–1.26), septic shock (OR, 9.78; 95% CI, 4.56–20.95), endocarditis (OR, 3.4; 95% CI, 1.75–6.61), and persistent SAB at 48 hours (OR, 2.36; 95% CI, 1.27–4.37). Conclusions Mortality due to S. aureus infection remains high and mainly occurs in the first 30 days, which could guide end points in future studies. [ABSTRACT FROM AUTHOR]

Background Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19. Methods In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses. Results The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval,.65–2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval,.71–1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine. Conclusions BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection. Clinical trials registration EU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bacteremia (SAB) is in 10% to 20% of cases complicated by infective endocarditis. Clinical prediction scores may select patients with SAB at highest risk for endocarditis, improving the diagnostic process of endocarditis. We compared the accuracy of the Prediction Of Staphylococcus aureus Infective endocarditiseTime to positivity, Iv drug use, Vascular phenomena, preExisting heart condition (POSITIVE), Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT), and VIRSTA scores for classifying the likelihood of endocarditis in patients with SAB. Methods Between August 2017 and September 2019, we enrolled consecutive adult patients with SAB in a prospective cohort study in 7 hospitals in the Netherlands. Using the modified Duke Criteria for definite endocarditis as reference standard, sensitivity, specificity, negative predictive (NPV), and positive predictive values were determined for the POSITIVE, PREDICT, and VIRSTA scores. An NPV of at least 98% was considered safe for excluding endocarditis. Results Of 477 SAB patients enrolled, 33% had community-acquired SAB, 8% had a prosthetic valve, and 11% a cardiac implantable electronic device. Echocardiography was performed in 87% of patients, and 42% received transesophageal echocardiography (TEE). Eighty-seven (18.2%) had definite endocarditis. Sensitivity was 77.6% (65.8%–86.9%), 85.1% (75.8%–91.8%), and 98.9% (95.7%–100%) for the POSITIVE (n = 362), PREDICT, and VIRSTA scores, respectively. NPVs were 92.5% (87.9%–95.8%), 94.5% (90.7%–97.0%), and 99.3% (94.9%–100%). For the POSITIVE, PREDICT, and VIRSTA scores, 44.5%, 50.7%, and 70.9% of patients with SAB, respectively, were classified as at high risk for endocarditis. Conclusions Only the VIRSTA score had an NPV of at least 98%, but at the expense of a high number of patients classified as high risk and thus requiring TEE. Clinical Trials Registration Netherlands Trial Register code 6669. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus bacteraemia (SAB) is a serious and often fatal infectious disease. The quality of management of SAB is modifiable and can thus affect the outcome. Quality indicators (QIs) can be used to measure the quality of care of the various aspects of SAB management in hospitals, enabling professionals to identify targets for improvement and stimulating them to take action.Objectives: To develop QIs for the management of hospitalized patients with SAB.Methods: A RAND-modified Delphi procedure was used to develop a set of QIs for the management of SAB in hospitalized patients. First, available QIs for the management of SAB were extracted from the literature published since 1 January 2000 (MEDLINE and Embase databases). Thereafter, an international multidisciplinary expert panel appraised these QIs during two questionnaire rounds with an intervening face-to-face meeting.Results: The literature search resulted in a list of 39 potential QIs. After appraisal by 30 medical specialists, 25 QIs describing recommended care at patient level were selected. These QIs defined appropriate follow-up blood cultures (n=2), echocardiography (n=6), source control (n=4), antibiotic therapy (n=7), antibiotic dose adjustment (n=2), intravenous-to-oral switch (n=2), infectious disease consultation (n=1) and medical discharge report (n=1).Conclusions: A set of 25 QIs for the management of SAB for hospitalized patients was developed by using a RAND-modified Delphi procedure among international experts. These QIs can measure the quality of various aspects of SAB management. This information can be fed back to the relevant stakeholders in order to identify improvement targets and optimize care. [ABSTRACT FROM AUTHOR]