Baddour, Larry M.

Abstract Objective Antibiotic prophylaxis is recommended before invasive dental procedures to prevent endocarditis in those at high risk, but supporting data are sparse. We therefore investigated any association between invasive dental procedures and endocarditis, and any antibiotic prophylaxis effect on endocarditis incidence. Subjects and Methods Cohort and case‐crossover studies were performed on 1,678,190 Medicaid patients with linked medical, dental, and prescription data. Results The cohort study identified increased endocarditis incidence within 30 days of invasive dental procedures in those at high risk, particularly after extractions (OR 14.17, 95% CI 5.40–52.11, p < 0.0001) or oral surgery (OR 29.98, 95% CI 9.62–119.34, p < 0.0001). Furthermore, antibiotic prophylaxis significantly reduced endocarditis incidence following invasive dental procedures (OR 0.20, 95% CI 0.06–0.53, p < 0.0001). Case‐crossover analysis confirmed the association between invasive dental procedures and endocarditis in those at high risk, particularly following extractions (OR 3.74, 95% CI 2.65–5.27, p < 0.005) and oral surgery (OR 10.66, 95% CI 5.18–21.92, p < 0.0001). The number of invasive procedures, extractions, or surgical procedures needing antibiotic prophylaxis to prevent one endocarditis case was 244, 143 and 71, respectively. Conclusions Invasive dental procedures (particularly extractions and oral surgery) were significantly associated with endocarditis in high‐risk individuals, but AP significantly reduced endocarditis incidence following these procedures, thereby supporting current guideline recommendations.

Abstract Background Staphylococcus aureus has high mortality rates, which is influenced by several factors related to the host-pathogen interaction. The current study aims to provide a contemporary evaluation of predictors of 6-month mortality rate in a population-based cohort of incident Staphylococcus aureus bacteremia (SAB) cases. Methods Retrospective population-based study of 541 adult residents of Olmsted County, MN with monomicrobial SAB from January 1, 2006 through December 31, 2020. The study’s primary outcome was 6-month mortality rate, and a survival analysis was prepared by the Kaplan-Meier method. Multivariable Cox regression was used to investigate risk factors associated with 6-month mortality. Results The median (IQR) age of 541 patients with SAB was 66.8 (54.4-78.5) years and 39.6% were female. The median Charlson Comorbidity Index (CCI) was 2 (1-4). SAB cases were healthcare-associated in 49.2% and 56.2% were methicillin-susceptible. Twenty percent of SAB cases had an unknown infection source and 38.3% had complicated bacteremia. There were 7 relapses within the first 12 weeks of follow-up, corresponding to a cumulative incidence rate of 1.3%. There were no re-infections through the remainder of the 6-month follow-up, although there were 2 recurrences after 7 months. Eighty-nine (16.5%) patients died within 1 month of SAB diagnosis and 144 (26.7%) patients died during the 6-month follow-up period. In a multivariable analysis, older age, elevated CCI, unknown source of SAB, and intensive care unit (ICU) admission were significant predictors of an increased 6-month mortality rate. In contrast, presence of diabetes mellitus was significantly associated with a decreased 6-month mortality rate; also, undergoing infectious diseases consultation was associated with reduced mortality in the first 2 weeks, but not for the remainder of the 6-month follow-up period. Conclusion To our knowledge, the current investigation represents the only contemporary population-based study determining significant predictors of mortality in SAB patients, namely, older age, higher CCI, unknown source of SAB, and ICU admission. This study also described one of the lowest 30-day mortality rates reported over the past 2 decades. Figure 1.Survival and reinfection rates of patients with SAB over 6 months. Abbreviations: SAB, Staphylococcus aureus bacteremia. Foot notes: The overall survival curve was derived by the Kaplan-Meier estimator, while the curve for reinfection was estimated by the cumulative incidence function taking into account the competing risk of death. Disclosures Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties.

Abstract Background Bloodstream infection (BSI) following arterial aneurysm repair may signify vascular graft infection (VGI). The incidence of BSI and its implications in patients with arterial grafts have received scant attention with limited contemporary study. Therefore, the aim of the current investigation is to describe the incidence and epidemiology of BSI following arterial aneurysm repair in a population-based cohort. Methods Retrospective case-cohort study using the expanded Rochester Epidemiology Project (e-REP) to identify all arterial aneurysm repairs performed in adults (&gt;18 years) residing in eight counties in southern Minnesota between January 1, 2010 and December 31, 2020. All repairs were performed at Mayo Clinic Rochester. Electronic health records were screened for initial BSI episode following aneurysm repair and complicating VGI. Results Overall, 643 patients underwent 708 aneurysm repairs: 417 endovascular and 291 open surgical repairs. Forty-two patients developed BSI during 2,992 cumulative person-years of follow-up. The median time from repair to BSI was 3.1 [interquartile range 0.5, 6.4] years. The BSI incidence rate, in cases per 1000 person-years, was 14.0 (95% CI 10.1-19.0) overall, including 18.2 (95% CI 11.9-26.7) following open surgical repair and 10.2 (95% CI 5.8-16.6) following endovascular repair (p=0.148). Thirty-nine (92.9%) of the BSI cases were monomicrobial, with 18 (46.2%) due to Gram-positive organisms and 21 (53.8%) due to Gram-negative organisms. Of the 42 patients with BSI, 10 (23.8%) had VGI. VGI occurred in 8/18 (44.4%) monomicrobial Gram-positive BSI as compared to 2/21 (9.5%) monomicrobial Gram-negative BSI (p=0.013). The 3-year mortality rate following BSI was 52.3%. Conclusion There was no statistically significant difference in incidence rates of BSI following open surgical repair and endovascular repair. Higher rates of VGI were seen with Gram-positive BSI as compared to Gram-negative BSI. Disclosures Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties.

Abstract Background Cardiovascular implantable electronic devices (CIED) infection carries significant morbidity, mortality, and financial burden. Bacteremia in patients with CIED increases risk of CIED infection. While several investigations have examined Staphylococcus aureus bacteremia and risk of CIED infection, data regarding non-S. aureus gram-positive coccal (non-SA GPC) bacteremia in patients with CIED has been both limited and dated. The current study examined the clinical characteristics of patients with CIED who developed non-SA GPC bacteremia and their proclivity of CIED infection. Methods We reviewed all patients with CIED who developed non-SA GPC bacteremia at Mayo Clinic between 2012–2019. Cases with a left ventricular assist device, non-hospitalization, and contaminated blood culture were excluded. The 2019 European Heart Rhythm Association International Consensus Document was used to define CIED infection. Results A total of 160 patients with CIED developed non-SA GPC bacteremia during the period. Ninety (56.2%) patients had CIED infection, with 60 (37.5%) classified as definite and 30 (18.8%) possible. This included 41/64 (64.1%) patients with coagulase-negative Staphylococcus (CoNS), 30/41 (73.2%) patients with Enterococcus, 13/19 (68.4%) patients with viridans group streptococci (VGS), and 6/36 (16.6%) patients with other non-SA GPC. The odds of CIED infection (with 95% CI) for CoNS, Enterococcus, and VGS bacteremia were 8.9 (3.2–24.6), 13.6 (4.5–41.6), and 10.8 (2.9–40.0) -fold higher, respectively, as compared to other non-SA GPC. Among those with infected CIED, 51 (56.7%) patients underwent complete device extraction after a median of 6 (IQR 3.5–10) days. In an unadjusted analysis of patients with CIED infection, the reduction in one-year mortality following device removal was not statistically significant (HR 0.59, 95% CI 0.26–1.33, p=0.198). Conclusion The overall prevalence of CIED infection following non-SA GPC bacteremia was higher than previously reported, particularly that due to CoNS, Enterococcus, and VGS. Further study with a larger cohort is needed to demonstrate the survival benefit from CIED extraction in patients with infected CIED due to non-SA GPC. Disclosures Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties Rizwan Sohail, M.D., Aziyo Biologics: Advisor/Consultant|Boston Scientific: Advisor/Consultant|Medtronic: Advisor/Consultant|Philips: Advisor/Consultant|Philips: Honoraria Malini Madhavan, M.B.B.S., Biosense Webster: Advisor/Consultant|Biotronik Inc: Advisor/Consultant|Boston Scientific: Grant/Research Support|Convatec: Advisor/Consultant.

Blood cultures have been the gold standard for identifying pathogens in infective endocarditis (IE). Blood culture-negative endocarditis (BCNE), however, occurs in 40% or more of IE cases with the bulk of them due to recent antibiotic exposure prior to obtaining blood cultures. Increasingly, molecular techniques are being used for pathogen identification in cases of BCNE and more recently has included metagenomic next-generation sequencing (mNGS). We therefore performed a literature search on August 31, 2022, that assessed the mNGS in IE and 13 publications were identified and included in a systematic review. Eight (61.5%) of them focused only on IE with mNGS performed on cardiac valve tissue in four studies, plasma in three studies and cardiac implantable electronic devices (CIED) in one study. Gram-positive cocci, including Staphylococcus aureus (n = 31, 8.9%), coagulase-negative staphylococci (n = 61, 17.6%), streptococci (n = 130, 37.5%), and Enterococcus faecalis (n = 23, 6.6%) were the predominant organisms identified by mNGS. Subsequent investigations are needed to further define the utility of mNGS in BCNE and its impact on patient outcomes. Despite some pitfalls, mNGS seems to be of value in pathogen identification in IE cases, particularly in those with BCNE. This study was registered and on the Open Science Framework platform.

Objective: To provide an evaluation of incidence and six-month mortality rates of polymicrobial Staphylococcus aureus bacteremia (p-SAB) in the United States (US). Methods: A retrospective population-based study of all incident adults with monomicrobial SAB (m-SAB) and p-SAB in Olmsted County, Minnesota (MN) from 1 January 2006, through 31 December 2020, was conducted. Demographics, clinical characteristics, in-hospital outcomes, and six-month survival were compared between groups. Results: Overall, 31 incident p-SAB cases occurred during the 15-year study period, corresponding to an overall age- and sex-standardized incidence rate of 1.9/100,000 person-years (95% CI, 1.3–2.6). One-third of p-SAB cases were due to MRSA, and almost one-half (15/31) were caused by Gram-positive bacteria. As compared to the 541 cases with incident m-SAB, p-SAB patients were more likely to have a catheter-related infection (p = 0.008) and less likely to be community-acquired cases (p = 0.027). The unadjusted risk of six-month mortality was greater in the p-SAB group (14/31, 45.2%) compared to the m-SAB group (144/541, 26.6%) (HR = 1.94, 95% CI = 1.12–3.36, p = 0.018). After adjusting for relevant covariates, this difference approached significance (HR = 1.93, 95% = CI 0.96–3.87, p = 0.064). Conclusions: To our knowledge, the current investigation represents the only US population-based study evaluating p-SAB patients. We found lower incidence rates for p-SAB than previously reported, with almost one-half of the cases caused by Gram-positive bacteria. Furthermore, these patients had poor survival compared to incident m-SAB cases.

AbstractSeptic pulmonary embolism (SPE) is a rare clinical entity that is distinct from the classic and more common non-septic thrombotic pulmonary embolism. SPE should be suspected in patients with a systemic acute inflammatory reaction or sepsis who develop signs and symptoms of pulmonary involvement. The diagnosis of SPE depends on the specific radiologic finding of multiple, peripheral, nodular, possibly cavitated lesions. SPE should prompt an immediate search for the primary source of infection; typically, right-sided infective endocarditis, cardiac implantable electronic devices, and septic thrombophlebitis as a complication of bone, skin, and soft tissue infection including Lemierre's syndrome, indwelling catheters, or direct inoculation via injection drug use. Invasive treatment of the infection source may be necessary; in thrombophlebitis, the efficacy and safety of anticoagulation remain undefined. Blood cultures may be negative, particularly among patients with recent antibiotic exposure, and broad-spectrum antimicrobial therapy should be considered. The in-hospital mortality of SPE ranges up to 20% in published case series. While trends in the incidence of SPE are unknown, the opioid epidemic, the growing use of cardiac implantable electronic devices worldwide, and the reported increase in cases of septic thrombophlebitis may be leading to an escalation in SPE cases. We provide a contemporary profile of SPE and propose a clinical management algorithm in patients with suspected or confirmed SPE.