Baddour, Larry

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.

Objective Antibiotic prophylaxis has been recommended for patients at increased risk of infective endocarditis (IE) undergoing specific invasive procedures (IPs) despite a lack of data supporting its use. Therefore, antibiotic prophylaxis recommendations ceased in the mid-2000s for all but those at high IE risk undergoing invasive dental procedures. We aimed to quantify any association between IPs and IE. Methods All 14 731 IE hospital admissions in England between April 2010 and March 2016 were identified from national admissions data, and medical records were searched for IP performed during the 15-month period before IE admission. We compared the incidence of IP during the 3 months immediately before IE admission (case period) with the incidence during the preceding 12 months (control period) to determine whether the odds of developing IE were increased in the 3 months after certain IP. Results The odds of IE were increased following permanent pacemaker and defibrillator implantation (OR 1.54, 95% CI 1.27 to 1.85, p<0.001), extractions/surgical tooth removal (OR 2.14, 95% CI 1.22 to 3.76, p=0.047), upper (OR 1.58, 95% CI 1.34 to 1.85, p<0.001) and lower gastrointestinal endoscopy (OR 1.66, 95% CI 1.35 to 2.04, p<0.001) and bone marrow biopsy (OR 1.76, 95% CI 1.16 to 2.69, p=0.039). Using an alternative analysis, bronchoscopy (OR 1.33, 95% CI 1.06 to 1.68, p=0.049) and blood transfusions/red cell/plasma exchange (OR 1.2, 95% CI 1.07 to 1.35, p=0.012) were also associated with IE. Conclusions This study identifies a significant association between specific IPs (permanent pacemaker and defibrillator implantation, dental extraction, gastrointestinal endoscopy and bronchoscopy) and subsequent IE that warrants re-evaluation of current antibiotic prophylaxis recommendations to prevent IE in high IE risk individuals.

Abstract Background Gram-negative bacteremia (GNB) as a manifestation of cardiovascular implantable electronic device (CIED) infection is uncommon. Moreover, echocardiography may be nonspecific in its ability to differentiate whether CIED lead masses are infected. We aimed to determine the rate of CIED infection in the setting of GNB. Methods All patients with CIED who were hospitalized with GNB during 2012–2019 at Mayo Clinic were investigated. The definition of CIED infection was based on criteria recommended by the 2019 European Heart Rhythm Association document. Results A total of 126 patients with CIED developed GNB. None of them had signs of pocket infection. Twenty (15.9%) patients underwent transesophageal echocardiography. Overall, 4 (3%) patients had definite CIED infection. None of them underwent CIED extraction; 3 died within 12 weeks and 1 received long-term antibiotic suppression. Ten (8%) patients had possible CIED infection; despite no CIED extraction, no patient had relapsing GNB. We observed a higher rate of CIED infection in patients with Serratia marcescens bacteremia as compared to that in patients with other GNB. Conclusions The rate of CIED infection following GNB was relatively low. However, accurate classification of CIED infection among patients presenting with GNB remains challenging, in part, due to a case definition of CIED infection that is characterized by a low pretest probability in the setting of GNB. Prospective, multicenter studies are needed to determine accurate identification of CIED infection among GNB, so that only patients with true infection undergo device removal.

Background Infective endocarditis is a heart infection with a first-year mortality rate of ≈ 30%. It has long been thought that infective endocarditis is causally associated with bloodstream seeding with oral bacteria in ≈ 40–45% of cases. This theorem led guideline committees to recommend that individuals at increased risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. However, to the best of our knowledge, there has never been a clinical trial to prove the efficacy of antibiotic prophylaxis and there is no good-quality evidence to link invasive dental procedures with infective endocarditis. Many contend that oral bacteria-related infective endocarditis is more likely to result from daily activities (e.g. tooth brushing, flossing and chewing), particularly in those with poor oral hygiene. Objective The aim of this study was to determine if there is a temporal association between invasive dental procedures and subsequent infective endocarditis, particularly in those at high risk of infective endocarditis. Design This was a self-controlled, case-crossover design study comparing the number of invasive dental procedures in the 3 months immediately before an infective endocarditis-related hospital admission with that in the preceding 12-month control period. Setting The study took place in the English NHS. Participants All individuals admitted to hospital with infective endocarditis between 1 April 2010 and 31 March 2016 were eligible to participate. Interventions This was an observational study; therefore, there was no intervention. Main outcome measure The outcome measure was the number of invasive and non-invasive dental procedures in the months before infective endocarditis-related hospital admission. Data sources NHS Digital provided infective endocarditis-related hospital admissions data and dental procedure data were obtained from the NHS Business Services Authority. Results The incidence rate of invasive dental procedures decreased in the 3 months before infective endocarditis-related hospital admission (incidence rate ratio 1.34, 95% confidence interval 1.13 to 1.58). Further analysis showed that this was due to loss of dental procedure data in the 2–3 weeks before any infective endocarditis-related hospital admission. Limitations We found that urgent hospital admissions were a common cause of incomplete courses of dental treatment and, because there is no requirement to record dental procedure data for incomplete courses, this resulted in a significant loss of dental procedure data in the 2–3 weeks before infective endocarditis-related hospital admissions. The data set was also reduced because of the NHS Business Services Authority’s 10-year data destruction policy, reducing the power of the study. The main consequence was a loss of dental procedure data in the critical 3-month case period of the case-crossover analysis (immediately before infective endocarditis-related hospital admission), which did not occur in earlier control periods. Part of the decline in the rate of invasive dental procedures may also be the result of the onset of illness prior to infective endocarditis-related hospital admission, and part may be due to other undefined causes. Conclusions The loss of dental procedure data in the critical case period immediately before infective endocarditis-related hospital admission makes interpretation of the data difficult and raises uncertainty over any conclusions that can be drawn from this study. Future work We suggest repeating this study elsewhere using data that are unafflicted by loss of dental procedure data in the critical case period. Trial registration This trial is registered as ISRCTN11684416. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 28. See the NIHR Journals Library website for further project information.

Abstract Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P &lt; .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P &lt; .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.