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Background Studies investigating cardiac implantable electronic device infective endocarditis (CIED-IE) epidemiological changes and prognosis over long periods of time are lacking. Methods Retrospective single cardiovascular surgery center cohort study of definite CIED-IE episodes between 1981–2020. A comparative analysis of two periods (1981–2000 vs 2001–2020) was conducted to analyze changes in epidemiology and outcome over time. Results One-hundred and thirty-eight CIED-IE episodes were diagnosed: 25 (18%) first period and 113 (82%) second. CIED-IE was 4.5 times more frequent in the second period, especially in implantable cardiac defibrillators. Age (63 [53-70] vs 71 [63–76] years, P <.01), comorbidities (CCI 3.0 [2–4] vs 4.5 [3–6], P >.01), nosocomial infections (4% vs 15.9%, P =.02) and transfers from other centers (8% vs 41.6%, P <.01) were significantly more frequent in the second period, as were methicillin-resistant coagulase-negative staphylococcal (MR-CoNS) (0% vs 13.3%, P <.01) and Enterococcus spp. (0% vs 5.3%, P =.01) infections, pulmonary embolism (0% vs 10.6%, P <.01) and heart failure (12% vs 28.3%, p <.01). Second period surgery rates were lower (96% vs 87.6%, P =.09), and there were no differences in in-hospital (20% vs 11.5%, P =.11) and one-year mortalities (24% vs 15%, P =.33), or relapses (8% vs 5.3%, P = 0.65). Multivariate analysis showed Charlson index (hazard ratios [95% confidence intervals]; 1.5 [1.16–1.94]) and septic shock (23.09 [4.57–116.67]) were associated with a worse prognosis, whereas device removal (0.11 [.02–.57]), transfers (0.13 [.02–0.95]), and second-period diagnosis (0.13 [.02–.71]) were associated with better one-year outcomes. Conclusions CIED-IE episodes increased more than four-fold during last 40 years. Despite CIED-IE involved an older population with more comorbidities, antibiotic-resistant MR-CoNS, and complex devices, one-year survival improved. [ABSTRACT FROM AUTHOR]

Background Outpatient parenteral antibiotic treatment (OPAT) programs are increasingly used to manage infective endocarditis (IE), but current criteria for indicating OPAT are markedly conservative. We aimed to investigate whether more liberal criteria for indicating OPAT in IE can be safely used. Methods This was a prospective multicenter nationwide cohort study (2008–2018). Rates of readmission, recurrences, and 1-year mortality were compared between hospital-based antibiotic treatment (HBAT) and OPAT. Risk factors for readmission and mortality in OPAT patients were investigated by logistic regression. Patients did not fulfill OPAT-GAMES (Grupos de Apoyo al Manejo de la Endocarditis en ESpaña) criteria if they had any of the following: cirrhosis, severe central nervous system emboli, undrained abscesses, severe conditions requiring cardiac surgery in nonoperable patients, severe postsurgical complications, highly difficult-to-treat microorganisms, or intravenous drug use. Results A total of 2279 HBAT patients and 1268 OPAT patients were included. Among OPAT patients, 307 (24.2%) did not fulfill OPAT-GAMES criteria. Overall, OPAT patients presented higher rates of readmission than HBAT patients (18.2% vs 14.4%; P = .004), but no significant differences were found in the propensity analysis. Patients not fulfilling OPAT-GAMES criteria presented significantly higher rates of readmission than HBAT and OPAT-GAMES (23.8%, 14.4%, 16.4%; P  < .001), whereas no significant differences were found in mortality (5.9%, 8%, 7.4%; P  = .103) or recurrences (3.9%, 3.1%, 2.5%; P  = .546). Not fulfilling OPAT-GAMES criteria was associated with higher risk of readmission (odds ratio [OR], 1.43; 95% CI, 1.03–1.97; P  = .03), whereas cardiac surgery was associated with lower risk (OR, 0.72; 95% CI, 0.53–0.98; P  = .03). Conclusions OPAT-GAMES criteria allow identification of IE patients at higher risk of long-term complications to whom OPAT cannot be safely administered. [ABSTRACT FROM AUTHOR]

Objective of this study was to assess the appropriate treatment duration for enterococcal central line-associated bloodstream infections (CLABSIs). This observational, retrospective, multicenter study conducted between 2011 and 2019 enrolled all hospitalized patients with monomicrobial enterococcal CLABSI. Those with infective endocarditis and non-survivors at least 7 days from index blood culture (BC) were excluded. Primary endpoint was 30-day mortality. We enrolled 113 patients, of whom 59% were male, median age was 64 (SD ± 15) and median Charlson's index score 5 (IQR 3–8). Enterococcus faecalis and Enterococcus faecium were found in 51% and 44% of cases, respectively. Median treatment duration was 11 days (IQR 6–17), and 32% of patients (n = 36) received ≤ 7 days. Characteristics of patients receiving more or less than 7 days of treatment were similar. Central line was removed in 82% (n = 93) of cases within a median of 3 days (1–8). At both uni- and multivariate analysis, duration of antibiotic treatment > 7 days was not associated with 30-day mortality [HR 0.41 (95% CI, 0.13–1.24), p = 0.12] even after adjustment with propensity score [HR 0.47 (95% CI 0.17–1.26), p = 0.13]. A 7-day treatment course appears to be safe in non-complicated enterococcal CLABSIs. [ABSTRACT FROM AUTHOR]

Background Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking. Methods Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality. Results Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P <.001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P <.001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P =.008, and 65.3% vs 57.4%, P =.030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P <.001), left-ventricle ejection fraction <60% (1.72; 1.22-2.40; P =.002), heart block (2.22; 1.41-3.47; P =.001), tachyarrhythmias (5.07; 3.13-8.19; P <.001), and acute kidney failure (2.29; 1.73-3.03; P <.001) were associated with higher likelihood of developing CS. Prosthetic endocarditis (2.03; 1.06 -3.88; P =.032), Staphylococcus aureus (3.10; 1.16 -8.30; P =.024), tachyarrhythmias (3.09; 1.50-10.13; P =.005), and not performing cardiac surgery (11.40; 4.83-26.90; P <.001) were associated with a higher risk of mortality. Conclusions AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery. [ABSTRACT FROM AUTHOR]

Background Little is known about the characteristics and impact of septic shock (SS) on the outcomes of infective endocarditis (IE). We aimed to investigate the characteristics and outcomes of patients with IE presenting with SS and to compare them to those of IE patients with sepsis (Se) and those with neither Se nor SS (no-Se-SS). Methods This is a prospective cohort study of 4864 IE patients from 35 Spanish centers (2008 to 2018). Logistic regression analyses were performed to identify risk factors for SS and mortality. Results Septic shock and Se presented in 597 (12.3%) and 559 (11.5%) patients, respectively. Patients with SS were younger and presented significantly higher rates of diabetes, chronic renal and liver disease, transplantation, nosocomial acquisition, Staphylococcus aureus , IE complications, and in-hospital mortality (62.5%, 37.7% for Se and 18.2% for no-Se-SS, P  < .001). Staphylococcus aureus (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.34–2.81; P  < .001), Gram negative (OR, 2.21; 95% CI, 1.25–3.91; P =.006), nosocomial acquisition (OR, 1.44; 95% CI, 1.07–1.94; P =.015), persistent bacteremia (OR, 1.82; 95% CI, 1.24–2.68; P =.002), acute renal failure (OR, 3.02; 95% CI, 2.28–4.01; P  < .001), central nervous system emboli (OR, 1.48; 95% CI, 1.08–2.01; P =.013), and larger vegetation size (OR, 1.01; 95% CI, 1.00–1.02; P. = 020) were associated with a higher risk of developing SS. Charlson score, heart failure, persistent bacteremia, acute renal failure, mechanical ventilation, worsening of liver disease, S aureus , and receiving aminoglycosides within the first 24 hours were associated with higher in-hospital mortality, whereas male sex, native valve IE, and cardiac surgery were associated with lower mortality. Conclusions Septic shock is frequent and entails dismal prognosis. Early identification of patients at risk of developing SS and early assessment for cardiac surgery appear as key factors to improve outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits.Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400.Results: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains.Conclusions: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE. [ABSTRACT FROM AUTHOR]

Background: Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD).Objectives: This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients.Methods: Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression.Results: A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p < 0.001). Cardiac surgery was less frequently performed among HD patients (30.6% vs. 46.2%; p < 0.001), whereas relapses were higher (9.4% vs. 2.7%; p < 0.001). Risk factors for 6-month mortality included Charlson score (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 1.11 to 1.44; p = 0.001), CNS emboli and other emboli (HR: 3.11; 95% CI: 1.84 to 5.27; p < 0.001; and HR: 1.73; 95% CI: 1.02 to 2.93; p = 0.04, respectively), persistent bacteremia (HR: 1.79; 95% CI: 1.11 to 2.88; p = 0.02), and acute onset heart failure (HR: 2.37; 95% CI: 1.49 to 3.78; p < 0.001).Conclusions: HD-IE is a health care-associated infection chiefly caused by S. aureus, with increasing rates of enterococcal IE. Mortality and relapses are very high and significantly larger than in non-HD-IE patients, whereas cardiac surgery is less frequently performed. [ABSTRACT FROM AUTHOR]

Background: Infective endocarditis (IE) in people who inject drugs (PWID) is an emergent public health problem.Objectives: The purpose of this study was to investigate IE in PWID and compare it with IE in non-PWID patients.Methods: Two prospective cohort studies (ICE-PCS and ICE-Plus databases, encompassing 8,112 IE episodes from 2000 to 2006 and 2008 to 2012, with 64 and 34 sites and 28 and 18 countries, respectively). Outcomes were compared between PWID and non-PWID patients with IE. Logistic regression analyses were performed to investigate risk factors for 6-month mortality and relapses amongst PWID.Results: A total of 7,616 patients (591 PWID and 7,025 non-PWID) were included. PWID patients were significantly younger (median 37.0 years [interquartile range: 29.5 to 44.2 years] vs. 63.3 years [interquartile range: 49.3 to 74.0 years]; p < 0.001), male (72.5% vs. 67.4%; p = 0.007), and presented lower rates of comorbidities except for human immunodeficiency virus, liver disease, and higher rates of prior IE. Amongst IE cases in PWID, 313 (53%) episodes involved left-side valves and 204 (34.5%) were purely left-sided IE. PWID presented a larger proportion of native IE (90.2% vs. 64.4%; p < 0.001), whereas prosthetic-IE and cardiovascular implantable electronic device-IE were more frequent in non-PWID (9.3% vs. 27.0% and 0.5% vs. 8.6%; both p < 0.001). Staphylococcus aureus caused 65.9% and 26.8% of cases in PWID and non-PWID, respectively (p < 0.001). PWID presented higher rates of systemic emboli (51.1% vs. 22.5%; p < 0.001) and persistent bacteremia (14.7% vs. 9.3%; p < 0.001). Cardiac surgery was less frequently performed (39.5% vs. 47.8%; p < 0.001), and in-hospital and 6-month mortality were lower in PWID (10.8% vs. 18.2% and 14.4% vs. 22.2%; both p < 0.001), whereas relapses were more frequent in PWID (9.5% vs. 2.8%; p < 0.001). Prior IE, left-sided IE, polymicrobial etiology, intracardiac complications, and stroke were risk factors for 6-month mortality, whereas cardiac surgery was associated with lower mortality in the PWID population.Conclusions: A notable proportion of cases in PWID involve left-sided valves, prosthetic valves, or are caused by microorganisms other than S. aureus. [ABSTRACT FROM AUTHOR]

Background: In vitro and in vivo activity of daptomycin alone or plus either cloxacillin or fosfomycin compared with cloxacillin alone and cloxacillin plus gentamicin were evaluated in a rabbit model of MSSA experimental endocarditis (EE).Methods: Five MSSA strains were used in the in vitro time-kill studies at standard (105-106 cfu/mL) and high (108 cfu/mL) inocula. In the in vivo EE model, the following antibiotic combinations were evaluated: cloxacillin (2 g/4 h) alone or combined with gentamicin (1 mg/kg/8 h) or daptomycin (6 mg/kg once daily); and daptomycin (6 mg/kg/day) alone or combined with fosfomycin (2 g/6 h).Results: At standard and high inocula, daptomycin plus fosfomycin or cloxacillin were bactericidal against 4/5 and 5/5 strains, respectively, while cloxacillin plus gentamicin was bactericidal against 3/5 strains at standard inocula but against none at high inocula. Fosfomycin, cloxacillin, gentamicin and daptomycin MIC/MBCs of the MSSA-678 strain used in the EE model were: 8/64, 0.25/0.5, 0.25/0.5 and 1/8 mg/L, respectively. Adding gentamicin to cloxacillin significantly reduced bacterial density in vegetations compared with cloxacillin monotherapy (P = 0.026). Adding fosfomycin or cloxacillin to daptomycin [10/11 (93%) and 8/11 (73%), respectively] significantly improved the efficacy of daptomycin in sterilizing vegetations [0/11 (0%), P < 0.001 for both combinations] and showed better activity than cloxacillin alone [0/10 (0%), P < 0.001 for both combinations] and cloxacillin plus gentamicin [3/10 (30%), P = 0.086 for cloxacillin plus daptomycin and P = 0.008 for fosfomycin plus daptomycin]. No recovered isolates showed increased daptomycin MIC.Conclusions: The addition of cloxacillin or fosfomycin to daptomycin is synergistic and rapidly bactericidal, showing better activity than cloxacillin plus gentamicin for treating MSSA EE, supporting their clinical use. [ABSTRACT FROM AUTHOR]

Background: Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking.Objectives: The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort.Methods: This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses.Results: Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse.Conclusions: Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE. [ABSTRACT FROM AUTHOR]

Background. Infective endocarditis (IE) caused by Abiotrophia (ABI) and Granulicatella (GRA) species is poorly studied. This work aims to describe and compare the main features of ABI and GRA IE. Methods. We performed a retrospective study of 12 IE institutional cases of GRA or ABI and of 64 cases published in the literature (overall, 38 ABI and 38 GRA IE cases). Results. ABI/GRA IE represented 1.51% of IE cases in our institution between 2000 and 2015, compared to 0.88% of HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)-related IE and 16.62% of Viridans group streptococci (VGS) IE. Institutional ABI/GRA IE case characteristics were comparable to that of VGS, but periannular complications were more frequent (P = .008). Congenital heart disease was reported in 4 (10.5%) ABI and in 11 (28.9%) GRA cases (P = .04). Mitral valve was more frequently involved in ABI than in GRA (P < .001). Patient sex, prosthetic IE, aortic involvement, penicillin susceptibility, and surgical treatment were comparable between the genera. New-onset heart failure was the most frequent complication without genera differences (P = .21). Five (13.2%) ABI patients and 2 (5.3%) GRA patients died (P = .23). Factors associated with higher mortality were age (P = .02) and new-onset heart failure (P = .02). The genus (GRA vs ABI) was not associated with higher mortality (P = .23). Conclusions. GRA/ABI IE was more prevalent than HACEK IE and approximately one-tenth as prevalent as VGS; periannular complications were more frequent. GRA and ABI genera IE presented similar clinical features and outcomes. Overall mortality was low, and related to age and development of heart failure. [ABSTRACT FROM AUTHOR]

We aimed to identify clinical factors associated with recurrent infective endocarditis (IE) episodes. The clinical characteristics of 2816 consecutive patients with definite IE (January 2008–2018) were compared according to the development of a second episode of IE. A total of 2152 out of 2282 (94.3%) patients, who were discharged alive and followed-up for at least the first year, presented a single episode of IE, whereas 130 patients (5.7%) presented a recurrence; 70 cases (53.8%) were due to other microorganisms (reinfection), and 60 cases (46.2%) were due to the same microorganism causing the first episode. Thirty-eight patients (29.2%), whose recurrence was due to the same microorganism, were diagnosed during the first 6 months of follow-up and were considered relapses. Relapses were associated with nosocomial endocarditis (OR: 2.67 (95% CI: 1.37–5.29)), enterococci (OR: 3.01 (95% CI: 1.51–6.01)), persistent bacteremia (OR: 2.37 (95% CI: 1.05–5.36)), and surgical treatment (OR: 0.23 (0.1–0.53)). On the other hand, episodes of reinfection were more common in patients with chronic liver disease (OR: 3.1 (95% CI: 1.65–5.83)) and prosthetic endocarditis (OR: 1.71 (95% CI: 1.04–2.82)). The clinical factors associated with reinfection and relapse in patients with IE appear to be different. A better understanding of these factors would allow the development of more effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) is a serious albeit relatively infrequent disease. Given the paucity of cases, particularly in non-referral centres, patient registries have progressively gained relevance to inform about the epidemiology, clinical presentation, and natural history of IE in the last two decades. Although they have become key to advancing knowledge of IE, registries also have shortcomings that lead to relevant consequences that are often overlooked. We aimed to discuss the strengths and limitations of registries in IE. We conducted a PubMed search of relevant articles published between January 2000 and June 2022. The backbone of the contemporary knowledge on IE has been built upon data collected in prospective registries, which has allowed us to collect data on relatively unknown aspects of the disease, identify knowledge gaps, and generate new hypotheses, serving as platforms for further research endeavours. Well-exploited registries can provide key information on how IE is distributed across populations and how it differentially impacts patients and subgroups. However, registries face several difficulties, such as the definition of IE, which includes subjective variables and changes over time. Other limitations include difficulty achieving a comprehensive collection of cases (which depends on both project funding and information systems), over-representation of the centres that created the registry, lack of inclusion of variables to assess endpoints that are relevant to patients in terms of quality of life and prognosis, and ethical issues. The review of the advantages and disadvantages of registries aims to improve the quality of the information collected, the viability of the registry itself, and the ability to answer questions that are relevant to both researchers and patients. [ABSTRACT FROM AUTHOR]