BACKGROUND:Patients with human immunodeficiency virus (HIV) infection have been gradually accepted as solid organ transplant recipients, although there is still concern that the burden of immunosuppression and HIV infection could increase the risk of post-transplant cancer. METHODS:The risk of de novo cancer was evaluated in a prospective cohort of 272 HIV-positive and 816 matched HIV-negative liver transplant recipients in Spain (2002-2012). All tumors, except hepatocellular carcinoma recurrence and non-melanoma skin cancer, after liver transplant were considered as events and death as competing event in this study. RESULTS:Despite matching, patients with HIV were significantly younger (45.8 vs 49.3 years). Sixteen (5.9%) patients with HIV and 61 (7.5%) HIV-negative patients developed de novo cancers (P = .39) after a median follow-up of 59.8 and 72.3 months, respectively. The most frequently diagnosed types of tumors were non-Hodgkin lymphoma (n = 19), lung cancer (n = 14), and head and neck cancer (n = 14). Time of onset, distribution, and tumor stage at diagnosis were similar in both groups. The cumulative incidences of de novo cancer at 5 and 10 years were, respectively, 6% and 12% in patients with HIV and 6% and 13% in uninfected patients. Survival after cancer diagnosis did not differ between groups. The only factor related to the development of de novo cancers was a higher age at transplantation. CONCLUSIONS:Human immunodeficiency virus infection per se is not associated to a higher risk of de novo cancer after liver transplantation.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Background Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied.Objectives To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA.Methods Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020.Results Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49-3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1-7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045).Conclusions MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes. In this prospective multicenter cohort with 4,548 infective endocarditis cases, mycotic aneurysms (MA) developed in 2%, with half being intracranial. Rupture was common, correlating with poor prognosis. A notable portion of initially intact intracranial MA ruptured within the initial days.

Objectives: To determine the incidence of cardiac device-related infection (CDRI) among patients with cardiac device (CD) during late-onset bloodstream infection (BSI) and to identify the risk factors associated with CDRI. Methods: Patients with a CD (cardiac implantable electronic devices -CIED- and/or prosthetic heart valve-PHV-) and late-onset-BSI (>1 year after the CD implantation/last manipulation) were selected from the PROBAC project, a prospective, observational cohort study including adult patients with bacteraemia consecutively admitted to 26 Spanish hospitals from October 2016 to March 2017. Multivariate analyses using logistic regression were performed to identify the risk factors associated with CDRI. Results: 317 BSI from patients carrying a CD were registered, 187 (56.2%) were late-onset-BSI. A total of 40 (21.4%) CDRI were identified during late-onset-BSI. The CDRI cumulative incidence in Gram-positive-BSI was 41.8% (38/91), with S. aureus, Enterococcus spp. and viridans streptococci showing the greatest percentages: 40% (12/30), 42% (11/26) and 75% (6/8), respectively. Independent predictors of CDRI were an unknown source of infection (OR: 2.88 [CI 95%:1.18-7.06], p = 0.02), Gram-positive-aetiology (23.1 [5.23-102.1], p < 0.001) and persistent bacteraemia (4.81 [1.21-19], p = 0.03). In an exploratory analysis, S. aureus (3.99 [1.37-11.65], p = 0.011), Enterococcus spp. (5.21 [1.76-15.4], p = 0.003) and viridans streptococci (28.7 [4.71-173.5], p < 0.001) aetiology were also found to be risk factors for CDRI. Conclusions: CDRI during late-onset-BSI is a frequent phenomenon. Risk of CDRI differs among species, happening in almost half of the Gram-positive-BSI. An unknown source of the primary infection, Gram-positive-aetiology -especially S. aureus, Enterococcus spp. and viridans streptococci-, and persistent bacteraemia were identified as risk factors for CDRI. (C) 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Several genetic polymorphisms of the innate immune system have been described to increase the risk of cytomegalovirus (CMV) infection in transplant patients. The aim of this study was to assess the impact of a polygenic score to predict CMV infection and disease in high risk CMV transplant recipients (heart, liver, kidney or pancreas). On hundred and sixteen CMV-seronegative recipients of grafts from CMV-seropositive donors undergoing heart, liver, and kidney or pancreas transplantation from 7 centres were prospectively included for this purpose during a 2-year period. All recipients received 100-day prophylaxis with valganciclovir. CMV infection occurred in 61 patients (53%) at 163 median days from transplant, 33 asymptomatic replication (28%) and 28 CMV disease (24%). Eleven patients (9%) had recurrent CMV infection. Clinically and/or functionally relevant single nucleotide polymorphisms (SNPs) from TLR2, TLR3, TLR4, TLR7, TLR9, AIM2, MBL2, IL28, IFI16, MYD88, IRAK2 and IRAK4 were assessed by real time polymerase chain reaction (RT-PCR) or sequence-based typing (PCR-SBT). A polygenic score including the TLR4 (rs4986790/rs4986791), TLR9 (rs3775291), TLR3 (rs3775296), AIM2 (rs855873), TLR7 (rs179008), MBL (OO/OA/XAO), IFNL3/IL28B (rs12979860) and IFI16 (rs6940) SNPs was built based on the risk of CMV infection and disease. The CMV score predicted the risk of CMV disease with an AUC of the model of 0.68, with sensitivity and specificity of 64.3 and 71.6%, respectively. Even though further studies are needed to validate this score, its use would represent an effective model to develop more robust scores predicting the risk of CMV disease in donor/recipient mismatch (D+/R-) transplant recipients.

Objectives (1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality. Methods We recruited 10 AE cases included in the GAMES cohort (January 2008-December 2018) and 51 cases from the literature published from January 2010 to July 2019. Results 4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%). Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26-13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07-0.72, p = .01). Conclusions AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole-based treatment combined with surgical resection are related to a better outcome.

BACKGROUND:Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. METHODS:In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). RESULTS:A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. CONCLUSIONS:Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. CLINICAL TRIALS REGISTRATION:NCT03123627.

Objective Successful clinical trials are subject to recruitment. Recently, the REJUVENATE trial, a prospective phase 2a open-label, single-arm interventional clinical trial conducted within the Innovative Medicines Initiative-supported Combatting Bacterial Resistance in Europe-Carbapenem Resistance project, was published, with 85% of the recruitment performed in Spain. We analysed the recruitment success in this trial by establishing a model of recruitment practice. Methods A descriptive qualitative study was performed from May 2016 to October 2017 at 10 participating Spanish centres. Data were extracted from: (1) feasibility questionnaires to assess the centre’s potential for patient enrolment; (2) delegation of responsibility records; (3) pre-screening records including an anonymised list of potentially eligible and (4) screening and enrolment records. A descriptive analysis of the features was performed by the participating centre. Pearson’s and Spearman’s correlation coefficients were calculated to determine factors of recruitment success. Results The highest recruitment rate was observed in Hospitals 3 and 6 (58.8 and 47.0 patients per month, respectively). All the study teams were multidisciplinary with a median of 15 members (range: 7–22). Only Hospitals 3, 5 and 6 had dedicated nursing staff appointed exclusively to this study. Moreover, in those three hospitals and in Hospital 9, the study coordinator performed exclusive functions as a research planner, and did not assume these functions for the other hospitals. The univariate analysis showed a significant association between recruitment success and months of recruitment (p=0.024), number of staff (p<0.001), higher number of pharmacists (p=0.005), infectious disease specialists (p<0.001), the presence of microbiologist in the research team (p=0.018) and specifically dedicated nursing staff (p=0.036). Conclusions The existence of broad multidisciplinary teams with staff dedicated exclusively to the study as well as the implementation of a well-designed local patient assessment strategy were the essential optimisation factors for recruitment success in Spain. Trial registration number NCT02655419 ; EudraCT 2015-002726-39; analysis of pre-screened patients.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006–2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01–2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27–0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76–2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E.

BACKGROUND:Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.METHODS:We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively.RESULTS:Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes.CONCLUSIONS:Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined.

[This corrects the article DOI: 10.1093/ofid/ofab250.].

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.

Current guidelines recommend against systematic screening for or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of posttransplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens.

Abstract Background Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results Of 5336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When comparing SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs 3.5%, P = .116); valve disorder, including perforation (22.2% vs 18.1%, P = .584), pseudoaneurysm (16.7% vs 8.3%, P = .108), or prosthesis dehiscence (1.4% vs 6.3%, P = .170); paravalvular complications, including abscess (25% vs 18.8%, P = .264) and intracardiac fistula (5.6% vs 3.5%, P = .485); heart failure (34.7% vs 38.9%, P = .655); or embolic events (41.7% vs 32.6%, P = .248). Indications for surgery (70.8% vs 70.8%; P = 1) and mortality (13.9% vs 16.7%; P = .741) were similar between groups. Conclusions SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG.

Objectives: To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. Methods: Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum beta-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. Results: MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. Conclusions: DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously. (C) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens.

Background. This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. Methods. CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-gamma [IFN-gamma] >= 0.2 IU/mL) indicated a positive CMV-CMI. Results. A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-gamma level (>12 IU/mL vs <= 12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P <.001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-gamma level <= 12 IU/mL. Conclusions. More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-gamma level, but not the ATG dose, shows a strong association with the kinetics of this recovery.

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.