Endocarditis infecciosas izquierdas, cambios con el nuevo milenio / Left endocarditis, changes in the new millennium

Introducción: Descripción de las características de las endocarditis infecciosas izquierdas con el cambio del milenio. Método: Estudio multicéntrico prospectivo de endocarditis izquierdas recogidas en la cohorte andaluza para el estudio de las infecciones cardiovasculares entre 1984-2014. Resultados: De 1.604 endocarditis recogidas 382 pertenecen al grupo 1 (período 1983-1999) y 1.222 al grupo 2 (2000-2014). Los pacientes del grupo 2 presentan mayor edad media, comorbilidad y enfermedades concomitantes, más nosocomialidad, endocarditis asociadas a la atención sanitaria y endocarditis complicadas. Se aprecia un aumento de los Staphylococcus aureus meticilín-resistentes, Enterococcus sp., bacilos gramnegativos y Streptococcus bovis. En el tratamiento aumenta el uso de cefalosporinas y desciende el de penicilina; hay más cirugía al ingreso y menos diferida. La mortalidad se sitúa alrededor del 30% en ambos milenios. En el análisis multivariante la mortalidad se asoció con: milenio anterior (grupo 1), edad, índice de Charlson, fracaso renal y shock séptico y, etiológicamente, Staphylococcus aureus. Conclusiones: La mortalidad se mantiene estable, pese a mejoras diagnósticas y terapéuticas, debido a que los pacientes son mayores, con mayor comorbilidad, endocarditis relacionadas con la atención sanitaria/nosocomialidad y gérmenes más agresivos

Introduction: a description of infective left endocarditis at the turn of the millennium. Method: A multicentre prospective study into the left endocarditis using data collected from the Andalusian cohort for the study of cardiovascular infections during 1984-2014. Results: Of the 1,604 endocarditis cases collected, 382 belonged to G1 (group-1, period 1983-1999) and 1,222 to G2 (group-2, 2000-2014). Patients in the new millennium have a significantly higher mean age, have more comorbidity and concomitant diseases, and nosocomial and health-related endocarditis are more frequent, as well as complications. An increase in methicillin-resistant Staphylococcus aureus, Enterococcus sp., Gram-negative bacilli and Streptococcus bovis was noted. Regarding treatment, there is an increase in the use of cephalosporins and a decrease in penicillins; there is more surgery when admitted to hospital and less delay. Mortality stands at around 30% in both millennia. In the multivariate analysis, mortality was associated with: previous millennium (G1), age, Charlson index, renal failure and septic shock, and aetiologically with Staphylococcus aureus. Conclusions: Mortality remains stable, despite diagnostic and therapeutic improvements, because patients are older, have greater comorbidity, a closer relationship with the health care system (nosocomial) and microorganisms are more aggressive

Role of age and comorbidities in mortality of patients with infective endocarditis.

PURPOSE: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. METHODS: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. RESULTS: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. CONCLUSION: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group.

Factors associated with development of nephrotoxicity in patients treated with vancomycin versus daptomycin for severe Gram-positive infections: A practice-based study / Factores asociados con el desarrollo de nefrotoxicidad en pacientes tratados con vancomicina frente a daptomicina en infecciones graves por grampositivos: Un estudio basado en la práctica clínica

Objectives. To evaluate nephrotoxicity development in patients treated with vancomycin (VAN) and daptomycin (DAP) for proven severe Gram-positive infections in daily practice. Patients and methods. A practice-based, observational, retrospective study (eight Spanish hospitals) was performed including patients ≥18 years with a baseline glomerular filtration rate (GFR)>30 mL/min and/or serum creatinine level<2 mg/dL treated with DAP or VAN for >48h. Nephrotoxicity was considered as a decrease in baseline GRF to <50 mL/min or decrease of >10 mL/min from a baseline GRF<50 mL/min. Multivariate analyses were performed to determine factors associated with 1) treatment selection, 2) nephrotoxicity development, and 3) nephrotoxicity development within each antibiotic group. Results. A total of 133 patients (62 treated with DAP, 71 with VAN) were included. Twenty-one (15.8%) developed nephrotoxicity: 4/62 (6.3%) patients with DAP and 17/71 (23.3%) with VAN (p=0.006). No differences in concomitant administration of aminoglycosides or other potential nephrotoxic drugs were found between groups. Factors associated with DAP treatment were diabetes mellitus with organ lesion (OR=7.81, 95%CI:1.39-4.35) and basal creatinine ≥0.9 mg/dL (OR=2.53, 95%CI:1.15-4.35). Factors associated with VAN treatment were stroke (OR=7.22, 95%CI:1.50-34.67), acute myocardial infarction (OR=6.59, 95%CI:1.51-28.69) and primary bacteremia (OR=5.18, 95%CI:1.03-25.99). Factors associated with nephrotoxicity (R2=0.142; p=0.001) were creatinine clearance<80 mL/min (OR=9.22, 95%CI:1.98-30.93) and VAN treatment (OR=6.07, 95%CI:1.86-19.93). Factors associated with nephrotoxicity within patients treated with VAN (R2=0.232; p=0.018) were congestive heart failure (OR=4.35, 95%CI:1.23-15.37), endocarditis (OR=7.63, 95%CI:1.02-57.31) and basal creatinine clearance<80 mL/min (OR=7.73, 95%CI:1.20-49.71). Conclusions. Nephrotoxicity with VAN was significantly higher than with DAP despite poorer basal renal status in the DAP group

Objectivos: Evaluar el desarrollo de nefrotoxicidad en la práctica clínica diaria en pacientes con infecciones graves probadas por grampositivos, tratados con vancomicina (VAN) y daptomicina (DAP). Pacientes y métodos: Se diseñó un estudio observacional retrospectivo, basado en la práctica clínica diaria (ocho hospitales españoles), en el que se incluyeron pacientes ≥ 18 años con una tasa basal de filtrado glomerular (GFR) > 30 mL/min y/o una creatinina sérica < 2 mg/dl para los pacientes tratados con DAP o vancomicina durante > 48 horas. La nefrotoxicidad fue considerada como una disminución del GRF basal a < 50 mL/min o una disminución de > 10 mL/min desde un GRF basal de < 50 ml/min. Se diseñaron análisis multivariantes para determinar los factores asociados con: 1) la selección del tratamiento, 2) el desarrollo de nefrotoxicidad y 3) el desarrollo de nefrotoxicidad con cada antibiótico. Resultados: Se incluyeron 133 pacientes (62 tratados con DAP, 71 con vancomicina). Veintiuno (15,8%) desarrollaron nefrotoxicidad: 4/62 (6,3%) pacientes con DAP y 17/71 (23,3%) con VAN (p=0,006). No se encontraron diferencias entre los grupos en la administración concomitante de aminoglucósidos u otros fármacos potencialmente nefrotóxicos. Los factores asociados con el tratamiento con DAP fueron diabetes mellitus con lesión orgánica (OR=7,81; IC95%:1,39-4,35) y una creatinina basal ≥0,9 mg/dL (OR=2,53; IC95%:1,15-4,35). Los factores asociados con tratamiento con VAN fueron ictus (OR=7,22; IC95%:1,50-34,67), infarto agudo de miocardio (OR=6,59; IC95%:1,51-28,69) y bacteriemia primaria (OR=5,18, IC95%:1,03-25,99). Los factores asociados con nefrotoxicidad (R2=0,142; p=0,001) fueron aclaramiento de creatinina <80 mL/min (OR=9,22; IC95%:1,98-30,93) y tratamiento con VAN (OR=6,07; IC95%:1,86-19,93). Los factores asociados con nefrotoxicidad en los pacientes tratados con VAN (R2=0,232; p=0,018) fueron insuficiencia cardíaca congestiva (OR=4.35; IC95%:1,23-15,37), endocarditis (OR=7,63; IC95%:1,02-57,31) y una creatinina basal <80 mL/min (OR=7,73; IC95%:1,20-49,71). Conclusiones: La nefrotoxicidad con VAN fue significativamente más alta que la de DAP a pesar del pobre status basal renal del grupo de DAP

Left endocarditis, changes in the new millennium. / Endocarditis infecciosas izquierdas, cambios con el nuevo milenio.

INTRODUCTION: a description of infective left endocarditis at the turn of the millennium. METHOD: A multicentre prospective study into the left endocarditis using data collected from the Andalusian cohort for the study of cardiovascular infections during 1984-2014. RESULTS: Of the 1,604 endocarditis cases collected, 382 belonged to G1 (group-1, period 1983-1999) and 1,222 to G2 (group-2, 2000-2014). Patients in the new millennium have a significantly higher mean age, have more comorbidity and concomitant diseases, and nosocomial and health-related endocarditis are more frequent, as well as complications. An increase in methicillin-resistant Staphylococcus aureus, Enterococcus sp., Gram-negative bacilli and Streptococcus bovis was noted. Regarding treatment, there is an increase in the use of cephalosporins and a decrease in penicillins; there is more surgery when admitted to hospital and less delay. Mortality stands at around 30% in both millennia. In the multivariate analysis, mortality was associated with: previous millennium (G1), age, Charlson index, renal failure and septic shock, and aetiologically with Staphylococcus aureus. CONCLUSIONS: Mortality remains stable, despite diagnostic and therapeutic improvements, because patients are older, have greater comorbidity, a closer relationship with the health care system (nosocomial) and microorganisms are more aggressive.

Left-sided infective endocarditis caused by Streptococcus agalactiae: rare and serious.

A comparative study of the behaviour of left-sided infective endocarditis (left-sided IE) due to Streptococcus agalactiae (GBS) with left-sided IE caused by Staphylococcus aureus (SA). A prospective, multicentre cohort study in eight public hospitals in Spain, from January 1984 to December 2015; comparative analysis and factors associated with mortality. In total, there were 1754 episodes of left-sided IE; 41 (2.3%) caused by GBS vs. 344 (19.6%) due to SA, definitive IE 39 vs. 324 cases, males, 25 vs. 213, respectively. There were no differences in age or comorbidity, and healthcare-associated acquirement was 10% vs. 43%, p 0.001. Transthoracic echocardiogram (TTE) was performed in 95% vs. 96.8% and a transesophageal echocardiogram (TEE) in 61% vs. 56%. Vegetations were detected in 80% and measured > 1 cm in a similar proportion. It affected native valves in 85.4% vs. 82.6% and late prosthetic valve in 14.6% vs. 9.6%. The course was acute in both groups. There were more skin manifestations in SA left-sided IE, 7.3% vs. 32%, p 0.001. Both groups had similar complications, but in SA, there was more renal failure, 24% vs. 45%, p 0.010. Surgical risk and operated patients were similar. Mortality was proportionally higher in the SA group, without significance 29% vs. 43% (150), p 0.09. Heart failure, septic shock and neurological deterioration conditioned mortality: HR 1.96, 1.69 and 1.37 (CI 95% 1.40-2.73; 1.19-2.39 and 0.99-1.88 respectively) and to a lesser degree SA as aetiology agent and age. Left-sided IE caused by GBS is similar in severity to left-sided IE caused by SA.

Gentamicin may have no effect on mortality of staphylococcal prosthetic valve endocarditis.

PURPOSE: To analyze the influence of adding gentamicin to a regimen consisting of ß-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). METHODS: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on ß-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. RESULTS: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84-11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03-6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29-3.38) in the multivariable analysis. CONCLUSIONS: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Endocarditis infecciosa sobre válvula aórtica bicúspide: características clínicas, complicaciones y pronóstico / Infective endocarditis in patients with bicuspid aortic valve: Clinical characteristics, complications, and prognosis

Introducción: La válvula aórtica bicúspide (VAB) es la malformación cardíaca congénita más frecuente. Se asocia a un mayor riesgo de complicaciones cardiovasculares, entre las que se incluye la endocarditis infecciosa (EI). Métodos: Estudio observacional, unicéntrico de cohorte, que incluye de forma prospectiva a todos los pacientes ingresados por EI entre 1996 y 2014. Se analizan datos epidemiológicos, clínicos, microbiológicos, ecocardiográficos, complicaciones durante la hospitalización, necesidad quirúrgica, mortalidad intrahospitalaria y seguimiento a un año. Se excluyen los casos con endocarditis sobre válvulas protésicas o en otras localizaciones, y aquellos de cuya válvula aórtica no se tienen datos certeros acerca de su morfología. Se ha realizado un análisis estadístico comparativo entre VAB y tricúspide (VAT). Resultados: De un total de 328 casos con EI, 118 (35,67%) fueron sobre válvula aórtica. Tenían VAB 18 (16,22%). Los casos con VAB eran más jóvenes que los portadores de VAT (51±19,06 vs. 60,83±15,73 años, p=0,021) y tenían menos comorbilidad (índice de Charlson 0,67±0,77 vs. 1,44±1,64, p=0,03). En el grupo con VAB observamos tendencia a EI causada por Staphylococcus spp. (38,9 vs. 21,5%, p=0,137). Con diferencia estadística, hubo más complicaciones perivalvulares entre los casos con VAB (55,6% vs. 16,1%, p=0,001) predominando los abscesos (38,9 vs. 16,1%, p=0,047). Ser portador de VAB fue el único factor predictor de las mismas (OR 7,87, IC del 95%, 2,38-26,64, p=0,001). Los pacientes con VAB se operaron más (83,3 vs. 44,1%, p=0,004) y la mortalidad durante el ingreso hospitalario fue menor, aunque no alcanzó significación estadística (5,6 vs. 25,8%, p=0,069). La supervivencia a un año fue significativamente superior en el grupo de VAB (93,8 vs 69,3%, p=0,048). Conclusiones:Los pacientes con EI sobre VAB son jóvenes, con poca comorbilidad asociada. Tienen frecuentemente complicaciones perivalvulares por lo que requieren cirugía precoz. La mortalidad intrahospitalaria comparada con EI sobre VAT es menor y la supervivencia a un año es significativamente mayor (AU)

Introduction: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. It is associated to a higher risk of cardiovascular complications, including infective endocarditis (IE). Methods: Retrospective, observational and single centre study that included all patients with IE diagnosed between 1996 and 2014. An analysis was made of the epidemiological, clinical, microbiological and echocardiographic data, complications during hospital admission, need for surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on prosthetic valves or other locations were excluded, as well as those for which the aortic valve morphology had not been accurately defined. A comparative statistical analysis was performed between BAV and tricuspid (TAV). Results: Of a total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%) of them being BAV. The BAV cases were younger than TAV (51±19.06 vs. 60.83±15.73 years, P=.021) and they had less comorbidity (Charlson 0.67±0.77 vs. 1.44±1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9 vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%, P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64, P=.001). Patients with BAV had more surgery during their admission (83.3 vs. 44.1%, P=.004), had less in-hospital mortality, with no statistical significance (5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs 69.3%, P=.048). Conclusions: Patients with IE on BAV are young, with low comorbidity. They frequently present with peri-valvular complications and they often require early surgery. Compared to TAV cases, in-hospital mortality is lower and 1-year survival is significantly higher(AU)

Etiología de la insuficiencia renal en pacientes con endocarditis infecciosa. Papel de los antibióticos / Aetiology of renal failure in patients with infective endocarditis. The role of antibiotics

Fundamento y objetivos: La toxicidad renal de ciertos antibióticos (AB) es conocida. El objetivo de nuestro trabajo es conocer el posible efecto de los tratamientos AB en el desarrollo de insuficiencia renal (IR) en pacientes con endocarditis infecciosa (EI). Material y método: Recogida en un registro nacional multicéntrico de los datos referentes a la función renal, tanto previa como su deterioro si existiese, durante el tratamiento de las EI y relacionarlo con los posibles factores causantes, entre ellos los AB. Resultados: Entre 2008 y 2012 se han analizado 1.853 episodios de EI remitidos desde 26 centros españoles. De ellos, un 21,6% presentaban una alteración previa de la función renal. Desarrollaron IR de novo o un empeoramiento de la función renal previa un 38,7% de los casos. En aquellos pacientes que presentaban IR previa, el deterioro fue más frecuente (64 frente a 31,7%; p<0,001). Globalmente los pacientes con IR tenían más edad (70,6 frente a 67 años; p<0,01) y comorbilidades (índice de Charlson 5 frente a 4; p<0,01), y la EI era por Staphylococcus aureus (32,1 frente a 16,5%; p<0,01). El uso de AB potencialmente nefrotóxicos solo se asoció a IR en el grupo de pacientes sin IR previa (aminoglucósidos: OR=1,47 [IC 95% 1,096-1,988], p=0,010; aminoglucósidos-vancomicina: OR=1,49 [IC 95% 1,069-2,09], p=0,019]). Conclusiones: En pacientes sin IR previa, los AB nefrotóxicos se asocian a un deterioro de la función renal. En pacientes con IR previa al episodio de EI, el deterioro de renal fue más frecuente, pero parece estar más relacionado con la gravedad de la infección (AU)

Background and objectives: The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). Material and method: Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. Results: Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001). Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988], P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019). Conclusions: In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection (AU)

Aetiology of renal failure in patients with infective endocarditis. The role of antibiotics. / Etiología de la insuficiencia renal en pacientes con endocarditis infecciosa. Papel de los antibióticos.

BACKGROUND AND OBJECTIVES: The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). MATERIAL AND METHOD: Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. RESULTS: Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001). Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988], P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019). CONCLUSIONS: In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection.

Infective endocarditis in patients with bicuspid aortic valve: Clinical characteristics, complications, and prognosis. / Endocarditis infecciosa sobre válvula aórtica bicúspide: características clínicas, complicaciones y pronóstico.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. It is associated to a higher risk of cardiovascular complications, including infective endocarditis (IE). METHODS: Retrospective, observational and single centre study that included all patients with IE diagnosed between 1996 and 2014. An analysis was made of the epidemiological, clinical, microbiological and echocardiographic data, complications during hospital admission, need for surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on prosthetic valves or other locations were excluded, as well as those for which the aortic valve morphology had not been accurately defined. A comparative statistical analysis was performed between BAV and tricuspid (TAV). RESULTS: Of a total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%) of them being BAV. The BAV cases were younger than TAV (51±19.06 vs. 60.83±15.73 years, P=.021) and they had less comorbidity (Charlson 0.67±0.77 vs. 1.44±1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9 vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%, P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64, P=.001). Patients with BAV had more surgery during their admission (83.3 vs. 44.1%, P=.004), had less in-hospital mortality, with no statistical significance (5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs 69.3%, P=.048). CONCLUSIONS: Patients with IE on BAV are young, with low comorbidity. They frequently present with peri-valvular complications and they often require early surgery. Compared to TAV cases, in-hospital mortality is lower and 1-year survival is significantly higher.

Endocarditis in patients with ascending aortic prosthetic graft: a case series from a national multicentre registry.

OBJECTIVES: Endocarditis in patients with ascending aortic prosthetic graft (AAPG) is a life-threatening complication. The purpose of this study was to examine the clinical presentation and prognosis of patients with AAPG endocarditis included in a large prospective infectious endocarditis multicentre study. METHODS: From January 2008 to April 2015, 3200 consecutive patients with infectious endocarditis according to the modified Duke criteria, were prospectively included in the 'Spanish Collaboration on Endocarditis Registry (GAMES)' registry. Twenty-seven definite episodes of endocarditis (0.8%) occurred in patients with AAPG. RESULTS: During the study period, 27 cases of endocarditis were detected in patients with AAPG. The median age of patients was 61 years [interquartile range (IQR) 51-68 years] and 23 (85.2%) patients were male. The median time from AAPG surgery to the episode of AAPG infection was 24 months (IQR 6-108 months). The most frequently isolated micro-organisms were coagulase-negative staphylococci and S. aureus (11 patients, 40.7%). Four patients (14.8%) underwent medical treatment, whereas surgery was performed in 21 (77.7%). Two patients (7.4%) died before surgery could be performed. The median hospital stay prior to surgery was 7 days (IQR 4-21 days). Surgery consisted of replacing previous grafts with a composite aortic graft (10 cases) or aortic homograft (2 patients), and removal of a large vegetation attached to the valve of a composite tube (1 case). Nine patients had an infected aortic valve prosthesis without evidence of involvement of the AAPG. Isolated redo-aortic valve replacement was performed in 8 (88.9%) of these patients. Reinfection occurring during 1 year of follow-up was not detected in any patient. Two patients (7.4%) died while awaiting surgery and 6 did so after surgery (22.2%). A New York Heart Association (NYHA) Class IV was associated with mortality in patients undergoing surgery (P < 0.019). CONCLUSIONS: Most cases of endocarditis in patients with AAPG occur late after initial surgery. Mortality rate of patients with AAPG endocarditis who undergo surgery is acceptable. NYHA Class IV before surgery is associated with an increased postoperative mortality.

Hepatic Safety of Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate Fixed-Dose Single-Tablet Regimen in HIV-Infected Patients with Active Hepatitis C Virus Infection: The hEPAtic Study.

OBJECTIVES: The aim of this study was to evaluate the frequency of transaminase elevations (TE) and total bilirubin elevations (TBE) during the first year of therapy with a single tablet regimen including RPV/FTC/TDF (EPA) in HIV/hepatitis C virus (HCV)-coinfected subjects in clinical practice. METHODS: In a retrospective analysis, HIV/HCV-coinfected subjects who started EPA at 17 centres throughout Spain were included as cases. Subjects who started an antiretroviral therapy (ART) other than EPA during the study period at the same hospitals were randomly selected as controls in a 1:2 ratio. Primary outcome variables were grade (G) 3-4 TE and G4 TBE. RESULTS: Of the 519 subjects included, 173 individuals started EPA. Nine (5.2%) subjects of the EPA group and 49 (14.2%) controls were naïve to ART. The median (Q1-Q3) follow-up was 11.2 (9.7-13.9) months. TE was observed in 2 [1.2%; 95% confidence interval (CI): 0.14%-4.1%] subjects receiving EPA and 11 (3.2%; 95%CI: 1.6%-5.6%) controls (p = 0.136), all events were G3. No patient discontinued ART due to TE. One (0.6%; 95%CI: 0.01%-3.1%) subject on EPA and 8 (2.3%; 95%CI: 1%-4.5%) subjects in the control group developed TBE (p = 0.141), without developing any other hepatic event during follow-up. Three (2.3%) subjects with cirrhosis versus 10 (3.1%) without cirrhosis showed G3-4 TE (p = 0.451). CONCLUSION: The frequency of severe liver toxicity in HIV/HCV-coinfected subjects receiving EPA under real-life conditions is very low, TE were generally mild and did not lead to drug discontinuation. All these data suggest that EPA can be safely used in this particular subpopulation.

Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort.

OBJECTIVE: To assess the current frequency of ART-associated grade 3-4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART. PATIENTS AND METHODS: A total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study. RESULTS: Forty-one (21.4%) subjects had been naïve to ART, median (IQR) follow-up was 11.6 (5.6-12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53%-9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417-37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3-4 TE. CONCLUSIONS: Currently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern.

Incidence and clinical impact of infective endocarditis after transcatheter aortic valve implantation.

AIMS: To describe the characteristics of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: This study was performed using the GAMES database, a national prospective registry of consecutive patients with IE in 26 Spanish hospitals. Of the 739 cases of IE diagnosed during the study, 1.3% were post-TAVI IE, and these 10 cases, contributed by five centres, represented 1.1% of the 952 TAVIs performed. Mean age was 80 years. All valves were implanted transfemorally. IE appeared a median of 139 days after implantation. The mean age-adjusted Charlson comorbidity index was 5.45. Chronic kidney disease was frequent (five patients), as were atrial fibrillation (five patients), chronic obstructive pulmonary disease (four patients), and ischaemic heart disease (four patients). Six patients presented aortic valve involvement, and four only mitral valve involvement; the latter group had a higher percentage of prosthetic mitral valves (0% vs. 50%). Vegetations were found in seven cases, and four presented embolism. One patient underwent surgery. Five patients died during follow-up: two of these patients died during the admission in which the valve was implanted. CONCLUSIONS: IE is a rare but severe complication after TAVI which affects about 1% of patients and entails a relatively high mortality rate. IE occurred during the first year in nine of the 10 patients.

Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/HCV-coinfected patients. Preliminary results of the hEPAtic Study.

INTRODUCTION: Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic events, such as transaminase elevations (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet regimen which is widely used in real life practice. Clinical trials showed an adequate profile of liver safety in the sub-population of HIV/HCV-coinfected patients receiving rilpivirine. However, the number of individuals included in these analyses is low (1). The aim of this ongoing study is to evaluate the incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of EPA-based therapy in a large population of HIV/HCV-coinfected subjects outside of clinical trials. PATIENTS AND METHODS: This is a retrospective analysis of HIV/HCV-coinfected subjects who started EPA at the infectious diseases units of 14 centres throughout Spain, included as cases. Subjects who started an ART different to EPA during the study period at the same hospitals were selected as controls. The primary outcome variables were grade 3 or 4 TE and grade 4 TBE. RESULTS: Of the 191 patients included, 31 (16.2%) subjects were naïve to ART. Eighty-seven individuals started EPA and the remaining ones were controls. The most common NRTI backbone among the controls was TDF/FTC [59 (56.7%) patients] followed by NRTI-sparing regimens [24 (23.1%) individuals] and ABC/3TC [17 (16.3%) subjects]. Among controls, 67 (64.4%) started a ritonavir-boosted protease inhibitor, mainly DRV/r [41 (39.4%) patients] followed by ATV/r [16 (15.4%) subjects]. EFV, ETV and RAL were started in 16 (15.4%), 12 (11.5%) and 13 (12.5%) subjects, respectively. The median (Q1-Q3) follow-up was 5.79 (3.65-8.61) months for the cases and 11.44 (5.8-12.88) months for the controls. TE was observed in two (2.3%) cases versus five (4.8%) controls (p=0.358), accounting for a density of incidence of 4.32/100 person-years versus 5.51/100 person-years [incidence rate difference (95% confidence interval): -1.88 (-9.95-6.2), p=0.354]. All TE were grade 3 and no patient discontinued ART due to TE. None of the cases developed TBE versus four (3.8%) controls, all of them receiving ATV/r. CONCLUSIONS: The frequency of grade 3-4 TE associated with EPA in HIV/HCV-coinfected patients under real life conditions is very low. In addition, TE in HIV/HCV-coinfected patients treated with EPA are usually mild and do not lead to treatment discontinuation. TBE was not seen in patients taking EPA. All these data confirm that EPA is safe in this particular subpopulation.

Valve surgery in active infective endocarditis: a simple score to predict in-hospital prognosis.

AIMS: Surgery for infective endocarditis (IE) is associated with high mortality. Our objectives were to describe the experience with surgical treatment for IE in Spain, and to identify predictors of in-hospital mortality. METHODS: Prospective cohort of 1000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. RESULTS: Surgery was performed in 437 patients (43.7%). Patients treated with surgery were younger and predominantly male. They presented fewer comorbid conditions and more often had negative blood cultures and heart failure. In-hospital mortality after surgery was lower than in the medical therapy group (24.3 vs 30.7%, p=0.02). In patients treated with surgery, endocarditis involved a native valve in 267 patients (61.1%), a prosthetic valve in 122 (27.9%), and a pacemaker lead with no clear further valve involvement in 48 (11.0%). The most common aetiologies were Staphylococcus (186, 42.6%), Streptococcus (97, 22.2%), and Enterococcus (49, 11.2%). The main indications for surgery were heart failure and severe valve regurgitation. A risk score for in-hospital mortality was developed using 7 prognostic variables with a similar predictive value (OR between 1.7 and 2.3): PALSUSE: prosthetic valve, age ≥ 70, large intracardiac destruction, Staphylococcus spp, urgent surgery, sex [female], EuroSCORE ≥ 10. In-hospital mortality ranged from 0% in patients with a PALSUSE score of 0 to 45.4% in patients with PALSUSE score >3. CONCLUSIONS: The prognosis of IE surgery is highly variable. The PALSUSE score could help to identify patients with higher in-hospital mortality.

Influencia de una estrategia de alerta multidisciplinaria en la mortalidad por endocarditis infecciosa izquierda / Influence of a Multidisciplinary Alert Strategy on Mortality Due to Left-sided Infective Endocarditis

Introducción y objetivos La mortalidad por endocarditis infecciosa izquierda continúa siendo muy elevada. El objetivo de este estudio es valorar el impacto en la mortalidad precoz de la endocarditis infecciosa izquierda de una estrategia de alerta multidisciplinaria (AMULTEI, basada en la alerta clínica, ecocardiográfica y microbiológica) iniciada en 2008 en un centro hospitalario de tercer nivel. Métodos Estudio de cohortes que compara nuestra serie histórica (1996-2007) con la serie de pacientes de 2008-2011 diagnosticada de endocarditis izquierda (AMULTEI).Resultados La cohorte AMULTEI incluye a 72 pacientes, frente a los 155 de la cohorte histórica. Los pacientes AMULTEI presentaron significativamente más edad (62,5 frente a 57,9 años en la cohorte histórica; p = 0,047) y más comorbilidad (índice de Charlson, 3,33 frente a 2,58 en la cohorte histórica; p = 0,023). Se observó una tendencia a más etiología enterocócica (el 20,8% del grupo AMULTEI frente al 11,6% de la cohorte histórica; p = 0,067). Se realizó cirugía sin demora durante el ingreso hospitalario más frecuentemente (el 48,6 frente al 23,2%; p < 0,001). Se redujo significativamente la incidencia de shock séptico (el 9,7 frente al 24,5%; p = 0,009) y hubo una tendencia a reducirse las complicaciones neurológicas (el 19,4 frente al 29,0%; p = 0,25) y la insuficiencia cardiaca grave (el 12,5 frente al 18,7%; p = 0,24). Las mortalidades hospitalaria y durante el primer mes de seguimiento disminuyeron significativamente (el 16,7 frente al 36,1%; p = 0,003).Conclusiones A pesar de la tendencia a mayor edad y más comorbilidad medida por índice de Charlson, los pacientes tratados con la estrategia AMULTEI presentaron una reducción significativa de la mortalidad precoz (AU)

Introduction and Objectives Mortality from left-sided infective endocarditis remains very high. The aim of this study was to assess the impact of a multidisciplinary alert strategy (AMULTEI), based on clinical, echocardiographic and microbiological findings, implemented in 2008 in a tertiary hospital. Methods Cohort study comparing our historical data series (1996-2007) with the number of patients diagnosed with left-sided endocarditis from 2008-2011 (AMULTEI).Results The AMULTEI cohort included 72 patients who were compared with 155 patients in the historical cohort. AMULTEI patients were significantly older (62.5 vs 57.9 years in the historical cohort; P=.047) and had higher comorbidity (Charlson index, 3.33 vs 2.58 in the historical cohort; P=.023). There was also a trend toward more enterococcal etiology in the AMULTEI group (20.8% vs 11.6% in the historical cohort; P=.067). In the AMULTEI group, early surgery was more frequently performed (48.6% vs 23.2%; P<.001) during hospitalization, the incidence of septic shock was significantly lower (9.7% vs 24.5%; P=.009) and there was a trend toward reductions in neurological complications (19.4% vs 29.0%; P=.25) and severe heart failure (12.5% vs 18.7%; P=.24). In-hospital mortality and mortality during the first month of follow-up were significantly lower in the AMULTEI group (16.7% vs 36.1%; P=.003).Conclusions Despite the trend toward older age and more comorbidity measured by the Charlson index, early mortality was significantly lower in patients treated with the AMULTEI strategy (AU)

Influence of a multidisciplinary alert strategy on mortality due to left-sided infective endocarditis.

INTRODUCTION AND OBJECTIVES: Mortality from left-sided infective endocarditis remains very high. The aim of this study was to assess the impact of a multidisciplinary alert strategy (AMULTEI), based on clinical, echocardiographic and microbiological findings, implemented in 2008 in a tertiary hospital. METHODS: Cohort study comparing our historical data series (1996-2007) with the number of patients diagnosed with left-sided endocarditis from 2008-2011 (AMULTEI). RESULTS: The AMULTEI cohort included 72 patients who were compared with 155 patients in the historical cohort. AMULTEI patients were significantly older (62.5 vs 57.9 years in the historical cohort; P=.047) and had higher comorbidity (Charlson index, 3.33 vs 2.58 in the historical cohort; P=.023). There was also a trend toward more enterococcal etiology in the AMULTEI group (20.8% vs 11.6% in the historical cohort; P=.067). In the AMULTEI group, early surgery was more frequently performed (48.6% vs 23.2%; P<.001) during hospitalization, the incidence of septic shock was significantly lower (9.7% vs 24.5%; P=.009) and there was a trend toward reductions in neurological complications (19.4% vs 29.0%; P=.25) and severe heart failure (12.5% vs 18.7%; P=.24). In-hospital mortality and mortality during the first month of follow-up were significantly lower in the AMULTEI group (16.7% vs 36.1%; P=.003). CONCLUSIONS: Despite the trend toward older age and more comorbidity measured by the Charlson index, early mortality was significantly lower in patients treated with the AMULTEI strategy.

Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study.

BACKGROUND: The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. METHODS AND RESULTS: This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P<0.01), although only moderate to severe ischemic stroke (HR 1.63) and brain hemorrhage (HR 1.73) were significantly associated with a poorer prognosis. Antimicrobial treatment reduced (by 33% to 75%) the risk of neurological complications. In patients with hemorrhage, mortality was higher when surgery was performed within 4 weeks of the hemorrhagic event (75% versus 40% in later surgery). CONCLUSIONS: Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.