Francisco J. Martínez-Marcos

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.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. # Clinical Perspective {#article-title-46}

Prognostic factors in left-sided endocarditis: results from the andalusian multicenter cohort

BackgroundDespite medical advances, mortality in infective endocarditis (IE) is still very high. Previous studies on prognosis in IE have observed conflicting results. The aim of this study was to identify predictors of in-hospital mortality in a large multicenter cohort of left-sided IE.MethodsAn observational multicenter study was conducted from January 1984 to December 2006 in seven hospitals in Andalusia, Spain. Seven hundred and five left-side IE patients were included. The main outcome measure was in-hospital mortality. Several prognostic factors were analysed by univariate tests and then by multilogistic regression model.ResultsThe overall mortality was 29.5% (25.5% from 1984 to 1995 and 31.9% from 1996 to 2006; Odds Ratio 1.25; 95% Confidence Interval: 0.97-1.60; p = 0.07). In univariate analysis, age, comorbidity, especially chronic liver disease, prosthetic valve, virulent microorganism such as Staphylococcus aureus, Streptococcus agalactiae and fungi, and complications (septic shock, severe heart failure, renal insufficiency, neurologic manifestations and perivalvular extension) were related with higher mortality. Independent factors for mortality in multivariate analysis were: Charlson comorbidity score (OR: 1.2; 95% CI: 1.1-1.3), prosthetic endocarditis (OR: 1.9; CI: 1.2-3.1), Staphylococcus aureus aetiology (OR: 2.1; CI: 1.3-3.5), severe heart failure (OR: 5.4; CI: 3.3-8.8), neurologic manifestations (OR: 1.9; CI: 1.2-2.9), septic shock (OR: 4.2; CI: 2.3-7.7), perivalvular extension (OR: 2.4; CI: 1.3-4.5) and acute renal failure (OR: 1.69; CI: 1.0-2.6). Conversely, Streptococcus viridans group etiology (OR: 0.4; CI: 0.2-0.7) and surgical treatment (OR: 0.5; CI: 0.3-0.8) were protective factors.ConclusionsSeveral characteristics of left-sided endocarditis enable selection of a patient group at higher risk of mortality. This group may benefit from more specialised attention in referral centers and should help to identify those patients who might benefit from more aggressive diagnostic and/or therapeutic procedures.

Ensayo clínico aleatorizado de tres pautas de quimioprofilaxis para prevenir la tuberculosis en pacientes infectados por el VIH con anergia cutánea

Introduccion Evaluar la eficacia de tres pautas de quimioprofilaxis antituberculosa en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con anergia cutanea Metodos Ensayo clinico prospectivo, multicentrico, aleatorizado, comparativo y abierto. La anergia cutanea se definio por la ausencia de reactividad a 3 antigenos aplicados por la tecnica de Mantoux (PPD, candidina y parotiditis). Los pacientes se distribuyeron de forma aleatoria a uno de los siguientes grupos de tratamiento: isoniacida durante 6 meses (6H), rifampicina mas isoniacida, 3 meses (3RH), rifampicina mas piracinamida, 2 meses (2RZ) o sin tratamiento (NT). Tras finalizar la quimioprofilaxis los pacientes fueron seguidos 2 anos Resultados Se incluyeron en el estudio 319 pacientes, 83 en la pauta 6H, 82 en 3RH, 77 en 2RZ y 77 en NT. El periodo de observacion tras el tratamiento fue de 88, 96, 81 y 126 personas anos, respectivamente para 6H, 3RH, 2RZ y NT. Se produjeron 11 casos de tuberculosis durante el seguimiento. Las tasas de tuberculosis (casos por 100 personas/ano) fueron respectivamente de 3,4, 3,1, 1,2 y 3,1 para 6H, 3RH, 2RZ y NT, con un riesgo relativo en las pautas 6H, 3RH y 2RZ respecto a NT de 1,07 (0,24-4,80), 0,98 (0,22-4,4) y 0,39 (0,04-3,48), estadisticamente no significativo. Durante el seguimiento fallecieron 29 pacientes, ninguno de ellos por tuberculosis, sin que se apreciaran diferencias entre grupos Conclusiones Nuestro estudio no demuestra una reduccion significativa del riesgo de tuberculosis en ninguna de las 3 pautas evaluadas y, por tanto, no apoya el empleo de quimioprofilaxis antituberculosa en pacientes con anergia cutanea

Streptococcus agalactiae left-sided infective endocarditis. Analysis of 27 cases from a multicentric cohort

SUMMARY OBJECTIVE To evaluate the current trends in the clinical characteristics and the prognosis of Streptococcus agalactiae infective endocarditis (IE), uncommon disease associated with high mortality. METHODS Descriptive analysis of 27 cases of a large cohort (961 episodes) of infective endocarditis collected in seven hospitals of Andalusia (Spain) between 1984 and 2008. RESULTS Native valves were affected in most cases (85. 2%), multiple valves were frequently involved (22.2%). The median age of the patients was 65 (51-76) years (59.3% men), with a comorbidity, according to the Charlson index, of 2.6+/-2.3. The most frequent underlying diseases were diabetes mellitus (25.9%), chronic obstructive pulmonary disease (14.8%), neoplasms (14.8%), urological disorders (11%) and chronic liver disease (11%). Clinical presentation was characterized by rapid worsening (median of 9 (5.7-15) days from onset of symptoms until diagnosis), a high rate of embolisms (37%) and cardiac complications (abscesses, fistulas or valve rupture) - 37% of cases. Surgery was performed in 12 patients (44.4%) and a high mortality (40.7%) was observed. CONCLUSION S. agalactiae IE is a serious disease with aggressive course and high mortality rate and affects patients with debilitating diseases. We must be alert of the development of complications and consider early valve surgery when it is necessary.

Ensayo clínico aleatorizado para evaluar tres pautas cortas de tratamiento de la infección latente tuberculosa en pacientes infectados por el VIH

Objetivo Evaluar la adherencia y seguridad de 3 pautas cortas de tratamiento de la infeccion latente tuberculosa (ILT) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). Pacientes y metodos Ensayo clinico, aleatorizado, multicentrico, comparativo y abierto, realizado en 12 hospitales espanoles. Los pacientes se distribuyeron de forma aleatoria a una de las siguientes 3 pautas de tratamiento, isoniazida durante 6 meses (6H) y rifampicina mas isoniazida durante 3 meses (3RH) y rifampicina mas pirazinamida durante 2 meses (2RZ). Tras finalizar el tratamiento los pacientes fueron seguidos durante un periodo de 2 anos. Resultados Se incluyeron en el estudio 316 pacientes, 105 en la pauta 2RZ, 103 en la pauta 3RH y 108 en la pauta 6H. El periodo de observacion tras la finalizacion del tratamiento fue de 115, 108 y 101 personas/ano, respectivamente, para 6H, 3RH y 2RZ. El 27% de los pacientes abandonaron voluntariamente el estudio antes de finalizar el tratamiento al que fueron asignados y el 9,7% abandonaron el mismo por reacciones adversas o interacciones. Se produjeron 7 retiradas del estudio por hepatotoxicidad, cinco en el grupo 6H y dos en 3RH. No se observaron retiradas por hepatotoxicidad en el brazo 2RZ. Se produjeron 11 casos de tuberculosis durante el seguimiento. Las tasas de tuberculosis (casos por 100 personas/ano) en los distintos grupos de tratamiento fueron de 3,48 en 6H, 4,63 en 3RH y 1,98 en 2RZ, con un riesgo relativo para tuberculosis en las pautas 6H y 3RH de 1,76 y 2,34, respectivamente, respecto a 2RZ. Conclusiones En nuestro estudio la seguridad de la pauta 2RZ en el tratamiento de la ILT de la pauta 2RZ fue similar a la observada con las pautas 6H y 3RH, no observandose una mayor incidencia de hepatotoxicidad en pacientes que recibieron 2RZ.

Influence of early surgical treatment on the prognosis of left-sided infective endocarditis: a multicenter cohort study.

OBJECTIVE To analyze the influence of early valve operation on mortality in patients with left-sided infective endocarditis (IE). PATIENTS AND METHODS A multicenter cohort study was carried out between 1990 and 2010. Data from consecutive patients with definite IE and possible left-sided IE were collected. Propensity score matching and adjustment for survivor bias were used to control for confounders. The primary outcome was in-hospital mortality. RESULTS A total of 1019 patients with a mean age of 61 years (interquartile range, 47-71 years) were included. Early surgical treatment was performed in 417 episodes (40.9%). By propensity score, we matched 316 episodes: 158 who underwent early surgical treatment and 158 who did not (medical treatment group). In-hospital mortality and late mortality were lower in the surgically treated group (26.6% vs 41.8%; absolute risk reduction [ARR], -15.2%; P=.004 and 29.7% vs 46.2%; ARR, -16.5%; P=.002, respectively). Operation was independently associated with a lower risk of in-hospital mortality (odds ratio, 0.42; 95% CI, 0.22-0.79; P=.007). Operation was associated with reduced mortality in patients with paravalvular complications (ARR, -40.5%), severe heart failure (ARR, -32%), and native valve endocarditis (ARR, -17.8%). CONCLUSION This study supports the benefit of surgical treatment in patients with left-sided IE carried out during the initial phase of hospitalization, especially in patients with moderate or severe heart failure and paravalvular extension of infection.

Comparison of Two Methods for the Assessment of Delayed-Type Hypersensitivity Skin Responses in Patients with Human Immunodeficiency Virus Infection

We compared two techniques for detecting delayed-type hypersensitivity (DTH) skin responses in 359 patients infected with human immunodeficiency virus (HIV) (mean CD4+ lymphocyte count, 387/microL). DTH responses were assessed with use of two antigenic panels administered simultaneously: tuberculin purified protein derivative (PPD) plus three control antigens (Candida albicans, mumps antigen, and tetanus toxoid) administered by the Mantoux method and by a multiple-puncture device delivering seven antigens percutaneously (MULTITEST CMI; Institut Mérieux, Lyon, France). Eighty-three patients (23%) were anergic, 216 (60%) reacted to both panels, 55 (15%) did not react to MULTITEST CMI but did react to the antigens administered by Mantoux method, and only five (1%) reacted to MULTITEST CMI without reacting to antigens administered by the Mantoux method (P < .001, McNemars test). Each of the three possible combinations of PPD plus two control antigens administered by the Mantoux method were also superior to MULTITEST CMI for classifying patients as nonanergic (P < .001, McNemars test). We conclude that the application of antigens by the Mantoux method is more efficient than MULTITEST CMI for detecting DTH skin responses in HIV-infected patients.

Endocarditis en válvulas nativas izquierdas por estafilococos coagulasa negativos: una entidad en alza

OBJECTIVES: To describe the epidemiological, clinical, and prognostic characteristics of patients with left-sided native valve endocarditis (LNVE) caused by coagulase-negative staphylococci (CoNS). PATIENTS AND METHOD: Prospective multicenter study of endocarditis cases reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2005. RESULTS: Among 470 cases of LNVE, 39 (8.3%) were caused by CoNS, a number indicating a 30% increase in the incidence of this infection over the last decade. The mean age of affected patients was 58.32 +/- 15 years and 27 (69.2%) were men. Twenty-one patients (53.8%) had previous known valve disease and half the episodes were considered nosocomial (90% of them from vascular procedures). Median time interval from the onset of symptoms to diagnosis was 14 days (range: 1-120). Renal failure (21 cases, 53.8%), intracardiac damage (11 cases, 28.2%), and central nervous system involvement (10 cases, 25.6%) were the most frequent complications. There were only 3 cases (7.7%) of septic shock. Surgery was performed in 18 patients (46.2%). Nine patients (23.1%) died, overall. Factors associated with higher mortality in the univariate analysis were acute renal failure (P = 0.023), left-sided ventricular failure (P = 0.047), and time prior to diagnosis less than 21 days (P = 0.018). As compared to LNVE due to other microorganisms, the patients were older (P = 0.018), had experienced previous nosocomial manipulation as the source of bacteremia (P < 0.001), and developed acute renal failure more frequently (P = 0.001). Mortality of LNVE due to CoNS was lower than mortality in Staphylococcus aureus infection, but higher than in Streptococcus viridans infection. CONCLUSIONS: Left-sided native valve endocarditis due to CoNS is now increasing because of the ageing of the population. This implies more frequent invasive procedures (mainly vascular) as a consequence of the concomitant disease. Nonetheless, the mortality associated with LNVE due to CoNS does not seem to be greater than infection caused by other pathogens.OBJECTIVES To describe the epidemiological, clinical, and prognostic characteristics of patients with left-sided native valve endocarditis (LNVE) caused by coagulase-negative staphylococci (CoNS). PATIENTS AND METHOD Prospective multicenter study of endocarditis cases reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2005. RESULTS Among 470 cases of LNVE, 39 (8.3%) were caused by CoNS, a number indicating a 30% increase in the incidence of this infection over the last decade. The mean age of affected patients was 58.32 +/- 15 years and 27 (69.2%) were men. Twenty-one patients (53.8%) had previous known valve disease and half the episodes were considered nosocomial (90% of them from vascular procedures). Median time interval from the onset of symptoms to diagnosis was 14 days (range: 1-120). Renal failure (21 cases, 53.8%), intracardiac damage (11 cases, 28.2%), and central nervous system involvement (10 cases, 25.6%) were the most frequent complications. There were only 3 cases (7.7%) of septic shock. Surgery was performed in 18 patients (46.2%). Nine patients (23.1%) died, overall. Factors associated with higher mortality in the univariate analysis were acute renal failure (P = 0.023), left-sided ventricular failure (P = 0.047), and time prior to diagnosis less than 21 days (P = 0.018). As compared to LNVE due to other microorganisms, the patients were older (P = 0.018), had experienced previous nosocomial manipulation as the source of bacteremia (P < 0.001), and developed acute renal failure more frequently (P = 0.001). Mortality of LNVE due to CoNS was lower than mortality in Staphylococcus aureus infection, but higher than in Streptococcus viridans infection. CONCLUSIONS Left-sided native valve endocarditis due to CoNS is now increasing because of the ageing of the population. This implies more frequent invasive procedures (mainly vascular) as a consequence of the concomitant disease. Nonetheless, the mortality associated with LNVE due to CoNS does not seem to be greater than infection caused by other pathogens.

Risk factors of pericardial effusion in native valve infective endocarditis and its influence on outcome: A multicenter prospective cohort study

BACKGROUND Pericardial effusion is a frequent finding in the setting of infective endocarditis. Limited data exists on clinical characteristics and outcomes in this group of patients. We aimed to determine the associated factors, clinical characteristics, and outcomes of patients who had pericardial effusion and native valve infective endocarditis. METHODS AND RESULTS A total of 1205 episodes of infective endocarditis from 25 Spanish centers between June 2007 and March 2013 within the Spanish Collaboration on Endocarditis (GAMES) registry were included. Echocardiogram at admission, clinical and microbiological variables, and one-year follow-up were analyzed. Pericardial effusion was observed in 7.8% (94/1205 episodes) of episodes of infective endocarditis, most of them being mild or moderate (93.6%). The presence of pericardial effusion was associated with a higher risk of heart failure during admission (OR 1.9; CI 95% 1.2-3.0). Patients with pericardial effusion had a higher rate of surgery (53.2% vs. 41.1%; p = 0.02); however, this association was no longer significant after adjusting for possible confounders (OR 1.4; CI 95% 0.9-2.2; p = 0.10). The presence of pericardial effusion was not associated with a higher in-hospital or one-year mortality (33.0% vs. 25.2%; p = 0.10 and 40.2% vs. 37.3%; p = 0.60 respectively). CONCLUSIONS The prevalence of pericardial effusion in patients with infective endocarditis was lower than previously reported. The presence of pericardial effusion is associated with the development of heart failure during hospitalization making it a warning sign, possibly reflecting indirectly a mechanical complication, which, however, if treated surgically in a timely manner does not change the final outcome of patients.

Broadened Definition of Health Care–Associated Infective Endocarditis and Risk of Misclassification for Some Community-Acquired Episodes

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