A. del Río

Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles

Objective: To evaluate the incidence and the clinical and echocardiographic features of infective endocarditis (IE) caused by Staphylococcus lugdunensis and to identify the prognostic factors of surgery and mortality in this disease. Design: Prospective cohort study. Setting: Study at two centres (a tertiary care centre and a community hospital). Patients: 10 patients with IE caused by S lugdunensis in 912 consecutive patients with IE between 1990 and 2003. Methods: Prospective study of consecutive patients carried out by the multidisciplinary team for diagnosis and treatment of IE from the study institutions. English, French, and Spanish literature was searched by computer under the terms “endocarditis” and “Staphylococcus lugdunensis” published between 1989 and December 2003. Main outcome measures: Patient characteristics, echocardiographic findings, required surgery, and prognostic factors of mortality in left sided cases of IE. Results: 10 cases of IE caused by S lugdunensis were identified at our institutions, representing 0.8% (four of 467), 1.5% (two of 135), and 7.8% (four of 51) of cases of native valve, prosthetic valve, and pacemaker lead endocarditis in the non-drug misusers. Native valve IE was present in four patients (two aortic, one mitral, and one pulmonary), prosthetic valve aortic IE in two patients, and pacemaker lead IE in the other four patients. All patients with left sided IE had serious complications (heart failure, periannular abscess formation, or shock) requiring surgery in 60% (three of five patients) of cases with an overall mortality rate of 80% (four of five patients). All patients with pacemaker IE underwent combined medical treatment and surgery, and mortality was 25% (one patient). In total 59 cases of IE caused by S lugdunensis were identified in a review of the literature. The combined analysis of these 69 cases showed that native valve IE (53 patients, 77%) is characterised by mitral valve involvement and frequent complications such as heart failure, abscess formation, and embolism. Surgery was needed in 51% of cases and mortality was 42%. Prosthetic valve endocarditis (nine of 60, 13%) predominated in the aortic position and was associated with abscess formation, required surgery, and high mortality (78%). Pacemaker lead IE (seven of 69, 10%) is associated with a better prognosis when antibiotic treatment is combined with surgery. Conclusions:S lugdunensis IE is an uncommon cause of IE, involving mainly native left sided valves, and it is characterised by an aggressive clinical course. Mortality in left sided native valve IE is high but the prognosis has improved in recent years. Surgery has improved survival in left sided IE and, therefore, early surgery should always be considered. Prosthetic valve S lugdunensis IE carries an ominous prognosis.

Streptococcus agalactiae Infective Endocarditis: Analysis of 30 Cases and Review of the Literature, 1962–1998

We describe 30 cases (1.7%) of community-acquired penicillin-susceptible Streptococcus agalactiae endocarditis among 1771 episodes of endocarditis diagnosed in 4 Spanish hospitals from 1975 through 1998. Endocarditis affected a native valve (most often the mitral valve) in 25 cases (83%). Surgical valve replacement was performed for 12 patients (40%). Fourteen patients (47%) died. Mortality rates for patients with native and prosthetic valve endocarditis were 36% and 100%, respectively (P=.01). The mortality rate for native valve endocarditis decreased during the last 6 years of the study (from 61% in 1975-1992 to 8% in 1993-1998; P<.05). Additionally, 115 cases in the literature from 1962-1998 were reviewed. During 1980-1998, the percentage of patients who underwent cardiac surgery increased from 24% (in the previous period, 1962-1979) to 43% (P=.05) and the mortality rate decreased from 45% to 34% (P=NS). S. agalactiae is an uncommon cause of endocarditis with a high mortality rate, although the prognosis of native valve endocarditis has improved in recent years, probably because of an increased use of cardiac surgery.

Daptomycin Is Effective for Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus epidermidis

ABSTRACT This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 μg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 μg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log10 CFU/g vegetation [interquartile range {IQR}, 0 to 1 log10 CFU/g vegetation] versus 2 log10 CFU/g vegetation [IQR, 2 to 2 log10 CFU/g vegetation] and 2 log10 CFU/g vegetation [IQR, 0 to 2.8 log10 CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log10 CFU/g vegetation [IQR, 2 to 6 log10 CFU/g vegetation] versus 7.1 log10 CFU/g vegetation [IQR, 5.2 to 8.5 log10 CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Calbindin immunoreactivity in normal human temporal neocortex.

Calbindin immunoreactivity in the temporal neocortex was examined in 4 subjects with no neurological, metabolic or malignant disease. The brains were obtained between 1 and 4 h after death and rapidly fixed by perfusion with 4% paraformaldehyde through the carotid arteries, cut into slabs, cryoprotected and stored at -80 degrees C. Sections of the whole left temporal lobe obtained with a freezing microtome were processed free-floating with a well known monoclonal antibody against calbindin according to the peroxidase-antiperoxidase (PAP) method. Calbindin-immunoreactive (CaBP-ir) neurons were found to be local-circuit neurons (interneurons) mainly distributed in the upper cortical layers (layers I, II and III), and were categorized as small multipolar neurons with ascending dendrites ramifying in the molecular layer, small bitufted cells, pyramid-like cells in layer II, horizontal neurons in the molecular layer, multipolar neurons with long descending dendrites, and large double-bouquet cells, some of them exhibiting a very long dendrite with claw-shaped terminals in layer V. Less than 10% of all CaBP-ir neurons were localized in the remaining cortical layers. Pyramidal cells were only very weakly or not stained at all. In addition, CaBP-ir fibres formed a dense plexus in the molecular layer, and vertical bundles 8-10 microns thick and 500-600 microns long, separated by blank spaces 20-40 microns wide were distributed in layers III and V/VI.(ABSTRACT TRUNCATED AT 250 WORDS)

Addition of Gentamicin or Rifampin Does Not Enhance the Effectiveness of Daptomycin in Treatment of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

ABSTRACT This study evaluated the activity of daptomycin combined with either gentamicin or rifampin against three methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in vitro and one isolate in vivo against a representative strain (MRSA-572). Time-kill experiments showed that daptomycin was bactericidal against these strains at concentrations over the MIC. Daptomycin at sub-MIC concentrations plus gentamicin at 1× and 2× the MIC yielded synergy, while the addition of rifampin at 2 to 4 μg/ml resulted in indifference (two strains) or antagonism (one strain). The in vivo activity of daptomycin (6 mg/kg of body weight once a day) was evaluated ± gentamicin (1 mg/kg intravenously [i.v.] every 8 h [q8h]) or rifampin (300 mg i.v. q8h) in a rabbit model of infective endocarditis by simulating human pharmacokinetics. Daptomycin plus gentamicin (median, 0 [interquartile range, 0 to 2] log10 CFU/g vegetation) was as effective as daptomycin alone (0 [0 to 2] log10 CFU/g vegetation) in reducing the density of bacteria in valve vegetations (P = 0.83), and both were more effective than daptomycin plus rifampin (3 [2 to 3.5] log10 CFU/g vegetation; P < 0.05) for the strain studied. In addition, daptomycin sterilized a ratio of vegetations that was similar to that of daptomycin plus gentamicin (10/15 [67%] versus 9/15 [60%]; P = 0.7), and both regimens did so more than daptomycin plus rifampin (3/15 [20%]; P = 0.01 and P = 0.02, respectively). No statistical difference was noted between daptomycin plus gentamicin and daptomycin alone for MRSA treatment. In the combination arm, all isolates from vegetations remained susceptible to daptomycin, gentamicin, and rifampin. Sixty-one percent of the isolates (8/13) acquired resistance to rifampin during monotherapy. In the daptomycin arm, resistance was detected in only one case, in which the daptomycin MIC rose to 2 μg/ml among the recovered bacteria. In conclusion, the addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in the treatment of experimental endocarditis due to MRSA.

Guía Europea de Prevención Cardiovascular en la Práctica Clínica. Adaptación española del CEIPC 2008

Presentamos la adaptacion espanola realizada por el Comite Espanol Interdisciplinario para la Prevencion Cardiovascular (CEIPC) de la Guia Europea de Prevencion de las Enfermedades Cardiovasculares 2008. Esta guia recomienda el modelo SCORE de riesgo bajo para valorar el riesgo cardiovascular. El objetivo es prevenir la mortalidad y la morbilidad debidas a las enfermedades cardiovasculares (ECV) mediante el tratamiento de sus factores de riesgo en la practica clinica. La guia hace enfasis en la prevencion primaria y en el papel del medico y el personal de enfermeria de atencion primaria en la promocion de un estilo de vida cardiosaludable, basado en el incremento de los grados de actividad fisica, la adopcion de una alimentacion saludable y, en los fumadores, el abandono del tabaco. La meta terapeutica para la presion arterial es en general

Fosfomycin plus β-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

ABSTRACT The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Profilaxis antibiótica de la endocarditis infecciosa: a quién y cuándo se debe recomendar

La Asociación Americana del Corazón (American Heart Association, AHA) ha publicado recientemente la actualización de sus recomendaciones en la prevención de la endocarditis infecciosa (EI). Los autores hacen una revisión de los criterios para establecer las pautas de profilaxis y valoran su utilidad con la evidencia científica de los pocos estudios llevados a cabo en estos años. Fruto de estas consideraciones son unas nuevas recomendaciones que limitan de forma muy notable los pacientes candidatos a recibir profilaxis y los procedimientos en que se tiene que aplicar. La EI es una enfermedad poco frecuente, pero que conlleva una elevada morbilidad y mortalidad. A pesar de los progresos médicos y quirúrgicos que se han hecho en su diagnóstico y tratamiento, la EI sigue siendo una enfermedad grave con una alta tasa de mortalidad en la fase inicial. La recomendación de administrar antibióticos de forma previa a un procedimiento médico que pueda provocar una bacteriemia transitoria en pacientes con riesgo de contraer EI ha sido ampliamente difundida durante décadas. Tradicionalmente, los comités de expertos se han basado en una secuencia lógica de premisas: la EI es una enfermedad poco frecuente, pero que conlleva una elevada morbimortalidad; se tiene constancia de que determinadas cardiopatías predisponen a la EI; determinados procedimientos dan lugar a bacteriemias transitorias que pueden causar una EI; en modelos experimentales en animales se ha demostrado la eficacia de la profilaxis antibiótica en prevenir la EI; la profilaxis en humanos es efectiva en la prevención de la EI asociada a procedimientos dentales, del tracto gastrointestinal o genitourinario, todo ello en pacientes con determinadas cardiopatías. El comité de expertos de la AHA en sus últimas recomendaciones confirma la validez de los primeros cuatro fundamentos pero pone en duda el último: la validez de la profilaxis antibiótica en el ser humano. Los estudios con modelos experimentales en animales han confirmado que la profilaxis antibiótica es efectiva en la prevención de la EI, pero ningún estudio prospectivo ha probado su eficacia en un ensayo clínico y los pocos estudios de casos y controles llevados a cabo no son concluyentes. Además, estudios recientes muestran los cambios etiológicos de la EI en las últimas décadas, pasando de un predominio tradicional de las EI causadas por estreptococos del grupo viridans a microorganismos no orales como Staphylococcus aureus lo que resta aún más consistencia a la profilaxis antibiótica de la EI tal y como se ha concebido hasta ahora. Las recomendaciones de los Comités de Expertos franceses y británicos en los últimos dos años se hacen eco de la falta de evidencias clínicas suficientes que justifiquen la práctica de la profilaxis antibiótica. Por ello recomiendan el uso de profilaxis sólo en pacientes de alto riesgo, siendo opcional la profilaxis antibiótica en los pacientes catalogados de bajo riesgo. El Comité Europeo es el más conservador y mantiene en sus recomendaciones del año 2004 un mayor número de procedimientos y pacientes candidatos a recibir la profilaxis. Las últimas recomendaciones de la AHA del año 2007 son más restrictivas que sus predecesoras. En ellas se recoge la opinión de expertos que han sugerido que las manipulaciones dentales o de la mucosa oral no son una causa importante de EI o que su efectividad no se compensa con los posibles costes, por lo que la profilaxis antibiótica en la mayoría de los casos no estaría justificada. Estas modificaciones y opiniones han generado un intenso debate en el entorno médico. En cambio, sí se ha demostrado que actividades cotidianas como cepillarse los dientes o masticar dan lugar a pequeñas bacteriemias transitorias que tendrían un efecto acumulativo muy superior al de un procedimiento dental aislado. Con este conocimiento, cobra mayor importancia la prevención con la educación del paciente en sus hábitos y el mantener una higiene dental correcta, recomendando revisiones de la boca por sistema, al menos dos veces al año. Debido a los cambios observados en la epidemiología de la EI, el Comité de Expertos francés recomienda evitar en los pacientes de riesgo cualquier procedimiento que ocasione heridas de la piel o mucosas como el “piercing”, tatuajes o la acupuntura a diferencia de las últimas recomendaciones de la AHA. También ponen especial atención en los catéteres para infusión que recomienda usar sólo cuando sea estrictamente obligatorio y preferiblemente catéteres periféricos a catéteres centrales y recomiendan el cambio sistemático de estos catéteres cada tres o cuatro días, hecho que no se menciona en las recomendaciones de la AHA, con el fin de reducir el riesgo de bacteriemia estafilocócica asociada a los catéteres, que tiene una elevada morbilidad.

265. Afectación del bazo en la endocarditis infecciosa: Un enemigo silencioso

Introduccion y objetivos La endocarditis infecciosa predispone al absceso esplenico, de incidencia mal definida y que aumenta la morbimortalidad. No esta estandarizado el momento para esplenectomia cuando se requiere intervencion por endocarditis. Se describe la experiencia con endocarditis y patologia esplenica asociada e indicacion quirurgica valvular y esplenica. Material y metodos Revision retrospectiva de la base de datos prospectiva de endocarditis, definida por criterios modificados de Duke. Analisis de pacientes diagnosticados de infarto/absceso esplenico mediante imagen/estudio post mortem . En los casos de esplenectomia, se practico en la misma intervencion despues del procedimiento valvular. Resultados Entre enero de 1995 – julio de 2011 se recogieron 737 episodios de endocarditis; 62 (8,41%) pacientes presentaron infarto/absceso esplenico con fiebre persistente y dolor abdominal; 6 (8,9%) requirieron esplenectomia; 5 (83%) eran varones. La edad media fue 52 (27–72). EuroSCORE logistico medio fue 37,42% (18,83–60,93%). La endocarditis fue mitral (3), aortica (2) y multivalvular (mitral y tricuspide). Se aislaron Enterococcus spp (2), Staphylococcus aureus (1), estreptococos del grupo viridans (1), Kingella kingae (1) y hemocultivos negativos (1). El absceso esplenico se diagnostico por tomografia (4); en 2 la intervencion fue urgente, sin imagen. Se practico sustitucion valvular. Tres (50%) fallecieron. En los 6 se confirmo absceso esplenico por histopatologia. El seguimiento de los supervivientes a la intervencion con esplenectomia fue de 16, 22 y 36 meses, sin recidiva. Conclusiones Debe sospecharse absceso esplenico en los pacientes con endocarditis, fiebre y dolor abdominal. La esplenectomia y la intervencion valvular pueden realizarse en el mismo acto dependiendo de la condicion del paciente.

104 SURGERY OF INFECTIVE ENDOCARDITIS IN PATIENTS WITH LIVER CIRRHOSIS: A DIFFICULT DECISION-MAKING PROCESS

IE and 1,110 cases of IE due to other pathogens (non-SA NVIE). Twogroup comparisons and adjusted survival analysis were performed. Results: Compared to non-SA NVIE, SA NVIE occurred more frequently in older subjects (p = 0.01). It was less often community-acquired (p < 10 4), more frequently diagnosed within the first month of symptoms onset (p < 10 4) and associated with comorbidities (p < 10 4). SA NVIE was more often complicated with stroke (p = 0.0009) and emboli (p = 0.008). By contrast the frequencies of cardiac failure and intracardiac abscess were the same in the two groups. EVS and 60day in-hospital mortality rate were lower (34.2% vs. 50.1%, p < 10 4) and higher (26.5% vs. 11.9%, p < 10 4), respectively. In multivariate analysis, when compared to non-SA NVIE: (1) the probability of EVS was significantly lower in SA NVIE (HR 0.66, 95 CI 0.54 0.80, p < 0.0001); (2) the probability of in-hospital death was significantly higher (HR 1.68, 95 CI 1.28 2.22, p < 0.0001), which was true both in operated and non-operated patients. Conclusion: This study confirms that SA NVIE is associated with higher rates of comorbidities and mortality. It is also associated with a lower rate of EVS, which is neither explained by a higher frequency of comorbidities/complications that would contraindicate surgery nor by a lower frequency of conditions that would require surgery.