Fosfomycin plus Beta-lactams: Synergistic Bactericidal Combinations in Methicillin-resistant (MRSA) and Glycopeptide-Intermediate Resistant (GISA) Staphylococcus aureus Experimental Endocarditis

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.Copyright © 2015, American Society for Microbiology. All Rights Reserved

One-year outcome following biological or mechanical valve replacement for infective endocarditis

Background: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. Methods and results: Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p < .0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). Conclusions: Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction

Epidemiology and prognosis of coagulase-negative staphylococcal endocarditis: impact of vancomycin minimum inhibitory concentration

This study describes coagulase-negative staphylococcal (CoNS) infective endocarditis (IE) epidemiology at our institution, the antibiotic susceptibility profile, and the influence of vancomycin minimum inhibitory concentration (MIC) on patient outcomes. One hundred and three adults with definite IE admitted to an 850-bed tertiary care hospital in Barcelona from 1995-2008 were prospectively included in the cohort. We observed that CoNS IE was an important cause of community-acquired and healthcare-associated IE; one-third of patients involved native valves. Staphylococcus epidermidis was the most frequent species, methicillin-resistant in 52% of patients. CoNS frozen isolates were available in 88 patients. Vancomycin MICs of 2.0 μg/mL were common; almost all cases were found among S. epidermidis isolates and did not increase over time. Eighty-five patients were treated either with cloxacillin or vancomycin: 38 patients (Group 1) were treated with cloxacillin, and 47 received vancomycin; of these 47, 27 had CoNS isolates with a vancomycin MIC <2.0 μg/mL (Group 2), 20 had isolates with a vancomycin MIC ≥2.0 μg/mL (Group 3). One-year mortality was 21%, 48%, and 65% in Groups 1, 2, and 3, respectively (P=0.003). After adjusting for confounders and taking Group 2 as a reference, methicillin-susceptibility was associated with lower 1-year mortality (OR 0.12, 95% CI 0.02-0.55), and vancomycin MIC ≥2.0 μg/mL showed a trend to higher 1-year mortality (OR 3.7, 95% CI 0.9-15.2; P=0.069). Other independent variables associated with 1-year mortality were heart failure (OR 6.2, 95% CI 1.5-25.2) and pacemaker lead IE (OR 0.1, 95%CI 0.02-0.51). In conclusion, methicillin-resistant S.epidermidis was the leading cause of CoNS IE, and patients receiving vancomycin had higher mortality rates than those receiving cloxacillin; mortality was higher among patients having isolates with vancomycin MICs ≥2.0 μg/mL

E-LEARNING THROUGH INTERNET: RADIOLOGICAL PROTECTION IN HEALTH SCIENCES TELE-ENSEÑANZA A TRAVÉS DE INTERNET: LA PROTECCIÓN RADIOLÓGICA EN CIENCIAS DE LA SALUD

The creation of an interdepartmental project subsidised by the Spanish Ministry of Education has made it possible to create teaching material for Radiological Protection, and led to the publication of several specific manuals and practical notebook. This material constitutes the working basis for the first continuous e-learning training course in Spanish via Internet on this subject (8 editions during the years 2000-2009). The use of appropriate teaching materials during the training cycles determines the level of knowledge that can be reached. Interactive multimedia teaching and e-learning increase interest in subjects that were previously regarded their as boring and difficult health science students’. When the students have finished their university studies, e-learning systems can provide continued professional training that achieves the basic goals of Radiological Protection, allowing professionals to acquaint themselves with this type of content, which they would usually fond difficult to do themselves.La obtención de un proyecto interdepartamental subvencionado por el Ministerio de Educación y Ciencia español ha permitido crear materiales didácticos específicos de Protección Radiológica que se han publicado en varios manuales y cuadernos de actividades prácticas. Estas publicaciones han constituido la base del primer curso continuado sobre Protección Radiológica realizado a través de Internet en España (8 ediciones, durante los años 2000-2009). Durante el pregrado y el grado, la utilización de material didáctico digital apropiado determina el nivel de conocimientos que puede alcanzarse. La enseñanza multimedia y la tele-educación incrementan el interés de los alumnos en los temas más complicados y difíciles en Ciencias de la Salud. Posteriormente, cuando se abandona la Universidad y comienza la actividad profesional, la tele-enseñanza permite la formación continuada en las actualizaciones básicas sobre Protección Radiológica, permitiendo a todos los profesionales familiarizarse con medios y recursos que difícilmente podrán utilizar de forma personal y directa.</div

TELE-ENSEÑANZA A TRAVÉS DE INTERNET: LA PROTECCIÓN RADIOLÓGICA EN CIENCIAS DE LA SALUD

La obtención de un proyecto interdepartamental subvencionado por el Ministerio de Educación y Ciencia español ha permitido crear materiales didácticos específicos de Protección Radiológica que se han publicado en varios manuales y cuadernos de actividades prácticas. Estas publicaciones han constituido la base del primer curso continuado sobre Protección Radiológica realizado a través de Internet en España (8 ediciones, durante los años 2000-2009). Durante el pregrado y el grado, la utilización de material didáctico digital apropiado determina el nivel de conocimientos que puede alcanzarse. La enseñanza multimedia y la tele-educación incrementan el interés de los alumnos en los temas más complicados y difíciles en Ciencias de la Salud. Posteriormente, cuando se abandona la Universidad y comienza la actividad profesional, la tele-enseñanza permite la formación continuada en las actualizaciones básicas sobre Protección Radiológica, permitiendo a todos los profesionales familiarizarse con medios y recursos que difícilmente podrán utilizar de forma personal y directa.</div

Teoría de la educación : educación y cultura en la sociedad de la información

Monográfico con el título: 'Avances tecnológicos digitales en metodologías de innovación docente en el campo de las Ciencias de la Salud en España'. Resumen basado en el de la publicaciónLos cambios producidos en el ámbito universitario español para su adaptación al Espacio Europeo de Educación Superior (EEES) traen como consecuencia una amplia serie de modificaciones en el modelo de enseñanza universitaria. Dentro de este contexto, la labor del docente precisa de una mayor creatividad y utilización de nuevas herramientas que permitan al alumnado hacerse más participativo en el aula, fuera de ella, y en su propio proceso de aprendizaje. Para lograr este objetivo, se elaboran diversos materiales didácticos especializados, posteriormente se realiza una evaluación docente de dicho material en dos cursos de estudiantes de Técnico Superior en Imagen para el Diagnóstico y, por último, se desarrollan cursos de tele-enseñanza a través de Internet. Finalmente, se concluye que durante el pregrado y el grado, la utilización de material didáctico digital apropiado determina el nivel de conocimientos que puede alcanzarse. La enseñanza multimedia y la tele-educación incrementan el interés de los alumnos en los temas más complicados y difíciles en Ciencias de la Salud y posteriormente, cuando se abandona la Universidad y comienza la actividad profesional, la tele-enseñanza permite la formación continuada en las actualizaciones básicas sobre Protección Radiológica, permitiendo a todos los profesionales familiarizarse con medios y recursos que difícilmente podrán utilizar de forma personal y directa.Castilla y LeónES

Daptomycin Is Effective in Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus▿

Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 μg/ml) and glycopeptide-intermediate S. aureus (GISA) ATCC 700788 (vancomycin MIC, 8 μg/ml). Time-kill experiments demonstrated that daptomycin was bactericidal in vitro against these two strains. The in vivo activity of daptomycin (6 mg/kg of body weight every 24 h) was evaluated by using a rabbit model of infective endocarditis and was compared with the activities of a high-dose (HD) vancomycin regimen (1 g intravenously every 6 h), the recommended dose (RD) of vancomycin regimen (1 g intravenously every 12 h) for 48 h, and no treatment (as a control). Daptomycin was significantly more effective than the vancomycin RD in reducing the density of bacteria in the vegetations for the MRSA strains (0 [interquartile range, 0 to 1.5] versus 2 [interquartile range, 0 to 5.6] log CFU/g vegetation; P = 0.02) and GISA strains (2 [interquartile range, 0 to 2] versus 6.6 [interquartile range, 2.0 to 6.9] log CFU/g vegetation; P < 0.01) studied. In addition, daptomycin sterilized more MRSA vegetations than the vancomycin RD (13/18 [72%] versus 7/20 [35%]; P = 0.02) and sterilized more GISA vegetations than either vancomycin regimen (12/19 [63%] versus 4/20 [20%]; P < 0.01). No statistically significant difference between the vancomycin HD and the vancomycin RD for MRSA treatment was noted. These results support the use of daptomycin for the treatment of aortic valve endocarditis caused by GISA and MRSA

Efficacy of Telavancin in the Treatment of Experimental Endocarditis Due to Glycopeptide-Intermediate Staphylococcus aureus▿

The efficacy of telavancin, a novel lipoglycopeptide, was evaluated in experimental endocarditis in rabbits using two clinical isolates of glycopeptide-intermediate Staphylococcus aureus: ATCC 700788 and HIP 5836. Infected rabbits were treated for 2 days with telavancin (10 mg/kg of body weight once daily intravenously) or vancomycin (1 g twice daily intravenously), administered with a computer-controlled infusion pump system simulating human serum kinetics. Vegetations were harvested at 16 h postinoculation in the control group and at the end of treatment in the drug-treated group. For ATCC 700788, MICs and minimal bactericidal concentrations (MBCs), respectively, were 1 mg/liter and 4 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. For HIP 5836, MICs and MBCs, respectively, were 4 mg/liter and 8 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. Peak and trough levels were 90 μg/ml and 6 μg/ml, respectively, for telavancin and 46 μg/ml and 6 μg/ml, respectively, for vancomycin. In glycopeptide-intermediate S. aureus ATCC 700788, telavancin sterilized 6 of 16 vegetations (37%), whereas vancomycin sterilized 4 of 20 (20%) (P = 0.29) compared with 0 of 17 in the control group. In HIP 5836 experiments, telavancin and vancomycin sterilized 5 of 16 (31%) and 1 of 15 (7%) vegetations (P = 0.17), respectively, compared with none in the control group. Telavancin reduced vegetation titers by 2.0 and 2.3 logs greater than vancomycin for the ATCC 700788 (4.6 [2.0 to 5.8] versus 6.6 [2.0 to 6.9] log CFU/g vegetation; P = 0.05) and HIP 5836 (4.4 [2.0 to 7.4] versus 6.7 [4.5 to 8.7] log CFU/g vegetation; P = 0.09) strains, respectively; these differences did not reach statistical significance. All isolates from vegetations remained susceptible to telavancin after therapy. The results suggest that telavancin may be an effective treatment for endocarditis caused by glycopeptide-intermediate S. aureus

Epidemiology and Prognosis of Coagulase-Negative Staphylococcal Endocarditis: Impact of Vancomycin Minimum Inhibitory Concentration

<div><p>This study describes coagulase-negative staphylococcal (CoNS) infective endocarditis (IE) epidemiology at our institution, the antibiotic susceptibility profile, and the influence of vancomycin minimum inhibitory concentration (MIC) on patient outcomes. One hundred and three adults with definite IE admitted to an 850-bed tertiary care hospital in Barcelona from 1995-2008 were prospectively included in the cohort. We observed that CoNS IE was an important cause of community-acquired and healthcare-associated IE; one-third of patients involved native valves. <i>Staphylococcus epidermidis</i> was the most frequent species, methicillin-resistant in 52% of patients. CoNS frozen isolates were available in 88 patients. Vancomycin MICs of 2.0 μg/mL were common; almost all cases were found among <i>S</i>. <i>epidermidis</i> isolates and did not increase over time. Eighty-five patients were treated either with cloxacillin or vancomycin: 38 patients (Group 1) were treated with cloxacillin, and 47 received vancomycin; of these 47, 27 had CoNS isolates with a vancomycin MIC <2.0 μg/mL (Group 2), 20 had isolates with a vancomycin MIC ≥2.0 μg/mL (Group 3). One-year mortality was 21%, 48%, and 65% in Groups 1, 2, and 3, respectively (<i>P</i>=0.003). After adjusting for confounders and taking Group 2 as a reference, methicillin-susceptibility was associated with lower 1-year mortality (OR 0.12, 95% CI 0.02-0.55), and vancomycin MIC ≥2.0 μg/mL showed a trend to higher 1-year mortality (OR 3.7, 95% CI 0.9-15.2; <i>P</i>=0.069). Other independent variables associated with 1-year mortality were heart failure (OR 6.2, 95% CI 1.5-25.2) and pacemaker lead IE (OR 0.1, 95%CI 0.02-0.51). In conclusion, methicillin-resistant <i>S</i>.<i>epidermidis</i> was the leading cause of CoNS IE, and patients receiving vancomycin had higher mortality rates than those receiving cloxacillin; mortality was higher among patients having isolates with vancomycin MICs ≥2.0 μg/mL.</p></div