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OBJECTIVES: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. METHODS: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. RESULTS: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. CONCLUSIONS: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.

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The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

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Background: Highly trained athletes are at increased risk of atrial fibrillation (AF) and flutter. Atrial dilatation and dysfunction might be the underlying substrate for the increased risk. The aim of the present study was to relate atrial size and deformation in a selected group of highly trained athletes and patients with paroxysmal atrial fibrillation (PAF). Methods: 20 professional male hand-ball players, 18 patients with PAF and 20 healthy age-matched, non-sportive males were compared. All subjects underwent a transthoracic echocardiogram with evaluation of left atrial (LA) dimensions. Left atrial strain (LASa) and strain rate (LASRa) derived from speckle tracking were used to evaluate LA deformation post atrial contraction. Results: LA volumes were significantly larger in athletes and PAF patients compared to controls (36 + 1.7 ml/m2; 36 ± 2.3 ml/m2 and 24 + 1 ml/m2, respectively, p < 0.01;). LASa and LASRa during active atrial contraction were decreased in PAF patients compared to athletes and controls (-10.6 ± 0.2 %; -12.2 ± 0.4 % and -14.5 ± 0.5 %, p < 0.01 for LASa and -1.2 ± 0.08 sec-1; -1.5 ± 0.12 sec-1; -1.7 ± 0.13 sec-1, p= 0.04 for LASRa respectively). Athletes with LA volume > 40 ml/m2 (n=7) showed reduced LASa compared to athletes with LA volume < 40 mL/m2 (-10.3 ± 0.4% versus -13.0 ± 0.5%, p < 0.01). PAF patients had LASa values similar to those of subjects with normal LA volume. Conclusion: Athletes with increased LA volume exhibit lower strain parameters compared to subjects with PAF. It is postulated that measurement of LA strain may be used to predict development of AF in highly trained athletes.

Introducción: Atletas de alto rendimiento tienen un riesgo aumentado de desarrollar fibrilacion auricular (FA) y flutter. La dilatación y disfunción auricular podrían ser el sustrato subyacente para este incremento en el riesgo. El objetivo fue analizar y relacionar el tamaño y deformación auricular en un grupo seleccionado de atletas y en pacientes con FA paroxística. Métodos: Se incluyeron 20 jugadores de balón-mano profesionales y 20 controles sedentarios, pareados por edad y sexo, junto a 18 pacientes con FA paroxística. En todos los sujetos se realizó un estudio ecocardiográfico bidimensional con evaluación de las dimensiones y de la deformación (post contracción auricular) por strain (Sa) y strain rate (SRa) de la aurícula izquierda (AI). Resultados: El volumen AI fue significativamente mayor en atletas y pacientes con FA respecto de los controles (36 + 1,7 ml/m2; 36 ± 2,3 ml/m2 y 24 + 1 ml/m2, p < 0,01; respectivamente). El SaAI y SRaAI durante la contracción auricular estaban disminuidos en los pacientes con FA paroxística respecto de atletas y controles (-10,6 ± 0,2 %; -12,2 ± 0,4 % y -14,5 ± 0,5 %, p < 0,01 para SaAI y -1,2 ± 0,08 sec-1; -1,5 ± 0,12 sec-1; -1,7 ± 0,13 sec-1, p= 0,04 para SRaAI, respectivamente). Los atletas con un volumen AI > 40 ml/m2 (n=7) mostraron valores reducidos de SaAI comparados con atletas con un volumen AI < 40 mL/m2 (-10,3 ± 0,4% versus -13,0 ± 0,5%, p < 0,01) y éstos fueron similares a los pacientes con FA (-10,3 ± 0,4% versus -10,6 ± 0,2%, p= 0,6). Conclusiones: Una proporción de atletas con dilatación AI presentan evidencia de disfunción contráctil de la AI, caracterizado por valores de strain disminuidos que son similares a los de pacientes con FA paroxística. Esto podría corresponder a un sustrato para el desarrollo posterior de arritmias auriculares en estos atletas.

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