[Comparative study of treatment with quinupristin-dalfopristin alone or in combination with gentamicin, teicoplanin, imipenem or levofloxacin in experimental endocarditis due to a multidrug-resistant Enterococcus faecium]. / Comparacion de la eficacia de quinupristina-dalfopristina en monoterapia y combinada con gentamicina, teicoplanina, imipenem o levofloxacino en un modelo experimental de endocarditis por Enterococcus faecium multirresistente.

The incidence of multidrug-resistant Enterococcus faecium is increasing despite advances in antibacterial therapy. Thus, new antibiotics are required to treat hospital- or community-acquired infections caused by these multidrug-resistant organisms. The aim of this study was to compare the therapeutic efficacy of quinupristin-dalfopristin (QD) alone, or in combination with gentamicin (G), teicoplanin (T), imipenem (I) or levofloxacin (L) against a strain of multidrug-resistant E. faecium in an experimental model of aortic valve endocarditis in rabbits. The study group consisted of 28 control animals. Eighty-two animals were treated with one of the following antibiotic regimens: G1: 18 animals QD (30 mg/kg/8 h); G2: 18 animals QD+G (6 mg/kg/12 h); G3: 16 animals QD+T (20 mg/kg/12 h); G4: 14 animals QD+I (60 mg/kg/8 h); and G5: 16 animals QD+L (20 mg/kg/12 h). The response to therapy was determined by the comparison of the number of CFU/g of E. faecium in each vegetation. In vitro, time-kill studies looking for synergy for the combinations that showed better efficacy in vivo were done. The sensitivity of the strain was intermediate to QD, resistant to T and I, and sensitive to L. There was no high-level resistance to G. QD alone revealed a significant decrease (p <0.001) in the CFU/g in the control group (9.49 vs. 7.31). There were no differences in the average of CFU/g between the QD alone (G1), QD+G (G2) and QD+T (G3) groups. These three groups revealed a significant difference in decrease of CFU/g respect of the group control (p <0.001). There were no differences in the average of CFU/g between QD+I (G4) and QD+T (G5). These two groups revealed the greatest decrease in average CFU/g (G4: 4.38 and G5: 4.04) with differences respect of the group control (p <0.0001) and respect of the groups G1, G2 and G3 (p <0.001). We did not detect any alteration of MIC from QD in the course of the treatment for either of the final isolations. Only the time kill corresponding to concentrations of I 32 mg/l (0.25 x MIC) and QD 1 mg/l (0.25 x MIC presents a descending slope in the curve at 4 and 8 h, suggesting an early synergy phenomenon, which was lost after 8 h. In light of these results, the combination QD with I and L may be considered suitable alternatives for the treatment of multiresistant E. faecium.

Comparación de la eficacia de quinupristina-dalfopristina en monoterapia y combinada con gentamicina, teicoplanina, imipenem o levofloxacino en un modelo experimental de endocarditis por Enterococcus faecium multirresistente / Comparative study of treatment with quinupristin-dalfopristin alone or in combination with gentamicin, teicoplanin, imipenem or levofloxacin in experimental endocarditis due to a multidrug-resistant Enterococcus faecium

La incidencia de infecciones por Enterococcus faecium multirresistentes va aumentando a pesar de los avances que se han producido en antibioticoterapia.Por ello, se necesitan nuevos antibióticos para tratar las infecciones nosocomiales o comunitarias causadas por este microorganismo.El objetivo principal del presente estudio fue comparar la eficacia de quinupristina-dalfopristina (QD), sola o combinada con gentamicina(G), teicoplanina (T), imipenem (I) o levofloxacino (L), en un modelo de endocarditis experimental en conejos por E. faecium multirresistente.Se utilizaron 110 animales, 28 como grupo control y 82 como grupos terapéuticos, que fueron G1: 18 animales con QD (30mg/kg/8 h); G2: 18 con QD+G (6 mg/kg/12 h); G3: 16 con QD+T (20 mg/kg/12 h); G4: 14 con QD+I (60 mg/kg/8 h); y G5: 16 con QD+L(20 mg/kg/12 h). Se valoró la respuesta terapéutica comparando la concentración de E. faecium en las vegetaciones cardiacas expresada comolog10 de las unidades formadoras de colonias por gramo de tejido (UFC/g). Se realizaron pruebas de cinética de letalidad bacteriana paralas asociaciones que mostraron mejor comportamiento in vivo: QD + I y QD + L. El patrón de sensibilidad de la cepa utilizada fue: sensiblepara L, intermedia para QD, resistente para T e I, y sin resistencia de alto grado para G. El tratamiento con QD logró una reducción significativa(p <0.001) en las UFC/g respecto al grupo control (9,49 frente a 7,31). No hubo diferencias significativas entre los grupos G1 (QDsola), G2 (QD + G) y G3 (QD + T), consiguiendo estos tres grupos una redución significativa respecto del grupo control (p <0.001). No hubodiferencias entre G4 (QD + I) y G5 (QD + L). Estos dos grupos se mostraron como los más eficaces en reducir la media de UFC/g en lasvegetaciones cardiacas (G4: 4,38 y G5: 4,04), con p <0.0001 respecto al grupo control y p <0.001 respecto a G1, G2 y G3. No se detectóningún cambio en la CMI de QD durante el tratamiento. Sólo la curva de letalidad correspondiente a la concentración de I de 32 mg/l (0,25x CMI) con QD 1 mg/l (0,25 x CMI) presentó una curva descendente a las 4 y 8 horas, sugiriendo una sinergia precoz que se perdió a las 8 horas.A la vista de estos resultados, la combinación de QD con I o L podría considerarse como alternativa terapéutica en la endocarditis porE. faecium multirresistente

The incidence of multidrug-resistant Enterococcus faecium is increasing despite advances in antibacterial therapy. Thus, new antibiotics arerequired to treat hospital- or community-acquired infections caused by these multidrug-resistant organisms. The aim of this study was tocompare the therapeutic efficacy of quinupristin-dalfopristin (QD) alone, or in combination with gentamicin (G), teicoplanin (T), imipenem(I) or levofloxacin (L) against a strain of multidrug-resistant E. faecium in an experimental model of aortic valve endocarditis in rabbits. Thestudy group consisted of 28 control animals. Eighty-two animals were treated with one of the following antibiotic regimens: G1: 18 animalsQD (30 mg/kg/8 h); G2: 18 animals QD+G (6 mg/kg/12 h); G3: 16 animals QD+T (20 mg/kg/12 h); G4: 14 animals QD+I (60 mg/kg/8 h);and G5: 16 animals QD+L (20 mg/kg/12 h). The response to therapy was determined by the comparison of the number of CFU/g of E. faeciumin each vegetation. In vitro, time-kill studies looking for synergy for the combinations that showed better efficacy in vivo were done.The sensitivity of the strain was intermediate to QD, resistant to T and I, and sensitive to L. There was no high-level resistance to G. QD alonerevealed a significant decrease (p <0.001) in the CFU/g in the control group (9.49 vs. 7.31). There were no differences in the average of CFU/gbetween the QD alone (G1), QD+G (G2) and QD+T (G3) groups. These three groups revealed a significant difference in decrease of CFU/grespect of the group control (p <0.001). There were no differences in the average of CFU/g between QD+I (G4) and QD+T (G5). These twogroups revealed the greatest decrease in average CFU/g (G4: 4.38 and G5: 4.04) with differences respect of the group control (p <0.0001)and respect of the groups G1, G2 and G3 (p <0.001). We did not detect any alteration of MIC from QD in the course of the treatment for eitherof the final isolations. Only the time kill corresponding to concentrations of I 32 mg/l (0.25 x MIC) and QD 1 mg/l (0.25 x MIC presents adescending slope in the curve at 4 and 8 h, suggesting an early synergy phenomenon, which was lost after 8 h. In light of these results, thecombination QD with I and L may be considered suitable alternatives for the treatment of multiresistant E. faecium

Enfermedad de Addison. Tratamiento sustitutivo con glucocorticoides y su monitorización / Addison´s disease. Hydrocortisone replacement therapy and its monitoring

En esta revisión se repasan algunos aspectos del tratamiento sustitutivo con glucocorticoides en pacientes con enfermedad de Addison. Según opinión de algunos autores, la dosis tradicional de 30 mg/día de hidrocortisona, repartida en dos tomas, podría ser excesiva para la mayoría de los enfermos, por lo que debería administrarse en tres tomas. Así, se ha señalado que la sobreexposición prolongada a los glucocorticoides podría aumentar el riesgo de padecer osteoporosis. Por otra parte, aunque los pacientes con enfermedad de Addison tratados pueden llevar una vida normal, muchos de ellos aquejan fatiga, cansancio y disminución de la tolerancia al estrés, y en varios estudios se demuestra que presentan una alteración significativa de la calidad de vida relacionada con la salud (CVRS). Una explicación para este hallazgo podría ser el déficit de deshidroepiandrosterona (DHEA) que presentan y que también justificaría, al menos en parte, la peor CVRS observada en las mujeres. El tratamiento de este déficit de DHEA mejora algunos aspectos psicológicos. Tampoco resulta fácil establecer una pauta de tratamiento que imite el perfil fisiológico de secreción de cortisol, en los pacientes con enfermedad de Addison, si se consideran criterios bioquímicos. Por todo ello, como recomendación general proponemos iniciar el tratamiento sustitutivo de estos enfermos con 10-5-5 mg/día de hidrocortisona y aumentar esta dosis en los casos en que se detecte alteración de la CVRS (AU)

Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients.

Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U-test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann-Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)