In Vitro Activities of Novel Antimicrobial Combinations against Extensively Drug-Resistant Acinetobacter baumannii.

Extensively drug-resistant (XDR) Acinetobacter spp. have emerged as a cause of nosocomial infections, especially under conditions of intensive care. Unfortunately, resistance to colistin is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDR Acinetobacter baumannii in an in vitro pharmacokinetics-pharmacodynamics (PK/PD) model. Three nonrelated clinical strains of XDR A. baumannii were investigated. Antibiotic-simulated regimens were colistin at 3 MU every 8 h (q8h) (first dose, 6 MU), daptomycin at 10 mg/kg of body weight q24h, imipenem at 1 g q8h, and ertapenem at 1 g q24h. Combination regimens included colistin plus daptomycin, colistin plus imipenem, and imipenem plus ertapenem. Samples were obtained at 0, 1, 2, 4, 8, and 24 h. Among the single-agent regimens, only the colistin regimen resulted in significant reductions in log10 CFU per milliliter compared to the control for all the strains tested. Although colistin achieved bactericidal activity at 4 h, it was not able to reach the limit of detection (1 log10 CFU/ml). One strain had significant regrowth at 24 h without the emergence of resistance. Daptomycin-colistin combinations led to a significant reduction in levels of log10 CFU per milliliter that were better than those achieved with colistin as a single-agent regimen, reaching the limit of detection at 24 h against all the strains. The combination of imipenem plus ertapenem outperformed the colistin regimen, although the results did not reach the limit of detection, with significant regrowth at 24 h. Similarly, colistin-plus-imipenem combinations reduced the levels of log10 CFU per milliliter at 8 h, with significant regrowth at 24 h but with development of resistance to colistin. We have shown some potentially useful alternatives for the treatment of extensively drug-resistant A. baumannii. Among them, the daptomycin-colistin combination was the most effective and should be investigated in future studies.

Rational application of adenosine deaminase activity in cerebrospinal fluid for the diagnosis of tuberculous meningitis.

PURPOSE: Tuberculous meningitis (TBM) is one of the most serious and difficult to diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and specificity. However, all available studies have been conducted in areas of high endemicity, so we sought to determine the accuracy of ADA in a low endemicity area. METHODS: This retrospective study included 190 patients (105 men) who had ADA tested in CSF for some reason. Patients were classified as probable/certain TBM or non-TBM based on clinical and Thwaite's criteria. Optimal ADA cutoff was established by ROC curves and a predictive algorithm based on ADA and other CSF biochemical parameters was generated. RESULTS: Eleven patients were classified as probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L with 91 % sensitivity and 77.7 % specificity. We also developed a predictive algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and leukocytes (≥13.5 cell/mm(3)) with increased accuracy (Se: 91 % Sp: 88 %). CONCLUSIONS: Optimal ADA cutoff value in areas of low TB endemicity is higher than previously reported. Our algorithm is more accurate than ADA activity alone with better sensitivity and specificity than previously reported algorithms.

[Metabolic syndrome in patients with essential hypertension]. / Síndrome metabólico en pacientes hipertensos esenciales.

We have studied 218 patients with Essential Hypertension. The aim of this study was to determine the prevalence of Metabolic Syndrome (MS) and Insulin resistance (IR) in hypertensive patients and to know the vascular risk associated with MS. Blood pressure (BP), body mass index (BMI), plasma insulin and serum lipids were measured. Plasma glucose was measured basal and after two hours of an oral load of 75 g. Vascular damage was evaluated by measurement of thickening of Intimal/Media complex (TI/MC) in carotid artery by ecco doppler ultrasonography and by the presence of microalbuminuria. IR was estimated by the calculation of the HOMA index of IR. A prevalence of MS of 62% was found and MS was statistically significant associated to vascular damage (p = 0.000). Fifty seven percent of the hypertensive patients who had MS had hypertrigliceridemia which was also related to vascular damage. The prevalence of microalbuminuria (MA) in this population of hypertensive patients was 28% and the presence of MA was significantly associated to (TI/MC) (p = 0000). The hypertensive patients who had vascular damage (a pathological value of TI/MC and or MA) were more frequently males with higher BP, higher BMI (30.45 +/- 4 vs 28.9 +/- 4.3 p = 0.014), more elevated plasma insulin levels (37.38 +/- 22 vs 24.86 +/- 12 p = 0.000) and higher triglyceride levels (2.33 +/- 1.29 vs 1.93 +/- 1.08 p = 0.019). IR was found in 75% of the patients. In a multivariate logistic analysis the independent variables that define vascular damage in hypertensive patients were: Age (p = 0.05), male sex (p = 0.01), Systolic BP (p = 0.002) and IR (p = 0.001). In conclusion, MS is a frequent finding in hypertensive patients. The presence of MS of any of their components increase the vascular risk (TI/MC of carotid artery and microalbuminuria). IR is a common finding in these patients and appears to be one of the most important markers of vascular risk.

Síndrome metabólico en pacientes hipertensos esenciales / Metabolic syndrome in patients with essential hypertension

Se estudian 218 pacientes con hipertensión arterial (HTA) esencial con el objetivo de determinar la frecuencia de Síndrome Metabólico (SM): HTA, intolerancia la glucosa, y dislipemia y evaluar en que medida éste síndrome se asocia a un mayor daño vascular. A todos los pacientes se les midió: Presión arterial (PA), índice de masa corporal (IMC), glucemia basal, curva de glucemia, insulinemia, resistencia a la insulina (RI) y lipidograma. El daño vascular fue evaluado mediante la medición del Engrosamiento del Complejo Íntima/Media (EC I/M) mediante eco doppler de arteria carotídea y por la presencia de microalbuminuria. Se encontró una frecuencia de SM del 62 por ciento, el cual se asoció de forma estadísticamente significativa al daño vascular (P = 0,000). El 57 por ciento de los pacientes con SM tenían hipertrigliceridemia, condición que se asoció de manera significativa al daño de carótida (P = 0,031). Encontramos microalbuminuria (MA) en el 28 por ciento de los hipertensos que también se asoció significativamente al ECI/M (P = 0,000).Los hipertensos con daño vascular eran con mayor frecuencia varones y con la PA más elevada. En ellos, el IMC era significativamente más alto (30,45 ñ 4 vs 28,9 ñ 4,3 p = 0,014), los niveles de insulina basal más elevados (37,38 ñ 22 vs 24,86,5 ñ 12 p = 0,000) y la cifra media de triglicéridos en plasma también era significativamente mayor (2,33 ñ 1,29 vs 1,93 ñ 1,08 p = 0,019). El 75 por ciento de los pacientes hipertensos tenía RI. En un análisis de regresión logística múltiple por pasos las variables independientes que definen el daño vascular en sujetos hipertensos fueron la edad (p = 0,05), el sexo varón (p = 0,01), la PA sistólica (p = 0,002), y la RI (p = 0,001).En conclusión, los sujetos hipertensos presentan con frecuencia SM o alguno de sus componentes lo que condiciona un marcado riesgo de daño vascular. La RI representa un nexo común entre la HTA y el SM y es la principal variable independiente asociada al daño vascular (AU)

La disfunción diastólica del hipertenso mal controlado

Se estudiaron 66 pacientes hipertensos estadio 3, entre 18 y 60 años, con el objetivo de determinar la frecuencia de disfunción diastólica y comprobar la posibilidad de revertir la misma con el uso de captopril frente al tratamiento convencional. A todos los pacientes se les realizó eco-doppler pulsado y los casos positivos fueron divididos al azar en dos grupos. Un grupo de 20 casos fue tratado con captopril en dosis de 50-75 mg diarios por tres meses, el otro integrado por 18 pacientes tratados con fármacos habituales que fue tomado como grupo control positivo. Se utilizó la prueba de Chi cuadrado y la "t" de Student en el análisis de los resultados. Se consideró significativo p < 0,05. Se encontró una frecuencia de disfunción diastólica de 59,0. por ciento en los casos estudiados. Se demostró una asociación estadísticamente significativa entre el tiempo de evolución de la HTA y la presencia de disfunción diastólica (p = 0,007). Se observó una evolución más favorable de la disfunción diastólica en el 55,0. por ciento de los pacientes tratados con captopril (p = 0,054) y se confirmó la eficacia de este fármaco en el control de la hipertensión arterial, resultando estadísticamente significativo (p = 0,037) el descenso de la presión arterial sistólica en relación al grupo control. Se concluye que la disfunción diastólica es un trastorno frecuente en el hipertenso estadio 3 mal controlado, y se destaca el papel de los inhibidores de la enzima de conversión de la angiotensina (captopril) no sólo en el control de la presión arterial, sino también en la regresión de la disfunción diastólica (AU)

Variable morphology of coronary atherosclerosis: characterization of atherosclerotic plaque and residual arterial lumen size and shape by epicardial echocardiography.

The purpose of this study was to evaluate the in vivo characteristics of coronary atherosclerosis by using high frequency epicardial echocardiography. High frequency epicardial echocardiography was used to evaluate residual lumen and wall morphology at the sites of maximal coronary atherosclerosis in 26 patients undergoing coronary artery bypass grafting. The maximal/minimal wall thickness ratio was 3.1 +/- 0.2 (mean +/- SEM) with a large range (1.3 to 7.5). Portions of the wall were normal in 16 of 31 lesions; the percent normal circumference ranged from 9% to 85%. Maximal/minimal lumen diameter ratio was 1.5 +/- 0.1 (range 1.1 to 2.9). The shape of the residual coronary lumen was noncircular in 16 lesions: oval in 13 and complex in 3. The residual coronary lumen was eccentrically placed within six arteries. These data emphasize the variability of residual lumen and wall geometry in atherosclerosis.