Population pharmacokinetics of amikacin in suspected cases of neonatal sepsis.

AIMS: This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin exposure. METHODS: Newborns aged ≥3 days who received at least 1 dose of amikacin during their hospitalization period were eligible for the study. Amikacin was administered intravenously during a 60-min infusion period. Three venous blood samples were taken from each patient during the first 48 h. Population pharmacokinetic parameter estimates were obtained using a population approach with the programme NONMEM. RESULTS: Data from 329 drug assay samples were obtained from 116 newborn patients (postmenstrual age [PMA] 38.3, range 32-42.4 weeks; weight 2.8, range 1.6-3.8 kg). Measured amikacin concentrations ranged from 0.8 to 56.4 mg/L. A 2-compartment model with linear elimination produced a good fit of the data. Estimated parameters for a typical subject (2.8 kg, 38.3 weeks) were clearance (Cl = 0.16 L/h), intercompartmental clearance (Q = 0.15 L/h), volume of distribution of the central compartment (Vc = 0.98 L) and peripheral volume of distribution (Vp = 1.23 L). Total bodyweight, PMA and the presence of sepsis positively influenced Cl. Plasma creatinine concentration and circulatory instability (shock) negatively influenced Cl. CONCLUSION: Our main results confirm previous findings showing that weight, PMA and renal function are relevant factors influencing newborn amikacin pharmacokinetics. In addition, current results showed that pathophysiological states of critically ill neonates, such as sepsis and shock, were associated with opposite effects in amikacin clearance and should be considered in dose adjustments.

[Clinic and epidemiologic description of Clostridium difficile infection in a pediatric population]. / Descripción clínica y epidemiológica de la infección por Clostridium difficile en población pediátrica.

BACKGROUND: Clostridium difficile (CUj-associated disease (CDAD) and the role of the hypervirulent strain NAP1 have not been well characterized in Pediatrics. AIMS: To describe clinical features of CDAD, and to estimate NAP1 frequency and association with disease severity in Pediatrics. METHODS: Descriptive, transversal surveillance of diarrheal episodes in Chilean children, hospitalized between February 2012 and December 2013, positive for CD by molecular diagnosis. RESULTS: A total of 66 episodes of diarrhea with identification of CD occurred thougout the study period in children between 1 month and 19 years of age of which 39% were younger than one year old. CD acquisition was predominantly nosocomial and the most common risk factors were: presence of comorbidities (98.6%), use of antibiotics (93.9%), proton pump inhibitors (84.8%), invasive mechanic ventilation (54.5%), feeding tube (48.5%) and immunosuppression (40.9%). Clinical course was mostly mild, but 12 cases presented an unfavorable course, of which 3/26 occurred in children less than one year. Only one case was positive for NAP1 and had a mild course. CONCLUSION: Diarrhea with identification of CD was present throughout all pediatric ages, including children less than one year old. Analytical and longitudinal studies are required to better characterize the pathogenic role of CD in this age group. CDAD occurred mostly in patients with risk factors, and the clinical course was predominantly mild.

Descripción clínica y epidemiológica de la infección por Clostridium difficile en población pediátrica / Clinic and epidemiologic description of Clostridium difficile infection in a pediatric population

Background: Clostridium difficile (CUj-associated disease (CDAD) and the role of the hypervirulent strain NAP1 have not been well characterized in Pediatrics. Aims: To describe clinical features of CDAD, and to estimate NAP1 frequency and association with disease severity in Pediatrics. Methods: Descriptive, transversal surveillance of diarrheal episodes in Chilean children, hospitalized between February 2012 and December 2013, positive for CD by molecular diagnosis. Results: A total of 66 episodes of diarrhea with identification of CD occurred thougout the study period in children between 1 month and 19 years of age of which 39% were younger than one year old. CD acquisition was predominantly nosocomial and the most common risk factors were: presence of comorbidities (98.6%), use of antibiotics (93.9%), proton pump inhibitors (84.8%), invasive mechanic ventilation (54.5%), feeding tube (48.5%) and immunosuppression (40.9%). Clinical course was mostly mild, but 12 cases presented an unfavorable course, of which 3/26 occurred in children less than one year. Only one case was positive for NAP1 and had a mild course. Conclusion: Diarrhea with identification of CD was present throughout all pediatric ages, including children less than one year old. Analytical and longitudinal studies are required to better characterize the pathogenic role of CD in this age group. CDAD occurred mostly in patients with risk factors, and the clinical course was predominantly mild.

Introducción: Aún no ha sido bien caracterizada la infección por Clostridium difficile ni el rol de la cepa hipervirulenta NAP1 en pediatría. Objetivos: Describir las características clínicas de la infección por C. difficile, la frecuencia de NAP1 y su asociación con gravedad en población pediátrica. Material y Método: Estudio transversal, descriptivo, de episodios de diarrea con identificación molecular de C. difficile en niños chilenos hospitalizados entre febrero de 2012 y diciembre de 2013. Resultados: Se estudiaron 66 episodios de diarrea por C. difficile, en niños entre 1 mes y 19 años, teniendo 39% menos de un año de edad. La adquisición fue predominantemente nosocomial. Los factores de riesgo más frecuentes fueron: co-morbilidades, uso de antimicrobianos, inhibidores de bomba de protones, ventilación mecánica invasora, sonda de alimentación e inmunosupresión. El curso clínico fue mayoritariamente benigno, con 12 casos de evolución desfavorable incluyendo lactantes bajo un año de edad. Un niño presentó la cepa NAP1, con un curso clínico leve. Discusión: En esta serie, la diarrea con identificación de C. difficile se presentó en niños de todas las edades, incluyendo aquellos bajo un año. Se necesitan estudios analíticos y longitudinales para determinar el rol patógeno en este último grupo etario. La infección afecta a niños con factores de riesgo y es de evolución predominantemente satisfactoria.

[Antifungal effect of high molecular weight chitosan on Candida spp isolated from clinical samples]. / Efecto antifúngico de quitosán de alto peso molecular en cepas de Candida sp aisladas de muestras clínicas.

UNLABELLED: Chitosan is a D-glucosamine polysaccharide derived from chitin that displays an antimicrobial activity against bacteria and fungi. OBJECTIVE: to evaluate the antifungal effect of high molecular weight chitosan (HMWC) in clinical strains of Candida spp. METHODOLOGY: the susceptibility of forty strains of Candida spp. to HMWC was studied (16 C albicans, 11 C glabrata, 5 C. tropicalis, 5 C krusei, 2 C parapsilosis and 2 C. famata) by broth microdilution at pH 7.0 and pH 4.0. RESULTS: of 40 strains, only 2 were inhibited at pH 7.0 and corresponded to ATCC control strains (C. krusei 6258 and C parapsilosis 22019). On the other hand, 37/40 strains (92.5%) were inhibited by concentrations lower than 1.25 mg/mL of HMWC at pH 4.0. CONCLUSION: these results show that HMWC, presents activity against clinical Candida spp. strains, including C glabrata, and that this activity is present at acid pH (4.0). This compound could potentially be used in vulvovaginal candidiasis since it occurs at pH 4.0-4.5.

Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer's disease.

During the past few years, an increasing set of evidence has supported the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration. Neurons and glial cells, together with brain vessels, constitute an integrated system for brain function. Inflammation is a process related with the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Several hypotheses have been postulated to explain the pathogenesis of AD, but none provides insight into the early events that trigger metabolic and cellular alterations in neuronal degeneration. The amyloid hypothesis was sustained on the basis that Abeta-peptide deposition into senile plaques is responsible for neurodegeneration. However, recent findings point to Abeta oligomers as responsible for synaptic impairment in neuronal degeneration. Amyloid is only one among many other major factors affecting the quality of neuronal cells. Another explanation derives from the tau hypothesis, supported by the observations that tau hyperphosphorylations constitute a common feature of most of the altered signaling pathways in degenerating neurons. Altered tau patterns have been detected in the cerebrospinal fluids of AD patients, and a close correlation was observed between the levels of hyperphosphorylated tau isoforms and the degree of cognitive impairment. On the other hand, the anomalous effects of cytokines and trophic factors share in common the activation of tau hyperphosphorylation patterns. In this context, a neuroimmunological approach to AD becomes relevant. When glial cells that normally provide neurotrophic factors essential for neurogenesis are activated by a set of stressing events, they overproduce cytokines and NGF, thus triggering altered signaling patterns in the etiopathogenesis of AD. A solid set of discoveries has strengthened the idea that altered patterns in the glia-neuron interactions constitute early molecular events within the cascade of cellular signals that lead to neurodegeneration in AD. A direct correlation has been established between the Abeta-induced neurodegeneration and cytokine production and its subsequent release. In effect, neuroinflammation is responsible for an abnormal secretion of proinflammatory cytokines that trigger signaling pathways that activate brain tau hyperphosphorylation in residues that are not modified under normal physiological conditions. Other cytokines such as IL-3 and TNF-alpha seem to display neuroprotective activities. Elucidation of the events that control the transitions from neuroprotection to neurodegeneration should be a critical point toward elucidation of AD pathogenesis.