Metabolomic analysis in Amycolatopsis keratiniphila disrupted the competing ECO0501 pathway for enhancing the accumulation of vancomycin.

Vancomycin is a clinically important glycopeptide antibiotic against Gram-positive pathogenic bacteria, especially methicillin-resistant Staphylococcus aureus. In the mutant strain of Amycolatopsis keratiniphila HCCB10007 Δeco-cds4-27, the production of ECO-0501 was disrupted, but enhanced vancomycin yield by 55% was observed compared with the original strain of A. keratiniphila HCCB10007. To gain insights into the mechanism of the enhanced production of vancomycin in the mutant strain, comparative metabolomics analyses were performed between the mutant strain and the original strain, A. keratiniphila HCCB10007 via GC-TOF-MS and UPLC-HRMS. The results of PCA and OPLS-DA revealed a significant distinction of the intracellular metabolites between the two strains during the fermentation process. 64 intracellular metabolites, which involved in amino acids, fatty acids and central carbon metabolism, were identified as differential metabolites. The high-yield mutant strain maintained high levels of glucose-1-phosphate and glucose-6-phosphate and they declined with the increases of vancomycin production. Particularly, a strong association of fatty acids accumulation as well as 3,5-dihydroxyphenylacetic acid and non-proteinogenic amino acid 3,5-dihydroxyphenylglycine (Dpg) with enhancement of vancomycin production was observed in the high-yield mutant strain, indicating that the consumption of fatty acid pools might be beneficial for giving rise to 3,5-dihydroxyphenylacetic acid and Dpg which further lead to improve vancomycin production. In addition, the lower levels of glyoxylic acid and lactic acid and the higher levels of sulfur amino acids might be beneficial for improving vancomycin production. These findings proposed more advanced elucidation of metabolomic characteristics in the high-yield strain for vancomycin production and could provide potential strategies to enhance the vancomycin production.

Leonurine alleviates vancomycin nephrotoxicity via activating PPARγ and inhibiting the TLR4/NF-κB/TNF-α pathway.

Vancomycin (VCM) is the first-line antibiotic for severe infections, but nephrotoxicity limits its use. Leonurine (Leo) has shown protective effects against kidney damage. However, the effect and mechanism of Leo on VCM nephrotoxicity remain unclear. In this study, mice and HK-2 cells exposed to VCM were treated with Leo. Biochemical and pathological analysis and fluorescence probe methods were performed to examine the role of Leo in VCM nephrotoxicity. Immunohistochemistry, q-PCR, western blot, FACS, and Autodock software were used to verify the mechanism. The present results indicate that Leo significantly alleviates VCM-induced renal injury, morphological damage, and oxidative stress. Increased intracellular and mitochondrial ROS in HK-2 cells and decreased mitochondrial numbers in mouse renal tubular epithelial cells were reversed in Leo-administrated groups. In addition, molecular docking analysis using Autodock software revealed that Leo binds to the PPARγ protein with high affinity. Mechanistic exploration indicated that Leo inhibited VCM nephrotoxicity via activating PPARγ and inhibiting the TLR4/NF-κB/TNF-α inflammation pathway. Taken together, our results indicate that the PPARγ inhibition and inflammation reactions were implicated in the VCM nephrotoxicity and provide a promising therapeutic strategy for renal injury.

Sub-MIC vancomycin enhances the antibiotic tolerance of vancomycin-intermediate Staphylococcus aureus through downregulation of protein succinylation.

Bacteria develop tolerance after transient exposure to antibiotics, and tolerance is a significant driver of resistance. The purpose of this study is to evaluate the mechanisms underlying tolerance formation in vancomycin-intermediate Staphylococcus aureus (VISA) strains. VISA strains were cultured with sub-minimum inhibitory concentrations (sub-MICs) of vancomycin. Enhanced vancomycin tolerance was observed in VISA strains with distinct genetic lineages. Western blot revealed that the VISA protein succinylation (Ksucc) levels decreased with the increase in vancomycin exposure. Importantly, Ksucc modification, vancomycin tolerance, and cell wall synthesis were simultaneously affected after deletion of SacobB, which encodes a desuccinylase in S. aureus. Several Ksucc sites were identified in MurA, and vancomycin MIC levels of murA mutant and Ksucc-simulated (MurA(K69E) and MurA(K191E)) mutants were reduced. The vancomycin MIC levels of K65-MurA(K191E) in particular decreased to 1 mg/L, converting VISA strain K65 to a vancomycin-susceptible S. aureus strain. We further demonstrated that the enzymatic activity of MurA was dependent on Ksucc modification. Our data suggested the influence of vancomycin exposure on bacterial tolerance, and protein Ksucc modification is a novel mechanism in regulating vancomycin tolerance.

Novedades en cirugía de columna vertebral en 2015 / No disponible

En este artículo de revisión, queremos destacar las principales novedades y curiosidades alrededor de la cirugía de columna que se han publicado el año 2015. Aunque, el año pasado no han sido publicadas grandes novedades en nuestra área de estudio, nosotros queremos hacer hincapié en los aspectos que nos han parecido más relevantes sobre cirugía de columna. Dado que la cirugía de columna representa una importante carga asistencial sanitaria y social. Los estudios aquí reflejados intentan dar respuestas a las múltiples demandas pendientes. Así es como abordaremos temas como la artrodesis cervical vs prótesis cervicales, uso local de vancomicina en polvo, vitamina D, mejoras en las técnicas de cementación vertebral, uso de agentes biológicos, escoliosis idiopática del adolescente y factores de riesgo para la cirugía de columna

In this revision article we want to highlight some news and curiosities around the spine surgery published during 2015. Although last year, they have not been published major innovations in spinal surgery, we want to emphasize some aspects that we consider interesting and useful in our working area. Spinal surgery is a major social and health burden, so the studies reflected here attempt to answer outstanding claims. This is how we address issues such as cervical arthrodesis vs cervical prostheses, use of local powder vancomycin, use of vitamin D, improving vertebral cementation techniques, risk factors for spine surgery, use of biological agents and adolescent idiopathic scoliosis

Absorción sistémica de vancomicina oral en pacientes con colitis. A propósito de 2 casos / Systemic absorption of oral vancomycin in colitis patients. A propos of 2 cases

No disponible

Actividad de vancomicina, teicoplanina y linezolid en Staphylococcus coagulasanegativos resistentes a meticilina en aislados de hemocultivos pediátricos / Activity of vancomycin, teicoplanin and linezolid in methicillin resistant coagulase-negative Staphylococci isolates from paediatric blood cultures

Introducción. Los Staphylococcus coagulasa negativos (ECN) son la principal causa de bacteriemia y sepsis en los recién nacidos. La resistencia meticilina y la pérdida de sensibilidad a glucopéptidos dificultan considerablemente el tratamiento antimicrobiano en infecciones por cocos grampositivos. Objetivos. Estudiar la CMI para vancomicina, teicoplanina y linezolid en diferentes especies de ECN meticilín resistentes aislados en hemocultivos procedentes de pacientes pediátricos. Métodos. Analizar los ECN resistentes a meticilina y clínicamente significativos, procedentes de hemocultivos de pacientes ingresados en diferentes Áreas del Servicio de Pediatría. Los aislamientos se identificaron mediante pruebas bioquímicas contenidas en los paneles Combo 31 de MicroScan (Dade Behring Siemens). La resistencia a oxacilina y la susceptibilidad frente a vancomicina, teicoplanina y linezolid se realizó mediante microdilución en placa contenida en los mismos paneles. Además se realizó Etest para teicoplanina y linezolid. Resultados. Se aislaron 50 cepas resistentes a meticilina: 37 (74%) S. epidermidis, 7 (14%) S. hominis, 4 (8%) S. haemolyticus y 2 (4%) Staphylococcus spp. Se observaron 26 cepas con sensibilidad disminuida para vancomicina, CMI de 2 mg/L, (22 S. epidermidis, 2 S. haemolyticus y 2 Staphylococcus spp.) y 21 cepas con disminución de sensibilidad a teicoplanina, CMI de 4-16 mg/L (20 S. epidermidis y 1 S. haemolyticus). Ningún ECN fue resistente a linezolid. Conclusiones. Existe una relación entre el aumento de CMI de vancomicina y el aumento de CMI de teicoplanina. Se observa una elevación estadísticamente significativa (p<0,001) en la CMI de teicoplanina en el grupo de vancomicina de 2 mg/L con respecto al grupo de vancomicina de ≤1 mg/L. Se observaron niveles muy bajos de CMI para linezolid en todas las cepas(AU)

Introduction. Coagulase-negative-Staphylococci (CNS) are the major cause of bacteraemia and sepsis in newborns. CNS methicillin resistance and its loss of sensitivity to glycopeptide antibiotics, make treatment significantly more difficult in positive cocci infections. Objective. To study MIC vancomycin, teicoplanin and linezolid in different species of CNS methicillin resistant isolates from blood cultures from paediatric patients. Methods. Clinically relevant CNS methicillin resistant isolates from paediatric blood cultures from different hospitalization wards were tested. The isolates were identified by biochemical tests by means in the Combo panels 31 of MicroScan (Dade Behring, Siemens). Resistance to oxacillin and susceptibility to vancomycin, teicoplanin and linezolid were tested by microdilution panels as cited above. We also tested teicoplanin and linezolid sensitivity using Etest. Results. 50 methicillin resistant strains were isolated: 37 (74%) S. epidermidis, 7 (14%) S. hominis, 4 (8%) S. haemolyticus and 2 (4%) Staphylococcus spp. 26 strains were observed with reduced susceptibility to vancomycin MIC = 2 mg/L, (22 S. epidermidis, 2 S. haemolyticus and 2 Staphylococcus spp.) and 21 strains with loss of susceptibility to teicoplanin, MIC = 4-16 mg/L (20 S. epidermidis and 1 S. haemolyticus). No CNS linezolid resistant was found. Conclusions. There is a linear correlation between increased vancomycin MIC and teicoplanin MIC. There is a statistically significant difference (p <0.001) in the MIC of teicoplanin in the vancomycin group = 2 mg/L with respect to the vancomycin group ≤ 1 mg/L. We also observed very low levels of linezolid MIC for all strains(AU)

Influencia de cefazolina y vancomicina en la resistencia al desgaste del cemento óseo / Impact of cefazolin and vancomycin on resistance to bone cement wear

Objetivo: Evaluar experimentalmente la influencia de la mezcla de dos antibióticos, vancomicina y cefazolina, sobre la resistencia al desgaste del cemento óseo (PMMA). Material y métodos: Se definieron seis grupos de estudio en función del antibiótico y su dosis, realizando tres muestras por grupo, que fueron sometidas a desgaste de su superficie utilizando un tribómetro, según el estándar ASTM G99-05. Se midieron los coeficientes de rozamiento y se cuantificó el desgaste volumétrico de cada una de ellas. Obtuvimos imágenes de microscopía electrónica de barrido de cada muestra para observar las existencia de modificaciones en la superficie de las muestras. Resultados: Todos los grupos presentaron datos de desgaste por debajo de los máximos admitidos para uso comercial. No se demostraron diferencias significativas en el coeficiente de fricción o en el desgaste volumétrico, salvo el grupo 4 (vancomicina 2,5% + cefazolina 2,5%), que presentó un mayor desgaste frente al grupo 3 (vancomicina 2,5%) (p<0,05). Vimos una tendencia de mayor desgaste y menor homogeneidad en los grupos con cefazolina en su composición. Conclusiones: Los cementos óseos actuales pueden soportar mezclas con altas dosis de antibióticos sin modificar sus propiedades mecánicas. Además de la cantidad de antibiótico, es determinante su elección, puesto que no todos los antibióticos afectan por igual a las propiedades del PMMA (AU)

Objective: To evaluate experimentally the impact of the mixture of two antibiotics, vancomycin, and cefazolin, on resistance to bone cement wear (PMMA). Material and Methods: Six study groups were defined according to antibiotic and dose, performing three samples per group, which were subjected to wearing of the surface using a tribometer according to the ASTM G99-05 standard. The friction coefficients were measured and volumetric wear of each of them was quantified. We obtained electron scanning microscope images of each sample to observe the presence of changes in the surface of the samples. Results: All groups had wear data below the maximum admitted for commercial use. No significant differences were shown in friction coefficient or volumetric wear, except in group 4 (2.5% vancomycin + 2.5% cefazolin), which showed greater wear versus group 3 (2.5% vancomycin) (p<0.05). We saw a tendency towards greater wear and lower homogeneity in groups with cefazolin in its composition. Conclusions: Current bone cements can withstand mixtures with high doses of antibiotics without altering their mechanical properties. In addition to the amount of antibiotic, the choice is decisive, as not all antibiotics equally affect the properties of PMMA (AU)

Activity of vancomycin, ciprofloxacin, daptomycin and linezolid against coagulasenegative staphylococci bacteremia

Objetivo. Las infecciones por Staphylococcus coagulasa negativos (CNS) resistentes a meticilina aumentado considerablemente en los pacientes hospitalizados. Hemos estudiado la actividad de vancomicina, ciprofloxacino, daptomicina y linezolid en cepas de CNS resistente a meticilina aisladas en hemocultivos clínicamente significativos. Material y Métodos. Se estudiaron 87 cepas de distintas especies de CNS de hemocultivos positivos. Los estafilococos fueron identificados mediante el sistema automático MicroScan Walkaway (Dade Behring, Siemens) y con Api ID 32 Staph (Bio- Merieux, Francia). La sensibilidad a oxacilina, vancomicina y ciprofloxacino fue realizada por dicho sistema MicroScan. La susceptibilidad frente a daptomicina y linezolid fue realizada mediante Etest (AB BioMerieux, Solna, Suecia). Para los criterios de interpretación se siguieron las indicaciones del CLSI. Resultados. Se estudiaron 87 cepas, 55 (63%) fueron S. epidermidis, 15 (17%) fueron S. haemolyticus, 10 (12%) fueron S. hominis, y 7 (8%) pertenecieron a otras especies. 53 (61%) cepas presentaron una MIC para vancomicina de 2 mg/L. La resistencia a ciprofloxacino, MIC > 2 mg/L fue observada en 56 (64%) cepas. No se encontraron resistencia a daptomicina, con un rango de sensibilidad entre 0.032-1 mg/L y un valor modal de 0,25 mg/L. Se aislaron 10 (11,5%) cepas resistentes a linezolid. Nueve pacientes estuvieron ingresados en la Unidad de Cuidados Intensivos, donde la estancia media fue de 38 días (rango 16-58 días), y uno perteneció al Servicio de Cirugía Hepato-Pancreática, con una estancia de 64 días. Conclusiones. Es frecuente aislar cepas de CNS con pérdida de sensibilidad para vancomicina en nuestro hospital, mientras que daptomicina presenta una alta sensibilidad frente a este tipo de microorganismos. El uso masivo y continuado de linezolid ha llevado a la aparición de resistencias(AU)

Objective. Multiresistant coagulase-negative staphylococci (CNS) infections are mainly increased in hospitalized patients. We have studied the activity of vancomycin, ciprofloxacin, daptomycin and linezolid in methicillin-resistant CNS strains, isolated from true blood cultures. Methods. We collected 87 strains of different CNS species from positive blood cultures. Staphylococci were identified by MicroScan Walkaway (Dade Behring, Siemens) and with the Api ID 32 Staph (BioMerieux, France). The susceptibility to oxacillin, vancomycin and ciprofloxacin was performed by automatic microdilution plate as cited above. The susceptibility to daptomycin and linezolid was performed by Etest (AB BioMerieux, Solna, Sweden). Interpretative criteria were done following the CLSI guidelines. Results. Eighty-seven CNS strains were studied: 55 (63%) were S. epidermidis, 15 (17%) S. haemolyticus, 10 (12%) S. hominis, and 7 (8%) other species. Fifty-three (61%) strains showed loss of susceptibility to vancomycin, MIC = 2 mg/L. Ciprofloxacin resistance, MIC > 2 mg/L, was observed in 56 (64%) strains. Daptomycin resistance was not observed, with a susceptibility range between 0.032-1 mg/L and modal value of 0.25 mg/L. Ten strains (11.5%) resistant to linezolid were observed. Nine patients were in ICU, where the average length of stay was 38 days (range 16- 58 days) and one belonged to Hepato-Pancreatic Surgery, where he stayed for 64 days. Conclusions. Low susceptibility to vancomycin is frecuent in the CNS strains studied in our hospital. Daptomycin shows a high efficacy against CNS, and it could be useful for the treatment of primary bacteremia or catheter associated bacteremia. The massive and continuous use of linezolid has led to the appearance of resistance(AU)

Estudo experimental de implantes bioabsorviveis de poli(L-acido latico) / poli(oxido de etileno) associados ao cloridrato de vancomicina no reparo osseo / An experimental study of the use of bioabsorbable polyl(L-lactic acid) / poly(ethylene oxide) microspheres containing vancomycin for bone repair

A necessidade da utilização de enxertos naturais e/ou materiais sintéticos para auxiliar no reparo ósseo é diretamente proporcional a perda tecidual nas lesões. A administração de substâncias antibióticas é necessária para prevenir, ou mesmo combater a ação de agentes bacterianos que possam vir a retardar o reparo tecidual. Este estudo teve como objetivo avaliar a aplicação de um polímero bioabsorvível associado à uma droga antobiótica na regenereção óssea. Foram realizados implantes ósseos de microesferas da blenda de poli(L-ácido lático)PLLA/poli(óxido de etileno)PEO na composição 80:20 associadas ao cloridrato de vancomicina e não associados ao cloridrato de vancomicina em ratos. Os implantes foram colocados em cavidades de 3 mm de diâmetro realizadas em tíbias de ratos da linhagem Wistar. Grupos com 5 animais cada. foram submetidos a períodos experimentais de 2 e 4 dias e 1, 2, 4, 8, 16 e 32 semanas. Os achados morfológicos foram semelhantes em ambos grupos. Houve primeiramente a formação de malha de fibrina e hemorragia ao redor das microesferas, as quais foram gradualmente sendo substituídas por tecido de granulação. A partir do quarto dia, houve a formação inicial de matriz óssea envolvendo as microesferas centripetamente, tornando-se mais evidente e madura da primeira até a trigésima segunda semana de implantação. A comparação entre os achados histomorfométricos...

The use of natural graft and synthetic materials to help bone regeneration is directly relative to cause of bone injury and bone requirement to compose a graft. The antibiotics drugs management is necessary to prevent and combat bacterial agents that could retard the tissue repair The aim of this study was to evaluate the bioabsorbable polymeric implants antibiotic associated behavior during the bone healing. Poly(L-lactic acid)PLLA/poly(ethylene oxide)PEO microspheres blends 80:20 vancomicyn associated bone implants, was compared with PLLA/PEO blend without vancomycin. The implants were inserted in a 3 mm proximal tibiae defect in adult Wistar rats. Periods from 2 and 4 days and 1. 2, 4, 8 16 and 32 weeks were evaluated in 5 animals per group. The histological findings were similar among groups. A fibrin net and hemorrhage were observed primarily around the microspheres and both were progressively replaced by granulation tissue. In four-day implant, the initial bone formation around microspheres was noted. The growth of bone tissue was initially characterized by wolven bone with progressive maturation to lamellar bone, centripetally to microspheres group. The quantity of new bone growth, measured by histomorphometric method and semi-quantitative analysis showed no differences between groups in each experimental interval. Therefore we conclude that mixing vancomycin chloridrate into PLLA/PEO microspheres did not affect...

Monitoreo de vancomicina administrada intraventricularmente en lactantes durante el tratamiento de ventriculitis / Monitoring of intraventricularly administered vancomycin in infants in the treatment of ventriculitis

El objetivo de este estudio fue establecer pautas para el monitoreo de Vancomicina cuando la misma es administrada intraventricularmente en lactantes. En este estudio se incluyeron once pacientes con derivaciones ventrículo-peritoneal. Todos los pacientes recibieron una dosis de Vancomicina intraventricular (IVT). Las muestras de líquido cefalorraquídeo (LCR) fueron analizadas y se calcularon los parámetros farmacocinéticos: constante de velocidad de eliminación (ke) y volumen de distribución (Vd) para poder llevar a cabo un ajuste posológico. Las medias referidas al Vd y a la semivida de eliminación para estos pacientes fueron de 244(±162) mL y 37.1(±23.3) horas respectivamente. En algunos pacientes se observó una gran variabilidad en el Vd. Este cambio en Vd se correlacionó con problemas en el tamaño ventricular o con ventrículos septados. En todos los casos, se propuso una nueva dosis de acuerdo a los parámetros calculados. Debido a variaciones en el sistema a lo largo de la terapia, se propuso un protocolo para la recolección de muestras de LCR de forma tal de individualizar la dosis de Vancomicina con los parámetros farmacocinéticos obtenidos

The objective of this study was to establish guidelines for the monitoring of intraventricularly administered Vancomycin in infants. Eleven patients with ventriculo-peritoneal shunts who developed ventriculitis were included in the study. All patients were given an intraventricular (IVT) dose of Vancomycin. Cerebrospinal fluid (CSF) samples were analysed and pharmacokinetic parameters: elimination rate constant (ke) and distribution volume (Vd) were calculated in order to adjust the dose. Mean values of Vd and elimination half-life for these patients were 244 (± 162) mL and 37.1 (±23.3) hours respectively. A great variability in the Vd was observed in some patients. This change in Vd correlates with problems in the ventricle size or with septated ventricles. In all cases a new dose was suggested according to the calculated parameters. Due to variations in the system throughout therapy, a protocol for CSF samples collection was proposed in order to individualise Vancomycin dosage according to pharmacokinetic parameters