Enfoque del paciente con sospecha de neuroinfección en urgencias

Las infecciones del sistema nervioso son importantes fuentes de morbilidad y mortalidad en el mundo, debido a diferentes factores como son el amplio uso de antibióticos que aunque contribuyen con éxito al manejo de infecciones, pero el mal uso por automedicación o tratamientos incompletos favorecen la emergencia de organismos resistentes y la existencia de “mimos infecciosos” que incluyen el síndrome de reconstitución inflamatoria (IRIS). Adicionalmente el crecimiento de las poblaciones inmunocomprometidas por el síndrome de inmunodeficiencia adquirida (SIDA) y por tratamientos agresivos para trasplante sólido o hematopoyético han mejorado la sobrevida de diferentes tipos de malignidades y alteraciones reumatológicas pero son poblaciones que tienen más susceptibilidad a contraer infecciones y encefalitis mediadas inmunológicamente, como son la encefalomielitis diseminada aguda (ADEM) o la encefalitis contra el receptor de N-metil-D aspartato (NMDA).

Mediastinitis post revascularización miocárdica: impacto del cambio de profilaxis antibiótica en la fundación Cardioinfantil 2012 - 2013

INTRODUCCIÓN. La mediastinitis posterior a cirugía de revascularización miocárdica es una infección infrecuente, pero potencialmente fatal. En la Fundación Cardioinfantil se ha observado una tendencia al incremento de la misma en los últimos años, obligando a un cambio en las medidas de profilaxis antimicrobiana, pasando de cefalosporinas a vancomicina – gentamicina, sin embargo no se conoce aún el impacto de estas medidas. OBJETIVO: Determinar si el cambio de la profilaxis antibiótica en pacientes sometidos a revascularización miocárdica influye en una disminución de la incidencia de mediastinitis durante los años 2012 – 2013. METODOLOGÍA: Estudio de cohortes retrospectivo, evaluando la incidencia de mediastinitis post revascularización miocárdica, en pacientes expuestos a 2 diferentes tipos de profilaxis antimicrobiana (cefalosporinas vs vancomicina-gentamicina). Se describieron los patrones de susceptibilidad y resistencia de los patógenos encontrados en mediastinitis y la mortalidad de esta patología. RESULTADOS: Los patógenos más frecuentemente aislados en la mediastinitis fueron Staphylococcus aureus y Klebsiella pneumoniae, en la mayoría monomicrobiano. Se encontraron patógenos con perfiles de resistencia como betalactamasas de espectro extendido en Gram negativos y resistencia a la meticilina en cocos Gram positivos. El RR de mediastinitis del grupo expuesto a vancomicina-gentamicina respecto al grupo de cefalosporinas fue de 0,9 con IC 95% 0,28 – 3,28. CONCLUSIÓN: la epidemiologia microbiana de la mediastinitis no difiere de la reportada en otras series. La profilaxis antimicrobiana con vancomicina - gentamicina en pacientes sometidos a revascularización miocárdica, no redujo la incidencia de mediastinitis. Se propone regresar a la terapia de profilaxis con cefalosporinas.

Osteomielitis esternal: utilidad de las pruebas de diagnóstico por imágenes con enfoque en medicina nuclear

Introducción: El diagnóstico de osteomielitis esternal post-esternotomía resulta difícil empleando síntomas clínicos o de laboratorio y las imágenes morfológicas orientan a sospecha más que al diagnóstico. Un diagnóstico precoz ofrece calidad de vida y el mejor tratamiento para reducir una mortalidad que oscila entre 14% y 47%. La gammagrafía con leucocitos marcados ofrece el mejor rendimiento diagnóstico para infecciones y se destaca como el patrón de oro diagnóstico. Objetivo: Identificar el desempeño y utilidad de la gammagrafía con leucocitos autólogos marcados con 99mTc-HMPAO en los estudios realizados para la evaluación de osteomielitis esternal. Materiales y métodos: Se realizó un estudio descriptivo, retrospectivo de prueba diagnóstica en la Fundación Cardioinfantil de Bogotá entre enero/2010 y mayo/2015 evaluando gammagrafías con leucocitos marcados ante la sospecha de osteomielitis posterior a esternotomía. Resultados: Se evaluaron 52 pacientes, en los que la gammagrafía con leucocitos mostró 23 pacientes (44,2%) con osteomielitis esternal, logrando una sensibilidad y especificidad del 88,46% y 100% respectivamente. El valor predictivo positivo fue de 100%, y el valor predictivo negativo fue de 89,66%. El impacto de una prueba negativa no modificó el manejo médico inicial en el 93% de los casos mientras que una prueba positiva lo modificó en el 83%. Conclusiones: La gammagrafía con leucocitos autólogos radiomarcados con 99mTc-HMPAO continúa siendo el patrón de oro de referencia no invasiva para el diagnóstico de osteomielitis, y en el caso de osteomielitis esternal se convierte en la prueba de elección pertinente en la selección de pacientes que ameritan una re-intervención quirúrgica.

Patogénese de infecções causadas por bactérias da flora endógena

A flora microbiana humana cujos elementos major são bactérias, tem sido caracterizada como uma componente essencial do corpo humano. A sua importância baseia-se no seu envolvimento benéfico numa variedade de funções metabólicas, imunitárias e antimicrobianas. Os resultados destas funções incluem a homeostasia do organismo humano. Contudo, a flora microbiana humana tem sido associada com o desenvolvimento de numerosas infecções denominadas por infecções endógenas tais como as infecções orais. Estas infecções são comuns nos hospedeiros comprometidos, o que contribui para o aumento do seu significado clínico. Nesta dissertação foi feita uma abordagem à patogénese bacteriana assim como aos passos do processos infecciosos e aos factores de virulência. Foi também feita a associação destes à susceptibilidade do hospedeiro com o propósito de compreender os seus contributos para o desenvolvimento das infecções endógenas. Por outro lado, foram exploradas algumas consequências sistémicas infecciosas (endocardite infecciosa) e não infecciosas (aterosclerose) de infecções orais causadas pela flora bacteriana oral.

Transmission properties of Iranian wheat stripe virus

Transmission properties of Iranian wheat stripe virus (IWSV), a tentative member of the genus Tenuivirus, were studied. Results showed that similar to other tenuiviruses, IWSV multiplies in its vector, Unkanodes tanasijevici. In bioassay experiments, IWSV transmission rate by individual U. tanasijevici showed an increase with time after acquisition. IWSV was transovarially transmitted to 88-100% of progeny. The nymphs continued to be infective in the adult stage but with decreased efficiency. Males and females transmitted the virus with equal efficiency. Transmission properties of IWSV confirm the position of the virus in the genus Tenuivirus.

Influence of temperature on the production and infectivity of entomopathogenic nematodes against larvae and pupae of vine weevil, Otiorhynchus sulcatus, (Coleoptera: Curculionidae)

Susceptibility of late instar vine weevil Otiorhynchus sulcatus larvae and pupae to four species entomopathogenic nematodes were tested. Bioassays on production and infectivity to larvae and pupae were compared for two steinernematids and two heterorhabditis such as Steinernema carpocapsae, S. feltiae, Heterorhabditis indica and H. bacteriophora. Nematodes production of all species was determined by the number infective juveniles (IJs) established in vine weevil larvae and pupae O. sulcatus using sand and filter paper bioassay. S. feltiae produced the maximum number in larvae and pupae at 20°C as compared to other nematodes but production of H. indica, was better at 25°C in larvae and pupae followed by H. bacteriophora, S. carpocapsae and Infectivity test of larvae and pupae was also done in sand media. Infective juveniles recovered from larvae and pupae when infected with S. feltiae produced maximum infective juveniles at 20°C temperatures than all other isolates. H. bacteriophora produced higher number of IJs in larvae and pupae than all other nematode isolates at 25°C. This paper indicates the application of nematodes with the knowledge of insect pest biology represents a possible new strategy for O. sulcatus larvae and pupae.

The effects of infection by Tetracapsuloides bryosalmonae (Myxozoa) and temperature on Fredericella sultana (Bryozoa)

The myxozoan, Tetracapsuloides bryosalmonae, exploits freshwater bryozoans as definitive hosts, occurring as cryptic stages in bryozoan colonies during covert infections and as spore-forming sacs during overt infections. Spores released from sacs are infective to salmonid fish, causing the devastating Proliferative Kidney Disease (PKD). We undertook laboratory studies using mesocosm systems running at 10, 14 and 20 degrees C to determine how infection by T bryosalmonae and water temperature influence fitness of one of its most important bryozoan hosts, Fredericella sultana, over a period of 4 weeks. The effects of infection were context-dependent and often undetectable. Covert infections appear to pose very low energetic costs. Thus, we found that growth of covertly infected F. sultana colonies was similar to that of uninfected colonies regardless of temperature, as was the propensity to produce dormant resting stages (statoblasts). Production of statoblasts, however, was associated with decreased growth. Overt infections imposed greater effects on correlates of host fitness by: (i) reducing growth rates at the two higher temperatures: (ii) increasing mortality rates at the highest temperature: (iii) inhibiting statoblast production. Our results indicate that parasitism should have a relatively small effect on host fitness in the field as the negative effects of infection were mainly expressed in environmentally extreme conditions (20 degrees C for 4 weeks). The generally low virulence of T. bryosalmonae is similar to that recently demonstrated for another myxozoan endoparasite of freshwater bryozoans. The unique opportunity for extensive vertical transmission in these colonial invertebrate hosts couples the reproductive interests of host and parasite and may well give rise to the low virulence that characterises these systems. Our study implies that climate change can be expected to exacerbate PKD outbreaks and increase the geographic range of PKD as a result of the combined responses of T. bryosalmonae and its bryozoan hosts to higher temperatures. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

Transmission properties of Iranian wheat stripe virus

Transmission properties of Iranian wheat stripe virus (IWSV), a tentative member of the genus Tenuivirus, were studied. Results showed that similar to other tenuiviruses, IWSV multiplies in its vector, Unkanodes tanasijevici. In bioassay experiments, IWSV transmission rate by individual U. tanasijevici showed an increase with time after acquisition. IWSV was transovarially transmitted to 88-100% of progeny. The nymphs continued to be infective in the adult stage but with decreased efficiency. Males and females transmitted the virus with equal efficiency. Transmission properties of IWSV confirm the position of the virus in the genus Tenuivirus.

Temperature-driven proliferation of Tetracapsuloides bryosalmonae in bryozoan hosts portends salmonid declines

Proliferative kidney disease (PKD) is an emerging disease of salmonid fishes. It is provoked by temperature and caused by infective spores of the myxozoan parasite Tetracapsuloides bryosalmonae, which develops in freshwater bryozoans. We investigated the link between PKD and temperature by determining whether temperature influences the proliferation of T bryosalmonae in the bryozoan host Fredericella sultana. Herein we show that increased temperatures drive the proliferation of T bryosalmonae in bryozoans by provoking, accelerating and prolonging the production of infective spores from cryptic stages. Based on these results we predict that PKD outbreaks will increase further in magnitude and severity in wild and farmed salmonids as a result of climate-driven enhanced proliferation in invertebrate hosts, and urge for early implementation of management strategies to reduce future salmonid declines.

Evaluation of malacosporean life cycles through transmission studies

Myxozoans, belonging to the recently described Class Malacosporea, parasitise freshwater bryozoans during at least part of their life cycle, but no complete malacosporean life cycle is known to date. One of the 2 described malacosporeans is Tetracapsuloides bryosalmonae, the causative agent of salmonid proliferative kidney disease. The other is Buddenbrockia plumatellae, so far only found in freshwater bryozoans. Our investigations evaluated malacosporean life cycles, focusing on transmission from fish to bryozoan and from bryozoan to bryozoan. We exposed bryozoans to possible infection from: stages of T bryosalmonae in fish kidney and released in fish urine; spores of T bryosalmonae that had developed in bryozoan hosts; and spores and sac stages of B. plumatellae that had developed in bryozoans. Infections were never observed by microscopic examination of post-exposure, cultured bryozoans and none were detected by PCR after culture. Our consistent negative results are compelling: trials incorporated a broad range of parasite stages and potential hosts, and failure of transmission across trials cannot be ascribed to low spore concentrations or immature infective stages. The absence of evidence for bryozoan to bryozoan transmissions for both malacosporeans strongly indicates that such transmission is precluded in malacosporean life cycles. Overall, our results imply that there may be another malacosporean host which remains unidentified, although transmission from fish to bryozoans requires further investigation. However, the highly clonal life history of freshwater bryozoans is likely to allow both long-term persistence and spread of infection within bryozoan populations, precluding the requirement for regular transmission from an alternate host.

One-pot synthesis of multivalent arrays of mannose mono- and disaccharides

The synthesis of a selection of multivalent arrays of mannose mono- and disaccharides, that are of potential use as anti-infective agents against enterobacteria infections, is described. (C) 2003 Elsevier Ltd. All rights reserved.

A double-blind, randomized, controlled crossover trial of glutamine supplementation in home parenteral nutrition

Objective: Studies suggest clinical benefit of glutamine-supplemented parenteral nutrition. The aim was to determine if the inclusion of 10 g of glutamine as part of the nitrogen source of home parenteral nutrition (HPN) reduces infectious complications. Subjects/Methods: Thirty-five patients on HPN were recruited and 22 completed the study. Patients were randomized to receive either standard HPN or glutamine-supplemented HPN. Patients were assessed at randomization, 3 and 6 months later then they were crossed over to the alternative HPN and reassessed at 3 and 6 months. Assessments included plasma amino acid concentrations, intestinal permeability and absorption, nutritional status, oral and parenteral intake, quality of life, routine biochemistry and haematology. Results: No difference was seen between the groups at randomization. No difference was detected between the treatment phases for infective complications (55% in the standard treatment phase and 36% in the glutamine-supplemented phase P 0.67). There were no differences in nutritional status, intestinal permeability, plasma glutamine concentrations or quality of life. Conclusion: Although limited by the sample size, the study has shown that glutamine as part of the nitrogen source of parenteral nutrition can be given to patients on HPN for 6 months without any adverse effects.

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement(1), increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively(2,3). Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement(4). Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2,3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Techniques for image analysis of movement of juveniles of root-knot nematodes encumbered with Pasteuria penetrans spores

Root-knot nematodes (Meloidogyne spp.) are the most significant plant-parasitic nematodes that damage many crops all over the world. The free-living second stage juvenile (J2) is the infective stage that enters plants. The J2s move in the soil water films to reach the root zone. The bacterium Pasteuria penetrans is an obligate parasite of root-knot nematodes, is cosmopolitan, frequently encountered in many climates and environmental conditions and is considered promising for the control of Meloidogyne spp. The infection potential of P. penetrans to nematodes is well studied but not the attachment effects on the movement of root-knot nematode juveniles, image analysis techniques were used to characterize movement of individual juveniles with or without P. penetrans spores attached to their cuticles. Methods include the study of nematode locomotion based on (a) the centroid body point, (b) shape analysis and (c) image stack analysis. All methods proved that individual J2s without P. penetrans spores attached have a sinusoidal forward movement compared with those encumbered with spores. From these separate analytical studies of encumbered and unencumbered nematodes, it was possible to demonstrate how the presence of P. penetrans spores on a nematode body disrupted the normal movement of the nematode.

Development and application of a method for the purification of free shigatoxigenic bacteriophage from environmental samples

Shiga toxin producing Escherichia coli (STEC) strains are foodborne pathogens whose ability to produce Shiga toxin (Stx) is due to the integration of Stx-encoding lambdoid bacteriophage (Stx phage). Circulating, infective Stx phages are very difficult to isolate, purify and propagate such that there is no information on their genetic composition and properties. Here we describe a novel approach that exploits the phage's ability to infect their host and form a lysogen, thus enabling purification of Stx phages by a series of sequential lysogen isolation and induction steps. A total of 15 Stx phages were rigorously purified from water samples in this way, classified by TEM and genotyped using a PCR-based multi-loci characterisation system. Each phage possessed only one variant of each target gene type, thus confirming its purity, with 9 of the 15 phages possessing a short tail-spike gene and identified by TEM as Podoviridae. The remaining 6 phages possessed long tails, four of which appeared to be contractile in nature (Myoviridae) and two of which were morphologically very similar to bacteriophage lambda (Siphoviridae).