Participation of the spleen in the neuroinflammation after pilocarpine-induced status epilepticus: Implications for epileptogenesis and epilepsy.

Epilepsy, a chronic neurological disorder characterized by recurrent seizures, affects millions of individuals worldwide. Despite extensive research, the underlying mechanisms leading to epileptogenesis, the process by which a normal brain develops epilepsy, remain elusive. We here explored the immune system and spleen responses triggered by pilocarpine-induced status epilepticus (SE) focusing on their role in the epileptogenesis that follows SE . Initial examination of spleen histopathology revealed transient disorganization of white pulp, in animals subjected to SE. This disorganization, attributed to immune activation, peaked at 1-day post-SE (1DPSE) but returned to control levels at 3DPSE. Alterations in peripheral blood lymphocyte populations, demonstrated a decrease following SE, accompanied by a reduction in CD3+ T-lymphocytes. Further investigations uncovered an increased abundance of T-lymphocytes in the pyriform cortex and  choroid plexus at 3DPSE, suggesting a specific mobilization towards the Central Nervous System. Notably, splenectomy mitigated brain reactive astrogliosis, neuroinflammation, and macrophage infiltration post-SE, particularly in the hippocampus and piriform cortex. Additionally, splenectomized animals exhibited reduced lymphatic follicle size in the deep cervical lymph nodes. Most significantly, splenectomy correlated with improved neuronal survival, substantiated by decreased neuronal loss and reduced degenerating neurons in the piriform cortex and hippocampal CA2-3 post-SE. Overall, these findings underscore the pivotal role of the spleen in orchestrating immune responses and neuroinflammation following pilocarpine-induced SE, implicating the peripheral immune system as a potential therapeutic target for mitigating neuronal degeneration in epilepsy.

Detrimental Effects of HMGB-1 Require Microglial-Astroglial Interaction: Implications for the Status Epilepticus -Induced Neuroinflammation.

Temporal Lobe Epilepsy (TLE) is the most common form of human epilepsy and available treatments with antiepileptic drugs are not disease-modifying therapies. The neuroinflammation, neuronal death and exacerbated plasticity that occur during the silent period, following the initial precipitating event (IPE), seem to be crucial for epileptogenesis. Damage Associated Molecular Patterns (DAMP) such as HMGB-1, are released early during this period concomitantly with a phenomenon of reactive gliosis and neurodegeneration. Here, using a combination of primary neuronal and glial cell cultures, we show that exposure to HMGB-1 induces dendrite loss and neurodegeneration in a glial-dependent manner. In glial cells, loss of function studies showed that HMGB-1 exposure induces NF-κB activation by engaging a signaling pathway that involves TLR2, TLR4, and RAGE. In the absence of glial cells, HMGB-1 failed to induce neurodegeneration of primary cultured cortical neurons. Moreover, purified astrocytes were unable to fully respond to HMGB-1 with NF-κB activation and required microglial cooperation. In agreement, in vivo HMGB-1 blockage with glycyrrhizin, immediately after pilocarpine-induced status epilepticus (SE), reduced neuronal degeneration, reactive astrogliosis and microgliosis in the long term. We conclude that microglial-astroglial cooperation is required for astrocytes to respond to HMGB-1 and to induce neurodegeneration. Disruption of this HMGB-1 mediated signaling pathway shows beneficial effects by reducing neuroinflammation and neurodegeneration after SE. Thus, early treatment strategies during the latency period aimed at blocking downstream signaling pathways activated by HMGB-1 are likely to have a significant effect in the neuroinflammation and neurodegeneration that are proposed as key factors in epileptogenesis.

Pilocarpine-Induced Status Epilepticus Is Associated with P-Glycoprotein Induction in Cardiomyocytes, Electrocardiographic Changes, and Sudden Death.

Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE. P-gp was also detected after brain or cardiac hypoxia. We have previously demonstrated that repetitive pentylenetetrazole (PTZ)-induced seizures increase P-gp expression in the brain, which is associated with membrane depolarization in the hippocampus, and in the heart, which is associated with fatal SE. SE can produce hypoxic-ischemic altered cardiac rhythm (HIACR) and severe arrhythmias, and both are related with SUDEP. Here, we investigate whether SE induces the expression of hypoxia-inducible transcription factor (HIF)-1α and P-gp in cardiomyocytes, which is associated with altered heart rhythm, and if these changes are related with the spontaneous death rate. SE was induced in Wistar rats once a week for 3 weeks, by lithium-pilocarpine-paradigm. Electrocardiograms, HIF-1α, and P-gp expression in cardiomyocytes, were evaluated in basal conditions and 72 h after SE. All spontaneous deaths occurred 48 h after each SE was registered. We observed that repeated SE induced HIF-1α and P-gp expression in cardiomyocytes, electrocardiographic (ECG) changes, and a high rate of spontaneous death. Our results suggest that the highly accumulated burden of convulsive stress results in a hypoxic heart insult, where P-gp expression may play a depolarizing role in cardiomyocyte membranes and in the development of the ECG changes, such as QT interval prolongation, that could be related with SUDEP. We postulate that this mechanism could explain, in part, the higher SUDEP risk in patients with RE or SE.

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy.

The lithium-pilocarpine model of epilepsy reproduces several features of temporal lobe epilepsy in humans, including the chronological timeline of an initial latency period followed by the development of spontaneous seizures. Epilepsy therapies in humans are implemented, as a rule, after the onset of the spontaneous seizures. We here studied the potential effect on epileptogenesis of starting an early treatment during the latency period, in order to prevent the development of spontaneous seizures. Adult male Wistar rats were treated with 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once status epilepticus (SE) was achieved, it was allowed to last for 20 min, and then motor seizures were controlled with the administration of 20 mg/kg diazepam. At 1DPSE (DPSE, days post-status epilepticus), animals started to receive 400 mg/kg/day gabapentin or saline for 4 days. At 5DPSE, we observed that SE induced an early profuse microglial and astroglial reactivity, increased synaptogenic trombospondin-1 expression and reduced AQP4 expression in astroglial ending feet. Blood brain barrier (BBB) integrity seemed to be compromised, as infiltrating NG2+ macrophages and facilitated access to the CNS was observed by transplanting eGFP+ blood cells and bone marrow-derived progenitors in the SE animals. The early 4-day gabapentin treatment successfully reduced microglial cell reactivity and blood-borne cell infiltration, without significantly altering the mRNA of proinflammatory cytokines IL-1ß and TNFα immediately after the treatment. After 21DSPE, another group of animals that developed SE and received 4 days of gabapentin treatment, were re-exposed to subconvulsive accumulative doses of pilocarpine (10 mg/kg/30 min) and were followed by recording the Racine scale reached. Early 4-day gabapentin treatment reduced the Racine scale reached by the animals, reduced animal mortality, and reduced the number of animals that achieved SE (34% vs. 72%). We conclude that early gabapentin treatment following SE, during the latency period, is able to reduce neuroinflammation and produces a persistent effect that limits seizures and increases convulsive threshold, probably by restricting microglial reactivity and spurious synaptogenesis.

S100B protein activates a RAGE-dependent autocrine loop in astrocytes: implications for its role in the propagation of reactive gliosis.

Extracellular S100B dramatically increases after brain injury. While low S100B levels are neuroprotective, micromolar S100B levels have shown in vitro to activate microglia and facilitate neuronal death. In astrocytes, S100B exposure activates nuclear factor kappa B (NF-κB) and induces pro-inflammatory mediators. On microglia and neurons S100B effects are essentially mediated by receptor for advanced glycation end products (RAGE)/NF-κB, but it is not clear if these intracellular cascades are activated by different S100B levels in astrocytes and whether increased extracellular S100B is sufficient to induce reactive gliosis. A better understanding of these pathways is essential for developing successful strategies to preserve the beneficial S100B effects after brain injury. Here, we show that microglia-depleted cultured astrocytes exposed to S100B mimicked several features of reactive gliosis by activating RAGE/Rac-1-Cdc42, RAGE/Erk-Akt or RAGE/NF-κB-dependent pathways. S100B effects include RAGE/Rac1-Cdc42-dependent astroglial hypertrophy and facilitation of migration as well as increased mitosis. S100B exposure improved the astrocytic survival to oxidative stress, an effect that requires Erk/Akt. S100B also activates NF-κB in a dose-dependent manner; increases RAGE proximal promoter transcriptional activity and augmented endogenous RAGE expression. S100B-exposed astrocytes showed a pro-inflammatory phenotype with expression of Toll-like receptor 2 (TLR 2), inducible nitric oxide synthase (iNOS) and interleukin 1-beta (IL-1ß), and facilitated neuronal death induced by oxygen-glucose deprivation. In vivo, intracerebral infusion of S100B was enough to induce an astroglial reactive phenotype. Together, these findings demonstrate that extracellular S100B in the micromolar level activates different RAGE-dependent pathways that turn astrocytes into a pro-inflammatory and neurodegenerative phenotype. We propose that S100B turns astrocytes into a reactive phenotype in a RAGE-dependent manner but engaging different intracellular pathways. While both nanomolar and micromolar S100B turn astrocytes into a reactive phenotype, micromolar S100B induces a conversion into a pro-inflammatory-neurodegenerative profile that facilitates neuronal death of OGD-exposed neurons. We think that S100B/RAGE interaction is essential to expand reactive gliosis in the injured brain being a tempting target for limiting reactive gliosis to prevent the glial conversion into the neurodegenerative profile.

Gabapentin administration reduces reactive gliosis and neurodegeneration after pilocarpine-induced status epilepticus.

The lithium-pilocarpine model of epilepsy reproduces in rodents several features of human temporal lobe epilepsy, by inducing an acute status epilepticus (SE) followed by a latency period. It has been proposed that the neuronal network reorganization that occurs during latency determines the subsequent appearance of spontaneous recurrent seizures. The aim of this study was to evaluate neuronal and glial responses during the latency period that follows SE. Given the potential role of astrocytes in the post-SE network reorganization, through the secretion of synaptogenic molecules such as thrombospondins, we also studied the effect of treatment with the α2δ1 thrombospondin receptor antagonist gabapentin. Adult male Wistar rats received 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once SE was achieved, seizures were stopped with 20 mg/kg diazepam. Animals then received 400 mg/kg/day gabapentin or saline for either 4 or 14 days. In vitro experiments were performed in dissociated mixed hippocampal cell culture exposed to glutamate, and subsequently treated with gabapentin or vehicle. During the latency period, the hippocampus and pyriform cortex of SE-animals presented a profuse reactive astrogliosis, with increased GFAP and nestin expression. Gliosis intensity was dependent on the Racine stage attained by the animals and peaked 15 days after SE. Microglia was also reactive after SE, and followed the same pattern. Neuronal degeneration was present in SE-animals, and also depended on the Racine stage and the SE duration. Polysialic-acid NCAM (PSA-NCAM) expression was increased in hippocampal CA-1 and dentate gyrus of SE-animals. Gabapentin treatment was able to reduce reactive gliosis, decrease neuronal loss and normalize PSA-NCAM staining in hippocampal CA-1. In vitro, gabapentin treatment partially prevented the dendritic loss and reactive gliosis caused by glutamate excitotoxicity. Our results show that gabapentin treatment during the latency period after SE protects neurons and normalizes PSA-NCAM probably by direct interaction with neurons and glia.

CARB-9, a carbenicillinase encoded in the VCR region of Vibrio cholerae non-O1, non-O139 belongs to a family of cassette-encoded beta-lactamases.

The gene bla(CARB-9) was located in the Vibrio cholerae super-integron, but in a different location relative to bla(CARB-7). CARB-9 (pI 5.2) conferred beta-lactam MICs four to eight times lower than those conferred by CARB-7, differing at Ambler's positions V97I, L124F, and T228K. Comparison of the genetic environments of all reported bla(CARB) genes indicated that the CARB enzymes constitute a family of cassette-encoded beta-lactamases.

New carbenicillin-hydrolyzing beta-lactamase (CARB-7) from Vibrio cholerae non-O1, non-O139 strains encoded by the VCR region of the V. cholerae genome.

In a previous study, an analysis of 77 ampicillin-nonsusceptible (resistant plus intermediate categories) strains of Vibrio cholerae non-O1, non-O139, isolated from aquatic environment and diarrheal stool, showed that all of them produced a beta-lactamase with a pI of 5.4. Hybridization or amplification by PCR with a probe for bla(TEM) or primers for bla(CARB) gene families was negative. In this work, an environmental ampicillin-resistant strain from this sample, ME11762, isolated from a waterway in the west region of Argentina, was studied. The nucleotide sequence of the structural gene of the beta-lactamase was determined by bidirectional sequencing of a Sau3AI fragment belonging to this isolate. The gene encodes a new 288-amino-acid protein, designated CARB-7, that shares 88.5% homology with the CARB-6 enzyme; an overall 83.2% homology with PSE-4, PSE-1, CARB-3, and the Proteus mirabilis N29 enzymes; and 79% homology with CARB-4 enzyme. The gene for this beta-lactamase could not be transferred to Escherichia coli by conjugation. The nucleotide sequence of the flanking regions of the bla(CARB-7) gene showed the occurrence of three 123-bp V. cholerae repeated sequences, all of which were found outside the predicted open reading frame. The upstream fragment of the bla(CARB-7) gene shared 93% identity with a locus situated inside V. cholerae's chromosome 2. These results strongly suggest the chromosomal location of the bla(CARB-7) gene, making this the first communication of a beta-lactamase gene located on the VCR island of the V. cholerae genome.

Plasmidic extended-spectrum beta-lactamases in Vibrio cholerae O1 El Tor isolates in Argentina.

Since 1992 there have been seven major outbreaks of cholera in Argentina. Susceptibility analysis of 1,947 isolates (40% of reported cases) of Vibrio cholerae O1 biotype El Tor suggested the presence of extended-spectrum beta-lactamases (ESBLs) in 28 isolates. Because of their different susceptibility profiles, V. cholerae isolates M1502, M1516, M1573, and M3030 (all of which are of the Ogawa serotype) were selected for the present study. By susceptibility analysis, isoelectric focusing, and PCR-based restriction fragment length polymorphism analysis, CTX-M-type enzymes were identified in three isolates, whereas a PER-2-type enzyme, in addition to a TEM-1-like enzyme, was identified in the other isolate. The presence of these ESBLs in V. cholerae isolates resulted in MICs well below those commonly observed for members of the family ENTEROBACTERIACEAE: Genes that encode both ESBLs were transferred to Escherichia coli by conjugation, together with all determinants of resistance to non-beta-lactam antibiotics (gentamicin, kanamycin, and sulfamethoxazole for all isolates; amikacin and streptomycin for three isolates; trimethoprim, tetracycline, and chloramphenicol for two isolates). Plasmid profile analysis and Southern blotting revealed the presence of single plasmids of about 150 kb in the four V. cholerae isolates and their respective transconjugants and revealed that the plasmids harbored genes encoding CTX-M-type or PER-2-type ESBLs. These results strongly suggest the broad spread of these ESBLs among genera belong to families other than the ENTEROBACTERIACEAE:

Actitudes de los ingresantes a ciencias médicas respecto de la genética y sus avances e implicancias sociales / Attitudes of scholl medicine students about genetics, its advances and social implications

Se muestra la importancia de las actitudes en todo proceso educativo y se resalta la necesidad de investigarlas en el campo de la genética, sus avances, aplicaciones e implicancias sociales. Luego del marco teórico introductorio, se presenta el instrumento utilizado para la detección y valoración de los componentes afectivo y conductual de las actitudes, en las dimensiones imagen social de la genética, enseñanza-aprendizaje de la genética, responsabilidad solidaria. Finalmente se exponen los resultados obtenidos al aplicar dicho instrumento a una muestra de ingresantes universitarios de ciencias médicas

Actitudes de los ingresantes a ciencias médicas respecto de la genética y sus avances e implicancias sociales / Attitudes of scholl medicine students about genetics, its advances and social implications

Se muestra la importancia de las actitudes en todo proceso educativo y se resalta la necesidad de investigarlas en el campo de la genética, sus avances, aplicaciones e implicancias sociales. Luego del marco teórico introductorio, se presenta el instrumento utilizado para la detección y valoración de los componentes afectivo y conductual de las actitudes, en las dimensiones imagen social de la genética, enseñanza-aprendizaje de la genética, responsabilidad solidaria. Finalmente se exponen los resultados obtenidos al aplicar dicho instrumento a una muestra de ingresantes universitarios de ciencias médicas (AU)

Impacto de Streptococcus pneumoniae en las neumonias del niño latinoamericano / Impact of Streptococcus pneumoniae in Latin American children

La neumonia adquirida en la comunidad es una de las principales causas de morbilidad y mortalidad en la infancia. Estudios realizados en paises en desarrollo indican que los cuadros de neumonia mas graves se asocian a causas bacterianas, con predominio de Streptococcus pneumoniae, seguido por Haemophilus influenzae tipo b. El manejo de esas infecciones en los menores de 2 años se ve dificultado por la carencia de vacunas apropiadas y por la disminucion de la susceptibilidad de S. pneumoniae a la penicilina y a otros antibioticos. En 1993, por iniciativa del Sistema Regional de Vacunas (SIREVA) de la Organizacion Panamericana de la Salud y con la financiacion de la Agencia Canadiense para el Desarrollo Internacional (Canadian International Development Agency: (CIDA), se diseño un estudio para identificar los tipos capsulares de S. pneumoniae que causan enfermedad invasora en los niños latinoamericanos menores de 5 años, con el proposito de determinar tanto la composicion ideal de una vacuna conjugada que pudiera emplearse en la Region como la susceptibilidad a la penicilina de los aislados de S. pneumoniae. La iniciativa fue aceptada por Argentina, Brasil, Colombia, Chile, Mexico y Uruguay. En este informe se analiza la informacion sobre la neumonia por S. pneumoniae generada en los paises participantes. Se captaron 3.393 niños con infecciones sistemicas por S. pneumoniae, de las cuales 1.578 correspondian a neumonias. El analisis se concentro en los 1.409 casos de neumonia de Argentina, Brasil, Colombia, Mexico y Uruguay. La distribucion por edades evidencio un franco predominio de los menores de 2 años (63.8 por ciento). Se identificaron 12 tipos capsulares prevalentes, de los cuales los serotipos 14, 5 y 1 ocuparon los tres primeros lugares en la mayoria de los paises

Impacto de Streptococcus pneumoniae en las neumonias del niño latinoamericano / Impact of Streptococcus pneumoniae in Latin American children

La neumonia adquirida en la comunidad es una de las principales causas de morbilidad y mortalidad en la infancia. Estudios realizados en paises en desarrollo indican que los cuadros de neumonia mas graves se asocian a causas bacterianas, con predominio de Streptococcus pneumoniae, seguido por Haemophilus influenzae tipo b. El manejo de esas infecciones en los menores de 2 años se ve dificultado por la carencia de vacunas apropiadas y por la disminucion de la susceptibilidad de S. pneumoniae a la penicilina y a otros antibioticos. En 1993, por iniciativa del Sistema Regional de Vacunas (SIREVA) de la Organizacion Panamericana de la Salud y con la financiacion de la Agencia Canadiense para el Desarrollo Internacional (Canadian International Development Agency: (CIDA), se diseño un estudio para identificar los tipos capsulares de S. pneumoniae que causan enfermedad invasora en los niños latinoamericanos menores de 5 años, con el proposito de determinar tanto la composicion ideal de una vacuna conjugada que pudiera emplearse en la Region como la susceptibilidad a la penicilina de los aislados de S. pneumoniae. La iniciativa fue aceptada por Argentina, Brasil, Colombia, Chile, Mexico y Uruguay. En este informe se analiza la informacion sobre la neumonia por S. pneumoniae generada en los paises participantes. Se captaron 3.393 niños con infecciones sistemicas por S. pneumoniae, de las cuales 1.578 correspondian a neumonias. El analisis se concentro en los 1.409 casos de neumonia de Argentina, Brasil, Colombia, Mexico y Uruguay. La distribucion por edades evidencio un franco predominio de los menores de 2 años (63.8 por ciento). Se identificaron 12 tipos capsulares prevalentes, de los cuales los serotipos 14, 5 y 1 ocuparon los tres primeros lugares en la mayoria de los paises. En el periodo 1993-1998, la resistencia a la penicilina aumento en los cinco paises; al comienzo del estudio, los mayores porcentajes correspondieron a Mexico (47.0 por ciento) y los menores a Colombia (12.1 por ciento). La resistencia a la penicilina se asocio con un reducido numero de serotipos capsulares, fundamentalmente el 14 y el 23F, el primero resistente a la penicilina y a la trimetoprima-sulfametoxazol, y el segundo multirresistente. La frecuencia de la resistencia a la trimetoprima-sulfametoxazol, fue elevada en todos los paises y el valor maximo correspondio a Argentina (58.0 por ciento). La disminucion de la susceptibilidad al cloranfenicol tuvo baja frecuencia, salvo en Colombia (23.4 por ciento). La resistencia a la eritromicina fue baja en todos los paises y todos los aislados fueron sensibles a la vancomicina

Vigilancia de la resistencia a los antibacterianos en Argentina : programa WHONET, 1995-1996 / Monitoring antimicrobial resistance in Argentina : the WHONET program, 1995-1996

La Organización Mundial de la Salud ha puesto en marcha un programa para la vigilancia de la resistencia a los antibacterianos, denominado WHONET, que se desarrolló en Argentina mediante una red de 23 laboratorios de instituciones hospitalarias públicas y privadas sometidos a programas nacionales e internacionales de control de calidad. Entre enero de 1995 y diciembre de 1996 se determinó por el método de difusión en agar la sensibilidad a los antibacterianos de 16.073 aislados clínicos consecutivos, siguiendo las recomendaciones del Comité Nacional de Estándares para Laboratorios Clínicos (National Committee for Clinical Laboratory Standards: NCCLS) de los Estados Unidos de América. Más de la mitad de los aislados urinarios de Escherichia coli fueron resistentes a la ampicilina, y más de 30 por ciento a la trimetoprima-sulfametoxazol. Cuando se comparó la sensibilidad de los aislados urinarios de pacientes ambulatorios y hospitalizados, se observó una marcada diferencia en los perfiles de actividad (porcentaje de microorganismos resistentes aislados en pacientes hospitalizados frente a pacientes ambulatorios) de la gentamicina (8 por ciento frente a 2 por ciento), la norfloxacina (6 por ciento frente a 2 por ciento) y las cefalosporinas de tercera generación (18 por ciento frente a 10 por ciento). Los aislados de Klebsiella pneumoniae recuperados de hemocultivos presentaron resistencia a las cefalosporinas de tercera generación y a la gentamicina en 71 y 60 por ciento de los casos, respectivamente. La proporción de Staphylococcus aureus resistentes a la oxacilina fue de 39 por ciento. Cerca de la mitad de los aislados de Enterococcus spp. presentaron resistencia de alto nivel a los aminoglucósidos, pero no se detectó resistencia los glicopéptidos. En nuestro medio, la ampicilina y la trimetoprima-sulfametoxazol no fueron apropiadas para el tratamiento de las diarreas; Shigella flexneri presentó mayor porcentaje de aislados resitentes a ambos fármacos (87 y 74 por ciento, respectivamente) que Shigella sonnei (47 y 71 por ciento, respectivamente). Se detectó resistencia a las cefalosporinas de tercera generación en 40 por ciento de los aislados de Salmonella spp. recuperados en hospitales pediátricos. En casos de meningitis bacteriana, las tasas de resistencia de Streptococcus pneumoniae a la penicilina (18 por ciento) y de Haemophilus influenzae a la ampicilina (19 por ciento) se situaron en el rango intermedio de las descritas en países americanos y europeos

Vigilancia de la resistencia a los antibacterianos en Argentina: programa WHONET, 1995-1996 / Monitoring antimicrobial resistance in Argentina: the WHONET program, 1995-1996

La Organización Mundial de la Salud ha puesto en marcha un programa para la vigilancia de la resistencia a los antibacterianos, denominado WHONET, que se desarrolló en Argentina mediante una red de 23 laboratorios de instituciones hospitalarias públicas y privadas sometidos a programas nacionales e internacionales de control de calidad. Entre enero de 1995 y diciembre de 1996 se determinó por el método de difusión en agar la sensibilidad a los antibacterianos de 16.073 aislados clínicos consecutivos, siguiendo las recomendaciones del Comité Nacional de Estándares para Laboratorios Clínicos (National Committee for Clinical Laboratory Standards: NCCLS) de los Estados Unidos de América. Más de la mitad de los aislados urinarios de Escherichia coli fueron resistentes a la ampicilina, y más de 30 por ciento a la trimetoprima-sulfametoxazol. Cuando se comparó la sensibilidad de los aislados urinarios de pacientes ambulatorios y hospitalizados, se observó una marcada diferencia en los perfiles de actividad (porcentaje de microorganismos resistentes aislados en pacientes hospitalizados frente a pacientes ambulatorios) de la gentamicina (8 por ciento frente a 2 por ciento), la norfloxacina (6 por ciento frente a 2 por ciento) y las cefalosporinas de tercera generación (18 por ciento frente a 10 por ciento). Los aislados de Klebsiella pneumoniae recuperados de hemocultivos presentaron resistencia a las cefalosporinas de tercera generación y a la gentamicina en 71 y 60 por ciento de los casos, respectivamente. La proporción de Staphylococcus aureus resistentes a la oxacilina fue de 39 por ciento. Cerca de la mitad de los aislados de Enterococcus spp. presentaron resistencia de alto nivel a los aminoglucósidos, pero no se detectó resistencia los glicopéptidos. En nuestro medio, la ampicilina y la trimetoprima-sulfametoxazol no fueron apropiadas para el tratamiento de las diarreas; Shigella flexneri presentó mayor porcentaje de aislados resitentes a ambos fármacos (87 y 74 por ciento, respectivamente) que Shigella sonnei (47 y 71 por ciento, respectivamente). Se detectó resistencia a las cefalosporinas de tercera generación en 40 por ciento de los aislados de Salmonella spp. recuperados en hospitales pediátricos. En casos de meningitis bacteriana, las tasas de resistencia de Streptococcus pneumoniae a la penicilina (18 por ciento) y de Haemophilus influenzae a la ampicilina (19 por ciento) se situaron en el rango intermedio de las descritas en países

Actividad in vitro de trovafloxacina, otras fluoroquinolonas y de diferentes antimicrobianos frente a aislamiento clinicos / In vitro activity of trovafloxacin, of other fluoroquinolones and of related antimicrobials against clinical isolates

Se evaluó la actividad in vitro de trovafloxacina en comparación con la de otros antimicrobianos frente a 5671 aislamientos clínicos recuperados por instituciones representativas de diferentes provincias del país. Entre las enterobacterias, los porcentajes de resistencia a gentamicina y cefalosporinas de tecera generación fueron elevados: 17 por ciento y 16 por ciento respectivamente, con una variación considerable según la especie analizada. La resistencia a ciprofloxacina (CIP) y trovafloxacina (TRV) afectó a aproximadamente el 9 por ciento de los aislamientos, no observándose diferencias significativas entre ambas drogas. Sobre 166 aislamientos de Salmonella spp., 208 de Shigella flexneri y 76 de Shigella sonnei, las quinolonas fluoradas (QF) presentaron una excelente actividad: sólo 1 aislamiento de S. sonnei fue resistente a CIP, pero sensible a TRV. Alrededor de la mitad de los aislamientos de Salmonella spp. y S.sonnei y la casi totalidad de los de S. flexneri fueron resistentes a ampicilina y más del 60 por ciento de Shigella spp. presentaron resistencia a trimetoprima-sulfametaxazol. El 41 por ciento y 55 por ciento de los aislamientos de Staphylococcus aureus y Staphylococcus coagulasa negativa fueron resistentes a oxacilina presentando una elevada multirresistencia acompañante. La resistencia a QF también estuvo fuertemente asociada a la oxacilino-resistencia, pero la resistencia a TRV fue significativamente menor que a CIP: 9 por ciento vs 57 por ciento para S. aureus y 4 por ciento vs 41 por ciento para a Stafilococcus coagulasa negativa. Un comportamamiento similar se observó frente a Enterococcus spp., donde el 54 por ciento fue resistente a norfloxacina y sólo el 13 por ciento lo fue a TRV. No se detectaron aislamientos de Streptococcus pneumoniae (n=193) y Haemophilus influenzae (n=139) resistentes a TRV.