Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy.

BACKGROUND: Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). RESULTS: One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively. CONCLUSION: Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.

Genes involucrados con resistencia antimicrobiana en hospitales del Ecuador / Genes involved with antimicrobial resistance in Ecuadorian hospitals

INTRODUCCIÓN. La resistencia a los antimicrobianos es un problema de salud pública actual asociado con alta mortalidad, hospitalización prolongada, alternativas terapéuticas reducidas, mayores costos económicos y la posibilidad de brotes hospitalarios. OBJETIVO. Describir los principales genes involucrados con resistencia antimicrobiana en hospitales del Ecuador. MATERIALES Y MÉTODOS. Se realizó una descripción retrospectiva no experimental, de artículos indexados relacionados con resistencia antimicrobiana en hospitales del Ecuador, con evidencia desde el año 2009 al 2022. La revisión de bibliografías se llevó a cabo en bases de datos como Pubmed, Science Direct y Google Scholar. RESULTADOS. De un grupo original de 77 artículos, se seleccionaron 33 documentos. En Ecuador, varios estudios han descrito los mecanismos moleculares involucrados en la resistencia bacteriana. Sin embargo, en bacterias menos comunes, falta investigación sobre los genes asociados. CONCLUSIONES. Las principales bacterias multirresistentes descritas en Ecuador son Klebsiella pneumoniae, Escherichia coli y Acinetobacter baumanni, las cuales presentan genes involucrados en la producción de carbapenemasas (blaKPC, blaNDM, blaOXA-48). Estas bacterias presentan altos niveles de resistencia a los antibióticos y son objeto de vigilancia epidemiológica por parte del sistema nacional de salud. A nivel local, otras bacterias presentan mecanismos de resistencia a los carbapenémicos (Pseudomonas aeruginosa, Enterobacter sp., Serratia marcescens, Citrobacter sp.), pero no existen descripciones detalladas del genotipo, sus características microbiológicas o la clínica del paciente. El conocimiento de las tasas de resistencia a los antimicrobianos en los diferentes hospitales, la implementación de un plan de administración de antibióticos, el uso correcto de los equipos de protección personal, el aislamiento de las personas con infecciones multirresistentes, así como el trabajo colaborativo entre las diferentes áreas del hospital, son esenciales para reducir la propagación de estos patógenos.

INTRODUCTION. Antimicrobial resistance is a current public health problem associated with high mortality, prolonged hospitalization, reduced therapeutic alternatives, increased economic costs, and the potential for hospital outbreaks. OBJECTIVE. To describe the main genes involved with antimicrobial resistance in hospitals in Ecuador. MATERIALS AND METHODS. A retrospective non-experimental description of indexed articles related to antimicrobial resistance in hospitals in Ecuador was carried out, with evidence from 2009 to 2022. The review of bibliographies was carried out in databases such as Pubmed, Science Direct and Google Scholar. RESULTS. From an original group of 77 articles, 33 papers were selected. In Ecuador, several studies have described the molecular mechanisms involved in bacterial resistance. However, in less common bacteria, research on the associated genes is lacking. CONCLUSIONS. The main multidrug-resistant bacteria described in Ecuador are Klebsiella pneumoniae, Escherichia coli and Acinetobacter baumanni, which present genes involved in the production of carbapenemases (blaKPC, blaNDM, blaOXA-48). These bacteria present high levels of antibiotic resistance and are subject to epidemiological surveillance by the national health system. Locally, other bacteria present mechanisms of resistance to carbapenemics (Pseudomonas aeruginosa, Enterobacter sp., Serratia marcescens, Citrobacter sp.), but there are no detailed descriptions of the genotype, their microbiological characteristics or the patient's clinic. Knowledge of antimicrobial resistance rates in different hospitals, the implementation of an antibiotic stewardship plan, the correct use of personal protective equipment, the isolation of individuals with multidrug-resistant infections, as well as collaborative work between different areas of the hospital, are essential to reduce the spread of these pathogens.

Genomic Amplification of UBQLN4 Is a Prognostic and Treatment Resistance Factor.

Ubiquilin-4 (UBQLN4) is a proteasomal shuttle factor that directly binds to ubiquitylated proteins and delivers its cargo to the 26S proteasome for degradation. We previously showed that upregulated UBQLN4 determines the DNA damage response (DDR) through the degradation of MRE11A. However, the regulatory mechanism at DNA level, transcriptionally and post-transcriptional levels that control UBQLN4 mRNA levels remains unknown. In this study, we screened 32 solid tumor types and validated our findings by immunohistochemistry analysis. UBQLN4 is upregulated at both mRNA and protein levels and the most significant values were observed in liver, breast, ovarian, lung, and esophageal cancers. Patients with high UBQLN4 mRNA levels had significantly poor prognoses in 20 of 32 cancer types. DNA amplification was identified as the main mechanism promoting UBQLN4 upregulation in multiple cancers, even in the early phases of tumor development. Using CRISPR screen datasets, UBQLN4 was identified as a common essential gene for tumor cell viability in 81.1% (860/1,060) of the solid tumor derived cell lines. Ovarian cancer cell lines with high UBQLN4 mRNA levels were platinum-based chemotherapy resistant, while they were more sensitive to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi). Our findings highlight the utilities of UBQLN4 as a significant pan-cancer theranostic factor and a precision oncology biomarker for DDR-related drug resistance.

Anticoagulant rodenticide blood-clotting dose-responses and resistance factors for Tyrosine139Cysteine (Y139C) heterozygous- and homozygous-resistant house mice (Mus musculus).

BACKGROUND: The house mouse (Mus musculus) is a globally distributed rodent pest species against which anticoagulant rodenticides are widely used for the protection of human and animal health and the conservation of threatened wildlife. Anticoagulant-resistant house mice have been known for more than half a century. A house mouse strain was developed in the laboratory that was homozygous resistant for the single nucleotide polymorphism (SNP) Tyrosine139Cysteine (Y139C) and, subsequently, heterozygous resistant animals were produced from this strain by crossing with the homozygous susceptible strain. RESULTS: Using blood clotting response tests, resistance factors at the ED50 level in the homozygous resistant strain for the first-generation anticoagulants warfarin, chlorophacinone, diphacinone and coumatetralyl were in the range 31.5 to 628.0 for males (M) and 21.6 to 628.0 for females (F), thus indicating that Y139C house mice are substantially resistant to all these substances. Resistance factors at the ED50 level for the homozygous strain generated against the second-generation compounds were: brodifacoum (M, 1.7; F, 1.9), bromadiolone (M, 16.6; F, 21.0), difenacoum (M, 1.2; F, 2.7), difethialone (M, 1.5; F, 1.5), and flocoumafen (M, 0.9; F, 1.2). Equivalent values for the heterozygous strain were: brodifacoum (M, 1.6; F, 1.4), bromadiolone (M, 5.6; F, 6.5), difenacoum (M, 1.0; F, 1.3), difethialone (M, 1.1; F, 1.1), flocoumafen (M, 0.9; F, 1.1). CONCLUSION: Y139C SNP homozygous resistant mice are more resistant to anticoagulants than heterozygous resistant animals. All first-generation anticoagulants are highly resisted and, among the second-generation compounds, Y139C mice are resistant to bromadiolone and sometimes to difenacoum. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

T Cell Defects: New Insights Into the Primary Resistance Factor to CD19/CD22 Cocktail CAR T-Cell Immunotherapy in Diffuse Large B-Cell Lymphoma.

Despite impressive progress, a significant portion of patients still experience primary or secondary resistance to chimeric antigen receptor (CAR) T-cell immunotherapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The mechanism of primary resistance involves T-cell extrinsic and intrinsic dysfunction. In the present study, a total of 135 patients of DLBCL treated with murine CD19/CD22 cocktail CAR T-therapy were assessed retrospectively. Based on four criteria (maximal expansion of the transgene/CAR-positive T-cell levels post-infusion [Cmax], initial persistence of the transgene by the CAR transgene level at +3 months [Tlast], CD19+ B-cell levels [B-cell recovery], and the initial response to CAR T-cell therapy), 48 patients were included in the research and divided into two groups (a T-normal group [n=22] and a T-defect [n=26] group). According to univariate and multivariate regression analyses, higher lactate dehydrogenase (LDH) levels before leukapheresis (hazard ratio (HR) = 1.922; p = 0.045) and lower cytokine release syndrome (CRS) grade after CAR T-cell infusion (HR = 0.150; p = 0.026) were independent risk factors of T-cell dysfunction. Moreover, using whole-exon sequencing, we found that germline variants in 47 genes were significantly enriched in the T-defect group compared to the T-normal group (96% vs. 41%; p<0.0001), these genes consisted of CAR structure genes (n=3), T-cell signal 1 to signal 3 genes (n=13), T cell immune regulation- and checkpoint-related genes (n=9), cytokine- and chemokine-related genes (n=13), and T-cell metabolism-related genes (n=9). Heterozygous germline UNC13D mutations had the highest intergroup differences (26.9% vs. 0%; p=0.008). Compound heterozygous CX3CR1I249/M280 variants, referred to as pathogenic and risk factors according to the ClinVar database, were enriched in the T-defect group (3 of 26). In summary, the clinical characteristics and T-cell immunodeficiency genetic features may help explain the underlying mechanism of treatment primary resistance and provide novel insights into CAR T-cell immunotherapy.

Patrones de resistencia en agentes bacterianos involucrados en otitis caninas en Medellín, Colombia, durante 2019: análisis retrospectivo / Patterns of resistance in bacterial agents involved in canine otitis at Medellín, Colombia, during 2019: retrospective analysis

RESUMEN Dentro de los agentes patógenos en los procesos otíticos bacterianos, se destacan microorganismos como Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabi-lis, Escherichia coli, Corynebacterium spp., Enterococcus spp. y Streptococcus spp., para los cuales se ha descrito resistencia frente a los antibióticos empleados para combatirlos. En Colombia son pocos los reportes acerca de la resistencia antibiótica de microorganismos causantes de otitis. Por ello, el objetivo de esta investigación fue determinar los agentes bacterianos más frecuentemente aislados en infecciones otíticas de caninos remitidas a un laboratorio veterinario de Medellín durante el 2019 y su resistencia a antibióticos. Para llevarlo a cabo, se realizó un estudio descriptivo transversal retrospectivo. Se analizaron los resultados de los antibiogramas realizados a partir de cultivos bacterianos en muestras óticas remitidas a un laboratorio de referencia de la ciudad de Medellín. Además, se efectuó un análisis de frecuencias para la muestra total. Se encontró que los principales microorganismos bacterianos aislados fueron Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabili y Staphylococcus aureus. La gentamicina fue el medicamento que mayor porcentaje de resistencia presentó y la cefalexina el que menos resistencia presentó. Se pudo concluir que el Staphylococcus pseudintermedius está presente en más del 60% de los casos de otitis bacteriana. Adicionalmente, se observó una variación de la resistencia presentada por los microorganismos en el tiempo. Estos presentaron mayor resistencia ante los antibióticos aminoglucósidos.

ABSTRACT Among the pathogens in bacterial otic processes, microorganisms such as Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabilis, Escherichia coli, Corynebac-terium spp., Enterococcus spp., and Streptococcus spp. stand out, for which resistance to antibiotics has been described employed to combat them. In Colombia there are few reports about the antibiotic resistance of microorganisms that cause otitis. For that reason, the purpose of this study was to determine the bacterial agents most frequently isolated from canine ear infections and their resistance to antibiotics from samples of ear secretions sent to a veterinary laboratory in Medellín during 2019. In order to do that, an cross-sectional, retrospective descriptive study was done. The results of the antibiograms performed from bacterial cultures obtained from ear samples sent to a reference laboratory in the city of Medellín were analyzed. A frequency analysis was carried out for the total sample. It was found that the main isolated bacterial microorganisms were Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabili and Staphylococcus aureus. Gentamicin was the drug with the highest percentage of resistance and cephalexin the one with the least resistance. It was possible to conclude that Staphylococcus pseudintermedius is linked in more than 60% of cases of bacterial otitis and the resistance presented by microorganisms varies over time. The group of aminoglycosides antibiotics was the one which microorganisms are manifesting more percentage of resistance.

Model-based analysis of response and resistance factors of cetuximab treatment in gastric cancer cell lines.

Targeted cancer therapies are powerful alternatives to chemotherapies or can be used complementary to these. Yet, the response to targeted treatments depends on a variety of factors, including mutations and expression levels, and therefore their outcome is difficult to predict. Here, we develop a mechanistic model of gastric cancer to study response and resistance factors for cetuximab treatment. The model captures the EGFR, ERK and AKT signaling pathways in two gastric cancer cell lines with different mutation patterns. We train the model using a comprehensive selection of time and dose response measurements, and provide an assessment of parameter and prediction uncertainties. We demonstrate that the proposed model facilitates the identification of causal differences between the cell lines. Furthermore, our study shows that the model provides predictions for the responses to different perturbations, such as knockdown and knockout experiments. Among other results, the model predicted the effect of MET mutations on cetuximab sensitivity. These predictive capabilities render the model a basis for the assessment of gastric cancer signaling and possibly for the development and discovery of predictive biomarkers.

Carbapenemasas y sensibilidad a los antibióticos no ß-lactámicos en Klebsiella pneumoniae resistente a los carbapenémicos en un hospital de tercer nivel de complejidad. Quito ­ Ecuador / Carbapenemases and sensitivity to non-ß-lactam antibiotics in Klebsiella pneumoniae resistant to carbapenems in a third level hospital. Quito - Ecuador

INTRODUCCIÓN. La resistencia de Klebsiella pneumoniae a carbapenémicos ha aumentado con los años, reduciendo opciones terapéuticas. Puede deberse a dos mecanismos principales, como: la producción de carbapenemasas y alteración de la permeabilidad de la membrana. OBJETIVO. Analizar la frecuencia de Klebsiella pneumoniae resistente a carbapenémicos, junto al mecanismo de resistencia informado por el Laboratorio Nacional de Referencia y la sensibilidad a antibióticos usados para uso terapéutico. MATERIA-LES Y MÉTODOS. Estudio retrospectivo, de población y muestra conocida. Se determinó la sensibilidad/resistencia de Klebsiella pneumoniae: todos los datos aislados de Klebsiella pneumoniae. Se reportaron 11 809 bacilos gram negativos pertenecientes a la familia Enterobacteriaceae. Se utilizó el sistema Whonet 5.6 2017 y BacLink2, así como la revisión de los resultados enviados al Centro Nacional de Referencia para la Resistencia a los Antimicrobianos del Instituto Nacional de Investigación de Salud Pública Izquieta Pérez para investigación de carbapenemasas en el Hospital de Especialidades Carlos Andrade Marín,en el período abril 2016 a mayo 2018. RESULTADOS. El 20,5% (2 421; 11 809) correspondieron a Klebsiella pneumoniae y de estos, 32,9% (797; 2 421) mostraron resistencia a Meropenem. Existió mayor frecuencia en muestra de orina, secreción, sangre y aspirado traqueal. Predominó en varones de más de 61 años. Se clasificó en 15 grupos fenotípicos según los perfiles de resistencia a los antibióticos utilizados como alternativa terapéutica. CONCLUSIÓN. La presencia de Klebsiella pneumoniae produjo una carbapenemasa resistente a los medi-camentos utilizados como tratamiento, llevó a pensar en el uso de otros medicamentos como: fosfomicina o ceftazidima/viabactam; sin embargo, se desarrolló medidas de control y prevención de infecciones, así como programas para el uso de antibióticos.

INTRODUCTION. The resistance of Klebsiella pneumoniae to carbapenems has increased over the years, reducing therapeutic options. It can be due to two main mechanisms, such as: the production of carbapene-mases and alteration of membrane permeability. OBJECTIVE. Analyse the frequency of carbapenem-resistant Klebsiella pneumoniae, along with the resistance mechanism reported by the National Reference Laboratory and sensitivity to antibiotics used for therapeutic use. MATERIALS AND METHODS. Retrospective study, po-pulation and known sample. The sensitivity / resistance of Klebsiella pneumoniae was determined: all isolated were Klebsiella pneumoniae. 11 809 gram negative bacillus belonging to the Enterobacteriaceae family were reported. The Whonet 5.6 2017 and BacLink2 system was used, as well as the review of the results sent to the National Reference Center for the Antimicrobial Resistance of the National Institute of Public Health Research Izquieta Pérez for carbapenemases research at the Carlos Andrade Marín Speciality Hospital, in the period april 2016 to may 2018. RESULTS. 20,5% (2 421; 11 809) were Klebsiella pneumoniae and of these, 32,9% (797; 2 421) showed resistance to Meropenem. There was a higher frequency in urine sample, secretion, blood and tracheal aspiration. Predominance in males over 61 years old. It was classified into 15 phenotypic groups according to antibiotic resistance profiles used as a therapeutic alternative. CONCLUSION. The pre-sence of Klebsiella pneumoniae produced a carbapenemase drug-resistance used as treatment, leading to thought on the use of other medicines such as phosphomycin or ceftazidima/avibactam; however, infection control and prevention measures were developed, as well as programs for the use of antibiotics.

Escenario actual de la resistencia a la colistina mediada por plásmidos en América Latina / Current scenario of plasmid-mediated colistin resistance in Latin America

Colistin resistance can occur by chromosomal mutations and by acquisition of plasmid-carrying determinants, mainly mcr-1. In the recent years, we have observed the out-burst of this resistance gene in our region. Due to the risk of the rapid dissemination of mcr-1, this finding has worried and alerted different actors from the health field and has become one of the most prolific topics. Our review compiles available reports of well-documented mcr-1-positive strains of Enterobacteriaceae, obtained from different samples in Argentina and other countries of Latin America. Furthermore, it addresses the association of mcr-1 with ESBL resistance markers and outlines the platforms involved in their dissemination.

La resistencia a la colistina puede ocurrir por mutaciones cromosómicas o por la adquisición de determinantes localizados en plásmidos, el principal es mcr-1. En los últimos años hemos observado la explosiva aparición de este gen de resistencia en nuestra región. Debido al riesgo que implica la rápida diseminación de mcr-1, este hallazgo ha preocupado y alertado a los diferentes actores del área de la salud, y se ha convertido en uno de los temas de investigación más importantes. La presente revisión compila los informes de aislamientos portadores de mcr-1 debidamente documentados en Enterobacteriaceae, obtenidos de diferentes muestras en Argentina y otros países de América Latina. Además, aborda la asociación de mcr-1 con otros marcadores de resistencia, como las BLEE, y describe las plataformas involucradas en su diseminación.

Factores asociados al desarrollo de tuberculosis pulmonar multidrogoresistente en el departamento de Piura, Perú 2009-2014 / Associated factors with the development of multidrug resistant pulmonary tuberculosis in the department of Piura, Peru 2009-2014

Objetivo: Conocer los factores socio-económicos asociados para el desarrollo de tuberculosis pulmonar (TB) multidrogo resistente (MDR) en la población piurana durante los años 2009-2014. Materiales y métodos: Estudio observacional en pacientes con TB-MDR y no MDR. Se tomaron los datos de los expedientes de la Estrategia Sanitaria Prevención y Control de Tuberculosis, de la Dirección Regional de Salud del departamento de Piura. Se realizó un análisis estadístico de asociación y sus intervalos de confianza, con el uso de modelos lineales generalizados. Resultados: Los factores que tuvieron asociación a la TB-MDR fueron el ser diagnosticados como fracaso de tratamiento al ingreso, el tener un contacto con un paciente TB-MDR/XDR, el que haya tenido un tratamiento irregular, el ser catalogado como fracaso comprobado, el haber tenido un antecedente de tratamiento y que este tratamiento haya sido con varias drogas. En el análisis multivariado, el único que mantuvo la asociación fue el antecedente de ser paciente multitratado RP=4,47 (IC95%: 1,28-15,63). Conclusiones: El haber sido multitratado mostró una gran asociación con la mayor frecuencia de desarrollar TB-MDR, por lo que puede ser tomado en cuenta como un estudio base, desarrollado en una ciudad del norte del Perú y que comparte características con otras ciudades nacionales y de otros países de realidades similares.

Objetive: To know the associated socio-economic factors for the development of multidrug-resistant (MR) pulmonary tuberculosis (PT) in Piurana population during the years 2009-2014. Materials and methods: Observational study in patients with PT MR and non MR. Data from the records of the Tuberculosis Prevention and Control Strategy of the Regional Health Department of the department of Piura were taken. A statistical analysis of association and its confidence intervals was performed, with the use of generalized linear models statistics and their confidence intervals, with the use of generalized linear models. Results: Factors that had an association with PT MR were diagnosed as treatment failure at admission, having a contact with a MR/XDR PT patient, who had an irregular treatment, being classified as a proven failure, having a history of treatment and that this treatment was with several drugs. In the multivariate analysis, the only one who maintained the association was the antecedent of being a multi-treated patient, had an PR = 4.47 (95% CI: 1.28-15.63). Conclusions: Being multi-treated showed a great association with the greater frequency of PT MR, so it can be taken into account as a baseline study, developed in a city in northern Peru and that shares characteristics with other cities and other countries with similar realities.

Factors associated with the efficiency of acaricides on different populations of Rhipicephalus microplus / Fatores associados à eficiência de acaricidas sobre diferentes populações de Rhipicephalus microplus

Tick infestation causes major problems in cattle. Tick parasitism accounts for significant economic losses in many beef and dairy herds in the vast majority of the states in the Brazilian territory including the State of Santa Catarina in the southern region of the country. Tick resistance to several active principles occurs due to a number of factors including the indiscriminate, injudicious and inadequate use of tick insecticides. Considering the great importance of fighting off tick infestations in cattle, we evaluated the efficiency of 8 different topical active principles against the ixodid tick R. microplus and identified the main factors that contribute to the development of ticks that are resistant to acaricides in the farms and bovine herds studied. For such purpose, R. microplus telegionae were collected in 39 farms locates in different municipalities of the West of Santa Catarina, south Brazil. At the time of sample collection, information about the management, the history of the acar used in the herd, the number of annual applications of these pesticides, the frequency of acaricide rotation, and the frequency of technical monitoring for strategic tick control were retrieved. We collected this data in order determine contributing factors to the development resistant R. microplus populations. For the sensitivity profile of these ticks to a number of different acaricides tested, 10 engorged females for each principle and a control were used. The results of our study show that most associations between pyrethroids and organophosphates had an efficiency between 96.6% and 100% in the control of R. microplus except for the combination of Alfacipermetrine 15%, Ethion 16%, and Chlorpyrifos 8.5% that had 93.4% of efficiency. Among the chemicals not associated with any other type of compound, Amitraz 12.5% ​​was effective in 98.3% of the cases. In contrast, Cypermethrin 15% had an efficiency in only 25.8% of the farms/herds analyzed. Based on the results of the present study, we may infer that the methods of control and management used by producers may be related to the low indexes of resistance to topical acaricides in the different populations of ticks in the study area.

A infestação por carrapatos em bovinos gera grandes problemas, sendo esse parasito responsável por elevados prejuízos econômicos em diversos rebanhos de produção de corte e também de leite na maioria das regiões brasileiras, inclusive em Santa Catarina. A resistência dos carrapatos frente aos diversos princípios ativos pode ser decorrente de fatores como o uso indiscriminado de carrapaticidas, bem como a inadequada forma de aplicação dos mesmos. Tendo em vista a grande importância em combater essas infestações, buscou-se avaliar a eficiência de oito diferentes princípios ativos de contato contra o carrapato Rhipicephalus microplus, bem como identificar os principais fatores que possam contribuir com a seleção de carrapatos resistentes nas propriedades avaliadas. Para isso, teleóginas de R. microplus foram coletadas em 39 propriedades de diferentes municípios do Oeste de Santa Catarina. No momento da coleta também foram obtidas informações referentes ao sistema de manejo dos animais, histórico dos carrapaticidas utilizados, número de aplicações anuais, frequência de rodízios de acaricidas, e frequência de acompanhamento técnico para controle estratégico, com a finalidade de evidenciar os diferentes fatores que possam estar contribuindo para o surgimento de eventual resistência das populações do R. microplus. A avaliação de suscetibilidade foi realizada através da técnica de biocarrapaticidograma, utilizando 10 teleóginas ingurgitadas para cada princípio e mais o controle. Dentre os principais resultados obtidos, a maioria das associações entre piretróides e organofosforados demonstraram ter eficiência entre 96,6% e 100%, com exceção da associação de Alfacipermetrina 15%, Ethion 16% e Clorpirifós 8,5% com 93,4% de eficiência. Dentre as bases químicas sem nenhum tipo de associação o Amitraz 12,5% demonstrou ser eficaz em 98,3%, em contrapartida a Cipermetrina 15% teve eficiência em apenas 25,8% das propriedades analisadas. A partir dos resultados obtidos, pode se afirmar que as formas de controle e manejo adotados pelos produtores podem estar relacionadas com os baixos índices de resistência aos carrapaticidas de contato, nas diferentes populações de carrapato na região do estudo.

Análise dos mecanismos de resistência relacionados às enterobactérias com sensibilidade diminuída aos carbapenêmicos isoladas em um hospital de referência em doenças infecto-contagiosas / Analysis of resistance mechanisms related to enterobacteria with decreased susceptibility to carbapenems isolated from a referral hospital in infectious diseases

Objetivo: Dentre os mecanismos de resistência aos carbapenêmicos, a produção de carbapenemases tem o impacto mais significativo na saúde humana. Esse trabalho tem como objetivo analisar os mecanismos de resistência relacionados às enterobactérias com sensibilidade diminuída aos carbapenêmicos isoladas no Hospital Eduardo de Menezes da Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Brasil. Métodos: Trata-se de um estudo retrospectivo das cepas de enterobactérias onde houve a detecção fenotípica de provável produção de carbapenemases e análise molecular. Resultados: Esse estudo mostrou que a principal carbapenemase encontrada entre os isolados foi a KPC, no entanto chama a atenção o isolamento de uma cepa produtora de NDM. Conclusão: A detecção de carbapenemases codificadas em elementos móveis reforça a necessidade de uma vigilância epidemiológica constante na instituição.

Infecciones intrahospitalarias en una unidad de cuidados intensivos: epidemiología y tratamiento empírico / Nosocomial infections at the ICU: Epidemilogy and empirical treatment

Hon en día entre el 5-10% de los pacientes que ingresan a un hospital adquiere una infección nosocomial, 20% de estas son reportadas en la Unidad de Cuidados Intensivos. La incidencia es 2 a 5 veces más alta que en otros servicios hospitalarios. Objetivos: Describir la epidemiología de los patógenos intrahospitalarios en la Unidad de Cuidados Intensivos y su resistencia antibiótica. Material y métoos: Estudio transversal. La información se obtuvo de expedientes en la Unidad de Cuidados Intensivos siendo considerados solos los pacientes que desarrollaron una infección nosocomial. Resultados: Un total de 35 muestras fueron analizadas, dos grupos se obtuvieron, 24 gram positivos y 11 gram negativos. La edad media de los pacientes fue de 41.79 (78-18) ± 21.22 años. El principal sitio de infección reportado en ambos grupos, gram-negativos y gram-positivos fue la vía respiratoria baja en un 58,.3% y 81.1% respectivamente. Para el grupo de gram negativos los tres principales organismos aislados en los cultivos fueron: Klebsiella pneumoniae in 29.2% (n=7)., Acinetobacter baumanii en 25% (n=6) y Pseudomonas aeruginosa en 16.7% (n=4) por otra parte para el grupo de gram positivos la principal bacteria aislada fue: Enterococcus facalis in 27.3% (n=3). A su vez, con respecto al tratamiento inicial en el grupo de gram negativos fue en un 79.2% con dos o más antibióticos, 16.7% con ceftriaxona y 4.2% con cefazolina. Aunado a ello el tratamiento inicial para el grupo de gram positivos en ocho casos, dos o más antibióticos fueron usados, en 2 metropenem fue usado y en uno con ceftriaxona. En relación con la resistencia antibiótica para gram negativos el principal fue para ampicilina y ceftriaxona en un 100%, cefazolina y aztreonam en un 95.8%. A su vez par el grupo de gram positivos, los antibióticos asociados a resistencia fueron eritromicina y claritromicina en un 90.9%. Conclusión: De esta investigación, los médicos podrán orientarse en esta unidad, para el tratamiento de las infecciones nosocomiales, las guías nacionales establecen que el tratamiento empírico debe ser realizado con el conocimiento de las resistencias bacterianas a antibióticos

Nowadays, between 5-10% of the general in-patient hospital population gets a nosocomial inflection, 20% of these infections are reported in the Intensive Care Unit. It has been reportd that the incidence of nosocomial infections at the Intensive Care Unit is about 2 to 5 times higher than in other hospital services. Objectives: Describe the epidemiology of intrahospital pathogens in the Intensive Care Unit and their antimicrobial resistance. Material and methods: Cross-sectional study. Information was obtained from medical records of patients at the Intensive Care Unit considering only the ones whom developed a nosocomial infection. Thirty-five samples were considered, from these, two groups, were obtained. The period of time considered for this study was from June to December 2016 at the High Specialty Medical Unit, Hospital of Trauma and Orthopedic of the Instituto Mexicano del Seguro Social (IMSS). Results: A total of 35 samples were analyzed, two groups were obtained, 24 gram positive and 11 gram negative. The mean age of the patients was of 41.79 (78-18) ±21.22 years old. Principal site of infection reported in both groups, gram- negative and gram-positive was the respiratory low tract in a 58.3% and 81.1% respectively. For gram negative group three main organisms were isolated in cultures Klebsiella pneumoniae in 29.2% (n=7). Acinetobacter baumannii in 25% (n=6) and Pseudomonas aeruginosa in a 16.7% (n=4) besides for gram pisitive group the main bactria isolated in cultures was. Enterococcus faecalis in 27.3% (n=3). On the other band, corresponding to initial treatment in gram negative group 79.2% were treated sith two or more antibiotics, 16.7% with ceftriaxone and 4.2% with cefazolin. In addition to initial treatment for gram positive group in 8 cases, 2 or ore antibiotics were used, in 2 meropenem was used and 1 with ceftriaxone. In relation to antibiotic resistance for gram negative group the greatest was for ampicillin and ceftriaxone with a 100% resistance, cefazolin and aztreonam in a 95.8%. As well, for gram positive group, antibiotics associated with resistance were erythomycin and clarithromycin 980.9%. Conclusion: From this investigation, medical practitiioners could be oriented for the treatment of nosocomial infections in this unit, as a matter of fact national guidelines establish that empirical treatmente should be assed with the knowledge of the microorganism's resistences

Resistance of Corynebacterium pseudotuberculosis in the Brazilian semiarid environment / Resistência de Corynebacterium pesudotuberculosis no ambiente do semiárido brasileiro

The semiarid northeast of Brazil contains a unique biome known as caatinga, with a maximum temperature of 40 ºC and a relativity humidity of 56%. The caatinga is characterized by a variety of plants, including Cereus jamacaru Dc (mandacaru), Poincianella microphylla Mart. ex G. Don (catingueira), Pilosocereus gounellei FAC Weber (xique-xique) and Mimosa tenuiflora (Willd.) Poir (jurema preta). Sheep and goat industries are economically strong in that region, despite the fact that caseous lymphadenitis is highly prevalent. The aim of the present study was to assess the survival and biofilm production of Corynebacterium pseudotuberculosis isolates in the environment and under controlled temperatures (28°C, 37°C and 42°C) under different surfaces (plants, soil, wood, wire and thorns). In addition, we investigated the effects of applying the disinfectants chlorhexidine, hypochlorite and quaternary ammonia in soil, tiles, wood and vegetation cover. Four strains of C. pseudotuberculosis were selected (two from goats and two from sheep) for inoculation according to their in vitro biofilm production. Adherence to microplates was used to assess the biofilm-forming ability of the bacteria. Lower survival rates were observed when isolates of C. pseudotuberculosis were subjected to a temperature of 42°C. In terms of caatinga biome plants, contamination of jurema-preta plants resulted in the lowest survival rates. The disinfectant quaternary ammonia promoted a lower inoculum survival in all surfaces. The disinfectants and the higher temperature contributed to the reduction of biofilm production in isolates of C. pseudotuberculosis. knowledge of these patterns is important for the establishment of disease control measures, given the questionable efficacy of the treatment and the immuno-prophylaxis of caseous lymphadenitis.(AU)

O semiárido nordestino do Brasil possui um bioma exclusivo, a caatinga, que apresenta temperatura máxima de 40oC e uma umidade relativa do ar de 56%. A caatinga é caracterizada por uma diversidade de plantas, entre elas Cereus jamacaru DC. (mandacaru), Poincianella microphylla Mart ex G. Don (catingueira), Pilosocereus gounellei F.A.C. Weber (xique-xique) e Mimosa tenuiflora (Willd.) Poir (jurema preta). A produção de ovinos e caprinos está em franca expansão, porém a linfadenite caseosa é uma enfermidade de alta prevalência na região. Objetiva-se com o presente estudo, verificar a sobrevivência e produção de biofilme em isolados de Corynebacterium pseudotuberculosis em temperaturas de 28oC, 37oC e 42oC, quando inoculado em superfícies de solo, madeira, arame e espinho e em plantas nas condições ambientais da caatinga. Além disto, foi verificado o efeito da aplicação dos desinfetantes clorexidine, hipoclorito e amônia quaternária sobre o solo, piso (lajota), madeira e vegetação de cobertura do solo. Foram selecionadas quatro amostras de C. pseudotuberculosis (dois caprinos e dois ovinos) para inoculação de acordo com a sua produção in vitro de biofilme. A adesão a microplacas foi utilizado para avaliar a capacidade de formação de biofilme das bactérias. As menores taxas de sobrevivência foram observadas quando isolados de C. pseudotuberculosis foram submetidos a uma temperatura de 42°C. Com relação as plantas do bioma caatinga, a contaminação na planta jurema-preta apresentou menores índices de sobrevivência. O desinfetante amônia quartenária promoveu uma menor sobrevivência do inóculo em todas as superfícies. Os desinfetantes e temperatura contribuíram para a redução na produção de biofilme nos isolados de Corynebacterium pseudotuberculosis. O conhecimento destes padrões é importante para o estabelecimento de medidas de controle da enfermidade, dada a eficiência questionável do tratamento e imunoprofilaxia da linfadenite caseosa.(AU)

Avaliação de mutações de resistência ao tratamento com análogos de nucleos(t)ídeos e de escape vacinal do vírus da hepatite B (VHB) em pacientes com hepatite crônica / Evaluation of treatment resistance mutations with nuclei analogues (t) ide and vaccine escape the hepatitis B virus (HBV) in patients with chronic hepatitis

INTRODUÇÃO: A hepatite B (VHB) é uma infecção dinâmica crônica, que apesar de existir programas de imunização e tratamento antiviral disponível, existe o risco de emergência de mutações de resistência aos análogos de núcleos(t)ídeos (AN) que devem ser rastreadas, devido as suas implicações clínicas. O Brasil disponibiliza pelo SUS cinco drogas para o tratamento antiviral: IFN, LAM, ADF, ETV e TDF e um guia de conduta clínica para orientar o tratamento no território nacional, o Protocolo de Diretrizes Terapêuticas para Hepatite B e co-infecções. OBJETIVO: O objetivo do presente estudo foi avaliar as mutações de resistência aos AN, mutações de escape vacinal e genótipos circulantes em pacientes com hepatite B crônica em dois centros de referencia em Hepatites, na Bahia (região Nordeste) e no Acre (região Norte) do Brasil. MATERIAL E MÉTODOS: Foi utilizadas ferramentas de biologia molecular e bioinformática, através de nested PCR e sequenciamento direto das amostras, para rastrear as mutações de resistência, a região alvo foi a transcriptase reversa (RT) do gene P e as mutações de escape vacinal foi a região do gene S do VHB, como também os genótipos e subgenotipos do VHB. RESULTADOS: Foram incluídos 527 pacientes durante o período de 2011-2015, sendo 320 pacientes do HUPES/BA e 207 do FUNDHACRE/AC. Os pacientes que representam a região Nordeste foram 59,3 % do sexo masculino e uma média de idade de 44,75±12,4 DP, os pacientes da região Norte 42% foram do sexo masculino e a média de idade foi de 40,36±13,9 DP. Todos os pacientes incluídos apresentaram AgHBs persistente por mais de seis meses e 86,1% apresentaram AgHBe negativo. Foram sequenciadas 296 amostras dos pacientes com VHB crônica. Foram encontradas mutações de resistência aos AN na Região Norte 1,2% (2), Região Nordeste 7,4%(8) e no global 3,8%(20). Os padrões de mutações de resistência primária encontrados foram: rtA194T, (3) rtL180M+M204V, rtL180M+M204I, rtS202I, rtM204I, rtA181S, rtA181E e rtA184S. Em relação ao escape vacinal a frequencia para a Região Norte foi de 7,1% (11), Região Nordeste 8,4% (9) e no global 7,6% (20). Nos pacientes virgens de tratamento (n=189), a frequência de mutações de resistência foi de 6%, somente nas amostras da região Nordeste. Não houve diferença estatisticamente significante entre o grupo com ou sem mutação dos pacientes virgens de tratamento. Não foram encontradas mutações de resistência nas amostras da região Norte. Os genótipos circulantes nas duas regiões foram A, D e F, e a região Nordeste foi encontrada o genótipo C (C2). CONCLUSÃO: Os resultados demonstram a importância de rastrear e monitorar as mutações de resistência aos AN e de escape vacinal devido a importância epidemiológica e clínica na conduta terapêutica.

INTRODUTION: Hepatitis B virus (HBV) is a chronic dynamic infection, which although there immunization programs and antiviral therapy available, there is a risk of emergence of resistance mutations cores analogs (t) ide to be screened, because of their implications clinics. The Brazil offers the SUS five drugs for antiviral treatment: IFN, LAM, ADF, ETV and TDF and clinical guide of conduct to guide treatment in the country, the Therapeutic Guidelines Protocol for Hepatitis B and coinfections. AIM: The aim of this study was to evaluate the resistance mutations core analogues (t) ide, vaccine escape mutations and circulating genotypes in patients with chronic hepatitis B in two reference centers in Hepatitis, Bahia (Northeast) and Acre (Northern region) of Brazil. MATERIAL AND METHODS: Was used tools of molecular biology and bioinformatics by nested PCR and direct sequencing of samples to track resistance changes, the target region is the reverse transcriptase (RT) P gene and vaccine escape mutations was region of the gene S of HBV, as well as the HBV genotypes and subgenotipos. RESULTS: 527 patients were included during the period 2011-2015, with 320 patients HUPES / BA and 207 FUNDHACRE / AC. Patients representing the Northeast were 59.3% male and an average age of 44.75 ± 12.4 PD patients in the northern region 42% were male and the average age was 40, 36 ± 13.9 DP. All patients had persistent HBsAg for more than six months and 86.1% were HBeAg negative. We were sequenced 296 samples from patients with chronic HBV. the cores of similar resistance mutations were found (t) ide in the North 1.2% (2), Northeast 7.4% (8) and 3.8% overall (20). The patterns of primary resistance mutations were: rtA194T (3) rtL180M + M204V, M204I + rtL180M, rtS202I, rtM204I, rtA181S, and rtA181E rtA184S. Regarding vaccine escape the frequency for the Northern Region was 7.1% (11), Northeast 8.4% (9) and the global 7.6% (20). In treatment-naïve patients (n = 189), the frequency of resistance mutations was 6%, only the samples in the Northeast. There was no statistically significant difference between the groups with or without mutation of naive patients. There were no resistance mutations in samples from the North. Circulating genotypes in the two regions A, D and F, and the Northeast found the C genotype (C2). CONCLUSION: The results demonstrate the importance of tracking and monitoring the resistance mutations similar cores (t) ide and vaccine escape due to epidemiological and clinical importance in the therapeutic approach.

Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5α

A spontaneous fluoroquinolone-resistant mutant (STM1) was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi) clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5α and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A) conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5α, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5α, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5α.

Infección por neisseria gonorrhoeaey fenotipos de resistencia antimicrobiana,Mar del Plata, 2005-2010 / Neisseria gonorrhoeae infection and phenotypes of antimicrobial resistance, Mar del Plata, 2005-2010 / Infecção por Neisseria gonorrhoeae e fenótipos de resistência antimicrobiana, Mar del Plata, 2005-2010

Se realizó un estudio epidemiológico de tipo descriptivo retrospectivo, para determinar la tasa de infección por Neisseria gonorrhoeae y sus fenotipos de resistencia a los antimicrobianos, en 666 pacientes adultos de ambos sexos que asistieron al servicio al Servicio de ITS del Instituto Nacional de Epidemiología "Dr. Juan H. Jara"- ANLIS "Dr. Carlos G. Malbrán", de la ciudad de Mar del Plata, entre los años 2005-2010. Para el diagnóstico de infección por N. gonorrhoeae, las muestras fueron obtenidas por hisopados endocervicales e hisopados uretrales a varones y luego cultivadas. Los aislamientos fueron remitidos al Laboratorio Nacional de Referencia en ITS para completar el estudio de sensibilidad antimicrobiana. Se obtuvo una tasa de infección por N. gonorrhoeae del 12,2% [IC 95%: 9,83-14,95]. Los fenotipos de resistencia más prevalentes resultaron QRNG/CMRNG (resistencia a quinolonas conjuntamente con resistencia cromosómica a penicilina y tetraciclina), QRNG (resistencia a quinolonas), PPNG (cepa productora de penicilinasa) y CMTR (resistencia cromosómica a tetraciclina). En el marco de la vigilancia epidemiológica de las infecciones producidas por N. gonorrhoeae, el rol del laboratorio consiste no sólo en monitorear la incidencia de casos en la población sino también el perfil de resistencia a los antibióticos de uso terapéutico, a fin de controlar la enfermedad.

An epidemiological retrospective descriptive study was conducted in order to determine the rate of Neisseria gonorrhoeae infection and the antimicrobial resistance phenotypes in 666 adult patients of both sexes who attended the Sexually Transmitted Disease Service, at the National Institute of Epidemiology "Dr. Juan H. Jara"- ANLIS city of Mar del Plata, between the years 2005- 2010. For the diagnosis of N. gonorrhoeae infection, samples were obtained by endocervical swabs and urethral swabs in men. Microbiological growth on selective culture medium was identified using carbohydrate utilization. N. gonorrhoeae isolates were subsequently submitted to the National Reference Laboratory in STI for the study of antimicrobial susceptibility by determining the minimum inhibitory concentration. The N. gonorrhoeae infection rate was 12.2% [CI 95%: 9.83-14.95]. The most prevalent resistance phenotypes were QRNG/CMRNG (quinolone resistance in addition to chromosomal resistance to penicillin and tetracycline), QRNG (resistance to quinolone), PPNG (penicillinase producing strain) and CMTR (chromosomal resistance to tetracycline). As part of the epidemiological surveillance of infections by N. gonorrhoeae, the role of the laboratory is not only to monitor the incidence of cases in the population but also the antibiotic resistance profile for therapeutic use, in order to control the disease.

Um estudo epidemiológico de tipo descritivo retrospectivo foi realizado para determinar a taxa de infecção por Neisseria gonorrhoeae e seus fenótipos de resistência aos antimicrobianos em 666 pacientes adultos de ambos os sexos que compareceram no Serviço de ITS do Instituto Nacional de Epidemiología "Dr. Juan H. Jara, ANLIS "Dr. Carlos G. Malbrán" da cidade de Mar del Plata, entre os anos de 2005-2010. Para o diagnóstico de infecção por N. gonorrhoeae, as amostras foram obtidas por esfregaços endocervicais e esfregaços uretrais em homens e em seguida cultivadas. Os isolados foram encaminhados para o Laboratório Nacional de Referência em ITS para completar o estudo da sensibilidade antimicrobiana. Uma taxa de infecção de 12,2% em N. gonorrhoeae [IC 95%: 9,83-14,95] foi obtida. Os fenótipos de resistência mais prevalentes foram QRNG/CMRNG (resistência às quinolonas em conjunto com a resistência cromossômica à penicilina e tetraciclina), QRNG (resistência a quinolonas), PPNG (cepa produtora de penicilinase) e CMTR (resistência cromossômica à tetraciclina). Sob o controle epidemiológico das infecções produzidas por N. gonorrhoeae, o papel do laboratório é não só monitorar a incidência de casos na população, mas também o perfil de resistência aos antibióticos de uso terapêutico, visando a controlar a doença.

Resistencia antibiótica del Helicobacter pylori en América Latina y el Caribe / Antibiotic Resistance of Helicobacter pylori in Latin America and the Caribbean

El tratamiento de la infección por Helicobacter pylori continúa siendo un problema no resuelto en la práctica clínica con un alto porcentaje de fallas en su erradicación; la principal causa es la resistencia antibiótica que varía dependiendo del área geográfica estudiada. Se han desarrollado diversas técnicas para el estudio de la sensibilidad in vitro, pero su utilización en la práctica clínica es difícil de aplicar y costosa. También es importante reconocer que no siempre esta tiene una relación directa con los estudios in vivo pero pueden contribuir a mejorar los resultados de erradicación. En el presente artículo se revisan los mecanismos de resistencia y los artículos publicados en América Latina, sobre resistencia in vitro a los antibióticos más empleados en los esquemas de erradicación. La revisión encontró 35 estudios en Latinoamérica con un total de 3.358 aislados. Las técnicas de sensibilidad empleadas en los estudios de la región fueron E-test 48%, dilución en agar 37% y la difusión en agar 8%. Los estudios presentan bastante heterogeneidad con importantes diferencias entre los países de la región e incluso en estudios realizados en un mismo país. La resistencia in vitro, parametronidazol fue de 65,7%, para amoxicilina de 6,5%, para claritromicina de 14%, para tetraciclina de 8,3%, para levofloxacina de 39% y para furazolidona de 6,9%.

Treatment of Helicobacter pylori infections remains an unsolved problem in clinical practice because of the high percentage of failures to eradicate the bacteria. The main cause is that antibiotic resistance varies with the geographical area under study. Several techniques have been developed to study the bacteria’s sensitivity in vitro, but they are difficult to use in clinical practice, and they are costly. It is also important to recognize that sensitivity in vitro is not always directly related to sensitivity in vivo. Nevertheless, these techniques can help improve the results of eradication. This article reviews the mechanisms of resistance and reviews articles published in Latin America on in vitro resistance to the antibiotics most frequently used in eradication schemes. The review found 35 studies in Latin America with a total of 3,358 isolates. Forty-eight percent of the studies used the E-test for sensitivity, 37% used agar dilution, and 8% used agar diffusion. The studies show considerable heterogeneity with important differences among countries in the region and even among studies in the same country. In vitro resistance to metronidazole was 65.7%, in vitro resistance to amoxicillin was 6.5 in vitro resistance to clarithromycin was 14%, in vitro resistance to tetracycline was 8.3% to, in vitro resistance to levofloxacin was 39% and in vitro resistance to furazolidone was 6.9%.

Transfer of the amino-terminal nuclear envelope targeting domain of human MX2 converts MX1 into an HIV-1 resistance factor.

UNLABELLED: The myxovirus resistance 2 (MX2) protein of humans has been identified recently as an interferon (IFN)-inducible inhibitor of human immunodeficiency virus type 1 (HIV-1) that acts at a late postentry step of infection to prevent the nuclear accumulation of viral cDNA (C. Goujon et al., Nature 502:559-562, 2013, http://dx.doi.org/10.1038/nature12542; M. Kane et al., Nature 502:563-566, 2013, http://dx.doi.org/10.1038/nature12653; Z. Liu et al., Cell Host Microbe 14:398-410, 2013, http://dx.doi.org/10.1016/j.chom.2013.08.015). In contrast, the closely related human MX1 protein, which suppresses infection by a range of RNA and DNA viruses (such as influenza A virus [FluAV]), is ineffective against HIV-1. Using a panel of engineered chimeric MX1/2 proteins, we demonstrate that the amino-terminal 91-amino-acid domain of MX2 confers full anti-HIV-1 function when transferred to the amino terminus of MX1, and that this fusion protein retains full anti-FluAV activity. Confocal microscopy experiments further show that this MX1/2 fusion, similar to MX2 but not MX1, can localize to the nuclear envelope (NE), linking HIV-1 inhibition with MX accumulation at the NE. MX proteins are dynamin-like GTPases, and while MX1 antiviral function requires GTPase activity, neither MX2 nor MX1/2 chimeras require this attribute to inhibit HIV-1. This key discrepancy between the characteristics of MX1- and MX2-mediated viral resistance, together with previous observations showing that the L4 loop of the stalk domain of MX1 is a critical determinant of viral substrate specificity, presumably reflect fundamental differences in the mechanisms of antiviral suppression. Accordingly, we propose that further comparative studies of MX proteins will help illuminate the molecular basis and subcellular localization requirements for implementing the noted diversity of virus inhibition by MX proteins. IMPORTANCE: Interferon (IFN) elicits an antiviral state in cells through the induction of hundreds of IFN-stimulated genes (ISGs). The human MX2 protein has been identified as a key effector in the suppression of HIV-1 infection by IFN. Here, we describe a molecular genetic approach, using a collection of chimeric MX proteins, to identify protein domains of MX2 that specify HIV-1 inhibition. The amino-terminal 91-amino-acid domain of human MX2 confers HIV-1 suppressor capabilities upon human and mouse MX proteins and also promotes protein accumulation at the nuclear envelope. Therefore, these studies correlate the cellular location of MX proteins with anti-HIV-1 function and help establish a framework for future mechanistic analyses of MX-mediated virus control.

Hipertensión arterial resistenteEstrategias de tratamiento y papel de la terapia de denervación simpática renal / Resistant hypertension Treatment strategies and role of renal sympathetic denervation therapy

Resumen Introducción: la hipertensión arterial (HTA) es una de las enfermedades crónicas de mayor prevalencia en el mundo, es así como se estima que afecta a 77.9 millones de americanos mayores de 20 años, de los cuales 78% eran conscientes de su diagnóstico, 68% usaron medicación antihipertensiva, pero tan solo 64% de los pacientes tratados estaban controlados. Métodos: se realizó una búsqueda sistemática de la literatura científica en las bases de datos PUBMED, SCIELO y EMBASE, de artículos primarios y secundarios con una estrategia definida, limitados a idioma español e inglés, utilizando diversas combinaciones de términos libres y tipo Mesh que incluyeron: hipertensión arterial resistente, hipertensión arterial secundaria, pseudorresistencia y denervación simpática renal Resultados: la HTA resistente se define como aquella que permanece fuera de metas, >140/90 mmHg en población general, luego del uso de tres agentes antihipertensivos de diferentes clases, en dosis óptimas y donde uno de ellos es un diurético. También se incluyen pacientes que a pesar de estar controlados, requieren del uso de cuatro medicamentos o más. La tasa de HTA resistente se ha incrementado en los últimos años, de la mano de la obesidad y la diabetes. El fenómeno está relacionado con causas secundarias, pseudorresistencia e hiperactividad simpática. La búsqueda y control de estos factores en conjunto con la optimización del manejo médico, constituyen el pilar fundamental del tratamiento. En pacientes que no se controlan adecuadamente a pesar de estas medidas, la terapia de denervación simpática renal se convierte en un arma terapéutica efectiva. Conclusión: la prevalencia de la HTA resistente ha aumentado en forma significativa en la última década. El manejo médico óptimo y la consideración de la terapia de denervación simpática renal se convierte en la piedra angular del tratamiento. (Acta Med Colomb 2014; 39: 57-63).

Abstract Introduction: hypertension ( HT) is one of the most prevalent chronic diseases in the world, and affects an estimated 77.9 million Americans over 20 years old, of which 78% were aware of their diagnosis, 68 % used antihypertensive medication , but only 64% of the treated patients were controlled. Methods: a systematic search of the scientific literature on the basis of PUBMED , SCIELO and EMBASE data of primary and secondary items with a defined strategy limited to Spanish and English was performed using various combinations of free terms and Mesh type that included: resistant hypertension, secondary high blood pressure, pseudo-resistance and renal sympathetic denervation. Results: resistant hypertension is defined as that which remains outside goals, > 140/90 mmHg in the general population after the use of three antihypertensive agents of different classes at optimal doses being one of them a diuretic. Patients who despite being controlled required the use of four or more drugs were also included. The rate of resistant hypertension has increased in recent years along with obesity and diabetes. The phenomenon is related to secondary causes, pseudo-resistance and sympathetic hyperactivity. Search and control of these factors together with the optimization of medical management are the mainstay of treatment. In patients not adequately controlled despite these measures, the renal sympathetic denervation therapy becomes an effective therapeutic tool. Conclusion: the prevalence of resistant hypertension has increased significantly in the last decade. Optimal medical management and consideration of renal sympathetic denervation therapy becomes the mainstay of treatment. (Acta Med Colomb 2014; 39: 57-63).