Mapa microbiológico hospitalario: Herramienta para monitorear la resistencia a los antimicrobianos / Hospital microbiological map: tool to monitor resistance to antimicrobials

El objetivo del mapa microbiológico es determinar la frecuencia y distribución de los microorganismos a través de su perfil de sensibilidad/resistencia antimicrobiana según el tipo de muestra clínica, localización de la infección, tipo de infección, servicio y caracterizar el fenotipo y genotipo de resistencia en pacientes hospitalizados y ambulatorios

Structural elucidation, mechanism of action, antibacterial proficiency and synergistic forte of purified Euphorbia hirta whole plant extract against multi-drug resistant otitis media infection / Elucidación estructural, mecanismo de acción, competencia antibacteriana y fuerza sinérgica del extracto de planta entera de Euphorbia hirta purificado contra la infección por otitis media resistente a múltiples fármacos

This study investigated the antibacterial potential of Euphorbia hirtawhole plant extracts, honey and conventional antibiotics and their synergistic effects against selected multidrug resistant and typed bacterial strains associated with otitis media. E. hirtawhole plant extract was purified using column chromatography technique. The antibacterial assays of extracts were done using standard microbiological procedures. Protein, sodium and potassium ion leakage of the synergistic mixtures was determined using flame-photometry. At 100 mg/ml, acetone extracts presented highest inhibition against S. aureus (NCTC 6571) with 32 ± 0.83 mm zone of inhibition. The fractional inhibitory concentration indices displayed higher synergism in combination of plant extract, honey and ciprofloxacin against P. mirabilisat 0.02 compared to drug combination synergy standard (≤ 0.5). This work revealed augmentation of ciprofloxacin potency when combined with purified E. hirta acetone extract and honey and implies their high potential in the treatment of multidrug resistant infectionof otitis media.

Este estudio investigó el potencial antibacteriano de extractos de plantas enteras de Euphorbia hirta, miel y antibióticos convencionales y sus efectos sinérgicos contra cepas bacterianas seleccionadas multirresistentes y tipificadas asociadas con la otitis media. El extracto de la planta entera de E. hirtase purificó usando la técnica de cromatografía en columna. Los ensayos antibacterianos de extractos se realizaron utilizando procedimientos microbiológicos estándar. La fuga de iones de proteínas, sodio y potasio de las mezclas sinérgicas se determinó mediante fotometría de llama. A 100 mg/ml, los extractos de acetona presentaron la mayor inhibición contra S. aureus (NCTC 6571) con una zona de inhibición de 32 ± 0,83 mm. Los índices de concentración inhibitoria fraccional mostraron un mayor sinergismo en combinación de extracto de planta, miel y ciprofloxacina contra P. mirabilisa 0,02 en comparación con el estándar de sinergia de combinación de fármacos (≤ 0,5). Este trabajo reveló un aumento de la potencia de la ciprofloxacina cuando se combina con extracto de acetona purificado de E. hirtay miel e implica sualto potencial en el tratamiento de infecciones de otitis media resistentes a múltiples fármacos.

Rendimiento diagnóstico del cultivo y susceptibilidad de Helicobacter pylori en pacientes peruanos: resultados de un laboratorio centinela / Diagnostic performance of the culture and susceptibility of Helicobacter pylori in peruvian patients: results from a sentinel laboratory

RESUMEN Objetivo: Analizar la susceptibilidad antimicrobiana de Helicobacter pylori a 5 antibióticos de referencia, en pacientes dispépticos del Servicio de Gastroenterología del Hospital Cayetano Heredia y la Clínica Cayetano Heredia en Lima, Perú. Materiales y métodos: Se colectaron biopsias gástricas de 500 pacientes diagnosticados con dispepsia. A partir de estas biopsias, se aislaron y cultivaron 273 cepas de H. pylori para confirmar la infección mediante el diagnóstico histológico y por cultivo. Finalmente, se analizó la susceptibilidad antimicrobiana mediante el método de microdilución en caldo y se evaluaron los perfiles de resistencia de cada antimicrobiano y los patrones de multirresistencia. Resultados: El diagnóstico de H. pylori por cultivo, comparado con la prueba histológica, reportó una sensibilidad del 83,8%, una especificidad del 89,9% y un área bajo la curva de 0,87 (IC95%: 0,84 a 0,90). La frecuencia de la infección en los servicios de gastroenterología del Hospital y la Clínica Cayetano Heredia fueron del 56,6% (237/419) y 44,4% (36/81), respectivamente. Según el Hospital/Clínica, se determinó la resistencia para amoxicilina (45,1%/29,6%), levofloxacino (71,8%/74,1%) y metronidazol (69,8%/63,0%). Los patrones de resistencia a múltiples antimicrobianos demostraron que las resistencias (dobles y triples) más frecuentes fueron con levofloxacino, metronidazol y amoxicilina. Conclusiones: La resistencia antimicrobiana de H. pylori ha aumentado con respecto a los años previos. Además, la resistencia múltiple de H. pylori presenta altas frecuencias en pacientes infectados. El método de microdilución en caldo podría ser implementado en los diferentes hospitales del Perú como una herramienta de vigilancia de la resistencia de H. pylori a los antimicrobianos.

ABSTRACT Objective: To analyze the antimicrobial susceptibility of Helicobacter pylori to 5 reference antibiotics, in a population of 500 dyspeptic patients from the Gastroenterology Service of the Cayetano Heredia Hospital (n = 419) and the Cayetano Heredia Clinic (n = 81) in Lima, Peru. Materials and methods: Gastric biopsies were collected from 500 patients diagnosed with dyspepsia. From these biopsies, 273 H. pylori strains were isolated and cultured to confirm H. pylori infection by histological and culture diagnosis. Finally, antimicrobial susceptibility was analyzed using the broth microdilution method, and the resistance profiles of each antimicrobial and multi-resistance patterns were evaluated by statistical analysis. Results: The diagnosis of H. pylori infection by culture, compared to histological testing, reported a sensitivity of 83.8%, a specificity of 89.9% and an area under the curve (AUC) of 0.87 (95% CI: 0.84 to 0.90). The frequency of infection in the gastroenterology services of the Cayetano Heredia Hospital and Clinic was 56.6% (237/419) and 44.4% (36/81), respectively. An increase in antimicrobial resistance to Amoxicillin (45.1% / 29.6%), Levofloxacin (71.8%/ 74.1%) and Metronidazole (69.8% / 63.0%) was found in the Hospital and the Clinic, respectively. Multiple resistance patterns showed that the most frequent resistance (double and triple) was to Levofloxacin, Metronidazole and Amoxicillin. Conclusions: The antimicrobial resistance of H. pylori has increased compared to that reported in previous years. Furthermore, H. pylori multiple resistance presents high frequencies in infected patients. The broth microdilution method could be implemented in different hospitals in Peru as a surveillance tool for H. pylori antimicrobial resistance.

Anthelmintic resistance in Creole horses in the South of Rio Grande do Sul, Brazil / [Resistência anti-helmíntica em equinos da raça Crioula no sul do Rio Grande do Sul, Brasil]

The objective of the study was to evaluate the antiparasitic resistance against horse nematodes in the South of Rio Grande do Sul, Brazil. The results concerning the tests of anthelmintic efficacy on horses, stored in the database of the Parasitic Diseases Study Group (GEEP) - Veterinary Faculty, at the Federal University of Pelotas (UFPel), were carried out in the laboratory from 2018 to 2019. Stool samples were received from farms with breeding of adult female and male Criollo horses naturally infected, located in municipalities in the country's southern region. The antiparasitic agents tested were Triclorfon + Fenbendazole, Closantel + Albendazole, Ivermectin + Praziquantel, Fenbendazole, Ivermectin, Doramectin, Mebendazole and Moxidectin. Techniques such as Gordon and Whitlock, Coproculture and Fecal Egg Count Reduction Test were performed. Of all the antiparasitic drugs tested, it was observed that only treatments with Ivermectin 2% showed desired values. The observed results indicate that resistance to macrocyclic lactones is usual in equine parasites in this Brazilian region, despite the results with isolated Ivermectin.(AU)

O objetivo deste estudo é avaliar a resistência antiparasitária contra nematodeos de equinos no sul do Rio Grande do Sul, Brasil. Os resultados referentes aos testes de eficácia anti-helmíntica em cavalos, armazenados no banco de dados do Grupo de Estudos de Doenças Parasitárias (GEEP) - Faculdade de Veterinária, da Universidade Federal de Pelotas (UFPel), foram realizados em laboratório, no período de 2018 a 2019. Amostras de fezes foram recebidas de fazendas com criação de cavalos Crioulos adultos fêmeas e machos naturalmente infectados, localizadas em municípios da região Sul do país. Os agentes antiparasitários testados foram triclorfon + fenbendazol, closantel + ivermectina + praziquantel, fenbendazol, ivermectina, doramectina, mebendazol e moxidectina. Técnicas como Gordon e Whitlock, coprocultura e teste de redução da contagem de ovos fecais foram realizadas. De todos os antiparasitários testados, observou-se que apenas os tratamentos com ivermectina 2% apresentaram os valores desejados. Os resultados indicam que a resistência às lactonas macrocíclicas é comum em parasitas equinos nessa região brasileira, apesar dos resultados com ivermectina isolada.(AU)

Leptospirosis, una zoonosis que impacta a la salud: diagnóstico, tratamiento y nuevas alternativas de control / Leptospirosis a zoonosis that impacts health: diagnosis, treatment and new alternatives of control

La leptospirosis es una zoonosis con potencial epidémico y de difícil diagnóstico que requiere un manejo integral para orientar las medidas de prevención y control; sin embargo, una de las dificultades es la existencia de más de 300 serovares, la supervivencia de la bacteria en el ambiente por más de 180 días y la importancia del agua como vehículo de transmisión. Esto asociado con los efectos adversos de los antibióticos y su efecto sobre la multirresistencia generada por la mayoría de las bacterias, hace que se evalúen nuevas alternativas a partir de la biodiversidad. Por lo tanto, el objetivo de este artículo es abordar la leptospirosis y su diagnóstico enfatizando en el control convencional de la infección y las alternativas de tratamiento a partir del uso de plantas medicinales. Para esto se realizó una revisión exhaustiva de artículos en bases de datos. La información encontrada permitió establecer los aspectos relevantes de la enfermedad, su diagnóstico y tratamiento, tanto con antimicrobianos convencionales como frente a nuevas alternativas de origen natural. Se concluye que es importante realizar investigaciones orientadas hacia la búsqueda de principios activos que puedan contribuir al control de Leptospira spp., agente causal de la leptospirosis, una de las zoonosis más importantes por su impacto en salud humana, veterinaria y del ecosistema(AU)

Leptospirosis is a potentially epidemic zoonosis of difficult diagnosis which requires comprehensive management to indicate appropriate prevention and control measures. However, some of the difficulties are the existence of more than 300 serovars, survival of the bacteria in the environment for more than 180 days, and the role of water as a route of transmission. The above situation, alongside the adverse effects of antibiotics and their effect on the multi-drug resistance developed by most bacteria, lead to the search for new alternatives based on biodiversity. The purpose of the study was therefore to address leptospirosis and its diagnosis highlighting conventional control of the infection as well as treatment options based on the use of medicinal plants. To achieve this end, an exhaustive review was conducted of papers included in databases. The information obtained made it possible to determine the relevant aspects of the disease, its diagnosis and its treatment with conventional antimicrobials as well as new alternatives of a natural origin. Conclusions point to the importance of conducting research aimed at the search for active principles potentially contributing to control of Leptospira spp., the causative agent of leptospirosis, one of the most relevant zoonoses in terms of its impact on the health of humans, animals and the ecosystem(AU)

Reversal of Drug Resistance in K562/ADM Cells Caused by RA and the Related Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of ursane triterpenoids 3β,19α-dihydroxyursu-12-ene-23,28-dicarboxylic acid (Rotundioic acid, RA) on the sensitivity of adriamycin-resistant K562 cells (K562/ADM Cell) anti-tumor drug, and to explore the effect and mechanism of RA on the multidrug resistance of K562/ADM cells.@*METHODS@#CCK-8 method was used to detect the effect of RA on the sensitivity of K562 cells and K562/ADM cells to anti-tumor drug. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression level of mRNA and the protein in K562 and K562/ADM cells, and the effect of RA on the expression of MDR1 mRNA and P-gp in K562/ADM cells was also detected; Western blot was used to detect the expression of p-JNK, p-p38 and p-ERK1/2 in K562/ADM cells.@*RESULTS@#RA could increased the sensitivity of K562/ADM cells to adriamycin(the reversal factor was 1.61 times), the difference showed statistically significantly (P<0.05); the resistance factor of K562/ADM to ADM was 41.76 times. The expression of MDR1 mRNA in K562 cells was extremely low, and the protein product P-glycoprotein (P-gp) was almost not expressed; MDR1 mRNA and P-gp in K562/ADM cells were highly expressed; RA could down-regulate the expression levels of MDR1 and P-gp in K562/ADM cells. In addition, RA could upregulate the phosphorylation levels of p38 and ERK1/2 in K562/ADM cells, but it has no effect on the expression of p-JNK.@*CONCLUSION@#RA may participate in the regulation of MAPK signaling pathway by upregulating the expression levels of p-p38 and p-ERK1/2 in K562/ADM cells, and thus inhibit the transcription and translation levels of MDR1, and finally reverse the multidrug resistance of leukemia cells.

Progression on Multifunctional Nanoparticles Interfering with Cell Membrane Transporters-associated Drug Resistance / 中国医学科学院学报

Multi-drug resistance(MDR)refers to the loss of sensitivity of tumor cells to traditional chemotherapeutics agents under the mediation of various mechanisms,resulting in the reduction of chemotherapy efficacy.Current studies suggest that a variety of factors,including cell membrane transporter-mediated efflux of anti-tumor drugs,special microenvironment in tumor tissue,DNA self-repair and anti-apoptotic process,and epithelial-mesenchymal cell transformation,may contribute to the formation of MDR.Cell membrane transporter-mediated drug efflux refers to an increase in the amount of anti-tumor drug pumped out of the cell through the up-regulation of the ATP-binding cassette transporter on tumor cell membrane,which reduces the concentration of the drug in the cell,thus forming MDR.An effective method to inhibit the efflux pump caused by overexpression of membrane transporters plays an important role in overcoming MDR.As a promising drug delivery system,multifunctional nanoparticles have demonstrated many advantages in antitumor therapy.Meanwhile,nanoparticles with tailored design are capable of overcoming MDR when combined with a variety of strategies.This paper described in detail the studies relevant to the use of multifunctional nano-sized drug delivery system combined with different strategies,such as co-delivery of agents,external responsiveness or target modification for intervention with efflux pump in order to reverse MDR.This paper provides reference for the development of nano-sized drug delivery system and the formulation of reversal strategy in the future.

Research progress of correlation between multidrug resistance and transporters and traditional Chinese medicine intervention / 中国中药杂志

With the emergence of drug resistance in Western medicine, the repeated administration of clinical first-line drugs becomes more severe. There are many factors leading to multidrug resistance(MDR), so it is very difficult to solve the problem. Since traditional Chinese medicine(TCM) has been used in the field of MDR in recent years, the research on the transporter-associated drug resistance and intervention of TCM has gradually become a hot spot. Therefore, in order to further explore the relationships among drug resistance, transporters, and TCM intervention, we review the relevant research progress in recent years and comb the achievements and limitations of this research at present. In the end, we put forward the research direction of changing body's ADME through the host's transporters and gastrointestinal flora, which provides new ideas for future research.

Risk factors for chemoresistance in metastatic high-risk Gestational Trophoblastic Neoplasia / Philippine Journal of Obstetrics and Gynecology

Background@#Gestational trophoblastic neoplasia (GTN) is a tumor known to be sensitive to chemotherapy. However, a subset of patients still develop resistance to the primary intensive chemotherapy. @*Objective@#This study aimed to determine the risk factors for multidrug resistance among high-risk metastatic GTN patients at University of the Philippines–Philippine General Hospital from January 2014 to December 2018. @*Materials and Methods@#A case–control study involving 111 high-risk metastatic GTN patients who underwent primary intensive chemotherapy Etoposide Methotrexate Actinomycin Cyclophosphamide Oncovin (EMACO) was done at the Philippine General Hospital from January 2014 to December 2018. The medical records of eligible patients were retrieved and reviewed. A comparison of the profile between patients who achieved remission (controls) and those who exhibited chemoresistance (cases) to the EMACO regimen was done. Stepwise logistic regression analysis and Cox's proportional hazards regression were used to determine the significant risk factors that could predict EMACO chemoresistance among these high-risk patients.@*Results@#The cases and controls were comparable in terms of their clinicodemographic profiles. Adjusting for confounders, multivariate analysis showed that the number of metastasis, FIGO stage, and World Health Organization (WHO) prognostic scores were all predictors of survival. Using the fitted logistic regression model, the accuracy of predicted death and survival was 85.16%. @*Conclusions@#The pretreatment serum beta-human chorionic gonadotropin level, number of metastasis, tumor size, FIGO stage, and WHO prognostic score were significant predictors of treatment failure. A higher number of metastatic lesions, stage, and WHO prognostic scores indicated poor survival.

Infecciones del Tracto Urinario: métodos diagnósticos, tratamiento empírico y multirresistencia en una Unidad de Adultos Área de Emergencias / Urinary Tract Infections: diagnostic methods, empirical treatment and multidrug resistance in an Adult Emergency Area Unit

INTRODUCCIÓN. Las infecciones del tracto urinario por variedad de bacterias uropatógenas multiresistentes se deben al uso de tratamiento empírico o automedicación. OBJETIVO. Describir en las infecciones de tracto urinario los métodos diagnósticos, tratamiento empírico y la multirresistencia. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, retrospectivo. Población y muestra de 73 Historias Clínicas de pacientes atendidos en la Unidad de Adultos Área de Emergencias del Hospital de Especialidades Carlos Andrade Marín en el período enero a diciembre 2018. Se incluyeron pacientes mayores de 18 años, de ambos sexos, con diagnóstico clínico y por laboratorio de infección del tracto urinario superior e inferior. La información se obtuvo mediante la base de datos AS400, y se procesó en Epi-info y Excel. RESULTADOS. El 71,23% (52; 73) de mujeres tuvieron infección del tracto urinario. Escherichia coli fue frecuente en un 48,39% (15; 31), con mayor resistencia al Clotrimoxazol. El tratamiento empírico con Ciprofloxacino fue utilizado en 27,40% (20; 73). DISCUSIÓN: Se observó controversia en los tipos de estudios de imagen solicitados para el diagnóstico acorde a la clase de infección de tracto urinario así como el tratamiento empírico por factores propios de cada localidad que evitaron resistencia. CONCLUSIÓN. Escherichia coli se aisló de manera frecuente y registró mayor resistencia al Clotrimoxazol; el principal antibiótico prescrito como tratamiento empírico fue la Ciprofloxacina; el examen más solicitado fue la Urotomografía.

INTRODUCTION. Urinary tract infections due to a variety of multi-resistant uropathogenic bacteria are due to the use of empirical treatment or self-medication. OBJECTIVE. Describe diagnostic methods, empirical treatment and multidrug resistance in urinary tract infections. MATERIALS AND METHODS. Observational, descriptive, retrospective study. Population and sample of 73 Medical Records of patients treated in the Emergency Area Adult Unit of the Carlos Andrade Marín Specialty Hospital in the period january to december 2018. Patients older than 18 years of age, of both sexes, with clinical diagnosis and due to upper and lower urinary tract infection laboratory. The information was obtained through the AS400 database, and was processed in Epi-info and Excel. RESULTS. 71,23% (52; 73) of women had urinary tract infection. Escherichia coli was frequent in 48,39% (15; 31), with greater resistance to Clotrimoxazole. Empirical treatment with Ciprofloxacin was used in 27,40% (20; 73). DISCUSSION: Controversy was observed in the types of imaging studies requested for diagnosis according to the class of urinary tract infection as well as the empirical treatment due to factors specific to each locality that prevented resistance. CONCLUSION. Escherichia coli was frequently isolated and showed greater resistance to Clotrimoxazole; the main antibiotic prescribed as empirical treatment was Ciprofloxacin; the most requested examination was the Urotomography.

Panorama de resistencia antimicrobiana de los aislamientos urinarios de pacientes adultos en los servicios de urgencias de Manizales, Caldas, durante el 2018 / Overview of antimicrobial resistance in urinary tract isolates from adult patients in the emergency room service of Manizales, Caldas, in 2018

Resumen Introducción: los servicios de urgencias requieren de la toma de medidas eficaces y oportunas en el manejo de los pacientes, esto incluye el uso adecuado de antibióticos. La resistencia antimicrobiana dificulta la instauración de terapias empíricas adecuadas, por lo que su vigilancia toma un papel fundamental en los programas de optimización de uso de antimicrobianos. Objetivo: describir el perfil microbiológico y la resistencia antibiótica de los aislamientos urinarios obtenidos de pacientes adultos de los servicios de urgencias de 7 instituciones de tercer nivel de la ciudad de Manizales, durante el año 2018. Resultados: se recolectaron 1991 aislamientos urinarios, el microorganismo más frecuentemente aislado fue Escherichia coli con un 62%. Se encontraron altas tasas de resistencia a cefazolina, trimetoprim/sulfametoxazol, ciprofloxacina y ampicilina/sulbactam. La resistencia a nitrofurantoína y fosfomicina al igual que a carbapenémicos es baja para Escherichia coli. Los aislamientos urinarios de Pseudomonas aeruginosa muestran niveles de resistencia superiores al promedio nacional. Conclusiones: es importante individualizar el manejo antibiótico empírico, teniendo en cuenta la estratificación por severidad, la presencia de factores de riesgo para bacterias multidrogorresistentes, y la epidemiología local; los análisis de cada institución y los resultados de este trabajo, pueden ser utilizados para establecer conductas terapéuticas más precisas en los casos de infecciones del tracto urinario, mejorando los desenlaces de estos pacientes y los costos derivados de la atención en salud.

Abstract Introduction: patient management in emergency rooms require swift and effective clinical decisions; this includes choosing antibiotics correctly. Antimicrobial resistance impairs the adequate choice of empirical therapy, making the surveillance of utmost importance for antimicrobial stewardship programs. Objective: we aimed to describe the microbiological and antimicrobial resistance profile of urinary isolates obtained from adult patients of the emergency services of seven tertiary institutions in the city of Manizales, during the year 2018. Results: from a total of 1991 urinary tract isolates, 62% corresponded to Escherichia coli, the most common bacteria cultured from the emergency room. Susceptibility analysis revealed high resistance levels to cefazolin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Resistance to nitrofurantoin, fosfomycin, and carbapenems was low for Escherichia coli isolates. Pseudomonas aeruginosa showed antimicrobial resistance levels above national averages. Conclusions: empirical antibiotic therapy must be tailored on a patient by patient basis, taking into account the severity of the disease, risk factors for multi-drug resistance bacteria, the institutional and local epidemiology depicted in this work. By using these results, the adjustment of empirical antimicrobial regimens for urinary tract infections could improve clinical outcomes and reduce health care costs.

Perfil de resistencia del Mycobacterium tuberculosis a fármacos antituberculosos de primera línea y sus combinaciones / Resistance profile of Mycobacterium tuberculosis to first-line antituberculosis drugs and their combinations

Introducción: En Colombia el control de la tuberculosis se ha visto amenazado por la resistencia a los fármacos antituberculosos y especialmente la tuberculosis multidrogorresistente. Objetivo: Determinar la resistencia global y perfiles de resistencia del Mycobacterium tuberculosis a fármacos antituberculosos de primera línea y combinaciones. Métodos: Estudio descriptivo, transversal, en el que se evaluaron 2 701 pacientes con tuberculosis en el Departamento del Atlántico (Colombia), durante los años 2011 a 2016. Se valoraron aspectos sociodemográficos, clínicos y condiciones de riesgo. Se realizó análisis de frecuencias relativas y absolutas, diferencia de proporciones ((2) y razón de prevalencias. Resultados: El 66,5 por ciento de los pacientes eran hombres, el 53 por ciento tenían entre 15 y 44 años de edad. El 47,34 por ciento con pérdida en el seguimiento y el 11,62 por ciento monorresistentes a isoniacida. La resistencia en casos nuevos fue 7,30 por ciento (IC95 por ciento: 6,3-8,5), para este grupo la multidrogorresistencia fue de 1,1 por ciento; mientras que en los previamente tratados la resistencia fue de 18,27 por ciento (IC95 por ciento: 15,6- 22,4) y la multidrogorresistencia de 5,7 por ciento. Los factores asociados a resistencia fueron presencia de VIH/TB (RP= 2,6; p= 0,000), otros factores inmunosupresores (RP= 3,5; p= 0,009), contacto de paciente con tuberculosis multidrogorresistente (RP= 16; p= 0,000) y caso previamente tratado (RP= 2,24; p= 0,00). Conclusiones: Se evidencia un descenso en la resistencia global a rifampicina e isoniacida, así como en la prevalencia multidrogorresistente tanto en casos nuevos como en previamente tratados en la población estudiada; lo que genera una línea base para la toma de decisiones que permita continuar mejorando la vigilancia y control de la resistencia del M. tuberculosis a fármacos de primera línea, debido a los nuevos retos que este microorganismo representa para la salud pública(AU)

Introduction: Tuberculosis control in Colombia has been hampered by resistance to antituberculosis drugs and particularly by multi-drug resistant tuberculosis. Objective: Determine the overall resistance and resistance profiles of Mycobacterium tuberculosis to first-line antituberculosis drugs and their combinations. Methods: A descriptive cross-sectional study was conducted of 2 701 tuberculosis patients from Atlántico Department in Colombia in the period 2011-2016. The evaluation included sociodemographic aspects, clinical characteristics and risk conditions. Data analysis was based on relative and absolute frequencies, proportion difference (x2) and prevalence ratio. Results: Of the total sample, 66.5 percent were men and 53 percent were aged 15-44 years. 47.34 percent were lost to follow-up and 11.62 percent were monoresistant to isoniazid. In new cases resistance was 7.30 percent (CI 95 percent: 6.3-8.5) and multi-drug resistance was 1.1 percent, whereas in previously treated cases resistance was 18.27 percent (CI 95 percent: 15.6-22.4) and multi-drug resistance was 5.7 percent. The factors associated to resistance were the presence of HIV/TB (AR= 2.6; p= 0.000), other immunosuppressive factors (AR= 3.5; p= 0.009), contact with multi-drug resistant tuberculosis patient (AR= 16; p= 0.000) and previously treated case (AR= 2.24; p= 0.00). Conclusions: A reduction is observed in overall resistance to rifampicin and isoniazid, as well as in the prevalence of multi-drug resistance, both in new cases and in previously treated cases, which creates a baseline for the taking of decisions aimed at the continuing improvement of the surveillance and control of M. tuberculosis resistance to first-line drugs, due to the new challenges posed by this microorganism to public health(AU)

Resistencia antimicrobiana. Importancia y esfuerzos por contenerla / Antimicrobial resistance. Its importance and efforts to control it

Resumen La Organización Mundial de la Salud estima que en 2050 la resistencia bacteriana ocasionará 10 millones de muertes. Como parte del Plan de Acción Mundial sobre la Resistencia a los Antimicrobianos propuso redes de laboratorios especializados, para conservar cepas y optimizar el uso de los antimicrobianos. En un estudio de 2019 se identificó que las principales bacterias del grupo ESKAPE (con alta resistencia a los antibióticos más usados) que causan infecciones en hospitales de México son Klebsiella spp. resistentes a múltiples fármacos (MDR) y productoras de betalactamasa de espectro extendido (BLEE), Enterobacter spp. BLEE, Acinetobacter baumannii, Pseudomonas aeruginosa MDR, Staphylococcus aureus meticilinorresistente y Enterococcus faecium resistente a vancomicina. Con la información de resistencia a los fármacos se recomiendan esquemas para tratar la infección causada por Helicobacter pylori, relacionado con el desarrollo de cáncer y cuya prevalencia en la población adulta de Latinoamérica se estima es de entre 60 y 70 %.

Abstract The World Health Organization estimates that bacterial resistance will cause 10 million deaths by 2050. As part of the Global Action Plan on Antimicrobial Resistance, it proposed networks of specialized laboratories in order to preserve strains and optimize the use of antimicrobials. In a 2019 study, the main bacteria of the ESKAPE group (which are highly-resistant to the most widely used antibiotics) that cause infections in Mexican hospitals were identified to be multidrug-resistant (MDR) and extended spectrum beta-lactamase (ESBL)-producing Klebsiella spp., ESBL-producing Enterobacter spp., Acinetobacter baumannii, MDR Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. With information on drug resistance, regimens are recommended to treat infection caused by Helicobacter pylori, a pathogen related to the development of cancer and whose prevalence in the adult population of Latin America is estimated to range between 60 and 70%.

Evaluation of antibacterial activity of silver nanoparticles against multidrug-resistant gram negative bacilli clinical isolates from Zagazig University Hospitals

Background: The growing incidence of multidrug resistant (MDR) bacterial infections has become a public health crisis. This work aims to evaluate the in-vitro activity of silver nanoparticles (AgNPs), alone and in combination with the antimicrobials amikacin and ceftazidime, against MDR Gram-negative bacilli (GNB) isolated from clinical cases in Zagazig University Hospitals. Methods: In a cross sectional study, MDR GNB were isolated from different clinical specimens and were tested to determine the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and bactericidal activity of AgNPs using broth microdilution method. The effect of combining subMIC levels of AgNPs (MIC/2 and MIC/4) with amikacin and ceftazidime, was also determined by broth microdilution. Results: A total of 63 MDR GNB was obtained during the study period (22 E. coli, 17 Klebsiella, 15 Pseudomonas aeruginosa and 9 Acinetobacter isolates). AgNPs demonstrated a bactericidal effect on all tested isolates with an MBC/MIC ratio of less than 4. When combined with amikacin, a synergistic effect was demonstrated on all tested E.coli and Klebsiella isolates at AgNPs MIC/2 and on 45.4%, 40% and 77.8% of E.coli, P.aeruginosa and Acinetobacter isolates, respectively at MIC/4. In combination with ceftazidime, AgNPs exhibited a synergistic effect on 100% of E. coli and 88.2% Klebsiella at both MIC/2 and MIC/4 and on 40% of P. aeruginosa isolates at AgNPs MIC/4. Conclusions: AgNPs exert a bactericidal activity on MDR GNB as well as a synergistic effect when combined with amikacin and ceftazidime suggesting them as a new weapon in the war against MDR GNB

Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin / 中南大学学报(医学版)

OBJECTIVES@#To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM.@*METHODS@#The K562 and K562/ADM cells were respectively treated with ADM and idelalisib at different concentrations. The 50% inhibitory concentration (IC@*RESULTS@#The cell survival rates were significantly decreased in a dose-dependent manner when the cells were treated with different doses of ADM (0.001-10.000 mg/L ). The IC@*CONCLUSIONS@#Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.

Reversal effect of peptide-modified chitosan tetramethylpyrazine nanoparticles on multidrug resistance in tumor cells / 中国中药杂志

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.

Interaction between PSF and cytokeratin 18 mediates PSF relocation to cell membrane and maintains chemosensitivity of myeloid leukemia / 北京大学学报(医学版)

OBJECTIVE@#To identify the chaperone of polypyrimidine tractor-binding protein-associated splicing factor (PSF) in myeloid leukemia cells, and to explore the mechanism and redistributive pattern to cell surface of PSF in chemo-sensitive HL60 cells and resistant HL60/DOX cells.@*METHODS@#The eukaryotic expression vector of PSF was transfected with liposomes transiently, then flow cytometry was used to detect the expression level of PSF on the cell surface 24 h, 48 h and 72 h after vector transfections. We constructed a chimeric expression vector, streptavidin binding peptide (SBP)-PSF, meanwhile this vector was transfected and made SBP-PSF fusion protein overexpress. In addition, we used streptavidin magnetic beads to precipitate the cellular chaperonin of PSF and then identified its chaperonin by mass spectrometry (MS). Lentiviral vectors containing cytokeratin18 (K18) interference sequences were transfected into 293T cells to prepare lentivirus. HL60 and HL60/DOX cells were infected with lentivirus to obtain stable interfering K18 cell lines. Next, flow cytometry was used to test the membrane relocation level of PSF. Together, these methods confirmed the similar or different mechanisms of the PSF redistributing to membrane synergistically mediated by K18 in HL60 and HL60/DOX cells.@*RESULTS@#The expression of membrane relocated PSF was detected every day for three days (at the end of 24 h, 48 h and 72 h) after transient overexpression. The expressing rate of PSF on the cell surface was 22.4%±3.5%, 37.9%±6.0%, 58.3%±8.8%, respectively in sensitive HL60 cells, while that was 4.7%±0.5%, 3.9%±0.6%, 2.9%±0.6% , respectively in resistant HL60/DOX cells. The difference of expressing rate on each day was significant, P<0.01. We identified K18 detected by co-immunoprecipitation and mass spectrum assay which was the cellular chaperone of PSF. We found that K18 knockdown decreased the PSF expression level which redistributed on cell surface from 48.9%±5.4% to 6.2%±1.0% in sensitive HL60 cells, and from 9.11%±1.2% to 2.21%±0.51% in resistant HL60/DOX cells, respectively.@*CONCLUSION@#K18 is the intracellular chaperonin of PSF. The interaction of PSF and K18 mediates its redistribution to cell membrane in sensitive cells. While in resistant cells, PSF failed to relocate at the cell surface and accumulated in cells, which mediated resistance to chemotherapeutics.

Multiple resistance in equine cyathostomins: a case study from military establishments in Rio Grande do Sul, Brazil / Múltipla resistência de ciatostomíneos de equinos: um estudo de caso em estabelecimentos militares no Rio Grande do Sul, Brasil

Abstract Semi-intensive equine breeding system favors gastrointestinal nematode infections. The treatment of these infections is based on the use of anthelmintics. However, the inappropriate use of these drugs has led to parasitic resistance to the available active principles. The objective of this study was to evaluate the efficacy of the main classes of antiparasitic (ATP) used in control in adult and young animals, including: benzimidazoles (fenbendazole), pyrimidines (pyrantel pamoate), macrocyclic lactones (ivermectin and moxidectin), as well as the combination of active ingredients (ivermectin + pyrantel pamoate). The study was carried out in two military establishments, located in Rio Grande do Sul (RS), from January to December, 2018. The intervals between the treatments of the animals were performed from 30 to 90 days. Coproparasitological evaluations were determined by the egg count reduction in the faeces. Cyatostomine larvae were identified in pre and post-treatment cultures. The results demonstrated the multiple parasitic resistance of cyathostomins to fenbendazole, moxidectin in young animals, and to fenbendazole, pyrantel pamoate in adult animals. Thus, it is necessary to define or diagnose parasitic resistance to assist in the creation of prophylactic parasitic control, using suppressive treatment with ATP associated with integrated alternatives. The progress of parasitic resistance can be slowed.

Resumo O sistema semi-intensivo de criação de equinos favorece infecções por nematoides gastrointestinais. O tratamento dessas infecções é baseado no uso de anti-helmínticos. No entanto, o uso inadequado desses medicamentos levou à resistência parasitária aos princípios ativos disponíveis. O objetivo deste estudo foi avaliar a eficácia das principais classes de antiparasitários (ATP), utilizados no controle em animais adultos e jovens, incluindo: benzimidazois (fenbendazol), pirimidinas (pamoato de pirantel), lactonas macrocíclicas (ivermectina e moxidectina), bem como a combinação de ingredientes ativos (ivermectina + pamoato de pirantel). O estudo foi realizado em dois estabelecimentos militares, localizados no Rio Grande do Sul (RS), de janeiro a dezembro de 2018. Os intervalos entre os tratamentos foram realizados de 30 a 90 dias. As avaliações coproparasitológicas foram determinadas pela redução da contagem de ovos nas fezes. Foram identificadas larvas de ciatostomíneos nas coproculturas pré e pós tratamentos. Os resultados demonstraram a resistência parasitária múltipla dos ciatostomíneos ao fenbendazol, moxidectina em animais jovens, febendazole e pamoato de pirantel em animais adultos. Estabelecer o diagnóstico da resistência parasitária auxiliará na elaboração de um controle parasitário profilático, reduzindo o tratamento supressivo com ATP juntamente com alternativas de controle integrado. Dessa forma, o avanço da resistência parasitária poderá ser retardado.

Livestock-associated methicillin-resistant Staphylococcus aureus in Korea: antimicrobial resistance and molecular characteristics of LA-MRSA strains isolated from pigs, pig farmers, and farm environment