Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.839
Filtrar
1.
Rev Panam Salud Publica ; 44, sept. 2020
Artigo em Inglês | PAHO-IRIS | ID: phr-52324

RESUMO

[ABSTRACT]. Objective. To describe the resistance profile and the genetic characteristics of Escherichia coli isolates that harbor the mobilizable colistin resistance gene mcr-1 in Argentina. Methods. This was a retrospective study of 192 E. coli isolates positive for mcr-1 obtained from 69 hospitals of Buenos Aires City and 14 Argentinean provinces in 2012 – 2018. The antimicrobial susceptibility was performed by agar diffusion, broth macrodilution, and/or agar dilution. Standard polymerase chain reaction (PCR) was performed to detect resistance genes and incompatibility groups; specific PCR was applied to discriminate between blaCTX-M allelic groups and mcr-1.5 variant. The genetic relatedness among isolates was evaluated by XbaI-pulsed field gel electrophoresis and multilocus sequence typing in a subset of isolates. Results. All E. coli isolates showed minimal inhibitory concentrations to colistin ≥ 4μg/mL; nearly 50% were resistant to third-generation cephalosporins, with CTX-M-2 being the main extended-spectrum β-lactamase detected. Five E. coli were carbapenemase-producers (3 NDM, 2 KPC). The mcr-1.5 variant was detected in 13.5% of the isolates. No genetic relationship was observed among the mcr-1-positive E. coli clinical isolates, but a high proportion (164/192; 85.4%) of IncI2 plasmids was detected. Conclusions. The presence of IncI2 plasmids among highly diverse E. coli clones suggests that the mcr-1 gene’s wide distribution in Argentina may be driven by the horizontal transmission of IncI2 plasmids.


[RESUMEN]. Objetivo. Describir el perfil de resistencia y las características genéticas de aislamientos clínicos de Escherichia coli que portan el gen movilizable de resistencia a colistina mcr-1 en Argentina. Métodos. Se realizó un estudio retrospectivo para analizar 192 aislamientos de E. coli mcr-1 positivo, obtenidos en 69 hospitales de la Ciudad de Buenos Aires y 14 provincias de Argentina entre 2012 y 2018. La sensibilidad a los antimicrobianos se analizó mediante los métodos de difusión en agar, macrodilución en caldo y/o dilución en agar. Se aplicó la técnica estándar de reacción en cadena de la polimerasa (PCR) para detectar genes de resistencia y grupos de incompatibilidad; se aplicó PCR específica para distinguir entre variantes alélicas del gen blaCTX-M y la variante mcr-1.5. La relación genética entre los aislamientos fue evaluada mediante la técnica de electroforesis en gel de campo pulsado usando la enzima Xbal y la tipificación por secuencias de múltiples locus en un subconjunto de aislamientos. Resultados. Todos los aislamientos de E. coli mostraron concentraciones inhibitorias mínimas de colistina ≥ 4μg/mL. Casi el 50% mostró resistencia a las cefalosporinas de tercera generación y CTX-M-2 fue la β-lactamasa de espectro extendido que más se detectó. Cinco aislamientos de E. coli mostraron ser productoras de carbapenemasas (3 NDM, 2 KPC). La variante mcr-1.5 se detectó en 13,5% de las cepas aisladas. No se observó relación genética entre los aislamientos clínicos estudiados de E. coli positivas para mcr-1, aunque sí se detectó una proporción elevada (164/192; 85,4%) de plásmidos Incl2. Conclusiones. La elevada ocurrencia de plásmidos IncI2 en un grupo altamente diverso de clones de E. coli podría indicar que la amplia difusión del gen mcr-1 en Argentina estaría asociada a la transmisión horizontal de plásmidos IncI2.


[RESUMO]. Objetivo. Descrever o perfil de resistência e as características genéticas de isolados clínicos de Escherichia coli que carregam o gene mobilizábel de resistência à colistina mcr-1 na Argentina. Métodos. Neste estudo retrospectivo, foram analizados 192 isolados de E. coli positivos para mcr-1 obtidos em 69 hospitais da Cidade de Buenos Aires e 14 províncias da Argentina, entre 2012 e 2018. A sensibilidade aos antimicrobianos foi examinada usando métodos de difusão em ágar, macrodiluição em caldo e/ou diluição em ágar. A técnica padrão de reação em cadeia da polimerase (PCR) foi aplicada para detectar genes de resistência e grupos de incompatibilidade; a PCR específica foi aplicada para discriminar entre variantes alélicas do gene blaCTX-M e a variante mcr-1.5. A relação genética entre os isolados foi avaliada por eletroforese em gel de campo pulsado usando a enzima XbaI e a tipagem por sequências de múltiplos lócus, em um subconjunto de isolados. Resultados. Todos os isolados de E. coli apresentaram concentrações inibitórias mínimas de colistina ≥4μg/ mL. Quase 50% foram resistentes às cefalosporinas de terceira geração, e CTX-M-2 foi a β-lactamase de espectro estendido mais detectada. Cinco isolados de E. coli foram produtores de carbapenemase (3 NDM, 2 KPC). A variante mcr-1.5 foi detectada em 13,5% dos isolados. Não foi observada relação genética entre os isolados clínicos de E. coli positivos para mcr-1, mas foi detectada uma alta proporção (164/192; 85,4%) de plasmídeos IncI2. Conclusões. A alta ocorrência de plasmídeos IncI2 em um grupo altamente diverso de clones de E. coli sugere que a ampla distribuição do gene mcr-1 na Argentina estaria associada a transmissão horizontal de plasmídeos IncI2.


Assuntos
Resistência a Múltiplos Medicamentos , Colistina , Enterobacteriaceae , Escherichia coli , Argentina , Resistência a Múltiplos Medicamentos , Colistina , Resistência a Múltiplos Medicamentos
2.
Rev Panam Salud Publica ; 44, sept. 2020
Artigo em Inglês | PAHO-IRIS | ID: phr-52314

RESUMO

[ABSTRACT]. Acinetobacter baumannii is considered to be a worldwide threat to public health due to its high antimicrobial resistance rates and the severe infections it can cause. Little is known about this pathogen’s resistance in Central America. This report aims to describe the antimicrobial resistance profile of A. baumannii at a tertiary hospital in Honduras. The cross-sectional analysis was conducted at the tertiary care laboratory hospital in San Pedro Sula in 2015 – 2017. A total of 113 consecutive microbiological reports were analyzed, comprising 100 individuals from whom A. baumannii was isolated. Epidemiological and microbiological data, including the isolation setting and patient information, were recorded. Prevalence of multi-drug and extensive-drug resistance was assessed according to international standards. The median age of individuals was 22 years (2 – 35 years); female was the predominant gender (53%). The hospital’s pediatric wards had the highest number of isolates (n = 48). The most frequent specimen from which A. baumannii was isolated was skin and soft tissue (n = 39). Resistance to carbapenems was reported to be 40.7% among the isolates (n = 46); multi-drug resistant, 35.4% (n = 40); and extensively-drug resistant, 7.1% (n = 8). This report reveals the threat of this pathogen to public health in Honduras and appeals for antibiotic stewardship programs throughout Central America.


[RESUMEN]. Acinetobacter baumannii se considera como una amenaza mundial para la salud pública debido a sus tasas elevadas de resistencia a los antimicrobianos y a las infecciones graves que puede causar. Es poco lo que se conoce acerca de la resistencia de este agente patógeno en Centroamérica, por lo que el propósito de este informe es describir el perfil de resistencia a los antimicrobianos de A. baumannii mediante un estudio llevado a cabo en un hospital de atención terciaria en Honduras. Entre el 2015 y el 2017, se realizó un análisis transversal en el laboratorio de atención terciaria en el Instituto Hondureño de Seguridad Social en San Pedro Sula. Se analizó un total de 113 informes de análisis microbiológicos consecutivos, en los que las cepas aisladas de A. Baumannii provenían de un grupo de 100 personas. Se registraron los datos epidemiológicos y microbianos, así como el entorno de aislamiento y la información del paciente. La prevalencia de la multirresistencia y la resistencia extensa se evaluó con base en las normas internacionales. La mediana de edad de las personas fue de 22 años (intervalo: de 2 a 35 años de edad) y predominó el sexo femenino (53%). Las salas de pediatría del hospital presentaron el número más alto de cepas aisladas (n = 48). La piel y el tejido blando (n = 39) fueron las muestras más frecuente de las cuales se aisló la cepa A. Baumannii. Se notificó 40,7% de resistencia a los fármacos carbapenémicos en las cepas aisladas (n = 46); 35,4% de multirresistencia (n = 40); y 7,1% de resistencia extensa (n = 8). Este informe pone en evidencia la amenaza que este agente patógeno representa para la salud pública en Honduras. Asimismo, sirve para alertar a los programas de optimización del uso de antibióticos en Centroamérica.


[RESUMO]. Acinetobacter baumannii é considerado uma ameaça à saúde pública em todo o mundo devido às suas altas taxas de resistência antimicrobiana e às graves infecções que pode causar. Sabe-se pouco sobre a resistência deste patógeno na América Central. Este artigo visa descrever o perfil de resistência antimicrobiana de A. baumannii em um hospital terciário em Honduras. Realizamos uma análise transversal no hospital terciário de San Pedro Sula, de 2015 a 2017. Analisamos um total de 113 laudos microbiológicos consecutivos, que envolveram 100 pessoas das quais foi isolado A. baumannii. Registramos dados epidemiológicos e microbiológicos, incluindo o ambiente onde foi feito o isolamento e informações sobre os pacientes. Avaliamos a prevalência de resistência a múltiplos fármacos e resistência extensiva, de acordo com padrões internacionais. A idade mediana dos participantes foi de 22 anos (intervalo, 2 a 35 anos); a maioria dos participantes foi do sexo feminino (53%). As enfermarias pediátricas do hospital tiveram o maior número de isolados (n = 48). A pele e os tecidos moles foram os espécimes mais frequentes de isolamento de A. baumannii (n = 39). A resistência aos carbapenens foi constatada em 40,7% dos isolados (n = 46), a resistência a múltiplos fármacos esteve presente em 35,4% (n = 40) e a resistência extensiva em 7,1% (n = 8). Este artigo revela a ameaça que este patógeno representa à saúde pública em Honduras e faz um apelo pela implantação de programas de gestão do uso de antibióticos em toda a América Central.


Assuntos
Resistência Microbiana a Medicamentos , Acinetobacter baumannii , Resistência a Múltiplos Medicamentos , Honduras , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos
3.
Lancet Child Adolesc Health ; 4(10): 775-789, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32946831

RESUMO

Malaria disproportionately affects children younger than 5 years. Falciparum malaria is responsible for more than 200 000 child deaths per year in Africa and vivax malaria is well documented as a cause of severe anaemia and excess mortality in children in Asia and Oceania. For the treatment of malaria in children, paediatric dosing recommendations for several agents, including parenteral artesunate and dihydroartemisinin-piperaquine, have belatedly been shown to be suboptimal. Worsening antimalarial resistance in Plasmodium falciparum in the Greater Mekong Subregion threatens to undermine global efforts to control malaria. Triple antimalarial combination therapies are being evaluated to try to impede this threat. The RTS,S/AS01 vaccine gives partial protection against falciparum malaria and is being evaluated in large, pilot studies in Ghana, Malawi, and Kenya as a complementary tool to other preventive measures. Seasonal malaria chemoprevention in west Africa has resulted in declines in malaria incidence and deaths and there is interest in scaling up efforts by expanding the age range of eligible recipients. Preventing relapse in Plasmodium vivax infection with primaquine is challenging because treating children who have G6PD deficiency with primaquine can cause acute haemolytic anaemia. The safety of escalating dose regimens for primaquine is being studied to mitigate this risk.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Bem-Estar da Criança/estatística & dados numéricos , Vacinas Antimaláricas/uso terapêutico , Malária/tratamento farmacológico , Malária/prevenção & controle , Criança , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Malária/epidemiologia , Masculino , Estações do Ano , Vacinação/estatística & dados numéricos
4.
Anticancer Res ; 40(9): 4921-4928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878780

RESUMO

BACKGROUND/AIM: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. MATERIALS AND METHODS: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. RESULTS: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 µM). Thioridazine was the most potent among the three phenothiazines. CONCLUSION: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.


Assuntos
Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Fenotiazinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Camundongos , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/química , Fenotiazinas/síntese química , Fenotiazinas/química
5.
Tumour Biol ; 42(9): 1010428320957506, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32914709

RESUMO

The development of the multidrug resistance phenotype is one of the major challenges faced in the treatment of cancer. The multidrug resistance phenotype is characterized by cross-resistance to drugs with different chemical structures and mechanisms of action. In this work, we hypothesized that the acquisition of resistance in cancer is accompanied by activation of the epithelial-to-mesenchymal transition process, where the tumor cell acquires a more mobile and invasive phenotype; a fundamental step in tumor progression and in promoting the invasion of other organs and tissues. In addition, it is known that atypical glycosylations are characteristic of tumor cells, being used as biomarkers. We believe that the acquisition of the multidrug resistance phenotype and the activation of epithelial-to-mesenchymal transition provoke alterations in the cell glycophenotype, which can be used as glycomarkers for chemoresistance and epithelial-to-mesenchymal transition processes. Herein, we induced the multidrug resistance phenotype in the PC-3 human prostate adenocarcinoma line through the continuous treatment with the drug paclitaxel. Our results showed that the induced cell multidrug resistance phenotype (1) acquired a mixed profile between epithelial and mesenchymal phenotypes and (2) modified the glycophenotype, showing an increase in the level of sialylation and in the number of branched glycans. Both mechanisms are described as indicators of poor prognosis.


Assuntos
Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Paclitaxel/farmacologia , Adenocarcinoma/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Glicosilação , Humanos , Células PC-3 , Fenótipo
6.
Ecotoxicol Environ Saf ; 202: 110940, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800223

RESUMO

Recent evidence indicates that chronic, low-dose exposure to mixtures of pesticides can cause adverse responses in a variety of cells, tissues and organs, although interactions between pesticides circulating in the blood and cancer cells remain largely unexplored. The aim of this study was to investigate the potential of a mixture of four pesticides to induce multidrug resistance against the chemotherapeutic agents cisplatin, 5-fluorouracil and temozolomide in the human U87 glioblastoma cell line, and to explore the molecular mechanisms underlying this resistance. We found that the repeated administration of the pesticide mixture (containing the insecticides chlorpyrifos-ethyl and deltamethrin, the fungicide metiram, and the herbicide glyphosate) induced a strong drug resistance in U87 cells. The resistance was durable and transferred to subsequent cell generations. In addition, we detected a significant over-expression of the ATP-binding cassette (ABC) membrane transporters P-gp/ABCB1 and BRCP/ABCG2 as well as a glutathione-S-transferase (GST)/M1-type cellular detoxification function, known to have important roles in multidrug resistance, thus providing molecular support for the acquired multidrug resistance phenotype and shedding light on the mechanism of resistance. We further determined that there was lower mortality in the resistant brain tumor cells and that the mitochondrial apoptosis pathway was activated at a lower rate after chemotherapy compared to non-resistant control cells. In addition, multidrug-resistant cells were found to have both higher motility and wound-healing properties, suggesting a greater metastatic potential. Our results suggest that the investigation of P-gp, BRCP and GST/M1 multidrug resistance gene expression and/or protein levels in biopsy specimens of brain tumor patients who were at risk of pesticide exposure could be beneficial in determining chemotherapy dose and prolonging patient survival.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Praguicidas/toxicidade , Testes de Toxicidade Crônica , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/farmacologia
7.
Plant Dis ; 104(10): 2563-2570, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32762501

RESUMO

Rhizoctonia solani is a widely distributed soilborne plant pathogen, and can cause significant economic losses to crop production. In chemical controls, SYP-14288 is highly effective against plant pathogens, including R. solani. To examine the sensitivity to SYP-14288, 112 R. solani isolates were collected from infected rice plants. An established baseline sensitivity showed that values of effective concentration for 50% growth inhibition (EC50) ranged from 0.0003 to 0.0138 µg/ml, with an average of 0.0055 ± 0.0030 µg/ml. The frequency distribution of the EC50 was unimodal and the range of variation factor (the ratio of maximal over minimal EC50) was 46.03, indicating that all wild-type strains were sensitive to SYP-14288. To examine the risk of fungicide resistance, 20 SYP-14288-resistant mutants were generated on agar plates amended with SYP-14288. Eighteen mutants remained resistant after 10 transfers, and their fitness was significantly different from the parental strain. All of the mutants grew more slowly but showed high virulence to rice plants, though lower than the parental strain. A cross-resistance assay demonstrated that there was a positive correlation between SYP-14288 and fungicides having or not having the same mode of action with SYP-14288, including fluazinam, fentin chloride, fludioxonil, difenoconazole, cyazofamid, chlorothalonil, and 2,4-dinitrophen. This result showed a multidrug resistance induced by SYP-14288, which could be a concern in increasing the spectrum of resistance in R. solani to commonly used fungicides.


Assuntos
Fungicidas Industriais/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Doenças das Plantas , Rhizoctonia/efeitos dos fármacos
8.
Nat Commun ; 11(1): 3418, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647286

RESUMO

The emergence and spread of antiviral drug-resistant viruses have been a worldwide challenge and a great concern for patient care. We report A4 antibody specifically recognizing and binding to the mutant I223R/H275Y neuraminidase and prove the applicability of A4 antibody for direct detection of antiviral multidrug-resistant viruses in various sensing platforms, including naked-eye detection, surface-enhanced Raman scattering-based immunoassay, and lateral flow system. The development of the A4 antibody enables fast, simple, and reliable point-of-care assays of antiviral multidrug-resistant influenza viruses. In addition to current influenza virus infection testing methods that do not provide information on the antiviral drug-resistance of the virus, diagnostic tests for antiviral multidrug-resistant viruses will improve clinical judgment in the treatment of influenza virus infections, avoid the unnecessary prescription of ineffective drugs, and improve current therapies.


Assuntos
Anticorpos Antivirais/imunologia , Resistência a Múltiplos Medicamentos/imunologia , Farmacorresistência Viral/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Mutação/genética , Neuraminidase/genética , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/química , Afinidade de Anticorpos/imunologia , Antígenos Virais/metabolismo , Líquidos Corporais/virologia , Análise Mutacional de DNA , Cães , Epitopos/química , Epitopos/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H3N2/enzimologia , Células Madin Darby de Rim Canino , Simulação de Acoplamento Molecular , Imagem Óptica , Ligação Proteica , Análise Espectral Raman
9.
BMC Infect Dis ; 20(1): 533, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698879

RESUMO

BACKGROUND: Plasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas. Notwithstanding, anti-malaria drug resistant biomarkers have not been characterized in blood donors with asymptomatic P. falciparum infection. METHODS: A total of 771 blood donors were selected from five districts in the Greater Accra Region, Ghana. Each donor sample was screened with malaria rapid diagnostic test (RDT) kit and parasitaemia quantified microscopically. Dried blood spots from malaria positive samples were genotyped for P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum multi-drug resistance (Pfmdr1), P. falciparum dihydropteroate-synthetase (Pfdhps), P. falciparum dihydrofolate-reductase (Pfdhfr) and Kelch 13 propeller domain on chromosome 13 (Kelch 13) genes. RESULTS: Of the 771 blood donors, 91 (11.8%) were positive by RDT. Analysis of sequence reads indicated successful genotyping of Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes in 84.6, 81.3, 86.8, 86.9 and 92.3% of the isolates respectively. Overall, 21 different mutant haplotypes were identified in 69 isolates (75.8%). In Pfcrt, CVIET haplotype was observed in 11.6% samples while in Pfmdr1, triple mutation (resulting in YFN haplotype) was detected in 8.1% of isolates. In Pfdhfr gene, triple mutation resulting in IRNI haplotype and in Pfdhps gene, quintuple mutation resulting in AGESS haplotype was identified in 17.7% parasite isolates. Finally, five non-synonymous Kelch 13 alleles were detected; C580Y (3.6%), P615L (4.8%), A578S (4.8%), I543V (2.4%) and A676S (1.2%) were detected. CONCLUSION: Results obtained in this study indicated various frequencies of mutant alleles in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes from P. falciparum infected blood donors. These alleles could reduce the efficacy of standard malaria treatment in transfusion-transmitted malaria cases. Incorporating malaria screening into donor screening protocol to defer infected donors is therefore recommended.


Assuntos
Doadores de Sangue , Resistência Microbiana a Medicamentos/genética , Resistência a Múltiplos Medicamentos/genética , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Plasmodium falciparum/genética , Adolescente , Adulto , Alelos , Antimaláricos/uso terapêutico , Doenças Assintomáticas , Biomarcadores , Cloroquina/uso terapêutico , Estudos Transversais , Di-Hidropteroato Sintase/genética , Feminino , Frequência do Gene , Gana/epidemiologia , Haplótipos , Humanos , Repetição Kelch/genética , Malária Falciparum/diagnóstico , Malária Falciparum/parasitologia , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Plasmodium falciparum/isolamento & purificação , Prevalência , Proteínas de Protozoários/genética , Tetra-Hidrofolato Desidrogenase/genética , Adulto Jovem
10.
PLoS One ; 15(7): e0234684, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702006

RESUMO

OBJECTIVE: To describe the clinical features, outcomes, and molecular epidemiology of an outbreak of multidrug resistant (MDR) A. baumannii. METHODS: We performed a retrospective analysis of all MDR A. baumannii isolates recovered during an outbreak from 2011 to 2015 in a tertiary care cancer hospital. Cases were classified as colonized or infected. We determined sequence types following the Bartual scheme and plasmid profiles. RESULTS: There were 106 strains of A. baumannii isolated during the study period. Sixty-six (62.3%) were considered as infection and 40 (37.7%) as colonization. The index case, identified by molecular epidemiology, was a patient with a drain transferred from a hospital outside Mexico City. Ninety-eight additional cases had the same MultiLocus Sequence Typing (MLST) 758, of which 94 also had the same plasmid profile, two had an extra plasmid, and two had a different plasmid. The remaining seven isolates belonged to different MLSTs. Fifty-three patients (50%) died within 30 days of A. baumanniii isolation: 28 (20%) in colonized and 45 (68.2%) in those classified as infection (p<0.001). In multivariate regression analysis, clinical infection and patients with hematologic neoplasm, predicted 30-day mortality. The molecular epidemiology of this outbreak showed the threat posed by the introduction of MDR strains from other institutions in a hospital of immunosuppressed patients and highlights the importance of adhering to preventive measures, including contact isolation, when admitting patients with draining wounds who have been hospitalized in other institutions.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Infecção Hospitalar/epidemiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/patogenicidade , Adulto , Idoso , Estudos de Casos e Controles , Surtos de Doenças , Resistência a Múltiplos Medicamentos/fisiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Hospitais Gerais , Humanos , Masculino , México , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular/métodos , Tipagem de Sequências Multilocus/métodos , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética , Estudos Retrospectivos , Análise de Sequência de DNA/métodos , beta-Lactamases/genética
11.
Yakugaku Zasshi ; 140(7): 909-912, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612055

RESUMO

In medical care, qualified physicians, nurses, and pharmacists have come to be recognized as a team integral to a patient's success, and this team approach to medical care has become popular. In the infectious disease field, more hospitals are practicing antimicrobial stewardship as a team, in addition to the conventional infection control team (ICT). As a result, infectious disease chemotherapy pharmacists are in demand. However, this specific qualification is hard to acquire for pharmacists working in a primary care pharmacy. The problem of multidrug-resistant bacteria is of vital interest today. The National Action Plan on Antimicrobial Resistance 2016-2020, published in Japan, includes an aim to largely reduce the consumption of each oral antimicrobial agent, in order to control the emergence of resistant bacteria. Hospitals and primary care pharmacies will achieve this aim differently. For infection control by primary care pharmacies, the emergence control of a resistant bacteria is important, as is the control of outbreak in a region.


Assuntos
Controle de Doenças Transmissíveis , Serviços Comunitários de Farmácia , Farmacêuticos , Atenção Primária à Saúde , Gestão de Antimicrobianos , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/microbiologia , Resistência a Múltiplos Medicamentos , Hospitais , Humanos , Equipe de Assistência ao Paciente
12.
Int J Food Microbiol ; 331: 108750, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-32559710

RESUMO

For the first time, this study evaluates consumer exposure via poultry meat to Enterobacteriaceae with capacity to develop severe extraintestinal infections by either bacterial virulence and/or antibiotic resistance traits. The characterization of 256 isolates and the assessment of five parameters, showed that 96 of 100 poultry meat samples from supermarkets of northwest Spain posed ≥ one potential risk: i) 96% carried Enterobacteriaceae resistant to antimicrobials of categories A (64% to monobactams) or B (95% to cephalosporins 3rd and 4rd- generation, quinolones and/or polymixins) of the new categorization of EMA. ii) More than one extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae species were recovered from 28% of poultry meat. iii) High-risk lineages of E. coli, including multidrug-resistant ST131-H22, were present in 62% of samples. iv) E. coli recovered from 25% of samples conformed the ExPEC status. v) E. coli from 17% of samples satisfied the UPEC status. Of note, the recovery from different samples of two E. coli CC10-A (CH11-54) carrying mcr-1.1-bearing IncX4 plasmids, and four E. coli CC10-A (eae-beta1) of the hybrid pathotype aEPEC/ExPEC. (ESBL)-producing K. pneumoniae were isolated from 27% of samples. In summary, poultry meat microbiota is a source of genetically diverse Enterobacteriaceae, resistant to relevant antimicrobials and potentially pathogenic for consumers.


Assuntos
Exposição Dietética/estatística & dados numéricos , Resistência a Múltiplos Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Microbiologia de Alimentos/estatística & dados numéricos , Carne/microbiologia , Animais , Antibacterianos/farmacologia , Galinhas/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/isolamento & purificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Plasmídeos/genética , Espanha/epidemiologia , Perus , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/isolamento & purificação
13.
Washington, D.C.; OPS; 2020-06-09.
em Espanhol | PAHO-IRIS | ID: phr-52261

RESUMO

Estas directrices unificadas se han actualizado con arreglo a los procesos del grupo de elaboración de las directrices que se llevaron a cabo entre el 2011 y el 2018 de conformidad con los requisitos de la OMS. Este documento sustituye a otras recomendaciones de la OMS relativas al tratamiento de la tuberculosis (TB) multirresistente y resistente a la rifampicina (TB-MDR/RR) publicadas desde el 201. En este documento se incluyen las preguntas sobre población, intervención, comparador y resultado (PICO, por su sigla en inglés) subyacentes a las recomendaciones y la posología revisada de los medicamentos utilizados en los esquemas de segunda línea, así como las referencias clave. En línea se puede encontrar más información sobre los procesos del grupo de elaboración de las directrices y los participantes en dicho grupo, los principales métodos utilizados para desarrollar las recomendaciones, los resúmenes de la evidencia de la clasificación de la valoración, elaboración y evaluación de las recomendaciones (GRADE por su sigla en inglés) resultante y los marcos de decisión para cada recomendación, así como datos inéditos, planes de análisis de datos e informes de revisiones sistemáticas. Las recomendaciones y demás información práctica para apoyar su implementación se reproducirán en una próxima actualización del manual de la OMS sobre el manejo programático de la TB.


Assuntos
Tuberculose , Resistência a Múltiplos Medicamentos
14.
Arch Microbiol ; 202(8): 2105-2115, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32500253

RESUMO

In this study, the antibacterial, anti-efflux, anti-biofilm, anti-slime (exopolysaccharide) production and urease inhibitory efficacies of green synthesized gold nanoparticles (AuNPs) coated Anthemis atropatana extract against multidrug- resistant (MDR) Klebsiella pneumoniae strains were evaluated. The green synthesized AuNPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffractometer (XRD), particle size distribution, zeta potential and Fourier-transform infrared spectroscopy (FTIR). Then, antibacterial, anti-slime (exopolysaccharide) production, anti-biofilm and anti-efflux activities of AuNPs were investigated using micro-dilation, Congored agar, microtiter plate and MIC of ethidium bromide methods, respectively. Subsequently, the expression of mrkA, wzm and acrB genes was evaluated using quantitative Real-Time PCR (qRT-PCR). The synthesized AuNPs exhibited antibacterial activity against MDR strains of K. pneumoniae (minimum inhibitory concentration (MIC) of 6.25-50 µg/ml), as well as showed significant anti-slime (exopolysaccharide) production, anti-biofilm and anti-efflux activities against MDR strains. AuNPs showed significant inhibition against jack-bean urease and down-regulated the expression of mrkA, wzm and acrB genes. Moreover, the in vitro cytotoxic activity confirmed by MTT assay on the HEK-293 normal cell line showed negligible cytotoxicity. Thus, the present study suggests the potential use of AuNPs in the development of novel therapeutics for the prevention of biofilm-associated K. pneumoniae infections.


Assuntos
Anthemis/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ouro/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Nanopartículas Metálicas , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ouro/química , Células HEK293 , Humanos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Urease/metabolismo
15.
PLoS One ; 15(6): e0235090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569270

RESUMO

Tumor is a prevalent great threat to public health worldwide and multidrug resistance (MDR) of tumor is a leading cause of chemotherapy failure. Nanomedicine has shown prospects in overcoming the problem. Doxorubicin (DOX), a broad-spectrum anticancer drug, showed limited efficacy due to MDR. Herein, a doxorubicin containing pectin nanocell (DOX-PEC-NC) of core-shell structure, a pectin nanoparticle encapsulated with liposome-like membrane was developed. The DOX-PEC-NC, spheroid in shape and sized around 150 nm, exerted better sustained release behavior than doxorubicin loading pectin nanoparticle (DOX-PEC-NP) or liposome (DOX-LIP). In vitro anticancer study showed marked accumulation of doxorubicin in different tumor cells as well as reversal of MDR in HepG2/ADR cells and MCF-7/ADR cells caused by treatment of DOX-PEC-NC. In H22 tumor-bearing mice, DOX-PEC-NC showed higher anticancer efficacy and lower toxicity than doxorubicin. DOX-PEC-NC can improve anticancer activity and reduce side effect of doxorubicin due to increased intracellular accumulation and reversal of MDR in tumor cells, which may be a promising nanoscale drug delivery vehicle for chemotherapeutic agents.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Nanopartículas/química , Pectinas/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Nanopartículas/ultraestrutura , Baço/patologia , Timo/patologia
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 758-766, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552933

RESUMO

OBJECTIVE: To investigate the effect of Bmi-1 gene silencing on drug resistance of leukemia cell K562/ADR and to explore its possible mechanism. METHODS: After two sequences of Bmi-1-siRNA were transfected into drug-resistant K562/ADR cells, the mRNA and protein expressions of Bmi-1 gene were detected. After Bmi-1 gene silencing the expression of P-gp and MDR1 were detected and the accumulation of doxorubicin in K562/ADR cells were detected by flow cytometry to determine the effect of Bmi-1 gene silencing on drug resistance of K562/ADR cells. The protein expression of NF-κB was analyzed after Bmi-1 gene silencing. Then after K562/ADR cells were treated with NF-κB inhibitor PDTC, the protein expression of P-gp and its functional changes were analyzed to determine the effect of NF-κB on drug resistance of leukemia cells. The protein expressions of PTEN, AKT and p-AKT after Bmi-1 gene silencing were detected and the effect of Bmi-1 gene silencing on PTEN/PI3K/AKT signaling pathway in drug-resistant cells was determined. After K562/ADR cells were treated with PI3K/AKT pathway inhibitor LY294002, the protein expressions of NF-κB and P-gp were analyzed to determine the regulation of AKT on the expression of NF-κB and P-gp. The protein expressions of AKT, p-AKT, NF-κB and P-gp were detected after the Bmi-1-siRNA transfected cells were treated by PTEN inhibitor BPV. Above-mentioned expression of mRNA was detected by RT-PCR, and the protein expression was detected by Western blot. RESULTS: The expression of Bmi-1 gene in K562/ADR cells decreased at both mRNA and protein levels and the doxorubicin accumulation increased after Bmi-1 gene silencing. The expression of MDR1/P-gp in Bmi-1-siRNA transfected cells was lower than that in K562/ADR cells (P<0.05). After Bmi-1 gene silencing, the activity of NF-κB decreased. The activity of NF-κB and P-gp expression was inhibited and the function of P-gp in K562/ADR cells was reduced by using NF-κB inhibitor (PDTC). The protein expression of PTEN increased while the protein expression of p-AKT decreased after Bmi-1 gene silencing (P<0.05). The protein expressions of p-AKT, P-gp and the activity of NF-κB were inhibited significantly by using PI3K/AKT inhibitor LY294002 (P<0.05). After the Bmi-1-siRNA transfected cells were treated by PTEN inhibitor BPV, the activity of NF-κB and the protein expressions of P-gp were restored. CONCLUSION: Bmi-1 plays a key role in MDR-mediated multidrug resistance in K562/ADR cells, which may be mediated by activating PTEN/AKT pathway to regulate NF-κB.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Doxorrubicina , Resistência a Múltiplos Medicamentos , Humanos , Células K562 , Proteína Quinase 7 Ativada por Mitógeno
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 1064-1068, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552983

RESUMO

Abstract  Chronic myeloid leukemia (CML) is a malignant myeloproliferative tumor which is originating from hematopoietic stem cells. Chemotherapy is the preferred made of treatment for the disease. However, in recent years, more and more patients have multidrug resistance (MDR) during treatment, which is the main cause of failure treatment, therefore, the search for effective reversal agents has important clinical significance. Traditional Chinese medicine derived reversal agents have the characteristics of multiple targets, low toxicity and high efficiency, which can reverse the drug resistance through different mechanisms, and the research potential is unlimited. In recent years, it has been widely concerned by scholars at home and abroad, especially the research on physcion, emodin, curcumin, matrine, gambogic acid, oridonin, ligustrazine, solanine and other monomers, which has made great advance. In this reviwe, the recent research advance on the reversal of MDR in chronic myeloid leukemia by Chinese medicine monomer is summarized briefly.


Assuntos
Resistência a Múltiplos Medicamentos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa
18.
PLoS One ; 15(6): e0233993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32484843

RESUMO

Multidrug resistance (MDR) to chemotherapeutic drugs remains one of the major impediments to the treatment of cancer. Discovery and development of drugs that can prevent and reverse the acquisition of multidrug resistance constitute a foremost challenge in cancer therapeutics. In this work, we screened a library of 1,127 compounds with known targets for their ability to overcome Pgp-mediated multidrug resistance in cancer cell lines. We identified four compounds (CHIR-124, Elesclomol, Tyrphostin-9 and Brefeldin A) that inhibited the growth of two pairs of parental and Pgp-overexpressing multidrug-resistant cell lines with similar potency irrespective of their Pgp status. Mechanistically, CHIR-124 (a potent inhibitor of Chk1 kinase) inhibited Pgp activity in both multidrug-resistant cell lines (KB-V1 and A2780-Pac-Res) as determined through cell-based Pgp-efflux assays. Other three inhibitors on the contrary, were effective in Pgp-overexpressing resistant cells without increasing the cellular accumulation of a Pgp substrate, indicating that they overcome resistance by avoiding efflux through Pgp. None of these compounds modulated the expression of Pgp in resistant cell lines. PIK-75, a PI3 Kinase inhibitor, was also determined to inhibit Pgp activity, despite being equally potent in only one of the two pairs of resistant and parental cell lines. Strong binding of both CHIR-124 and PIK-75 to Pgp was predicted through docking studies and both compounds inhibited Pgp in a biochemical assay. The inhibition of Pgp causes accumulation of these compounds in the cells where they can modulate the function of their target proteins and thereby inhibit cell proliferation. In conclusion, we have identified compounds with various cellular targets that overcome multidrug resistance in Pgp-overexpressing cell lines through mechanisms that include Pgp inhibition and efflux evasion. These compounds, therefore, can avoid challenges associated with the co-administration of Pgp inhibitors with chemotherapeutic or targeted drugs such as additive toxicities and differing pharmacokinetic properties.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Neoplasias/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Brefeldina A/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidrazinas/farmacologia , Hidrazonas/farmacologia , Neoplasias/genética , Neoplasias/patologia , Quinolinas/farmacologia , Quinuclidinas/farmacologia , Sulfonamidas/farmacologia , Tirfostinas/farmacologia
19.
Environ Pollut ; 265(Pt A): 114806, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32593928

RESUMO

Many countries are limiting the use of bisphenol A (BPA) because evidence shows it is dangerous to human health and wildlife. For the manufacturing of polycarbonate plastics, bisphenol S (BPS) and bisphenol F (BPF) are proposed as safer alternatives. They have already been released into the aquatic environment without previously available information about their potential adverse effects. In this study, we compared the effects of BPA, BPS and BPF exposure to the expression profile of genes involved in the endocrine pathway (EcR and E74), ecdysone metabolism (Cyp18a1 and Shadow), apoptosis (DRONC) and the multidrug resistance-associated protein 1 gene (MRP1) in the midge, Chironomus riparius (Diptera). The three toxicants increased Shadow expression, which is involved in ecdysone synthesis, but only BPF significantly altered Cyp18a1, which is implicated in ecdysone degradation. BPS and BPF modified EcR and E74 expression; BPF upregulated the effector caspase DRONC. Furthermore, BPA significantly increased MRP1 expression. This study provides insights into the action of bisphenols at the molecular level and highlights the potential risks of BPS and BPF as BPA alternatives.


Assuntos
Chironomidae , Animais , Apoptose , Compostos Benzidrílicos , Resistência a Múltiplos Medicamentos , Humanos , Fenóis , Sulfonas
20.
Arch Microbiol ; 202(7): 1849-1860, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32447432

RESUMO

The occurrence of multidrug-resistant pathogenic bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MDRAB), extended-spectrum ß-lactamase (ESBL) Escherichia coli, and Pseudomonas aeruginosa, has become a serious problem in animals and public. The objective of this study was to identify and isolate lactic acid bacterial (LAB) strains from the intestinal tracts of pigs and feces of dogs and then characterize them as potential probiotics with antimicrobial activity against multidrug-resistant pathogenic bacteria. In a preliminary isolation screening, 45 of 1167 isolated LAB strains were found to have anti-S. aureus ATCC 27,735 activity. Using 16S rDNA and 16S-23S rDNA intergenic spacer region (ISR) sequences, five of these isolates were further identified as Lactobacillus animalis 30a-2, Lactobacillus reuteri 4-12E, Weissella cibaria C34, Lactococcus lactis 5-12H, and Lactococcus lactis 6-3H. Antimicrobial substance assays suggest that the L. lactis 5-12H, L. lactis 6-3H, L. animalis 30a-2, L. reuteri 4-12E, and W. cibaria C34 strains might produce bacteriocins and hydrogen peroxide (H2O2) as antimicrobial substances. The L. animalis 30a-2 and W. cibaria C34 strains were further characterized for probiotic properties and shown to have high acid and bile salt tolerance. Additionally, they have broad antimicrobial spectra, and can significantly repress the growth of all of the tested strains of MRSA isolates, some MDRAB, ESBL E. coli, and P. aeruginosa isolates, along with food-borne pathogenic bacteria such as Bacillus cereus ATCC 11778, Listeria monocytogens ATCC 19111, Salmonella spp., Shigella spp., and Yersinia enterocolitica BCRC 12986. This is the first report of H2O2-producing L. animalis 30a-2 and W. cibaria C34 isolated from the intestinal tracts of pigs and feces of dogs that have good antimicrobial activity against multidrug-resistant and food-borne pathogenic bacteria and have excellent probiotic properties.


Assuntos
Antibiose/fisiologia , Fenômenos Fisiológicos Bacterianos , Resistência a Múltiplos Medicamentos , Lactobacillus/metabolismo , Probióticos , Animais , Antibacterianos/farmacologia , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Cães , Fezes/microbiologia , Peróxido de Hidrogênio/metabolismo , Intestinos/microbiologia , Lactobacillus/isolamento & purificação , Suínos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA