Respuesta de procalcitonina ante co-infección e infección secundaria por bacterias multirresistentes en pacientes COVID -19 / Procalcitonin response in co-infection and secondary infection by multidrug resistant bacteria in COVID -19 patients

INTRODUCCIÓN. La procalcitonina, es un biomarcador que puede usarse como apoyo diagnóstico en infecciones bacterianas y la monitorización del tratamiento antibiótico, sobre todo en pacientes con sepsis. De ahí que, fue utilizado durante la pandemia COVID-19 OBJETIVO. Determinar los valores de procalcitonina en pacientes con COVID-19 y definir una p osible correlación entre su incremento y vinculación en coinfección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa con multidrogo resistencia y resistencia extendida a los antibióticos. MATERIALES Y MÉTODOS. Estudio retrospectivo observacional, descriptivo transversal, realizado del 1 de mayo al 31 de octubre del 2020 en el Hospital de Especialidades Carlos Andrade Marín sobre 7028 pacientes adultos, hospitalizados, con diagnóstico de COVID-19, y resultados de procalcitonina, cuyas muestras de secreción traqueal y/o hemocultivo presentaron desarrollo de Klebsiella pneumoniae y Pseudomonas aeruginosa. Su análisis estadístico fue desarrollado mediante la prueba Chi Cuadrado de Pearson. RESULTADOS. Se recibieron 861 muestras de hemocultivo y 391 de secreción traqueal, obteniéndose: 32% aislamientos de Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente. Entre los pacientes COVID-19 que fallecieron, 34,4% mostraron incrementos de procalcitonina. Al contrario, entre los pacientes que sobrevivieron sólo en 8,8% se observó incrementos de procalcitonina evidenciándose un vínculo entre el incremento de procalcitonina y mortalidad. CONCLUSIONES. No existe diferencia en relación al incremento en los valores de procalcitonina en pacientes COVID-19 con co-infección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente y los valores de procalcitonina en pacientes con coinfección e infección secundaria con otro tipo de aislamientos bacterianos.

INTRODUCTION. Procalcitonin is a biomarker that can be used as a diagnostic support in bacterial infections and the monitoring of antibiotic treatment, especially in patients with sepsis. Hence, it was used during the COVID-19 pandemic OBJECTIVE. To determine the values of procalcitonin in patients with COVID-19 and to define a possible correlation between its increase and linkage in co-infection or secondary infection by Klebsiella pneumoniae and Pseudomonas aeruginosa with multidrug resistance and extended resistance to antibiotics. MATERIALS AND METHODS. Retrospective observational, descriptive cross-sectional study, conducted from May 1 to October 31, 2020 at the Hospital de Especialidades Carlos Andrade Marín on 7028 adult patients, hospitalized, with diagnosis of COVID-19, and procalcitonin results, whose tracheal secretion and/or blood culture samples presented development of Klebsiella pneumoniae and Pseudomonas aeruginosa. Their statistical analysis was developed using Pearson's Chi-squared test. RESULTS. We received 861 blood culture and 391 tracheal secretion samples, obtaining: 32% isolates of Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa. Among the COVID-19 patients who died, 34.4% showed increased procalcitonin levels. On the contrary, among patients who survived, only 8.8% showed increased procalcitonin levels, showing a link between increased procalcitonin levels and mortality. CONCLUSIONS. There is no difference in relation to the increase in procalcitonin values in COVID-19 patients with co-infection or secondary infection by Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa and procalcitonin values in patients with co-infection and secondary infection with other types of bacterial isolates.

Mortalidad de la sepsis en la unidad de cuidados intensivos / Mortality from sepsis in intensive care unit

INTRODUCCIÓN. La sepsis es un estado de disfunción multisistémica, que se produce por una respuesta desregulada del huésped a la infección. Diversos factores influyen en la gravedad, manifestaciones clínicas y progresión de la sepsis, tales como, heterogeneidad inmunológica y regulación dinámica de las vías de señalización celular. La evolución de los pacientes depende del tratamiento oportuno, las escalas de puntuación clínica permiten saber la mortalidad estimada. OBJETIVO. Evaluar la mortalidad en la unidad de cuidados intensivos; establecer el manejo y la utilidad de aplicar paquetes de medidas o "bundlers" para evitar la progresión a disfunción, fallo multiorgánico y muerte. METODOLOGÍA. Modalidad de investigación tipo revisión sistemática. Se realizó una búsqueda bibliográfica en bases de datos como Google académico, Mendeley, ScienceDirect, Pubmed, revistas como New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. Se obtuvo las guías "Sobreviviendo a la sepsis" actualización 2021, 3 guías internacionales, 10 estudios observacionales, 2 estudios multicéntricos, 5 ensayos aleatorizados, 6 revisiones sistémicas, 5 metaanálisis, 1 reporte de caso clínico, 4 artículos con opiniones de expertos y actualizaciones con el tema mortalidad de la sepsis en UCI con un total de 36 artículos científicos. RESULTADOS. La mortalidad de la sepsis en la unidad de cuidados intensivos, fue menor en el hospital oncológico de Guayaquil, seguido de Australia, Alemania, Quito, Francia, Estados Unidos de Norteamérica y Vietnan, La mortalidad más alta se observa en pacientes con enfermedades del tejido conectivo. DISCUSIÓN. La aplicación de los paquetes de medidas o "bundlers" en la sepsis, se asocia con una mejor supervivencia y menores días de estancia hospitalaria. CONCLUSIÓN. Las escalas SOFA, APACHE II y SAPS II ayudan a predecir la mortalidad de forma eficiente, en la detección y el tratamiento temprano en pacientes con enfermedades agudas y de alto riesgo.

INTRODUCTION. Sepsis is a state of multisystem dysfunction, which is caused by a dysregulated host response to infection. Several factors influence the severity, clinical manifestations and progression of sepsis, such as immunological heterogeneity and dynamic regulation of cell signaling pathways. The evolution of patients depends on timely treatment, clinical scoring scales allow to know the estimated mortality. OBJECTIVE. To evaluate mortality in the intensive care unit; to establish the management and usefulness of applying bundlers to prevent progression to dysfunction, multiorgan failure and death. METHODOLOGY. Systematic review type research modality. A bibliographic search was carried out in databases such as Google Scholar, Mendeley, ScienceDirect, Pubmed, journals such as New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. We obtained the guidelines "Surviving Sepsis" update 2021, 3 international guidelines, 10 observational studies, 2 multicenter studies, 5 randomized trials, 6 systemic reviews, 5 meta-analyses, 1 clinical case report, 4 articles with expert opinions and updates on the subject of sepsis mortality in ICU with a total of 36 scientific articles. RESULTS. The mortality of sepsis in the intensive care unit, was lower in the oncological hospital of Guayaquil, followed by Australia, Germany, Quito, France, United States of America and Vietnam, The highest mortality is observed in patients with connective tissue diseases. DISCUSSION. The application of bundlers in sepsis is associated with better survival and shorter days of hospital stay. CONCLUSIONS. The SOFA, APACHE II and SAPS II scales help to predict mortality efficiently in the early detection and treatment of patients with acute and high-risk disease.

Resistencia antimicrobiana, una pandemia silenciosa / Antimicrobial resistance, a silent pandemic / Resistência antimicrobiana, uma pandemia silenciosa

Introducción: la resistencia a los antimicrobianos ha sido una problemática creciente a nivel global, la problemática afecta no solo la salud de personas, animales y el ambiente en general, sino que ha generado impactos de índole productivo y comercial. Una de las estrategias para abordar esta problemática es el enfoque de una salud. Este enfoque destaca la participación multidisciplinaria para combatir la resistencia antimicrobiana; y es así que cada profesión o actividad laboral genera unas responsabilidades innatas para la profesión veterinaria. Los veterinarios tienen un rol fundamental para este propósito, ya que son ellos quienes integran la aplicabilidad de estrategias de promoción y prevención a nivel agropecuario, y de consolidación e interlocución entre los diferentes componentes del enfoque (animal, humano, ambiente) desde el ámbito de la salud pública veterinaria. Materiales y Método: se realizó una búsqueda de la literatura en diferentes bases de datos, con el objetivo de realizar una revisión actualizada sobre la resistencia antimicrobiana. Resultados: dentro de las principales estrategias se debería fomentar un uso adecuado y bajo prescripción de antimicrobianos en la producción animal. Promover buenas prácticas de higiene, bioseguridad y vacunación, facilitando un correcto diagnóstico de enfermedades infecciosas en animales. Discusión: la adopción de normas internacionales para el uso responsable de los antibióticos y las directrices establecidas por la Organización Mundial de la Salud y Organización de las Naciones Unidas para la Alimentación y la Agricultura, a través del Codex Alimentarius y la Organización Mundial de Sanidad Animal, son fundamentales para hacer frente al desafío que representa el problema de la resistencia a los antimicrobianos.

Introduction: Antimicrobial resistance has been a growing problem at a global level, affecting not only the health of people, animals and the environment in general, but it has also generated impacts of a productive and commercial nature. One of the strategies to address this problem is the one-health approach. This approach emphasizes multidisciplinary participation to combat antimicrobial resistance; and thus, each profession or work activity generates innate responsibilities for the veterinary profession. Veterinarians have a fundamental role for this purpose, since they are the ones who integrate the applicability of promotion and prevention strategies at the agricultural level, and of consolidation and interlocution between the different components of the approach (animal, human, environment) from the field of veterinary public health. Materials and Method: a literature search was carried out in different databases, with the aim of carrying out an updated review on antimicrobial resistance. Results: one of the main strategies should be to promote an adequate use and under prescription of antimicrobials in animal production. Promote good hygiene, biosecurity and vaccination practices, facilitating a correct diagnosis of infectious diseases in animals. Discussion: the adoption of international standards for the responsible use of antibiotics and the guidelines established by the World Health Organization and the Food and Agriculture Organization of the United Nations, through Codex Alimentarius and the World Organization for Animal Health, are fundamental to face the challenge posed by the problem of antimicrobial resistance.

Introdução: A resistência antimicrobiana tem sido um problema crescente em todo o mundo, afetando não apenas a saúde dos seres humanos, dos animais e do meio ambiente em geral, mas também causando impactos na produção e no comércio. Uma das estratégias para lidar com esse problema é a abordagem One Health. Essa abordagem enfatiza o envolvimento multidisciplinar no combate à resistência antimicrobiana, com cada profissão ou atividade de trabalho gerando responsabilidades inatas à profissão veterinária. Os veterinários têm um papel fundamental nesse sentido, pois são eles que integram a aplicabilidade das estratégias de promoção e prevenção em nível agropecuário e de consolidação e interlocução entre os diferentes componentes da abordagem (animal, humano, ambiental) do campo da saúde pública veterinária. Materiais e Métodos: foi realizada uma pesquisa bibliográfica em diferentes bases de dados, com o objetivo de realizar uma revisão atualizada sobre a resistência antimicrobiana. Resultados: uma das principais estratégias deve ser a promoção do uso adequado e com baixa prescrição de antimicrobianos na produção animal. Promover boas práticas de higiene, biossegurança e vacinação, facilitando o diagnóstico correto de doenças infecciosas em animais. Discussão: A adoção de padrões internacionais para o uso responsável de antibióticos e as diretrizes estabelecidas pela Organização Mundial da Saúde e pela Organização das Nações Unidas para Agricultura e Alimentação, por meio do Codex Alimentarius e da Organização Mundial de Saúde Animal, são essenciais para enfrentar o desafio representado pelo problema da resistência antimicrobiana.

Prevalence of multi-drug resistant Pseudomonas aeruginosa isolated from selected residential sewages in Dutsin-Ma, Katsina State, Nigeria

The global surge in Multidrug resistant (MDR) bacteria is an issue of great concern. Pseudomonas aeruginosa has been implicated in several nosocomial infections, where it has caused grave complications in immunocompromised patients. This is the first study to report the prevalence of MDR P. aeruginosa isolated from residential sewage in Dutsin-Ma, Katsina State, Nigeria. Pseudomonads count, isolation, biochemical characterization and antibiogram were carried out using standard microbiological procedures. This study examined sixty (60) samples from selected residential sewage in the study site collected at different intervals between July and September 2021. A total of 40 (66.7%) P. aeruginosa were isolated from the analyzed sewage samples. The highest (2.84x104) pseudomonad count was recorded from sewage samples collected from Kadangaru. Pseudomonas aeruginosa isolates from this sample site showed the highest (100%) resistance to cephalosporins (cefuroxime) and nitrofurantoin. Similarly, isolates from Miami area also demonstrated the highest (95%) resistance to a cephalosporin (ceftazidime). All (100%) isolates used in this study showed MDR resistance to tested antibiotics. The occurrence of MDR P. aeruginosa from a residential sewage site that may contaminate drinking water sources in the study area is of public health threat to the inhabitants. Surveillance and molecular epidemiology of antibiotics resistant bacteria are urgently needed in the study area.

Spectral analysis, in vitro cytotoxicity and antibacterial studies of bioactive principles from the leaves of Conocarpus lancifolius, a common tree of Jazan, Saudi Arabia / Análise espectral, citotoxicidade in vitro e estudos antibacterianos de princípios bioativos das folhas de Conocarpus lancifolius, uma árvore comum de Jazan, Arábia Saudita

The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2’:4’,2”-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-¹ representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p< 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.

O objetivo do presente estudo foi analisar os compostos bioativos das folhas de Conocarpus lancifolius (C. lancifolius). A análise por GC-MS do extrato metanólico quente das folhas (HMEL) de C. lancifolius exibiu os compostos bioativos como 1- (3-Metoxi-2-nitrobenzil) isoquinolina, morfina-4-ol-6,7- diona, 1-bromo-N-metil-, fitol, ácido hexadecanoico, 2,3-di-hidroxipropil éster, 2,2 ‘: 4’, 2 ” - tertiofeno, isoalocolato de etil, óxido de cariofileno, campesterol, epiglobulol, colestano -3-ol, 2-metileno-, (3á, 5à) -, dasycarpidan-1-metanol, acetato (éster) e ácido oleico, éster eicosílico. A análise FT-IR de HMEL de C. lancifolius mostrou um pico único em 3184, 2413, 1657 cm-¹ representando ácido cumarico, ácido clorogênico e ácido ferúlico. O HMEL de C. lancifolius inibiu ativamente a proliferação de células de câncer de mama MCF-7 ATCC na concentração de 72,66 ± 8,21 µg/ml como valor de IC50. O HMEL de C. lancifolius também revelou bom espectro de atividade contra culturas de bactérias Gram-positivas e Gram-negativas rastreadas neste trabalho. A atividade observada mostrou efeitos mais ou menos semelhantes contra bactérias rastreadas. No entanto, a magnitude da potencialidade foi significativamente menor em comparação com o disco de ciprofloxacina padrão em nível de p < 0,001 (intervalos de confiança de 99%). Além disso, o estudo demonstrando os compostos bioativos pode ser isolado das folhas de C. lancifolius.

Drug resistance and susceptibility testing of Gram negative bacterial isolates from healthy cattle with different β – Lactam resistance Phenotypes from Shandong province China / Teste de resistência a drogas e suscetibilidade de isolados bacterianos Gram negativos de bovinos saudáveis com diferentes fenótipos de resistência a β - lactâmicos da província de Shandong, China

The objective of this study was to evaluate the effectiveness of common antibiotics against different microorganisms in apparently healthy cattle in Shandong province and its suburb. A total of 220 nasal swab samples were collected and cultured for bacteriological evaluation. All the bacteria isolates after preliminary identification were subjected to antibiogram studies following disc diffusion method. It was found in the study that E. coli is the most commonly associated isolate (21%), followed by Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%), and Proteus spp (11%). While the antibiogram studies reveled that highest number of bacterial isolates showed resistance to Ampicillin (95%), followed by Augmentin (91%), Cefuroxime (85%) and Tetracycline (95%) of (Escherichia coli and Klebsiella spp). In the case of pseudomonas spp. and Salmonella the highest resistance was showed by Ampicillin (90%) followed by Amoxicillin + Clavulanic Acid (80%), Cefixime (90%), and Erythromycin (80%). In Shigella spp and Salmonella spp highest resistance was showed by Amoxicillin, Ceftazidime, Augmentin (60%), and Amoxicillin + Clavulanic Acid (50%). It is concluded that in vitro antibiogram studies of bacterial isolates revealed higher resistance for Ampicillin, Augmentin, Cefuroxime, Cefixime, Tetracycline, Erythromycin, and Amoxicillin + Clavulanic Acid. The high multiple Antibiotics resistance indexes (MARI) observed in all the isolates in this study ranging from 0.6 to 0.9. MARI value of >0.2 is suggests multiple antibiotic resistant bacteria and indicate presence of highly resistant bacteria.

O objetivo deste estudo foi avaliar a eficácia dos antibióticos comuns contra diferentes microrganismos em bovinos aparentemente saudáveis na província de Shandong e seus subúrbios. Um total de 220 amostras de esfregaço nasal foi coletado e cultivado para avaliação bacteriológica. Todos os isolados de bactérias após identificação preliminar foram submetidos a estudos de antibiograma seguindo o método de difusão em disco. Verificou-se no estudo que E. coli é o isolado mais comumente associado (21%), seguido por Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%) e Proteus spp (11%). Enquanto os estudos de antibiograma revelaram que o maior número de isolados bacterianos apresentou resistência à Ampicilina (95%), seguido por Augmentin (91%), Cefuroxima (85%) e Tetraciclina (95%) de (Escherichia coli e Klebsiella spp). No caso de Pseudomonas spp. e Salmonella, a maior resistência foi apresentada pela Ampicilina (90%) seguida pela Amoxicilina + Ácido Clavulânico (80%), Cefixima (90%) e Eritromicina (80%). Em Shigella spp e Salmonella spp, a maior resistência foi demonstrada por Amoxicilina, Ceftazidima, Augmentina (60%) e Amoxicilina + Ácido Clavulânico (50%). Conclui-se que estudos de antibiograma in vitro de isolados bacterianos revelaram maior resistência para Ampicilina, Augmentina, Cefuroxima, Cefixima, Tetraciclina, Eritromicina e Amoxicilina + Ácido Clavulânico. Os altos índices de resistência a antibióticos múltiplos (MARI) observados em todos os isolados neste estudo variaram de 0,6 a 0,9. O valor MARI de > 0,2 sugere várias bactérias resistentes a antibióticos e indica a presença de bactérias altamente resistentes.

The Role and Mechanism of MiR-451 in Multidrug Resistance of Leukemia Cell Line K562/A02 / 中国实验血液学杂志

OBJECTIVE@#To detect the differential expressions of miR-451, ABCB1 and ABCC2 in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of ABCB1 and ABCC2 , and the mechanism of miR-451 involved in drug resistance in leukemia.@*METHODS@#CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells. MiR-451 mimic and negative control (miR-NC), miR-451 inhibitor and negative control (miR-inNC) were transfected into K562 and K562/A02 cells respectively, then qRT-PCR and Western blot were used to detect the expression levels of mRNA and protein of ABCB1 and ABCC2 in K562 and K562/A02 cells and the transfected groups.@*RESULTS@#The drug resistance of K562/A02 cells to adriamycin was 177 times higher than that of its parent cell line K562. Compared with K562 cells, the expression of miR-451 in K562/A02 cells was significantly higher (P <0.001), and the mRNA and protein expression levels of ABCB1 and ABCC2 in K562/A02 cells were significantly higher than those in K562 cells (P <0.001). After transfected with miR-451 inhibitor, the expression of miR-451 was significantly down-regulated in K562/A02 cells (P <0.001), the sensitivity to chemotherapy drugs was significantly enhanced (P <0.05), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly decreased (P <0.01). After transfected with miR-451 mimic, the expression of miR-451 was significantly upregulated in K562 cells (P <0.001), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly increased (P <0.01).@*CONCLUSION@#There are significant differences in the expressions of miR-451, ABCB1 and ABCC2 between the drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, which suggests that miR-451 may affect the drug resistance of leukemia cells by regulating the expression of ABCB1 and ABCC2.

Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-β Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines.@*METHODS@#Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy.@*RESULTS@#Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified.@*CONCLUSION@#Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.

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

Effect of hypoxia on HIF -1 α/MDR1/VEGF expression in gastric cancer cells treated with 5 -fluorouracil / 中南大学学报(医学版)

OBJECTIVES@#Fluorouracil chemotherapeutic drugs are the classic treatment drugs of gastric cancer. But the problem of drug resistance severely limits their clinical application. This study aims to investigate whether hypoxia microenvironment affects gastric cancer resistance to 5-fluorouracil (5-FU) and discuss the changes of gene and proteins directly related to drug resistance under hypoxia condition.@*METHODS@#Gastric cancer cells were treated with 5-FU in hypoxia/normoxic environment, and were divided into a Normoxic+5-FU group and a Hypoxia+5-FU group. The apoptosis assay was conducted by flow cytometry Annexin V/PI double staining. The real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression level of hypoxia inducible factor-1α (HIF-1α), multidrug resistance (MDR1) gene, P-glycoprotein (P-gp), and vascular endothelial growth factor (VEGF) which were related to 5-FU drug-resistance. We analyzed the effect of hypoxia on the treatment of gastric cancer with 5-FU.@*RESULTS@#Compared with the Normoxic+5-FU group, the apoptosis of gastric cancer cells treated with 5-FU in the Hypoxia+5-FU group was significantly reduced (P<0.05), and the expression of apoptosis promoter protein caspase 8 was also decreased. Compared with the the Normoxic+5-FU group, HIF-1α mRNA expression in the Hypoxia+5-FU group was significantly increased (P<0.05), and the mRNA and protein expression levels of MDR1, P-gp and VEGF were also significantly increased (all P<0.05). The increased expression of MDR1, P-gp and VEGF had the same trend with the expression of HIF-1α.@*CONCLUSIONS@#Hypoxia is a direct influencing factor in gastric cancer resistance to 5-FU chemotherapy. Improvement of the local hypoxia microenvironment of gastric cancer may be a new idea for overcoming the resistance to 5-FU in gastric cancer.

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)

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.

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.

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.

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

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.

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.