Uropatogens : their antimicrobial resistance in 10 countries and the behavior of age and sex as associated factors

ANTECEDENTES: La resistencia bacteriana es un problema de salud pública mundial, puede atravesar fronteras nacionales e internacionales, a la preocupación global por el incremento en la resistencia bacteriana, se suma la disminución significativa en el desarrollo de nuevas moléculas con actividad antimicrobiana aprobadas por la Agencia Reguladora de Alimentos y medicamentos (FDA por sus siglas en Ingles) con lo cual está generando la “Tormenta perfecta”. JUSTIFICACIÓN: Los antibióticos están dentro de las drogas más prescritas y usadas en la práctica clínica, entre el 20– 50% no son bien utilizados siendo una de las causas del desarrollo de microorganismos multirresistentes. Si no se toma acciones de forma oportuna para reducir el incremento de la resistencia bacteriana, se estima que para el año 2050 el número de muertes ocasionado por esta causa alcanzará los 10 millones anuales y se estaría generando un costo acumulado a la economía global de USD 100 trillones de dólares. OBJETIVO: Determinar si factores como el sexo y la edad están asociados al desarrollo de resistencia antimicrobiana en dos uropatógenos de mayor prevalencia, analizando el programa de vigilancia epidemiológica SMART de los años 2013 al 2017 en 10 países. METODOLOGÍA: Mega estudio observacional analítico transversal utilizando 9,090 registros de la base de datos SMART del 2013 al 2017, que cumplen los criterios de inclusión y exclusión en tres etapas: la primera, descriptiva donde se caracterizó las variables demográficas y clínicas; la segunda consistió en análisis bivariado para estimar la asociación entre la variable dependiente (resistencia antimicrobiana) y las independientes, estimando prevalencia, intervalos de confianza IC 95% y RD. La tercera, obteniendo modelos de predicción que determinan el impacto de los factores y la fuerza de asociación. RESULTADOS: Se incluyeron 9,090 registros 6,332 (69,7%) del sexo femenino, 68,2% >51 años; 24,1% adultos, 2,4% adolescentes y 5,3% niño. El 48,8% de los registros correspondían a pacientes con 48 o más horas de hospitalización y 7% estaban hospitalizados en la unidad de cuidados intensivos; el 94,5% de los uropatógenos fue aislado en orina. Los factores asociados a la resistencia de E. coli a Ertapenem fueron: género masculino (RD 1,69; IC 95%: 1,28-2,23), tiempo de hospitalización mayor de 48 horas (RD 1,50; IC 95%: 1,14-1,98) y estar en UCI (RD 1,82; IC 95%: 1,17-2,85). Respecto a E. coli cuando el tratamiento es con Ceftriaxona los siguientes fueron los factores asociados significativamente: género masculino (RD 1,69; IC 95%: 1,52-1,89), más de 48 horas hospitalizado (RD 1,68; IC 95%: 1,52-1,86). En Klebsiella pneumoniae los factores que explican el desarrollo de resistencia antimicrobiana fueron: género masculino (RD 1,54; IC 95%: 1,24-1,91), más de 48 horas de hospitalización (RD 1,72; IC 95%: 1,39-2,14), atención en UCI (RD 2,02; IC 95%: 1,48-2,75) edad adolescente (RD 2,79; IC 95%: 1,09-7,15), adulto (RD 2,91; IC 95%: 1,43-5,93) y adulto mayor (RD 2,62; IC 95%: 1,32-5,20). Respecto a la resistencia a Ceftriaxona se explica por los siguientes factores: género masculino (RD 1,61; IC 95%: 1,34-1,92), más de 48 horas hospitalizado (OR 1,84; IC 95%: 1,54-2,19) UCI (OR 1,61; IC 95%: 1,21-2,15). CONCLUSIONES: De acuerdo a los hallazgos del estudio el género masculino, la estancia hospitalaria mayor a 48 horas, explican la disminución en la susceptibilidad de E. coli y Klebsiella pneumoniae a Ertapenem y Ceftriaxona; además la resistencia antimicrobiana es directamente proporcional al aumento de la edad. En nuestro estudio ser menor de 8 años fue un factor protector. Nuevas investigaciones son necesarias para evaluar otros factores clínicos que no se incluyeron en el presente estudio, así como los mecanismos de resistencia asociados.BACKGROUND: Bacterial resistance is a global public health problem. It can cross national and international borders. In addition to the global concern for the increase in bacterial resistance is the significant decrease in the development of new molecules with antimicrobial activity approved by the regulatory agency of food and medicine (fda), which is generating the “perfect storm.” JUSTIFICATION: Antibiotics are among the most prescribed and used drugs in clinical practice. Between 20-50% are not well used, being one of the causes of the development of multidrug-resistant microorganisms. If actions are not taken in a timely manner to reduce the increase in bacterial resistance, it is estimated that by 2050 the number of deaths caused by this cause will reach 10 million annually and a cumulative cost of USD $100 trillion to the global economy would be generated. OBJECTIVE: The objective is to determine if factors such as sex and age are associated with the development of antimicrobial resistance in two most prevalent uropathogens and analyze the SMART epidemiological surveillance program from 2013 to 2017 in 10 countries. METHODOLOGY: To use a mega cross-sectional analytical observational study using 9,090 records from the SMART database from 2013 to 2017, which meet the inclusion and exclusion criteria in three stages: the first, descriptive where demographic and clinical variables were characterized; the second one consisted of bivariate analysis to estimate the association between the dependent variable (antimicrobial resistance) and the independent ones estimating prevalence. 95% CI and RD confidence intervals; and the third one obtaining prediction models that determine the impact of the factors and strength of association. RESULTS: 9,090 records were included: 6,332 (69.7%) of the female sex, 68.2%> 51 years; 24.1% adults, 2.4% adolescents, and 5.3% children. 48.8% of the records corresponded to patients with 48 or more hours of hospitalization and 7% were hospitalized in the intensive care unit; 94.5% of uropathogens were isolated in urine. Factors associated with the resistance of E. coli to Ertapenem were: male gender (RD 1.69; 95% CI 1.28-2.23), hospitalization time greater than 48 hours (RD 1.50; CI 95 %: 1.14-1.98), and being in ICU (RD 1.82; 95% CI: 1.17-2.85). Regarding E. coli when the treatment is with Ceftriaxone, the following factors were significantly associated: male gender (RD 1.69; 95% CI 1.52-1.89), more than 48 hours hospitalized (RD 1.68; 95% CI: 1.52-1.86). In Klebsiella pneumoniae, the factors that explain the development of antimicrobial resistance were: male gender (RD 1.54; 95% CI: 1.24-1.91), more than 48 hours of hospitalization (RD 1.72; 95% CI : 1.39-2.14), ICU care (RD 2.02; 95% CI: 1.48-2.75) adolescent age (RD 2.79; 95% CI: 1.09-7.15 ), adult (RD 2.91; 95% CI: 1.43-5.93), and senior (RD 2.62; 95% CI: 1.32-5.20). Regarding Ceftriaxone resistance, it is explained by the following factors: male gender (RD 1.61; 95% CI 1.34-1.92), more than 48 hours hospitalized (OR 1.84; 95% CI: 1, 54-2,19), and ICU (OR 1.61; 95% CI: 1.21-2.15). CONCLUSIONS: According to the finding of the study of the male gender, hospital stay longer than 48 hours explain the decrease in the susceptibility of E. coli and Klebsiella pneumoniae to Ertapenem and Ceftriaxone. In addition, antimicrobial resistance is directly proportional to the increase in age. In our study, being under 8 years old was a protective factor. New research is necessary to evaluate other clinical factors that were not included in the present study, as well as the associated resistance mechanisms

Uropatogens : their antimicrobial resistance in 10 countries and the behavior of age and sex as associated factors

ANTECEDENTES: La resistencia bacteriana es un problema de salud pública mundial, puede atravesar fronteras nacionales e internacionales, a la preocupación global por el incremento en la resistencia bacteriana, se suma la disminución significativa en el desarrollo de nuevas moléculas con actividad antimicrobiana aprobadas por la Agencia Reguladora de Alimentos y medicamentos (FDA por sus siglas en Ingles) con lo cual está generando la “Tormenta perfecta”. JUSTIFICACIÓN: Los antibióticos están dentro de las drogas más prescritas y usadas en la práctica clínica, entre el 20– 50% no son bien utilizados siendo una de las causas del desarrollo de microorganismos multirresistentes. Si no se toma acciones de forma oportuna para reducir el incremento de la resistencia bacteriana, se estima que para el año 2050 el número de muertes ocasionado por esta causa alcanzará los 10 millones anuales y se estaría generando un costo acumulado a la economía global de USD 100 trillones de dólares. OBJETIVO: Determinar si factores como el sexo y la edad están asociados al desarrollo de resistencia antimicrobiana en dos uropatógenos de mayor prevalencia, analizando el programa de vigilancia epidemiológica SMART de los años 2013 al 2017 en 10 países. METODOLOGÍA: Mega estudio observacional analítico transversal utilizando 9,090 registros de la base de datos SMART del 2013 al 2017, que cumplen los criterios de inclusión y exclusión en tres etapas: la primera, descriptiva donde se caracterizó las variables demográficas y clínicas; la segunda consistió en análisis bivariado para estimar la asociación entre la variable dependiente (resistencia antimicrobiana) y las independientes, estimando prevalencia, intervalos de confianza IC 95% y RD. La tercera, obteniendo modelos de predicción que determinan el impacto de los factores y la fuerza de asociación. RESULTADOS: Se incluyeron 9,090 registros 6,332 (69,7%) del sexo femenino, 68,2% >51 años; 24,1% adultos, 2,4% adolescentes y 5,3% niño. El 48,8% de los registros correspondían a pacientes con 48 o más horas de hospitalización y 7% estaban hospitalizados en la unidad de cuidados intensivos; el 94,5% de los uropatógenos fue aislado en orina. Los factores asociados a la resistencia de E. coli a Ertapenem fueron: género masculino (RD 1,69; IC 95%: 1,28-2,23), tiempo de hospitalización mayor de 48 horas (RD 1,50; IC 95%: 1,14-1,98) y estar en UCI (RD 1,82; IC 95%: 1,17-2,85). Respecto a E. coli cuando el tratamiento es con Ceftriaxona los siguientes fueron los factores asociados significativamente: género masculino (RD 1,69; IC 95%: 1,52-1,89), más de 48 horas hospitalizado (RD 1,68; IC 95%: 1,52-1,86). En Klebsiella pneumoniae los factores que explican el desarrollo de resistencia antimicrobiana fueron: género masculino (RD 1,54; IC 95%: 1,24-1,91), más de 48 horas de hospitalización (RD 1,72; IC 95%: 1,39-2,14), atención en UCI (RD 2,02; IC 95%: 1,48-2,75) edad adolescente (RD 2,79; IC 95%: 1,09-7,15), adulto (RD 2,91; IC 95%: 1,43-5,93) y adulto mayor (RD 2,62; IC 95%: 1,32-5,20). Respecto a la resistencia a Ceftriaxona se explica por los siguientes factores: género masculino (RD 1,61; IC 95%: 1,34-1,92), más de 48 horas hospitalizado (OR 1,84; IC 95%: 1,54-2,19) UCI (OR 1,61; IC 95%: 1,21-2,15). CONCLUSIONES: De acuerdo a los hallazgos del estudio el género masculino, la estancia hospitalaria mayor a 48 horas, explican la disminución en la susceptibilidad de E. coli y Klebsiella pneumoniae a Ertapenem y Ceftriaxona; además la resistencia antimicrobiana es directamente proporcional al aumento de la edad. En nuestro estudio ser menor de 8 años fue un factor protector. Nuevas investigaciones son necesarias para evaluar otros factores clínicos que no se incluyeron en el presente estudio, así como los mecanismos de resistencia asociados.BACKGROUND: Bacterial resistance is a global public health problem. It can cross national and international borders. In addition to the global concern for the increase in bacterial resistance is the significant decrease in the development of new molecules with antimicrobial activity approved by the regulatory agency of food and medicine (fda), which is generating the “perfect storm.” JUSTIFICATION: Antibiotics are among the most prescribed and used drugs in clinical practice. Between 20-50% are not well used, being one of the causes of the development of multidrug-resistant microorganisms. If actions are not taken in a timely manner to reduce the increase in bacterial resistance, it is estimated that by 2050 the number of deaths caused by this cause will reach 10 million annually and a cumulative cost of USD $100 trillion to the global economy would be generated. OBJECTIVE: The objective is to determine if factors such as sex and age are associated with the development of antimicrobial resistance in two most prevalent uropathogens and analyze the SMART epidemiological surveillance program from 2013 to 2017 in 10 countries. METHODOLOGY: To use a mega cross-sectional analytical observational study using 9,090 records from the SMART database from 2013 to 2017, which meet the inclusion and exclusion criteria in three stages: the first, descriptive where demographic and clinical variables were characterized; the second one consisted of bivariate analysis to estimate the association between the dependent variable (antimicrobial resistance) and the independent ones estimating prevalence. 95% CI and RD confidence intervals; and the third one obtaining prediction models that determine the impact of the factors and strength of association. RESULTS: 9,090 records were included: 6,332 (69.7%) of the female sex, 68.2%> 51 years; 24.1% adults, 2.4% adolescents, and 5.3% children. 48.8% of the records corresponded to patients with 48 or more hours of hospitalization and 7% were hospitalized in the intensive care unit; 94.5% of uropathogens were isolated in urine. Factors associated with the resistance of E. coli to Ertapenem were: male gender (RD 1.69; 95% CI 1.28-2.23), hospitalization time greater than 48 hours (RD 1.50; CI 95 %: 1.14-1.98), and being in ICU (RD 1.82; 95% CI: 1.17-2.85). Regarding E. coli when the treatment is with Ceftriaxone, the following factors were significantly associated: male gender (RD 1.69; 95% CI 1.52-1.89), more than 48 hours hospitalized (RD 1.68; 95% CI: 1.52-1.86). In Klebsiella pneumoniae, the factors that explain the development of antimicrobial resistance were: male gender (RD 1.54; 95% CI: 1.24-1.91), more than 48 hours of hospitalization (RD 1.72; 95% CI : 1.39-2.14), ICU care (RD 2.02; 95% CI: 1.48-2.75) adolescent age (RD 2.79; 95% CI: 1.09-7.15 ), adult (RD 2.91; 95% CI: 1.43-5.93), and senior (RD 2.62; 95% CI: 1.32-5.20). Regarding Ceftriaxone resistance, it is explained by the following factors: male gender (RD 1.61; 95% CI 1.34-1.92), more than 48 hours hospitalized (OR 1.84; 95% CI: 1, 54-2,19), and ICU (OR 1.61; 95% CI: 1.21-2.15). CONCLUSIONS: According to the finding of the study of the male gender, hospital stay longer than 48 hours explain the decrease in the susceptibility of E. coli and Klebsiella pneumoniae to Ertapenem and Ceftriaxone. In addition, antimicrobial resistance is directly proportional to the increase in age. In our study, being under 8 years old was a protective factor. New research is necessary to evaluate other clinical factors that were not included in the present study, as well as the associated resistance mechanisms.2021-11-01 01:01:01: Script de automatizacion de embargos. info:eu-repo/date/embargoEnd/2021-10-312019-10-31 07:05:01: Script de automatizacion de embargos. No se encontró correo, se envió correo al autor: Cordial saludo respetado autor: Se ha realizado la publicación de su documento " Uropatogenos : su resistencia antimicrobiana en 10 países y el comportamiento de la edad y sexo como factores asociados" en el Repositorio Institucional EdocUR de la Universidad del Rosario. Usted escogió la opción "Restringido (Temporalmente bloqueado)", por lo que el documento ha quedado con embargo hasta el 1 de noviembre de 2021, en concordancia con las Políticas de Acceso Abierto de la Universidad. Si usted desea dejarlo con acceso abierto antes de finalizar dicho periodo o si por el contrario desea extender el embargo al finalizar este tiempo, puede enviar un correo a esta misma dirección realizando la solicitud. Tenga en cuenta que los documentos en acceso abierto propician una mayor visibilidad de su producción académica y científica. Quedo atento a cualquier inquietud o sugerencia

Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population

Abstract Coronavirus disease 2019 (COVID-19) was considered a major public health burden worldwide. Multiple studies have shown that susceptibility to severe infections and the development of long-term symptoms is significantly influenced by viral and host factors. These findings have highlighted the potential of host genetic markers to identify high-risk individuals and develop target interventions to reduce morbimortality. Despite its importance, genetic host factors remain largely understudied in Latin-American populations. Using a case–control design and a custom next-generation sequencing (NGS) panel encompassing 81 genetic variants and 74 genes previously associated with COVID-19 severity and long-COVID, we analyzed 56 individuals with asymptomatic or mild COVID-19 and 56 severe and critical cases. In agreement with previous studies, our results support the association between several clinical variables, including male sex, obesity and common symptoms like cough and dyspnea, and severe COVID-19. Remarkably, thirteen genetic variants showed an association with COVID-19 severity. Among these variants, rs11385942 (p < 0.01; OR = 10.88; 95% CI = 1.36–86.51) located in the LZTFL1 gene, and rs35775079 (p = 0.02; OR = 8.53; 95% CI = 1.05–69.45) located in CCR3 showed the strongest associations. Various respiratory and systemic symptoms, along with the rs8178521 variant (p < 0.01; OR = 2.51; 95% CI = 1.27–4.94) in the IL10RB gene, were significantly associated with the presence of long-COVID. The results of the predictive model comparison showed that the mixed model, which incorporates genetic and non-genetic variables, outperforms clinical and genetic models. To our knowledge, this is the first study in Colombia and Latin-America proposing a predictive model for COVID-19 severity and long-COVID based on genomic analysis. Our study highlights the usefulness of genomic approaches to studying host genetic risk factors in specific populations. The methodology used allowed us to validate several genetic variants previously associated with COVID-19 severity and long-COVID. Finally, the integrated model illustrates the importance of considering genetic factors in precision medicine of infectious diseases

A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy

Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals

Colombian surgical outcomes study insights on perioperative mortality rate, a main indicator of the lancet commission on global surgery – a prospective cohort studyResearch in context

Summary: Background: Surgical care holds significant importance in healthcare, especially in low and middle-income countries, as at least 50% of the 4.2 million deaths within the initial 30 days following surgery take place in these countries. The Lancet Commission on Global Surgery proposed six indicators to enhance surgical care. In Colombia, studies have been made using secondary data. However, strategies to reduce perioperative mortality have not been implemented. This study aims to describe the fourth indicator, perioperative mortality rate (POMR), with primary data in Colombia. Methods: A multicentre prospective cohort study was conducted across 54 centres (hospitals) in Colombia. Each centre selected a 7-day recruitment period between 05/2022 and 01/2023. Inclusion criteria involved patients over 18 years of age undergoing surgical procedures in operating rooms. Data quality was ensured through a verification guideline and statistical analysis using mixed-effects multilevel modelling with a case mix analysis of mortality by procedure-related, patient-related, and hospital-related conditions. Findings: 3807 patients were included with a median age of 48 (IQR 32–64), 80.3% were classified as ASA I or II, and 27% of the procedures had a low-surgical complexity. Leading procedures were Orthopedics (19.2%) and Gynaecology/Obstetrics (17.7%). According to the Clavien–Dindo scale, postoperative complications were distributed in major complications (11.7%, 10.68–12.76) and any complication (31.6%, 30.09–33.07). POMR stood at 1.9% (1.48–2.37), with elective and emergency surgery mortalities at 0.7% (0.40–1.23) and 3% (2.3–3.89) respectively. Interpretation: The POMR was higher than the ratio reported in previous national studies, even when patients had a low–risk profile and low-complexity procedures. The present research represents significant public health progress with valuable insights for national decision-makers to improve the quality of surgical care. Funding: This work was supported by Universidad del Rosario and Fundación Cardioinfantil-Instituto de Cardiología grant number CTO-057-2021, project-ID IV-FGV017