Riesgos asociados a la utilización de antimicrobianos en personas mayores

Objetivos: Describir los cambios fisiológicos más relevantes asociados al envejecimiento, las características de las infecciones en estos pacientes así como los efectos adversos más frecuentes e interacciones farmacológicas graves de los antimicrobianos en los mayores. Material y Métodos: Se realizó una revisión bibliográfica sobre los riesgos asociados al uso de antibióticos en ancianos. La información se apoyó en la actualización de la evidencia científica y la información de las Fichas Técnicas de los medicamentos. La búsqueda se limitó a los últimos 11 años, seleccionándose documentos publicados en español, inglés o francés. Se realizó una búsqueda electrónica de fuentes secundarias (revisiones sistemáticas) y una búsqueda manual “ad hoc”, partiendo de la bibliografía recuperada, estudios primarios, informes de agencias de evaluación de medicamentos, guías de práctica clínica y documentos de Sociedades Científicas. Se utilizaron como fuentes de información: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®. Resultados: Se localizaron 321 resultados, tras eliminar los que no cumplían criterios de inclusión 52 documentos, además de las fichas técnicas de todos los antibióticos citados, se incluyeron en la revisión bibliográfica. Conclusiones: Los pacientes mayores adquieren con mayor frecuencia infecciones por patógenos multi-resistentes y sufren más complicaciones graves de las infecciones. Los antibióticos son un grupo de fármacos especialmente sensibles a los cambios fisiológicos producidos por la edad, lo que puede condicionar la respuesta a los estos y exige en muchas ocasiones modificaciones posológicas con el fin de evitar intoxicaciones y/o fracasos terapéuticos. Este trabajo aporta información sobre estos cambios fisiológicos y los riesgos de los antibióticos en las personas mayores, aspectos necesarios para elegir un tratamiento adecuado.Aim: Describe the most important physiological changes associated with aging, the characteristics of infections in these patients and the most common side effects and severe interactions with antimicrobials in older people. Material and methods: We conducted a literature review on the risks associated with the use of antibiotics in the elderly. The information was based on the update of the scientific evidence and information from the drug Sheets. The search was limited to the past 11 years, selected papers published in English, Spanish or French. We performed an electronic search of secondary sources (systematic reviews) and a manual search “ad hoc” basis of the literature retrieved, primary studies, reports of drug evaluation agencies, clinical practice guidelines and documents of Scientific Societies. Information sources: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®. Results: We identified 321 results, after eliminating those who did not meet inclusion criteria 52 papers in addition to the technical specifications of all mentioned antibiotics were included in the literature review. Conclusion: Older patients can acquire infections more frequently multi-resistant pathogens and suffer more serious complications of infections. The antibiotics is a group of drugs sensitive to the physiological changes induced by aging, which may influence the response to these and often requires dosage modifications to avoid poisoning and / or therapeutic failures. This paper provides information on these physiological changes and risks of antibiotics in the elderly, aspects necessary to choose a proper treatment.Este trabajo ha sido realizado con la co- financiación de sendos proyectos de investigación: FISS PI/10/01152 y Consejería de Salud de la Junta de Andalucía PI-0160-2010

Risks associated with the use of antimicrobials in elderly

Objetivos: Describir los cambios fisiológicos más relevantes asociados al envejecimiento, las características de las infecciones en estos pacientes así como los efectos adversos más frecuentes e interacciones farmacológicas graves de los antimicrobianos en los mayores.Material y Métodos: Se realizó una revisión bibliográfica sobre los riesgos asociados al uso de antibióticos en ancianos. La información se apoyó en la actualización de la evidencia científica y la información de las Fichas Técnicas de los medicamentos. La búsqueda se limitó a los últimos 11 años, seleccionándose documentos publicados en español, inglés o francés. Se realizó una búsqueda electrónica de fuentes secundarias (revisiones sistemáticas) y una búsqueda manual “ad hoc”, partiendo de la bibliografía recuperada, estudios primarios, informes de agencias de evaluación de medicamentos, guías de práctica clínica y documentos de Sociedades Científicas. Se utilizaron como fuentes de información: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®.Resultados: Se localizaron 321 resultados, tras eliminar los que no cumplían criterios de inclusión 52 documentos, además de las fichas técnicas de todos los antibióticos citados, se incluyeron en la revisión bibliográfica.Conclusiones: Los pacientes mayores adquieren con mayor frecuencia infecciones por patógenos multi-resistentes y sufren más complicaciones graves de las infecciones. Los antibióticos son un grupo de fármacos especialmente sensibles a los cambios fisiológicos producidos por la edad, lo que puede condicionar la respuesta a los estos y exige en muchas ocasiones modificaciones posológicas con el fin de evitar intoxicaciones y/o fracasos terapéuticos. Este trabajo aporta información sobre estos cambios fisiológicos y los riesgos de los antibióticos en las personas mayores, aspectos necesarios para elegir un tratamiento adecuado.Aim: Describe the most important physiological changes associated with aging, the characteristics of infections in these patients and the most common side effects and severe interactions with antimicrobials in older people.Material and methods: We conducted a literature review on the risks associated with the use of antibiotics in the elderly. The information was based on the update of the scientific evidence and information from the drug Sheets. The search was limited to the past 11 years, selected papers published in English, Spanish or French. We performed an electronic search of secondary sources (systematic reviews) and a manual search “ad hoc” basis of the literature retrieved, primary studies, reports of drug evaluation agencies, clinical practice guidelines and documents of Scientific Societies. Information sources: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®.Results: We identified 321 results, after eliminating those who did not meet inclusion criteria 52 papers in addition to the technical specifications of all mentioned antibiotics were included in the literature review.Conclusion: Older patients can acquire infections more frequently multi-resistant pathogens and suffer more serious complications of infections. The antibiotics is a group of drugs sensitive to the physiological changes induced by aging, which may influence the response to these and often requires dosage modifications to avoid poisoning and / or therapeutic failures. This paper provides information on these physiological changes and risks of antibiotics in the elderly, aspects necessary to choose a proper treatment

Resultados clínicos iniciales y variables pronósticas en la implementación de un Código Sepsis en un Hospital Universitario de alta complejidad

Objective: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. Methods: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. Results: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p 65 years (OR 5.33, p 3 mmol/L (OR 5,85, p 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). Conclusions: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programsObjetivo. Evaluar el impacto de un programa educativo y organizativo llamado Código Sepsis, en los primeros siete meses de su aplicación en un hospital de alta complejidad. Material y métodos. Se realizó un estudio observacional durante un período consecutivo de siete meses (Febrero 2015-Septiembre 2015). Se analizó la relación con la mortalidad de los factores de riesgo y los valores analíticos usando análisis uni y multivariante. Resultados. Se incluyeron un total de 237 pacientes. La mortalidad intrahospitalaria a los 30 días fue del 24 % y del 27% a los 60 días. La mortalidad de los pacientes ingresados en Unidades de Cuidados Críticos fue del 30%. Se encontraron diferencias significativas entre los pacientes que murieron y los que sobrevivieron en sus valores medios de creatinina (2,30 vs 1,46 mg/dL, p <0,05), ácido láctico (6,10 vs 2,62 mmol/L, p <0,05) y procalcitonina (23,27 vs 12,73 mg/dL, p <0,05). Se encontró una tendencia lineal estadísticamente significativa entre los valores de la escala SOFA y la mortalidad (p <0,05). En el análisis multivariante se identificaron otros factores de riesgo independientes asociados con la muerte: edad > 65 años (OR 5,33, p 3 mmol/L (OR 5,85, p <0,05), creatinina > 1,2 mgr/dL (OR 4,54, p <0,05) y el shock (OR 6,57, P <0,05). Conclusiones. La mortalidad en este estudio se encuentra dentro de los límites de los ensayos clínicos más recientes de sepsis. El estudio ha identificado varios marcadores que podrían ser útiles a nivel local para estimar el riesgo en pacientes sépticos. Estudios como éste son necesarios para hacer mejoras en los programas de Código Sepsi

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defned. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confrmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n=58) or allogeneic stem cell transplantation (allo-SCT) (n=65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p=0.02). Prognostic factors identifed for day 45 overall mortality (OM) by logistic regression multivariate analysis included age>70 years [odds ratio (OR) 2.1, 95% con‑ fdence interval (CI) 1.2-3.8, p=0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p<0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p=0.02) whereas the use of hidroxycloroquine did not show signifcant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P=0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of infammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3–6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin’s lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research. We thank the Spanish Society of Hematology (SEHH) for its support on the study. We sincerely want to thanks the invaluable aid of microbiology services for their commitment in SARS-CoV-2-reactive IgG antibody monitoring in these highly immunosuppressed patients from all participating centers. Finally, we also want to thank the patients, nurses, and study coordinators for their foremost contributions in this study.Peer reviewe

Long-term impact of an educational antimicrobial stewardship programme in primary care on infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community: an interrupted time-series analysis

PIRASOA-FIS team.[Background] There is little evidence on the ecological effect and sustainability of antimicrobial stewardship programmes (ASPs) in primary-care settings. We aimed to determine whether a multimodal, educational ASP would be sustainable in the long-term and reduce the incidence of infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community by optimising antibiotic use.[Methods] We did this quasi-experimental intervention study in 214 primary health centres of four primary health-care districts in Andalusia, Spain. Local multidisciplinary teams, comprised of general practitioners, paediatricians, primary-care pharmacists, and epidemiologists, were created in each district and implemented a multimodal, education-based ASP. The core activity of the programme consisted of regular one-to-one educational interviews between a reference interviewing physician and prescribing physicians from each centre on the appropriateness of their most recent (same or preceding day) antibiotic prescriptions based on a structured questionnaire. Appropriate prescribing was defined as compliance of all checklist items with the reference guidelines. An average of five educational interviews were scheduled per prescriber per study year. We did an interrupted time-series analysis to assess the effect of the intervention on quarterly antibiotic use (prescription and collection by the patient) and quality of prescriptions (as defined daily doses per 1000 inhabitants per day) and incidence per 1000 inhabitants of E coli producing extended-spectrum β-lactamase (ESBL) isolated from urine samples.[Findings] The study was done between January, 2012, and December, 2017, in a pre-intervention period of 2012–13 and an intervention period of 2014–17. Throughout the study period, there were 1387 physicians (1116 general practicioners and 271 paediatricians) in the included health centres serving a mean population of 1 937 512 people (299 331 children and 1 638 181 adults). 24 150 educational interviews were done over the 4 years. Inappropriate antibiotic prescribing was identified in 1794 (36·5%) of 4917 educational interviews in 2014 compared with 1793 (26·9%) of 6665 in 2017 (p<0·0001). The intervention was associated with a sustained reduction in the use of ciprofloxacin (relative effect −15·9%, 95% CI −23·9 to −8·0) and cephalosporins (−22·6%, −35·9 to −9·2), and a sustained increase in the use of amoxicillin (22·2%, 6·4 to 38·0) and fosfomycin trometamol (6·1%, 2·6 to 9·6). The incidence density of ESBL-producing E coli decreased by −0·028 cases per 1000 inhabitants (95% CI −0·034 to −0·021) after the start of the programme, reversing the pre-intervention increase and leading to a relative reduction of −65·6% (−68·2 to −63·0) 4 years later.[Interpretation] Our data suggest that implementation of a multimodal ASP in primary care that is based on individual educational interviews improves the use of antibiotics and results in a sustained significant reduction of infections by ESBL-producing E coli in the community. This information should encourage the implementation of ASPs in primary care.Instituto de Salud Carlos III, Spanish Government (PI14/01523)

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.Ye

Guía de Terapéutica Antimicrobiana del Área Aljarafe, 3ª edición

Coordinadora: Rocío Fernández Urrusuno. Co-coordinadora: Carmen Serrano Martino.YesEstas guías son un recurso indispensable en los Programas de Optimización de Antibióticos (PROA). No sólo constituyen una herramienta de ayuda para la toma de decisiones en los principales síndromes infecciosos, proporcionando recomendaciones para el abordaje empírico de dichos procesos, sino que son el patrón/estándar de referencia que permitirá determinar la calidad o adecuación de los tratamientos realizados. Las guías pueden ser utilizadas, además, como herramienta de base para la formación y actualización en antibioterapia, ya que permiten mantener actualizados los conocimientos sobre las nuevas evidencias en el abordaje de las infecciones. Por último, deberían incorporar herramientas que faciliten el proceso de toma de decisiones compartidas con el paciente. El objetivo de esta guía es proporcionar recomendaciones para el abordaje de las enfermedades infecciosas más prevalentes en la comunidad, basadas en las últimas evidencias disponibles y los datos de resistencias de los principales patógenos que contribuyan a mejorar la calidad de la prescripción de antimicrobianos