Clinically important pharmacokinetic drug-drug interactions with antibacterial agents.

Antimicrobial agents are widely used, and drug interactions are challenging due to increased risk of adverse effects or reduced efficacy. Among the interactions, the most important are those affecting metabolism, although those involving drug transporters are becoming increasingly known. To make clinical decisions, it is key to know the intensity of the interaction, as well as its duration and time-dependent recovery after discontinuation of the causative agents. It is not only important to be aware of all patient treatments, but also of supplements and natural medications that may also interact. Although they can have serious consequences, most interactions can be adequately managed with a good understanding of them. Especially in patients with polipharmacy it is compulsory to check them with an electronic clinical decision support database. This article aims to conduct a narrative review focusing on the major clinically significant pharmacokinetic drug-drug interactions that can be seen in patients receiving treatment for bacterial infections.

Alternatives for the administration of oral antineoplastics in patients with swallowing difficulties.

Oncology patients often experience swallowing difficulties, which can compromise adherence to treatment and consequently reduce its effectiveness. Improper handling of these hazardous drugs can lead to the risk of inhalation of particles or other exposures endangering the health of the persons involved such as nurses and pharmacists. The aim of this review is to analyse and update the recommendations for the manipulation of oral antineoplastic drugs in patients with swallowing difficulties. A literature review of articles, websites, guidelines and other documents published up to about the conditions of handling and administration of oral antineoplastic agents in oncology and oncohaematology was carried out. A table of 110 active principles was compiled. The information was grouped according to the name of the drug, instructions for oral and nasogastric tube administration and suggested recommendations. Among the drugs reviewed, 66.4% were suitable for dissolution. Although there is a lot of information in the literature, the nonstop development of new oncological drugs requires continuous updating. Therefore, we have collected the most recent data to provide a consultation tool for healthcare professionals and patients with swallowing difficulties.

This review can be used by all types of healthcare professionals, especially nurses, who handle oncological medicinal drugs. In addition, the safest handling methods for the worker have been recommended.

Compatibilidad de los fármacos administrados en «Y» en las unidades de cuidados intensivos: revisión sistemática / Compatibility of drugs administered as Y-site infusion in intensive care units: A systematic review

Objetivos: Recopilar la información publicada sobre estabilidad de los fármacos usados en el paciente crítico, evaluar la calidad de los datos publicados y generar una tabla de compatibilidad con información actualizada. Diseño: 1) Se realizó una búsqueda sistemática en las bases de datos Medline, Stabilis, Handbook on Injectable Drugs y Micromedex, para completar y actualizar la información disponible. Se incluyeron los estudios publicados entre 1990 y 2017 redactados en inglés, español y francés; 2) se analizó la calidad de los artículos según los criterios indicados en las guías de práctica para estudios de estabilidad; 3) se construyó una tabla de compatibilidades con los datos hallados para las combinaciones binarias de 44 fármacos de uso frecuente en unidades de cuidados intensivos (UCI). Ámbito: UCI de hospitales españoles e internacionales. Resultados: La revisión sistemática incluyó 29 artículos (27 originales y 2 revisiones). Ningún estudio cumplió todos los criterios de calidad establecidos, aunque el 93% garantizaba una correcta reproducibilidad. La tabla final aporta datos de compatibilidad fisicoquímica de 475 de las 945 combinaciones posibles (50,3%), de las cuales 366 (77,1%) son compatibles y 80 (16,8%) son incompatibles. Conclusiones: Se proporciona una actualización de las compatibilidades entre los fármacos habitualmente empleados en las UCI, con la intención de contribuir a la administración segura de medicamentos en pacientes críticos

Objectives: To gather all published information about the stability of drugs commonly used in Intensive Care Units (ICU); evaluate the methodology of published data; and generate a compatibility table. Design: i) A systematic review was conducted searching the following databases: Medline, Stabilis, Handbook of Injectable Drugs and Micromedex. Articles published from 1990 to 2017 in English, Spanish and French were included. ii) Article quality was analyzed according to the stability studies practice guidelines. iii) A compatibility table was produced with data for 44 binary combinations of drugs frequently used in the ICU. Scope: Spanish and international hospital ICU. Results: The systematic review included 29 studies (27 originals, 2 reviews). None of the included studies followed all the methodological requirements. However, 93% guaranteed correct reproducibility. Accordingly, drug stability knowledge was available for 50.3% of the studied admixtures, in which 77.1% of the binary combinations proved compatible and 16.8% proved incompatible. Conclusions: This review provides new reliable evidence about the physicochemical stability of drugs commonly used in the critical care setting. The study contributes to the safe administration of intravenous drugs in critical patients with a view to avoiding adverse events in this frail population

Compatibility of drugs administered as Y-site infusion in intensive care units: A systematic review. / Compatibilidad de los fármacos administrados en «Y¼ en las unidades de cuidados intensivos: revisión sistemática.

OBJECTIVES: To gather all published information about the stability of drugs commonly used in Intensive Care Units (ICU); evaluate the methodology of published data; and generate a compatibility table. DESIGN: i) A systematic review was conducted searching the following databases: Medline, Stabilis, Handbook of Injectable Drugs and Micromedex. Articles published from 1990 to 2017 in English, Spanish and French were included. ii) Article quality was analyzed according to the stability studies practice guidelines. iii) A compatibility table was produced with data for 44 binary combinations of drugs frequently used in the ICU. SCOPE: Spanish and international hospital ICU. RESULTS: The systematic review included 29 studies (27 originals, 2 reviews). None of the included studies followed all the methodological requirements. However, 93% guaranteed correct reproducibility. Accordingly, drug stability knowledge was available for 50.3% of the studied admixtures, in which 77.1% of the binary combinations proved compatible and 16.8% proved incompatible. CONCLUSIONS: This review provides new reliable evidence about the physicochemical stability of drugs commonly used in the critical care setting. The study contributes to the safe administration of intravenous drugs in critical patients with a view to avoiding adverse events in this frail population.

Dosificación de cidofovir en un paciente crítico en hemodiafiltración continua venovenosa / Cidofovir dosage in a critically ill patient undergoing continuous veno-venous hemodiafiltration

No disponible

Dosificación de antibióticos antipseudomónicos en pacientes con disfunción renal aguda sometidos a técnicas continuas de depuración extrarenal / Dosage of antipseudomonal antibiotics in patients with acute kidney injury subjected to continuous renal replacement therapies

Pseudomonas es un patógeno frecuente en las unidades de pacientes críticos y puede ser causa de shock séptico y de fallo renal. Es fundamental en estos pacientes instaurar un tratamiento antibiótico precoz y a dosis adecuadas. La disfunción renal aguda es también habitual en pacientes críticos. En aquellos que necesitan depuración extrarenal, las técnicas continuas de depuración extrarenal (TCDE) son una alternativa a la hemodiálisis intermitente y es necesario tener en cuenta que muchos antibióticos se eliminan de forma sustancial por las TCDE. El objetivo de esta revisión es analizar la evidencia clínica disponible sobre el comportamiento farmacocinético y las recomendaciones posológicas de los principales grupos de antibióticos empleados en el tratamiento de infecciones por Pseudomonas spp. en pacientes críticos sometidos a técnicas continuas de depuración extrarenal (AU)

Critically ill patients are often affected by infections produced by Pseudomonas, which can be a cause of sepsis and renal failure. Early and adequate antibiotic treatment at correct dosage levels is crucial. Acute kidney injury is also frequent in critically ill patients. In those patients who require renal replacement therapy, continuous techniques are gaining relevance as filtering alternatives to intermittent hemodialysis. It must be taken into account that many antibiotics are largely cleared by continuous renal replacement therapies (CRRT).The aim of this review is to assess the clinical evidence on the pharmacokinetics and dosage recommendations of the main antibiotic groups used to treat Pseudomonas spp. infections in critically ill patients subjected to CRRT (AU)

[Dosage of antipseudomonal antibiotics in patients with acute kidney injury subjected to continuous renal replacement therapies]. / Dosificación de antibióticos antipseudomónicos en pacientes con disfunción renal aguda sometidos a técnicas continuas de depuración extrarenal.

Critically ill patients are often affected by infections produced by Pseudomonas, which can be a cause of sepsis and renal failure. Early and adequate antibiotic treatment at correct dosage levels is crucial. Acute kidney injury is also frequent in critically ill patients. In those patients who require renal replacement therapy, continuous techniques are gaining relevance as filtering alternatives to intermittent hemodialysis. It must be taken into account that many antibiotics are largely cleared by continuous renal replacement therapies (CRRT). The aim of this review is to assess the clinical evidence on the pharmacokinetics and dosage recommendations of the main antibiotic groups used to treat Pseudomonas spp. infections in critically ill patients subjected to CRRT.

Riesgos de la digoxina en el anciano / No disponible

No disponible

Utilización y coste de los antídotos en dos servicios de urgencias hospitalarios / Use and cost of antidotes in 2 hospital emergency department

Objetivo: Los antídotos constituyen una medida básica para el tratamiento de determinadas intoxicaciones agudas. El objetivo de este estudio es describir la utilización de antídotos en la práctica clínica de los servicios de urgencias (SU) de dos hospitales y precisar el coste que representa la terapéutica antidótica respecto al coste global del tratamiento farmacológico del enfermo intoxicado. Método: Estudio prospectivo y descriptivo, diseñado para conocer la utilización y el coste farmacéutico de los antídotos administrados en los SU de dos hospitales universitarios. El periodo de recogida de datos fue de marzo a noviembre de 2006. Las variables evaluadas fueron el uso, la idoneidad y la eficacia del antídoto, así como el coste del tratamiento farmacológico (antídotos y medicación concomitante).Resultados: Se realizaron 228 administraciones de 14 antídotos diferentes a 184 pacientes(el 8,7% de las intoxicaciones agudas atendidas durante el periodo de estudio).Se consideró que el uso del antídoto había estado justificada para intentar revertir los efectos del tóxico en el 85,3% de los casos, correspondientes a 10 de los 14 antídotos utilizados. Tras la administración, se consiguieron los efectos esperados en el 73,9% de los casos. El 16% de las administraciones de flumazenilo y el 4% de las de naloxona no estuvieron bien indicadas. Se observaron reacciones adversas en el 6,5% de las administraciones. El coste que representaron los antídotos respecto al coste global del tratamiento farmacológico de los pacientes intoxicados fue del 81,97%, cifra que supone el1,1% del gasto farmacológico total del SU durante el periodo de estudio. Conclusiones: La indicación de los antídotos en urgencias fue globalmente adecuada, pero no exenta de efectos secundarios. El flumazenilo y la naloxona fueron utilizados con excesiva frecuencia. El coste económico que representa el tratamiento con antídotos es muy bajo (AU)

Background and objectives: Antidotes are basic resources among the options available for treating certain types of acute intoxication. The aim of this study was to describe the use of antidotes in the emergency departments of 2hospitals and to determine the cost of using these drugs in the context of the overall treatment of patients who have been poisoned. Material and methods: Prospective descriptive study of the use and cost of antidotes administered in the emergency departments of 2 university teaching hospitals. Data were collected from March through November 2006. Variables assessed were the use, suitability, and efficacy of each antidote, and the total expenditure on drugs (antidotes plus other medications).Results: Antidotes were administered 228 times to 184 patients (8.7% of acute intoxications attended during the study period). Use of the antidote was considered justified in the attempt to reverse the effect of poisoning in 85.3% of the cases, corresponding to 10 of the 14 antidotes used. The expected reversal was achieved in 73.9% of the cases. Use was inappropriate in 16% of the administrations of flumazenil and 4% of the administrations of naloxone. Adverse events were recorded in 6.5% of the cases in which antidotes were used. Expenditure on antidotes accounted for 81.97% of the total amount spent on the pharmacologic treatment of poisoned patients and 1.1% of the amount spent on all drugs used in emergency department care during the study period. Conclusions: The use of antidotes in the emergency department is largely appropriate but not free of side effects. Flumazenil and naloxone were used too often. Expenditure on antidotes is very low (AU)

Impacto de distintos métodos de estimación de la función renal en la dosificación de meropenem, piperacilina/tazobactam y cefepima en pacientes críticos / No disponible

Objetivo: Evaluar las desviaciones de dosificación de 3 antibióticos betalactámicos eliminados por vía renal (meropenem, piperacili na/tazobactam y cefepima) mediante la comparación de 2 fórmulas de predicción de función renal, Cockroft-Gault (CG) y Modification of Diet in Renal Disease (MDRD), con el aclaramiento de creatinina en orina de 24h (ClCr24h) como método de referencia. Método: Las 125 muestras de 61 pacientes (cada una con sus valores de CG, MDRD y ClCr24h) de una unidad de cuidados intensivos (UCI) se clasificaron en los 5 estadios definidos por la National Kidney Foundation (NKF) en función del ClCr24h. Se estudiaron las discrepancias de dosificación de cada antibiótico según CG o MDRD en referencia al ClCr24h por acuerdo porcentual e índice kappa ponderado. En cada estadio de NKF se cuantificaron las diferencias de dosificación diaria (¿ = DosisCG-DosisClCr24h; ¿ = Dosis MDRD DosisClCr24h) y el porcentaje de muestras con discrepancias de dosificación por CG y MDRD en referencia al ClCr24h. Resultados: En ningún caso se observaron diferencias estadísticamente significativas entre ambas fórmulas con respecto al ClCr24h, obteniendo grados de concordancia buenos. Los porcentajes de desviaciones oscilaron del 15,2% al 28% y ocurrieron mayoritariamente por infradosificación en los estadios 1 y 2, y por sobredosificación en los estadios 4 y 5. Conclusiones: Las dos predicciones de función renal en pacientes de la UCI pueden ser empleadas indistintamente para la dosificación de betalactámicos, aunque la de CG es la más sencilla (AU)

The impact of different renal function measuring methods on the dosages of meropenem, piperacillin/tazobactam and cefepime in critically ill patients Objective: Assesment of dosage deviations of three â-lactam antibiotics eliminated through the kidneys (meropenem, piperacillin/tazobactam and cefepime) by comparison of two prediction formulae, Cockroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD)with 24 h urinary creatinine clearance (CrCl24h), as a reference method. Method: 125 samples of 61 critically ill patients (each one with CG,MDRD y CrCl24hvalues) were classified in one of the five stages of the National Kidney Foundation (NKF) according to CrCl24h. Dosage discrepancies for each antibiotic based on CG y MDRD were studied in reference to CrCl24hby percentage agreement and weighted kappa. At each of the NKF stages, daily dosage differences (∆=DosisCG-DosisCrCl24h;∆=DosisMDRD-DosisCrCl24h) and percentage of samples with dosage discrepancies by CG and MDRD in reference to CrCl24h were calculated. Results: There were no statistically significant differences between the two prediction formulae in respect to CrCl24h, achieving good degrees of concordance. Deviation percentages fluctuated between15.2% and 28% and occurred mainly by under dosing on stages 1and 2 and by overdosing on stages 4 and 5.Conclusions: The two renal function prediction formulae can be indistinctly used to optimize the â-lactam antibiotics dose regimen, CGbeing the easiest one (AU)

[The impact of different renal function measuring methods on the dosages of meropenem, piperacillin/tazobactam and cefepime in critically ill patients]. / Impacto de distintos métodos de estimación de la función renal en la dosificación de meropenem, piperacilina/tazobactam y cefepima en pacientes críticos.

OBJECTIVE: Assesment of dosage deviations of three ss-lactam antibiotics eliminated through the kidneys (meropenem, piperacillin/tazobactam and cefepime) by comparison of two prediction formulae, Cockroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) with 24 h urinary creatinine clearance (CrCl(24h)), as a reference method. METHOD: 125 samples of 61 critically ill patients (each one with CG, MDRD y CrCl(24h) values) were classified in one of the five stages of the National Kidney Foundation (NKF) according to CrCl(24h). Dosage discrepancies for each antibiotic based on CG y MDRD were studied in reference to CrCl(24h) by percentage agreement and weighted kappa. At each of the NKF stages, daily dosage differences (Delta=DosisCG-DosisCrCl(24h); Delta=DosisMDRD-DosisCrCl(24h)) and percentage of samples with dosage discrepancies by CG and MDRD in reference to CrCl(24h) were calculated. RESULTS: There were no statistically significant differences between the two prediction formulae in respect to CrCl(24h), achieving good degrees of concordance. Deviation percentages fluctuated between 15.2% and 28% and occurred mainly by underdosing on stages 1 and 2 and by overdosing on stages 4 and 5. CONCLUSIONS: The two renal function prediction formulae can be indistinctly used to optimize the ss-lactam antibiotics dose regimen, CG being the easiest one.

Intoxicaciones digitálicas agudas en pacientes de edad avanzada y propuesta de un nomograma de digitalización / No disponible

No disponible

[Drotrecogin alfa (activated): specific treatment for serious sepsis]. / Drotrecogina alfa (activada): tratamiento específico para la sepsis grave.

Severe sepsis is a high prevalent disease at Intensive Care Units with no specific treatment till recently. Several clinical trials show low serum levels of activated protein C in this kind of patients. Recently, drotrecogin alfa (activated), a recombinant human activated protein C, has been approved in Spain for severe sepsis treatment in addition to the best patient care. Protein C (activated) has antithrombotic, profibrinolitic an antiinflamatory properties. So far, Prowess (phase 3 trial) is the most important clinical trial conducted with drotrecogin alfa (activated) at the moment. It demonstrates not only its efficacy and safety, but also a 19.4% reduction in the relative risk of death. Nevertheless, it is difficult to decide which patients would be candidate for this new therapy due to its lack of experience, high cost and the risk-benefit relationship. This review attempts to provide an overview about this new hospital drug.